Cardiology

U.S. veterans of the post-9/11 wars who suffered a traumatic brain injury (TBI) are at increased risk of developing cardiovascular disease (CVD). More severe TBI is associated with higher risk of CVD, new research shows.

Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.

The study was published online  in JAMA Neurology.
 

Novel data

Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.

While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.

The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.

In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).

Unrecognized CVD risk factor?

Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”

“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.

In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”

“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.

The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

U.S. veterans of the post-9/11 wars who suffered a traumatic brain injury (TBI) are at increased risk of developing cardiovascular disease (CVD). More severe TBI is associated with higher risk of CVD, new research shows.

Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.

The study was published online  in JAMA Neurology.
 

Novel data

Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.

While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.

The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.

In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).

Unrecognized CVD risk factor?

Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”

“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.

In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”

“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.

The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

U.S. veterans of the post-9/11 wars who suffered a traumatic brain injury (TBI) are at increased risk of developing cardiovascular disease (CVD). More severe TBI is associated with higher risk of CVD, new research shows.

Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.

The study was published online  in JAMA Neurology.
 

Novel data

Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.

While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.

The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.

In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).

Unrecognized CVD risk factor?

Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”

“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.

In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”

“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.

The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

A version of this article first appeared on WebMD.com.

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

A version of this article first appeared on WebMD.com.

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

A version of this article first appeared on WebMD.com.

Heparin started in the ambulance or emergency department (ED) makes it more likely a patient with acute ST-segment elevation myocardial infarction (STEMI) will present to the cath lab without a coronary artery occlusion, suggests a large registry study.

An open infarct-related artery (IRA) at angiography on cath-lab arrival presents STEMI patients an opportunity for earlier reperfusion and a chance, in theory at least, for smaller infarcts and maybe improved clinical outcomes.

In the new analysis, which covers more than 40,000 patients with STEMI in Sweden, the 38% who received heparin before cath-lab arrival were 11% less likely to show IRA occlusion at angiography prior to direct percutaneous coronary intervention (PCI). They also showed a 13% lower 30-day mortality compared with patients who were started on heparin in the cath lab. Importantly, their risk of major bleeding in the hospital did not increase.

The “early reperfusion” associated with IRA patency at angiography “could have long-term benefit due to smaller infarct size,” potentially explaining the observed 30-day survival gain in the pretreatment group, Oskar Love Emilsson, Lund (Sweden) University, said in an interview.

Mr. Emilsson, a third-year medical student, reported the analysis at the annual congress of the European Society of Cardiology, and is lead author on its same-day publication in the journal EuroIntervention.

He mentioned a few cautions in interpreting the study, which is based primarily on data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). It included several sensitivity analyses that continued to back pretreatment heparin as a significant predictor of an unoccluded IRA but didn’t consistently support the 30-day mortality benefit seen in the primary analysis.

And, although the pretreatment group overall didn’t have more major bleeds, the risk did go up significantly for those older than 75 or those who weighed less than 60 kg (132 pounds) or underwent catheterization with an access route other than the radial artery. Extra caution should be exercised in such patients who receive heparin before cath-lab arrival for PCI, Mr. Emilsson observed.

“Our results suggest that heparin pretreatment might be a good option to improve patency of infarct related arteries in STEMI,” and potentially clinical outcomes, he said. “However, a definite answer would require a randomized controlled trial.”

Meanwhile, the current study may be the largest yet to look at clinical outcomes after pretreatment with unfractionated heparin before PCI for acute STEMI, the report states. There have been some observational studies, subanalyses of STEMI trials, and even a few limited randomized trials – including the HEAP trial published in 2000 – to weigh in on the subject. Some have supported the strategy, others have not.

“With rapid door-to-balloon times in STEMI, it can be challenging to show a significant difference between a prehospital heparin approach and heparin given in the lab,” observed Sunil V. Rao, MD, NYU Langone Health System, New York, who is not connected with the current study.

Many EDs in the United States have “a STEMI protocol that calls for an IV bolus of heparin. It would be tougher in the U.S. to give it in the ambulance but again, it’s not clear how much advantage that would really provide,” he told this news organization.

Support from randomized trials would be needed before the practice could be formally recommended. “The SCAAR registries have set the standard for how registries should be conducted,” Dr. Rao said. “This is a very well done observational study, but it is observational.”

The priority for STEMI patients, he added, “really should be to get them to the lab as fast as possible. If the ED protocol includes heparin before the cath lab, that’s great, but I don’t think we should delay getting these patients to the lab to accommodate pre–cath-lab heparin.”

The current analysis covered 41,631 patients with STEMI from 2008 through to 2016, of whom 38% were pretreated with heparin in an ambulance or the ED. The remaining 62% initiated heparin in the cath lab.

About one-third of the group had an open IRA at angiography. The adjusted risk ratio (RR) for IRA occlusion at angiography for patients pretreated vs. not pretreated with heparin was 0.89 (95% confidence interval [CI], 0.87-0.90).

The corresponding RR for death within 30 days was 0.87 (95% CI, 0.77-0.99), and for major in-hospital bleeding it was 1.01 (95% CI, 0.86-1.18).

The analysis was adjusted for other medications received before cath-lab arrival, especially a long list of antiplatelets and non-heparin antithrombins. That strengthens the case for heparin pretreatment as an independent predictor of an open IRA at initial angiography, Mr. Emilsson said.

Comparisons of propensity-score–matched subgroups of the total cohort, conducted separately for the IRA-occlusion endpoint and the endpoints of 30-day mortality and major bleeding, produced similar results.

Some observational data suggest that antiplatelet pretreatment with a P2Y12 inhibitor may promote IRA patency on angiography after cath lab arrival, Dr. Rao observed. “This indicates that there probably is a role of earlier antithrombotic therapy in STEMI patients, but the randomized trials have not shown a consistent benefit,” he said, referring in particular to the ATLANTIC trial.

Mr. Emilsson and Dr. Rao disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Heparin started in the ambulance or emergency department (ED) makes it more likely a patient with acute ST-segment elevation myocardial infarction (STEMI) will present to the cath lab without a coronary artery occlusion, suggests a large registry study.

An open infarct-related artery (IRA) at angiography on cath-lab arrival presents STEMI patients an opportunity for earlier reperfusion and a chance, in theory at least, for smaller infarcts and maybe improved clinical outcomes.

In the new analysis, which covers more than 40,000 patients with STEMI in Sweden, the 38% who received heparin before cath-lab arrival were 11% less likely to show IRA occlusion at angiography prior to direct percutaneous coronary intervention (PCI). They also showed a 13% lower 30-day mortality compared with patients who were started on heparin in the cath lab. Importantly, their risk of major bleeding in the hospital did not increase.

The “early reperfusion” associated with IRA patency at angiography “could have long-term benefit due to smaller infarct size,” potentially explaining the observed 30-day survival gain in the pretreatment group, Oskar Love Emilsson, Lund (Sweden) University, said in an interview.

Mr. Emilsson, a third-year medical student, reported the analysis at the annual congress of the European Society of Cardiology, and is lead author on its same-day publication in the journal EuroIntervention.

He mentioned a few cautions in interpreting the study, which is based primarily on data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). It included several sensitivity analyses that continued to back pretreatment heparin as a significant predictor of an unoccluded IRA but didn’t consistently support the 30-day mortality benefit seen in the primary analysis.

And, although the pretreatment group overall didn’t have more major bleeds, the risk did go up significantly for those older than 75 or those who weighed less than 60 kg (132 pounds) or underwent catheterization with an access route other than the radial artery. Extra caution should be exercised in such patients who receive heparin before cath-lab arrival for PCI, Mr. Emilsson observed.

“Our results suggest that heparin pretreatment might be a good option to improve patency of infarct related arteries in STEMI,” and potentially clinical outcomes, he said. “However, a definite answer would require a randomized controlled trial.”

Meanwhile, the current study may be the largest yet to look at clinical outcomes after pretreatment with unfractionated heparin before PCI for acute STEMI, the report states. There have been some observational studies, subanalyses of STEMI trials, and even a few limited randomized trials – including the HEAP trial published in 2000 – to weigh in on the subject. Some have supported the strategy, others have not.

“With rapid door-to-balloon times in STEMI, it can be challenging to show a significant difference between a prehospital heparin approach and heparin given in the lab,” observed Sunil V. Rao, MD, NYU Langone Health System, New York, who is not connected with the current study.

Many EDs in the United States have “a STEMI protocol that calls for an IV bolus of heparin. It would be tougher in the U.S. to give it in the ambulance but again, it’s not clear how much advantage that would really provide,” he told this news organization.

Support from randomized trials would be needed before the practice could be formally recommended. “The SCAAR registries have set the standard for how registries should be conducted,” Dr. Rao said. “This is a very well done observational study, but it is observational.”

The priority for STEMI patients, he added, “really should be to get them to the lab as fast as possible. If the ED protocol includes heparin before the cath lab, that’s great, but I don’t think we should delay getting these patients to the lab to accommodate pre–cath-lab heparin.”

The current analysis covered 41,631 patients with STEMI from 2008 through to 2016, of whom 38% were pretreated with heparin in an ambulance or the ED. The remaining 62% initiated heparin in the cath lab.

About one-third of the group had an open IRA at angiography. The adjusted risk ratio (RR) for IRA occlusion at angiography for patients pretreated vs. not pretreated with heparin was 0.89 (95% confidence interval [CI], 0.87-0.90).

The corresponding RR for death within 30 days was 0.87 (95% CI, 0.77-0.99), and for major in-hospital bleeding it was 1.01 (95% CI, 0.86-1.18).

The analysis was adjusted for other medications received before cath-lab arrival, especially a long list of antiplatelets and non-heparin antithrombins. That strengthens the case for heparin pretreatment as an independent predictor of an open IRA at initial angiography, Mr. Emilsson said.

Comparisons of propensity-score–matched subgroups of the total cohort, conducted separately for the IRA-occlusion endpoint and the endpoints of 30-day mortality and major bleeding, produced similar results.

Some observational data suggest that antiplatelet pretreatment with a P2Y12 inhibitor may promote IRA patency on angiography after cath lab arrival, Dr. Rao observed. “This indicates that there probably is a role of earlier antithrombotic therapy in STEMI patients, but the randomized trials have not shown a consistent benefit,” he said, referring in particular to the ATLANTIC trial.

Mr. Emilsson and Dr. Rao disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Heparin started in the ambulance or emergency department (ED) makes it more likely a patient with acute ST-segment elevation myocardial infarction (STEMI) will present to the cath lab without a coronary artery occlusion, suggests a large registry study.

An open infarct-related artery (IRA) at angiography on cath-lab arrival presents STEMI patients an opportunity for earlier reperfusion and a chance, in theory at least, for smaller infarcts and maybe improved clinical outcomes.

In the new analysis, which covers more than 40,000 patients with STEMI in Sweden, the 38% who received heparin before cath-lab arrival were 11% less likely to show IRA occlusion at angiography prior to direct percutaneous coronary intervention (PCI). They also showed a 13% lower 30-day mortality compared with patients who were started on heparin in the cath lab. Importantly, their risk of major bleeding in the hospital did not increase.

The “early reperfusion” associated with IRA patency at angiography “could have long-term benefit due to smaller infarct size,” potentially explaining the observed 30-day survival gain in the pretreatment group, Oskar Love Emilsson, Lund (Sweden) University, said in an interview.

Mr. Emilsson, a third-year medical student, reported the analysis at the annual congress of the European Society of Cardiology, and is lead author on its same-day publication in the journal EuroIntervention.

He mentioned a few cautions in interpreting the study, which is based primarily on data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). It included several sensitivity analyses that continued to back pretreatment heparin as a significant predictor of an unoccluded IRA but didn’t consistently support the 30-day mortality benefit seen in the primary analysis.

And, although the pretreatment group overall didn’t have more major bleeds, the risk did go up significantly for those older than 75 or those who weighed less than 60 kg (132 pounds) or underwent catheterization with an access route other than the radial artery. Extra caution should be exercised in such patients who receive heparin before cath-lab arrival for PCI, Mr. Emilsson observed.

“Our results suggest that heparin pretreatment might be a good option to improve patency of infarct related arteries in STEMI,” and potentially clinical outcomes, he said. “However, a definite answer would require a randomized controlled trial.”

Meanwhile, the current study may be the largest yet to look at clinical outcomes after pretreatment with unfractionated heparin before PCI for acute STEMI, the report states. There have been some observational studies, subanalyses of STEMI trials, and even a few limited randomized trials – including the HEAP trial published in 2000 – to weigh in on the subject. Some have supported the strategy, others have not.

“With rapid door-to-balloon times in STEMI, it can be challenging to show a significant difference between a prehospital heparin approach and heparin given in the lab,” observed Sunil V. Rao, MD, NYU Langone Health System, New York, who is not connected with the current study.

Many EDs in the United States have “a STEMI protocol that calls for an IV bolus of heparin. It would be tougher in the U.S. to give it in the ambulance but again, it’s not clear how much advantage that would really provide,” he told this news organization.

Support from randomized trials would be needed before the practice could be formally recommended. “The SCAAR registries have set the standard for how registries should be conducted,” Dr. Rao said. “This is a very well done observational study, but it is observational.”

The priority for STEMI patients, he added, “really should be to get them to the lab as fast as possible. If the ED protocol includes heparin before the cath lab, that’s great, but I don’t think we should delay getting these patients to the lab to accommodate pre–cath-lab heparin.”

The current analysis covered 41,631 patients with STEMI from 2008 through to 2016, of whom 38% were pretreated with heparin in an ambulance or the ED. The remaining 62% initiated heparin in the cath lab.

About one-third of the group had an open IRA at angiography. The adjusted risk ratio (RR) for IRA occlusion at angiography for patients pretreated vs. not pretreated with heparin was 0.89 (95% confidence interval [CI], 0.87-0.90).

The corresponding RR for death within 30 days was 0.87 (95% CI, 0.77-0.99), and for major in-hospital bleeding it was 1.01 (95% CI, 0.86-1.18).

The analysis was adjusted for other medications received before cath-lab arrival, especially a long list of antiplatelets and non-heparin antithrombins. That strengthens the case for heparin pretreatment as an independent predictor of an open IRA at initial angiography, Mr. Emilsson said.

Comparisons of propensity-score–matched subgroups of the total cohort, conducted separately for the IRA-occlusion endpoint and the endpoints of 30-day mortality and major bleeding, produced similar results.

Some observational data suggest that antiplatelet pretreatment with a P2Y12 inhibitor may promote IRA patency on angiography after cath lab arrival, Dr. Rao observed. “This indicates that there probably is a role of earlier antithrombotic therapy in STEMI patients, but the randomized trials have not shown a consistent benefit,” he said, referring in particular to the ATLANTIC trial.

Mr. Emilsson and Dr. Rao disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.

“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.

Mitchel L. Zoler/MDedge News

The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.

In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.

For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).

“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.

New analysis provides positive trial result

When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.

Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.

In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.

The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.

“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.

In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
 

Investigator, adjudicated outcomes differ

Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).

“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.

One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.

“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.

Mitchel L. Zoler/MDedge News

He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.

However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.

“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”

However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.

Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.

A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.

“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.

Mitchel L. Zoler/MDedge News

The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.

In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.

For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).

“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.

New analysis provides positive trial result

When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.

Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.

In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.

The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.

“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.

In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
 

Investigator, adjudicated outcomes differ

Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).

“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.

One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.

“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.

Mitchel L. Zoler/MDedge News

He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.

However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.

“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”

However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.

Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.

A post hoc analysis of the PARADISE-MI trial, although not intended to alter the conclusions generated by the published data, suggests that clinically relevant benefits were obscured, providing the basis for recommending different analyses for future studies that are more suited to capture the most clinically significant endpoints.

“What these data show us is that we need clinical trial designs moving towards more pragmatic information that better reflect clinical practice,” reported Otavio Berwanger, MD, PhD, director of the Academic Research Organization at Hospital Israelita Albert Einstein, São Paulo, Brazil.

Mitchel L. Zoler/MDedge News

The reevaluation of the PARADISE-MI data, presented at the annual congress of the European Society of Cardiology in Barcelona, was based on a win ratio analysis and on the inclusion of investigator-reported endpoints, not just adjudicated events. Both appear to reveal clinically meaningful benefits not reflected in the published study, according to Dr. Berwanger.

In PARADISE-MI, which was published in the New England Journal of Medicine last year, more than 5,500 patients were randomized to the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan or the ACE inhibitor ramipril after a myocardial infarction. A reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both were required for enrollment.

For the primary composite outcomes of death from cardiovascular (CV) causes or incident heart failure, the ARNI had a 10% numerical advantage, but it did not reach statistical significance (hazard ratio [HR], 0.90; P = .17).

“PARADISE-MI was a neutral trial. This post hoc analysis will not change that result,” Dr. Berwanger emphasized. However, the post hoc analysis does provide a basis for exploring why conventional trial designs might not be providing answers that are relevant and helpful for clinical practice.

New analysis provides positive trial result

When the data from PARADISE-MI are reevaluated in a hierarchical win ratio analysis with CV death serving as the most severe and important outcome, the principal conclusion changes. Whether events are reevaluated in this format by the clinical events committee (CEC) or by investigators, there is a greater number of total wins than total losses for the ARNI. Combined, sacubitril/valsartan was associated with a win ratio of 1.17 (95% confidence interval, 1.03-1.33; P = 0.015) over ramipril.

Using a sports analogy, Dr. Berwanger explained that the win ratio analysis divides the total number of wins to the total number of losses to provide a much more clinically relevant approach to keeping score. It also used a hierarchical analysis so that the most serious and important events are considered first.

In addition to CV death, this analysis included first hospitalization for heart failure and first outpatient heart failure events. CEC-defined events and events reported by investigators were evaluated separately.

The ARNI had more wins than losses in every category for all outcomes, whether CEC adjudicated or investigator reported, but most of this benefit was generated by the endpoint of CEC-adjudicated CV deaths. This accounted for 36.9% of all events (investigator-documented CV death accounted for 0.7%). This is important because PARADISE-MI, like many standard trials, was conducted on a time-to-primary event basis.

“In this type of analysis, the first event is what counts. Usually time-to-first-event analyses are dominated by nonfatal events,” Dr. Berwanger explained. He believes that placing more weight on the most serious events results in an emphasis on what outcomes are of greatest clinical interest.

In addition, Dr. Berwanger argued that it is important to consider investigator-reported events, not just CEC-adjudicated events. While adjudicated events improve the rigor of the data, Dr. Berwanger suggested it omits outcomes with which clinicians are most concerned.
 

Investigator, adjudicated outcomes differ

Again, using PARADISE-MI as an example, he reevaluated the primary outcome based on investigator reports. When investigator-reported events are included, the number of events increased in both the ARNI (443 vs. 338) and ramipril (516 vs. 373) arms, but the advantage of the ARNI over the ACE inhibitors now reached statistical significance (HR, 0.85; P = .01).

“The data suggest that maybe we should find definitions for adjudication that are closer to clinical judgment in the real world and clinical practice,” Dr. Berwanger said.

One possible explanation for the neutral result in PARADISE-MI is that benefit of an ARNI over an ACE inhibitor would only be expected in those at risk for progressive left ventricular dysfunction, and it is likely that a substantial proportion of patients enrolled in this trial recovered, according to Johann Bauersachs, MD, PhD, professor and head of cardiology at Hannover (Germany) Medical School.

“You cannot predict which patients with reduced LV function following an MI will go on to chronic remodeling and which will recover,” said Dr. Bauersachs, who was an ESC-invited discussant of Dr. Berwanger’s post hoc analysis.

Mitchel L. Zoler/MDedge News

He agreed that Dr. Berwanger has raised several important issues in standard trial design that might have prevented PARADISE-MI from showing a benefit from an ARNI, but he pointed out that there are other potential issues, such as the low use of mineralocorticoid antagonists in PARADISE-MI, that may have skewed results.

However, he agreed generally with the premise that there is a need for trial design likely to generate more clinically useful information.

“We have now seen the win-ratio approach used in several studies,” said Dr. Bauersachs, citing in particular the EMPULSE trial presented at the 2022 meeting of the American College of Cardiology. “It is a very useful tool, and I think we will be seeing it used more in the future.”

However, he indicated that the issues raised by Dr. Berwanger are not necessarily easily resolved. Dr. Bauersachs endorsed the effort to consider trial designs that generate data that are more immediately clinically applicable but suggested that different types of designs may be required for different types of clinical questions.

Dr. Berwanger reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Pfizer, Servier, and Novartis, which provided funding for the PARADISE-MI trial. Dr. Bauersachs reports financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, Vifor, and Zoll.

Young women (under 50) are increasingly having heart attacks without doctors really knowing why. This is where the Young Women Presenting Acute Myocardial Infarction in France (WAMIF) study comes in, the results of which were presented in an e-poster at the annual congress of the European Society of Cardiology by Stéphane Manzo-Silberman, MD, Institute of Cardiology, Pitié-Salpétrière, Paris. The results (yet to be published) fight several of the preconceived ideas on the topic, Dr. Manzo-Silberman commented in an interview.

Significantly higher hospital death rates in women

“Cardiovascular disease is the main cause of death in women, killing seven times more than breast cancer,” notes Dr. Manzo-Silberman. The hospital death rate is significantly higher in women and, despite going down, is significantly higher than in men (more than double), particularly in women under 50. What’s more, in addition to the typical risk factors, women present specific risk factors related to hormone changes, high-risk inflammatory profiles, and thrombophilia.”

The WAMIF study was designed to determine the clinical, biological, and morphological features linked to hospital mortality after 12 months in women under 50. The prospective, observational study included all women in this age range from 30 sites in France between May 2017 and June 2019.
 

90% with retrosternal chest pain

The age of the 314 women enrolled was 44.9 years on average. Nearly two-thirds (192) presented with ST-segment elevation myocardial infarction and the other 122 without. In terms of symptoms, 91.6% of these women presented with typical chest pain, and 59.7% had related symptoms.

“With more than 90% having retrosternal pain, the idea that myocardial infarction presents with atypical symptoms in women has been widely challenged, despite the fact that more than half present with related symptoms and it isn’t known in which order these symptoms occur, Dr. Manzo-Silberman said in an interview. But what we can say is that if at any point a young woman mentions chest pain, even when occurring as part of several other symptoms, MI must be deemed a possibility until it has been ruled out.”

The risk profile revealed that 75.5% were smokers, 35% had a family history of heart disease, 33% had pregnancy complications, and 55% had recently experienced a stressful situation. The analysis also showed that cannabis use and oral contraception were primary risk factors in women younger than 35.

“With regard to risk factors, when designing this study we expected that lots of these young women would have largely atypical autoimmune conditions, with high levels of inflammation. We looked for everything, but this was not actually the case. Instead, we found very many women to have classic risk factors; three-quarters were smokers, a modifiable risk factor, which can largely be prevented. The other aspect concerns contraception, and it’s why I insist that gynecologists must be involved insofar as they must inform their patients how to manage their risk factors and tweak their contraception.”

Coronary angiography findings showed that only 1% received a normal result, 29.3% had vessel damage, and 14.6% had aortic dissection. “We were surprised again here because we expected that with young women we would see lots of heart attacks without obstruction, [in other words] normal coronary arteries, atypical forms of MI,” commented Dr. Manzo-Silberman. “In fact, most presented with atheroma, often obstructive lesions, or even triple-vessel disease, in nearly a third of the cohort. So that’s another misconception dispelled – we can’t just think that because a woman is young, nothing will be found. Coronary catheterization should be considered, and the diagnostic process should be completed in full.”

After 1 year, there had been two cancer-related deaths and 25 patients had undergone several angioplasty procedures. Nevertheless, 90.4% had not experienced any type of CV event, and 72% had not even had any symptoms.

“The final surprise was prognosis,” he said. “Previous studies, especially some authored by Viola Vaccarino, MD, PhD, showed an excess hospital rate in women and we had expected this to be the case here, but no hospital deaths were recorded. However, not far off 10% of women attended (at least once) the emergency department in the year following for recurrent chest pain which was not ischemic – ECG normal, troponin normal – so something was missing in their education as a patient.”

“So, there are improvements to be made in terms of secondary prevention, follow-up, and in the education of these young female patients who have experienced the major event that is a myocardial infarction,” concluded Dr. Manzo-Silberman.

This content was originally published on Medscape French edition.

Young women (under 50) are increasingly having heart attacks without doctors really knowing why. This is where the Young Women Presenting Acute Myocardial Infarction in France (WAMIF) study comes in, the results of which were presented in an e-poster at the annual congress of the European Society of Cardiology by Stéphane Manzo-Silberman, MD, Institute of Cardiology, Pitié-Salpétrière, Paris. The results (yet to be published) fight several of the preconceived ideas on the topic, Dr. Manzo-Silberman commented in an interview.

Significantly higher hospital death rates in women

“Cardiovascular disease is the main cause of death in women, killing seven times more than breast cancer,” notes Dr. Manzo-Silberman. The hospital death rate is significantly higher in women and, despite going down, is significantly higher than in men (more than double), particularly in women under 50. What’s more, in addition to the typical risk factors, women present specific risk factors related to hormone changes, high-risk inflammatory profiles, and thrombophilia.”

The WAMIF study was designed to determine the clinical, biological, and morphological features linked to hospital mortality after 12 months in women under 50. The prospective, observational study included all women in this age range from 30 sites in France between May 2017 and June 2019.
 

90% with retrosternal chest pain

The age of the 314 women enrolled was 44.9 years on average. Nearly two-thirds (192) presented with ST-segment elevation myocardial infarction and the other 122 without. In terms of symptoms, 91.6% of these women presented with typical chest pain, and 59.7% had related symptoms.

“With more than 90% having retrosternal pain, the idea that myocardial infarction presents with atypical symptoms in women has been widely challenged, despite the fact that more than half present with related symptoms and it isn’t known in which order these symptoms occur, Dr. Manzo-Silberman said in an interview. But what we can say is that if at any point a young woman mentions chest pain, even when occurring as part of several other symptoms, MI must be deemed a possibility until it has been ruled out.”

The risk profile revealed that 75.5% were smokers, 35% had a family history of heart disease, 33% had pregnancy complications, and 55% had recently experienced a stressful situation. The analysis also showed that cannabis use and oral contraception were primary risk factors in women younger than 35.

“With regard to risk factors, when designing this study we expected that lots of these young women would have largely atypical autoimmune conditions, with high levels of inflammation. We looked for everything, but this was not actually the case. Instead, we found very many women to have classic risk factors; three-quarters were smokers, a modifiable risk factor, which can largely be prevented. The other aspect concerns contraception, and it’s why I insist that gynecologists must be involved insofar as they must inform their patients how to manage their risk factors and tweak their contraception.”

Coronary angiography findings showed that only 1% received a normal result, 29.3% had vessel damage, and 14.6% had aortic dissection. “We were surprised again here because we expected that with young women we would see lots of heart attacks without obstruction, [in other words] normal coronary arteries, atypical forms of MI,” commented Dr. Manzo-Silberman. “In fact, most presented with atheroma, often obstructive lesions, or even triple-vessel disease, in nearly a third of the cohort. So that’s another misconception dispelled – we can’t just think that because a woman is young, nothing will be found. Coronary catheterization should be considered, and the diagnostic process should be completed in full.”

After 1 year, there had been two cancer-related deaths and 25 patients had undergone several angioplasty procedures. Nevertheless, 90.4% had not experienced any type of CV event, and 72% had not even had any symptoms.

“The final surprise was prognosis,” he said. “Previous studies, especially some authored by Viola Vaccarino, MD, PhD, showed an excess hospital rate in women and we had expected this to be the case here, but no hospital deaths were recorded. However, not far off 10% of women attended (at least once) the emergency department in the year following for recurrent chest pain which was not ischemic – ECG normal, troponin normal – so something was missing in their education as a patient.”

“So, there are improvements to be made in terms of secondary prevention, follow-up, and in the education of these young female patients who have experienced the major event that is a myocardial infarction,” concluded Dr. Manzo-Silberman.

This content was originally published on Medscape French edition.

Young women (under 50) are increasingly having heart attacks without doctors really knowing why. This is where the Young Women Presenting Acute Myocardial Infarction in France (WAMIF) study comes in, the results of which were presented in an e-poster at the annual congress of the European Society of Cardiology by Stéphane Manzo-Silberman, MD, Institute of Cardiology, Pitié-Salpétrière, Paris. The results (yet to be published) fight several of the preconceived ideas on the topic, Dr. Manzo-Silberman commented in an interview.

Significantly higher hospital death rates in women

“Cardiovascular disease is the main cause of death in women, killing seven times more than breast cancer,” notes Dr. Manzo-Silberman. The hospital death rate is significantly higher in women and, despite going down, is significantly higher than in men (more than double), particularly in women under 50. What’s more, in addition to the typical risk factors, women present specific risk factors related to hormone changes, high-risk inflammatory profiles, and thrombophilia.”

The WAMIF study was designed to determine the clinical, biological, and morphological features linked to hospital mortality after 12 months in women under 50. The prospective, observational study included all women in this age range from 30 sites in France between May 2017 and June 2019.
 

90% with retrosternal chest pain

The age of the 314 women enrolled was 44.9 years on average. Nearly two-thirds (192) presented with ST-segment elevation myocardial infarction and the other 122 without. In terms of symptoms, 91.6% of these women presented with typical chest pain, and 59.7% had related symptoms.

“With more than 90% having retrosternal pain, the idea that myocardial infarction presents with atypical symptoms in women has been widely challenged, despite the fact that more than half present with related symptoms and it isn’t known in which order these symptoms occur, Dr. Manzo-Silberman said in an interview. But what we can say is that if at any point a young woman mentions chest pain, even when occurring as part of several other symptoms, MI must be deemed a possibility until it has been ruled out.”

The risk profile revealed that 75.5% were smokers, 35% had a family history of heart disease, 33% had pregnancy complications, and 55% had recently experienced a stressful situation. The analysis also showed that cannabis use and oral contraception were primary risk factors in women younger than 35.

“With regard to risk factors, when designing this study we expected that lots of these young women would have largely atypical autoimmune conditions, with high levels of inflammation. We looked for everything, but this was not actually the case. Instead, we found very many women to have classic risk factors; three-quarters were smokers, a modifiable risk factor, which can largely be prevented. The other aspect concerns contraception, and it’s why I insist that gynecologists must be involved insofar as they must inform their patients how to manage their risk factors and tweak their contraception.”

Coronary angiography findings showed that only 1% received a normal result, 29.3% had vessel damage, and 14.6% had aortic dissection. “We were surprised again here because we expected that with young women we would see lots of heart attacks without obstruction, [in other words] normal coronary arteries, atypical forms of MI,” commented Dr. Manzo-Silberman. “In fact, most presented with atheroma, often obstructive lesions, or even triple-vessel disease, in nearly a third of the cohort. So that’s another misconception dispelled – we can’t just think that because a woman is young, nothing will be found. Coronary catheterization should be considered, and the diagnostic process should be completed in full.”

After 1 year, there had been two cancer-related deaths and 25 patients had undergone several angioplasty procedures. Nevertheless, 90.4% had not experienced any type of CV event, and 72% had not even had any symptoms.

“The final surprise was prognosis,” he said. “Previous studies, especially some authored by Viola Vaccarino, MD, PhD, showed an excess hospital rate in women and we had expected this to be the case here, but no hospital deaths were recorded. However, not far off 10% of women attended (at least once) the emergency department in the year following for recurrent chest pain which was not ischemic – ECG normal, troponin normal – so something was missing in their education as a patient.”

“So, there are improvements to be made in terms of secondary prevention, follow-up, and in the education of these young female patients who have experienced the major event that is a myocardial infarction,” concluded Dr. Manzo-Silberman.

This content was originally published on Medscape French edition.

Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.

Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.

“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.

“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
 

Be proactive

“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.

“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.

The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.

Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg. 

The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.

Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.

The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
 

Even small changes can help

“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.

“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.

“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.

“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.

Dr. Wallace noted that diet changes don’t have to be drastic.

“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.

“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.

The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.

A version of this article first appeared on Medscape.com.

Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.

Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.

“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.

“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
 

Be proactive

“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.

“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.

The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.

Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg. 

The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.

Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.

The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
 

Even small changes can help

“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.

“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.

“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.

“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.

Dr. Wallace noted that diet changes don’t have to be drastic.

“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.

“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.

The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.

A version of this article first appeared on Medscape.com.

Healthy lifestyle changes to reduce systolic blood pressure to below 130 mm Hg may prevent 26,000 heart attacks and strokes and reduce health care costs over the next 10 years, a new simulation study suggests.

Among the various lifestyle changes, adopting the Dietary Approaches to Stop Hypertension diet, known as the DASH diet, may have the greatest impact for young and middle-aged adults with stage 1 hypertension.

“This research reveals that we should look to feasible ways our food system could make healthy eating the default option,” Kendra Sims, PhD, MPH, postdoctoral fellow at University of California, San Francisco, told this news organization.

“Above all, it means collaborating with the patient about nourishing choices that fit best into their culture and lifestyle,” Dr. Sims said.
 

Be proactive

“What is important is that people not wait until they have hypertension to start thinking about healthful diets,” commented Taylor Wallace, PhD, department of nutrition and food studies, George Mason University, Fairfax, Va., who was not involved in the study.

“It’s all about prevention in my mind. Whether you are hypertensive or are perfectly healthy, the DASH diet or any other dietary pattern that emphasizes consumption of fruits, vegetables, whole grains, lean meats, seafood, nuts/seeds, and low/non-fat dairy and decreased intake of saturated fats, added sugars, and sodium is a good idea,” Dr. Wallace said in an interview.

The study was presented at the American Heart Association Hypertension Scientific Sessions 2022 in San Diego.

Dr. Sims and colleagues used U.S. statistics from multiple sources to simulate CVD events, mortality, and health care costs between 2018 and 2027 in adults aged 35-64 years with untreated stage 1 hypertension, defined as systolic BP of 130 to 139 mm Hg. 

The researchers estimate that 8.8 million U.S. adults (5.5 million women) aged 35-64 years have untreated stage 1 hypertension and would be recommended for lifestyle change, such as physical activity, weight loss, moderating alcohol intake, and adoption of the DASH diet.

Controlling blood pressure to less than 130 mm Hg in this population could prevent 26,000 CVD events, avoid 2,900 deaths, and lead to $1.6 billion saved in associated health care costs, the researchers calculate.

The largest benefit would come from adoption of the DASH diet, with an estimated 15,000 CVD events prevented among men and 11,000 among women.
 

Even small changes can help

“Young and middle-aged adults with stage 1 hypertension aren’t as low risk as you – or even your doctor – might think,” Dr. Sims told this news organization.

“Millions of working-aged people are walking around with elevated blood pressure, which is symptomless but is also a leading preventable cause of disability and death. Most do not follow the recommended DASH diet,” Dr. Sims said.

“Unfortunately, the availability and affordability of healthy food sources does not easily allow people to follow the DASH diet,” Dr. Sims adds in a conference news release.

“Clinicians should consider whether their patients live in food deserts or places with limited walkability. Health counseling should include addressing these specific challenges to blood pressure control,” Dr. Sims says.

Dr. Wallace noted that diet changes don’t have to be drastic.

“Honestly, just increasing fruit and vegetable intake has been shown to displace calories from saturated fats, added sugars, and sodium,” he told this news organization.

“It’s hard for people to stick to ‘diets’ long-term, so shifting toward healthier dietary patterns without having to read a book on the DASH diet or count calories and carbs seems like a more practical solution for the general population, although I have no issues with the DASH diet and think it is a great dietary pattern for heart health,” Dr. Wallace said.

The study had no funding. Dr. Sims reports no relevant financial relationships. Dr. Wallace is principal and CEO of Think Healthy Group; chief food and nutrition scientist with Produce for Better Health Foundation; editor, Journal of Dietary Supplements; deputy editor, Journal of the American College of Nutrition; nutrition section editor, Annals of Medicine; and advisory board member with Forbes Health.

A version of this article first appeared on Medscape.com.

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

A version of this article first appeared on Medscape.com.

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

A version of this article first appeared on Medscape.com .

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

A version of this article first appeared on Medscape.com .

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

A version of this article first appeared on Medscape.com .

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

A version of this article first appeared on Medscape.com.

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

A version of this article first appeared on Medscape.com.

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

A version of this article first appeared on Medscape.com.

Intake of salt is a biological necessity, inextricably woven into physiologic systems. However, excessive salt intake is associated with high blood pressure. Hypertension is linked to increased cardiovascular morbidity and mortality, and it is estimated that excessive salt intake causes approximately 5 million deaths per year worldwide. Reducing salt intake lowers blood pressure, but processed foods contain “hidden” salt, which makes dietary control of salt difficult. This problem is compounded by growing inequalities in food systems, which present another hurdle to sustaining individual dietary control of salt intake.

Krisana Antharith / EyeEm / Getty Images

Of the 87 risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, high systolic blood pressure was identified as the leading risk factor for disease burden at the global level and for its effect on human health. A range of strategies, including primary care management and reduction in sodium intake, are known to reduce the burden of this critical risk factor. Two questions remain unanswered: “What is the relationship between mortality and adding salt to foods?” and “How much does a reduction in salt intake influence people’s health?”
 

Cardiovascular disease and death

Because dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, high sodium intake can be expected to curtail life span. A study tested this hypothesis by analyzing the relationship between sodium intake and life expectancy and survival in 181 countries. Sodium intake correlated positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries, which argues against dietary sodium intake curtailing life span or a being risk factor for premature death. These results help fuel a scientific debate about sodium intake, life expectancy, and mortality. The debate requires interpreting composite data of positive linear, J-shaped, or inverse linear correlations, which underscores the uncertainty regarding this issue.

In a prospective study of 501,379 participants from the UK Biobank, researchers found that higher frequency of adding salt to foods was significantly associated with a higher risk of premature mortality and lower life expectancy independently of diet, lifestyle, socioeconomic level, and preexisting diseases. They found that the positive association appeared to be attenuated with increasing intake of high-potassium foods (vegetables and fruits).

In addition, the researchers made the following observations:

• For cause-specific premature mortality, they found that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular disease mortality and cancer mortality (P-trend < .001 and P-trend < .001, respectively).
• Always adding salt to foods was associated with the lower life expectancy at the age of 50 years by 1.50 (95% confidence interval, 0.72-2.30) and 2.28 (95% CI, 1.66-2.90) years for women and men, respectively, compared with participants who never or rarely added salt to foods.

The researchers noted that adding salt to foods (usually at the table) is common and is directly related to an individual’s long-term preference for salty foods and habitual salt intake. Indeed, in the Western diet, adding salt at the table accounts for 6%-20% of total salt intake. In addition, commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors, including potassium. Therefore, adding salt to foods provides a way to evaluate the association between habitual sodium intake and mortality – something that is relevant, given that it has been estimated that in 2010, a total of 1.65 million deaths from cardiovascular causes were attributable to consumption of more than 2.0 g of sodium per day.
 

Salt sensitivity

Current evidence supports a recommendation for moderate sodium intake in the general population (3-5 g/day). Persons with hypertension should consume salt at the lower end of that range. Some dietary guidelines recommend consuming less than 2,300 mg dietary sodium per day for persons aged 14 years or older and less for persons aged 2-13 years. Although low sodium intake (< 2.0 g/day) has been achieved in short-term clinical trials, sustained low sodium intake has not been achieved in any of the longer-term clinical trials (duration > 6 months).

The controversy continues as to the relationship between low sodium intake and blood pressure or cardiovascular diseases. Most studies show that both in individuals with hypertension and those without, blood pressure is reduced by consuming less sodium. However, it is not necessarily lowered by reducing sodium intake (< 3-5 g/day). With a sodium-rich diet, most normotensive individuals experienced a minimal change in mean arterial pressure; for many individuals with hypertension, the values increased by about 4 mm Hg. In addition, among individuals with hypertension who are “salt sensitive,” arterial pressure can increase by > 10 mm Hg in response to high sodium intake.
 

The effect of potassium

Replacing some of the sodium chloride in regular salt with potassium chloride may mitigate some of salt’s harmful cardiovascular effects. Indeed, salt substitutes that have reduced sodium levels and increased potassium levels have been shown to lower blood pressure.

In one trial, researchers enrolled over 20,000 persons from 600 villages in rural China and compared the use of regular salt (100% sodium chloride) with the use of a salt substitute (75% sodium chloride and 25% potassium chloride by mass).

The participants were at high risk for stroke, cardiovascular events, and death. The mean duration of follow-up was 4.74 years. The results were surprising. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1,000 person-years; rate ratio, 0.86; 95% CI, 0.77-0.96; P = .006), as were the rates of major cardiovascular events and death from any cause. The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt.

Although there is an ongoing debate about the extent of salt’s effects on the cardiovascular system, there is no doubt that in most places in the world, people are consuming more salt than the body needs.

A lot depends upon the kind of diet consumed by a particular population. Processed food is rarely used in rural areas, such as those involved in the above-mentioned trial, with dietary sodium chloride being added while preparing food at home. This is a determining factor with regard to cardiovascular outcomes, but it cannot be generalized to other social-environmental settings.

In much of the world, commercial food preservation introduces a lot of sodium chloride into the diet, and most salt intake could not be fully attributed to the use of salt substitutes. Indeed, by comparing the sodium content of cereal-based products currently sold on the Italian market with the respective benchmarks proposed by the World Health Organization, researchers found that for most items, the sodium content is much higher than the benchmarks, especially with flatbreads, leavened breads, and crackers/savory biscuits. This shows that there is work to be done to achieve the World Health Organization/United Nations objective of a 30% global reduction in sodium intake by 2025.

This article was translated from Univadis Italy. A version of this article first appeared on Medscape.com.

Intake of salt is a biological necessity, inextricably woven into physiologic systems. However, excessive salt intake is associated with high blood pressure. Hypertension is linked to increased cardiovascular morbidity and mortality, and it is estimated that excessive salt intake causes approximately 5 million deaths per year worldwide. Reducing salt intake lowers blood pressure, but processed foods contain “hidden” salt, which makes dietary control of salt difficult. This problem is compounded by growing inequalities in food systems, which present another hurdle to sustaining individual dietary control of salt intake.

Krisana Antharith / EyeEm / Getty Images

Of the 87 risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, high systolic blood pressure was identified as the leading risk factor for disease burden at the global level and for its effect on human health. A range of strategies, including primary care management and reduction in sodium intake, are known to reduce the burden of this critical risk factor. Two questions remain unanswered: “What is the relationship between mortality and adding salt to foods?” and “How much does a reduction in salt intake influence people’s health?”
 

Cardiovascular disease and death

Because dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, high sodium intake can be expected to curtail life span. A study tested this hypothesis by analyzing the relationship between sodium intake and life expectancy and survival in 181 countries. Sodium intake correlated positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries, which argues against dietary sodium intake curtailing life span or a being risk factor for premature death. These results help fuel a scientific debate about sodium intake, life expectancy, and mortality. The debate requires interpreting composite data of positive linear, J-shaped, or inverse linear correlations, which underscores the uncertainty regarding this issue.

In a prospective study of 501,379 participants from the UK Biobank, researchers found that higher frequency of adding salt to foods was significantly associated with a higher risk of premature mortality and lower life expectancy independently of diet, lifestyle, socioeconomic level, and preexisting diseases. They found that the positive association appeared to be attenuated with increasing intake of high-potassium foods (vegetables and fruits).

In addition, the researchers made the following observations:

• For cause-specific premature mortality, they found that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular disease mortality and cancer mortality (P-trend < .001 and P-trend < .001, respectively).
• Always adding salt to foods was associated with the lower life expectancy at the age of 50 years by 1.50 (95% confidence interval, 0.72-2.30) and 2.28 (95% CI, 1.66-2.90) years for women and men, respectively, compared with participants who never or rarely added salt to foods.

The researchers noted that adding salt to foods (usually at the table) is common and is directly related to an individual’s long-term preference for salty foods and habitual salt intake. Indeed, in the Western diet, adding salt at the table accounts for 6%-20% of total salt intake. In addition, commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors, including potassium. Therefore, adding salt to foods provides a way to evaluate the association between habitual sodium intake and mortality – something that is relevant, given that it has been estimated that in 2010, a total of 1.65 million deaths from cardiovascular causes were attributable to consumption of more than 2.0 g of sodium per day.
 

Salt sensitivity

Current evidence supports a recommendation for moderate sodium intake in the general population (3-5 g/day). Persons with hypertension should consume salt at the lower end of that range. Some dietary guidelines recommend consuming less than 2,300 mg dietary sodium per day for persons aged 14 years or older and less for persons aged 2-13 years. Although low sodium intake (< 2.0 g/day) has been achieved in short-term clinical trials, sustained low sodium intake has not been achieved in any of the longer-term clinical trials (duration > 6 months).

The controversy continues as to the relationship between low sodium intake and blood pressure or cardiovascular diseases. Most studies show that both in individuals with hypertension and those without, blood pressure is reduced by consuming less sodium. However, it is not necessarily lowered by reducing sodium intake (< 3-5 g/day). With a sodium-rich diet, most normotensive individuals experienced a minimal change in mean arterial pressure; for many individuals with hypertension, the values increased by about 4 mm Hg. In addition, among individuals with hypertension who are “salt sensitive,” arterial pressure can increase by > 10 mm Hg in response to high sodium intake.
 

The effect of potassium

Replacing some of the sodium chloride in regular salt with potassium chloride may mitigate some of salt’s harmful cardiovascular effects. Indeed, salt substitutes that have reduced sodium levels and increased potassium levels have been shown to lower blood pressure.

In one trial, researchers enrolled over 20,000 persons from 600 villages in rural China and compared the use of regular salt (100% sodium chloride) with the use of a salt substitute (75% sodium chloride and 25% potassium chloride by mass).

The participants were at high risk for stroke, cardiovascular events, and death. The mean duration of follow-up was 4.74 years. The results were surprising. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1,000 person-years; rate ratio, 0.86; 95% CI, 0.77-0.96; P = .006), as were the rates of major cardiovascular events and death from any cause. The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt.

Although there is an ongoing debate about the extent of salt’s effects on the cardiovascular system, there is no doubt that in most places in the world, people are consuming more salt than the body needs.

A lot depends upon the kind of diet consumed by a particular population. Processed food is rarely used in rural areas, such as those involved in the above-mentioned trial, with dietary sodium chloride being added while preparing food at home. This is a determining factor with regard to cardiovascular outcomes, but it cannot be generalized to other social-environmental settings.

In much of the world, commercial food preservation introduces a lot of sodium chloride into the diet, and most salt intake could not be fully attributed to the use of salt substitutes. Indeed, by comparing the sodium content of cereal-based products currently sold on the Italian market with the respective benchmarks proposed by the World Health Organization, researchers found that for most items, the sodium content is much higher than the benchmarks, especially with flatbreads, leavened breads, and crackers/savory biscuits. This shows that there is work to be done to achieve the World Health Organization/United Nations objective of a 30% global reduction in sodium intake by 2025.

This article was translated from Univadis Italy. A version of this article first appeared on Medscape.com.

Intake of salt is a biological necessity, inextricably woven into physiologic systems. However, excessive salt intake is associated with high blood pressure. Hypertension is linked to increased cardiovascular morbidity and mortality, and it is estimated that excessive salt intake causes approximately 5 million deaths per year worldwide. Reducing salt intake lowers blood pressure, but processed foods contain “hidden” salt, which makes dietary control of salt difficult. This problem is compounded by growing inequalities in food systems, which present another hurdle to sustaining individual dietary control of salt intake.

Krisana Antharith / EyeEm / Getty Images

Of the 87 risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, high systolic blood pressure was identified as the leading risk factor for disease burden at the global level and for its effect on human health. A range of strategies, including primary care management and reduction in sodium intake, are known to reduce the burden of this critical risk factor. Two questions remain unanswered: “What is the relationship between mortality and adding salt to foods?” and “How much does a reduction in salt intake influence people’s health?”
 

Cardiovascular disease and death

Because dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, high sodium intake can be expected to curtail life span. A study tested this hypothesis by analyzing the relationship between sodium intake and life expectancy and survival in 181 countries. Sodium intake correlated positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries, which argues against dietary sodium intake curtailing life span or a being risk factor for premature death. These results help fuel a scientific debate about sodium intake, life expectancy, and mortality. The debate requires interpreting composite data of positive linear, J-shaped, or inverse linear correlations, which underscores the uncertainty regarding this issue.

In a prospective study of 501,379 participants from the UK Biobank, researchers found that higher frequency of adding salt to foods was significantly associated with a higher risk of premature mortality and lower life expectancy independently of diet, lifestyle, socioeconomic level, and preexisting diseases. They found that the positive association appeared to be attenuated with increasing intake of high-potassium foods (vegetables and fruits).

In addition, the researchers made the following observations:

• For cause-specific premature mortality, they found that higher frequency of adding salt to foods was significantly associated with a higher risk of cardiovascular disease mortality and cancer mortality (P-trend < .001 and P-trend < .001, respectively).
• Always adding salt to foods was associated with the lower life expectancy at the age of 50 years by 1.50 (95% confidence interval, 0.72-2.30) and 2.28 (95% CI, 1.66-2.90) years for women and men, respectively, compared with participants who never or rarely added salt to foods.

The researchers noted that adding salt to foods (usually at the table) is common and is directly related to an individual’s long-term preference for salty foods and habitual salt intake. Indeed, in the Western diet, adding salt at the table accounts for 6%-20% of total salt intake. In addition, commonly used table salt contains 97%-99% sodium chloride, minimizing the potential confounding effects of other dietary factors, including potassium. Therefore, adding salt to foods provides a way to evaluate the association between habitual sodium intake and mortality – something that is relevant, given that it has been estimated that in 2010, a total of 1.65 million deaths from cardiovascular causes were attributable to consumption of more than 2.0 g of sodium per day.
 

Salt sensitivity

Current evidence supports a recommendation for moderate sodium intake in the general population (3-5 g/day). Persons with hypertension should consume salt at the lower end of that range. Some dietary guidelines recommend consuming less than 2,300 mg dietary sodium per day for persons aged 14 years or older and less for persons aged 2-13 years. Although low sodium intake (< 2.0 g/day) has been achieved in short-term clinical trials, sustained low sodium intake has not been achieved in any of the longer-term clinical trials (duration > 6 months).

The controversy continues as to the relationship between low sodium intake and blood pressure or cardiovascular diseases. Most studies show that both in individuals with hypertension and those without, blood pressure is reduced by consuming less sodium. However, it is not necessarily lowered by reducing sodium intake (< 3-5 g/day). With a sodium-rich diet, most normotensive individuals experienced a minimal change in mean arterial pressure; for many individuals with hypertension, the values increased by about 4 mm Hg. In addition, among individuals with hypertension who are “salt sensitive,” arterial pressure can increase by > 10 mm Hg in response to high sodium intake.
 

The effect of potassium

Replacing some of the sodium chloride in regular salt with potassium chloride may mitigate some of salt’s harmful cardiovascular effects. Indeed, salt substitutes that have reduced sodium levels and increased potassium levels have been shown to lower blood pressure.

In one trial, researchers enrolled over 20,000 persons from 600 villages in rural China and compared the use of regular salt (100% sodium chloride) with the use of a salt substitute (75% sodium chloride and 25% potassium chloride by mass).

The participants were at high risk for stroke, cardiovascular events, and death. The mean duration of follow-up was 4.74 years. The results were surprising. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1,000 person-years; rate ratio, 0.86; 95% CI, 0.77-0.96; P = .006), as were the rates of major cardiovascular events and death from any cause. The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt.

Although there is an ongoing debate about the extent of salt’s effects on the cardiovascular system, there is no doubt that in most places in the world, people are consuming more salt than the body needs.

A lot depends upon the kind of diet consumed by a particular population. Processed food is rarely used in rural areas, such as those involved in the above-mentioned trial, with dietary sodium chloride being added while preparing food at home. This is a determining factor with regard to cardiovascular outcomes, but it cannot be generalized to other social-environmental settings.

In much of the world, commercial food preservation introduces a lot of sodium chloride into the diet, and most salt intake could not be fully attributed to the use of salt substitutes. Indeed, by comparing the sodium content of cereal-based products currently sold on the Italian market with the respective benchmarks proposed by the World Health Organization, researchers found that for most items, the sodium content is much higher than the benchmarks, especially with flatbreads, leavened breads, and crackers/savory biscuits. This shows that there is work to be done to achieve the World Health Organization/United Nations objective of a 30% global reduction in sodium intake by 2025.

This article was translated from Univadis Italy. A version of this article first appeared on Medscape.com.