Cardiology News

My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...

What is going on?

The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.

It’s pretty obvious that if the population and the health care systems of the United States were seriously interested in saving lives, they would strive diligently to control blood pressure, prevent obesity and diabetes, and eliminate combustible tobacco use.

We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.

All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.

That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?

At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.

A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.

PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.

At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.

These factors summarize why it works:

• Senior management belief, commitment, and leadership
• Informed buy-in from clinicians and patients
• A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
• An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
• Persistent clinician-patient follow-up
• Refusal to accept failure

Since this approach is so successful, why is its use not everywhere?

It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.

Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.

I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.

Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.

Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.

Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.

For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?

Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.

Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.

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

My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...

What is going on?

The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.

It’s pretty obvious that if the population and the health care systems of the United States were seriously interested in saving lives, they would strive diligently to control blood pressure, prevent obesity and diabetes, and eliminate combustible tobacco use.

We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.

All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.

That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?

At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.

A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.

PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.

At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.

These factors summarize why it works:

• Senior management belief, commitment, and leadership
• Informed buy-in from clinicians and patients
• A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
• An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
• Persistent clinician-patient follow-up
• Refusal to accept failure

Since this approach is so successful, why is its use not everywhere?

It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.

Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.

I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.

Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.

Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.

Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.

For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?

Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.

Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.

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

My Bing AI engine, when prompted, tells me that there are about 87 journals, 45 conferences, and 53 workshops presently dedicated exclusively to hypertension. All of that attention, and yet ...

What is going on?

The top killers of Americans remain coronary artery heart disease (26%), cancer (22%), and stroke (6%). The precursors and attributable risk factors for coronary artery heart disease include hypertension (40%), obesity (20%), diabetes (15%), and combustible tobacco use (15%). The key precursors and attributable risk factors for stroke are hypertension (53%), obesity (37%), diabetes (9%), and combustible tobacco use (11%). Obviously, these are estimates, with substantial overlap.

It’s pretty obvious that if the population and the health care systems of the United States were seriously interested in saving lives, they would strive diligently to control blood pressure, prevent obesity and diabetes, and eliminate combustible tobacco use.

We have addressed improving tobacco control and preventing obesity and diabetes on these pages many times, and lamented the medical, public health, and societal failings. Today we turn our attention to the control of hypertension. That is much easier and far less expensive.

All physicians and medical organizations know that hypertension is a major attributable cause of many serious, expensive, and fatal illnesses. As many as 119 million (48%) of American adults have hypertension. The American Heart Association (AHA), American Medical Association (AMA), American College of Cardiology (ACC), and hundreds of other organizations have set a new target of 130/80 (revised from 140/90) for blood pressure control and have launched a major initiative, Target: BP, to reach it.

That is just great. We all wish this massive effort to succeed where few others have. But do AHA, AMA, ACC, and others understand why most efforts to this point have failed? The blame is typically aimed at patients failing to adhere to their instructions. Maybe, but why? And how does Target: BP intend to convert chronic failure into success if it just continues to do everything they have been trying to do that doesn’t work?

At this point, the Centers for Disease Control and Prevention reports that fewer than 48% of American patients with hypertension meet even the less stringent historical 140/90 goal.

A group practice in Ohio, PriMed Physicians, has consistently exceeded 90% or even 95% blood pressure control for its patients with hypertension for more than 10 years. Exemplary. How do they do it? This video of the 13th annual Lundberg Institute lecture describes this unique and successful program.

PriMed’s clinicians use the MedsEngine AI tool from MediSync and the NICaS (noninvasive cardiac system with impedance cardiography) to determine each patient’s unique blood pressure pathophysiology. Clinicians and patients understand that the simplest explanation of this pathophysiology encompasses three factors: (1) the volume of “water” (blood) in the system; (2) the strength of the pumping (pulsatile) process; and (3) the tightness (resistance) of the tubes that carry the blood. Patients “get it” when it is explained this way, and they cooperate.

At the first patient encounter, the Food and Drug Administration–approved PhysioFlow is employed to assess those three vital hemodynamic factors. The individual patient’s data are loaded into a tightly programed EHR-based algorithm with 37 clinical factors and five classes of drugs, providing multiple ways to influence the three key pathophysiologic processes. In this way, they arrive at the precise drug(s) and dosages for that patient. During the second visit, most patients are already showing improvement. By the third visit, the blood pressures of most patients have reached target control. After that, it is maintenance and tweaking.

These factors summarize why it works:

• Senior management belief, commitment, and leadership
• Informed buy-in from clinicians and patients
• A test that determines root causes of too much fluid, too strong pump action, or too tight pipes, and their proportionality
• An AI tool that matches those three pathophysiologic factors and 35 other clinical factors with the best drug or drugs (of many, not just a few) and dosages
• Persistent clinician-patient follow-up
• Refusal to accept failure

Since this approach is so successful, why is its use not everywhere?

It is not as if nobody noticed, even if you and many organizations have not. The American Medical Group Association recognized the program’s success by giving its top award to PriMed in 2015.

Klepper and Rodis wrote about this approach for managing multiple chronic conditions in 2021. Here’s a background article and an explainer, Clinical use of impedance cardiography for hemodynamic assessment of early cardiovascular disease and management of hypertension.

I found one pragmatic controlled clinical trial of impedance cardiography with a decision-support system from Beijing that did demonstrate clinical and statistical significance.

Frankly, we do need more rigorous, unbiased, large, controlled clinical trials assessing the MedsEngine and NICaS approach to managing blood pressure to facilitate a massive switch from the old and established (but failing) approach to a starkly better way.

Almost no one ever “completes a database.” All decision makers must act based upon the best data to which they have access. Data are often incomplete. The difference between success and mediocrity is often the ability of an individual or system to decide when enough information is enough and act accordingly.

Cost-effectiveness studies in three countries (United Kingdom, United States, and China) confirm sharply lower lifelong costs when blood pressure is well controlled. Of course.

For the American medical-industrial complex, lowered costs for managing common serious diseases may be an undesired rather than a good thing. In money-driven medicine, lower costs to the payer and purchaser translate to less revenue for the providers. Imagine all of those invasive and noninvasive diagnostic and therapeutic procedures forgone by prevention of hypertension. Is it possible that such an underlying truth is the real reason why American medicine is habitually unsuccessful at controlling blood pressure?

Right now, if my blood pressure were not well controlled (it is), I would find my way to Cincinnati, to give PriMed physicians, MediSync, and MedsEngine a crack at prolonging my useful life.

Dr. Lundberg is editor in chief of Cancer Commons. He disclosed no relevant conflicts of interest.

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

I was running my 25th New York City Marathon. It was 2018, and I almost pulled out of running that year. I wasn’t myself, and maybe that’s an understatement.

A month earlier, I had been involved in a malpractice case. I was found liable for $10 million. My colleagues didn’t think I had done anything wrong, but the jury did. And the local newspapers made me look like a villain.

I was devastated. But my priest, my friends, and my family all told me, “You can’t quit.” So, I decided to run for them.

I started on the Verrazzano-Narrows Bridge that morning with some friends from work. I usually listen to music as I’m running, but I didn’t that year. I was just in my zone, enjoying the crowds. They’re huge. Millions of people on the streets.

I was running well. I did half the race in an hour and 57 minutes. My family always meets me at mile 17, and I was almost there. I had reached 59th Street and was about to make the turn onto First Avenue.

That’s one of the noisiest places in the marathon. There’s a kind of tunnel, and with the crowd and the throng of runners, it’s incredibly loud. But somehow, I heard somebody yell, “Help!”

Now, how I heard that, I don’t know. And if I’d been listening to music like I always do, no way I would’ve heard it. I could swear it was an angel on my shoulder that said, “Turn around, dummy. You’ve got a person that needs your help to your left.”

I turned around and about 30 feet behind me, I saw a woman waving her hands and a runner on the ground. I thought, Somebody fainted. I pushed through the crowd to get to them. The woman was crying, saying, “My friend went down to tie her shoe and she fell back. I think she’s seizing or something.”

I got down and tried to wake the other woman up. I lifted her legs up. But I quickly realized there was more to the story. I felt for pulses and couldn’t feel them. I screamed for a defibrillator and started to do CPR.

Some volunteers and police started coming toward us. The police officers looked at me like, What’s this guy doing? I explained that I was a physician, and one of them began helping me with the CPR. As we did that, someone brought a defibrillator.

Meanwhile, runners were going past, almost over us. The police officers were trying to create a barrier.

The machine gave the woman a shock, but we didn’t get a response, so we resumed CPR. At that point, my legs began to cramp so badly I couldn’t go on. So the police officer took over, and I yelled, “I need an ambu bag!” Somebody brought one, and I started giving her oxygen.

At that point, a paramedic team arrived with a bigger defibrillator. We shocked her again. And again. That time we got results, but she quickly went out again. The fourth time, we got her heart back and she started breathing on her own.

We finally got her into an ambulance. I wanted to go with them, but the woman’s friend needed to get in, so there wasn’t enough room.

And then they were gone, and I was just standing there.

A police officer put his arm around me. He said, “Doc, you’re amazing. What do you need? Where can I take you?”

I said, “Take me? My wife is waiting for me at mile 17.”

I took off and ran. When I got to my wife and kids, they were so worried. We all wear tracking devices, and they could see that I had stopped for more than 20 minutes.

I fell into my wife’s arms and told her what had happened. I was crying. “I don’t know what to do. I need to get to the hospital.”

And she said, “No, you need to go finish the race.”

So, I did. It was painful because of the cramps, but I was numb at that point. I was thinking about the woman the whole way. My time was 5 hours and 20 minutes.

As soon as I finished, I went to every police officer I could find, but nobody knew anything. Suddenly, I remembered my cousin. He had previously been the head of EMS for New York City. I called him. “Abdo, it’s Ted, you’ve got to do me a favor.”

“What?” he said. “Are you delirious from running the marathon?”

I told him what I needed. He called me back 5 minutes later and said, “Ted, what’d you do? Everybody wants to know who you are and where you are! The woman just went out again at New York Cornell. But they got her back, and they’re bringing her up to the cath lab.”

After every marathon that I run, we host a big party at our house. My family and friends and neighbors all celebrate while I’m dying on the couch. That night, my daughter told everyone the story of what happened.

But I was still not right. Still thinking about the malpractice suit.

Yes, I just did something great. But I’d recently been called the worst physician in the world. The distraction of the marathon was gone, and I was back to thinking, What am I going to do with my life? Who’s ever going to want to see me again? I’m a pariah.

Everybody said, “Ted, what happened a month ago isn’t you. What happened today was you.”

I told them to leave it alone, but my daughter and my neighbor started calling people anyway. The next day I got a call from the local newspaper. It was the same journalist who had written about me from the trial. I told him I didn’t want to talk. I was actually pretty nasty.

But my wife said, “Ted, what are you doing? That guy was trying to help you.” So, I called back and apologized.

“Dr. Strange, we knew that story wasn’t right,” he said. “We have to write this story.”

After the article came out, I started getting more calls from the media. Channel 7 News and CBS News did segments. The New York Knicks invited us to a game and presented me with a watch. It was incredible. But I was also really embarrassed by it.

People started calling me a hero. I’m not a hero. I just did what I’m supposed to do, what I’m trained to do. Shame on me if I don’t do that. Good guy and hopefully good physician, sure, but not a hero.

I also give credit to the City of New York Police Department, the FDNY, and the volunteers. Without them, I couldn’t have done what I did. It was a true team effort.

A few weeks later, the woman went home to Minnesota. She’ll never run a marathon again, but she’s still alive to this day. It turned out she had a single lesion called the “widow-maker” lesion. She was in perfect health and had just completed an ultramarathon a few months before; but she had a genetic predisposition. She still calls me every December to thank me for another Christmas.

There’s more.

One year after this whole thing, almost to the date, I got a call from my attorney. “The court just threw out the malpractice verdict,” he said. “You didn’t do anything wrong.”

I’m a man of faith. And I believe all this happened for a reason. Maybe God was sending me a message, and that’s why I heard a call for help on 59th Street in my 25th marathon among millions of people in a crowd.

I ran the marathon the next year. And when I got to that spot, I stopped and reflected. Nobody knew why I was standing there, but I knew. To this day, I could take you to that spot.

I turn 65 next July, and I plan to keep on running the race.
 

Dr. Strange is chair of medicine at Staten Island University Hospital, associate ambulatory physician executive of the Staten Island Region, and an internal medicine and geriatric medicine physician with Northwell Health.

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

I was running my 25th New York City Marathon. It was 2018, and I almost pulled out of running that year. I wasn’t myself, and maybe that’s an understatement.

A month earlier, I had been involved in a malpractice case. I was found liable for $10 million. My colleagues didn’t think I had done anything wrong, but the jury did. And the local newspapers made me look like a villain.

I was devastated. But my priest, my friends, and my family all told me, “You can’t quit.” So, I decided to run for them.

I started on the Verrazzano-Narrows Bridge that morning with some friends from work. I usually listen to music as I’m running, but I didn’t that year. I was just in my zone, enjoying the crowds. They’re huge. Millions of people on the streets.

I was running well. I did half the race in an hour and 57 minutes. My family always meets me at mile 17, and I was almost there. I had reached 59th Street and was about to make the turn onto First Avenue.

That’s one of the noisiest places in the marathon. There’s a kind of tunnel, and with the crowd and the throng of runners, it’s incredibly loud. But somehow, I heard somebody yell, “Help!”

Now, how I heard that, I don’t know. And if I’d been listening to music like I always do, no way I would’ve heard it. I could swear it was an angel on my shoulder that said, “Turn around, dummy. You’ve got a person that needs your help to your left.”

I turned around and about 30 feet behind me, I saw a woman waving her hands and a runner on the ground. I thought, Somebody fainted. I pushed through the crowd to get to them. The woman was crying, saying, “My friend went down to tie her shoe and she fell back. I think she’s seizing or something.”

I got down and tried to wake the other woman up. I lifted her legs up. But I quickly realized there was more to the story. I felt for pulses and couldn’t feel them. I screamed for a defibrillator and started to do CPR.

Some volunteers and police started coming toward us. The police officers looked at me like, What’s this guy doing? I explained that I was a physician, and one of them began helping me with the CPR. As we did that, someone brought a defibrillator.

Meanwhile, runners were going past, almost over us. The police officers were trying to create a barrier.

The machine gave the woman a shock, but we didn’t get a response, so we resumed CPR. At that point, my legs began to cramp so badly I couldn’t go on. So the police officer took over, and I yelled, “I need an ambu bag!” Somebody brought one, and I started giving her oxygen.

At that point, a paramedic team arrived with a bigger defibrillator. We shocked her again. And again. That time we got results, but she quickly went out again. The fourth time, we got her heart back and she started breathing on her own.

We finally got her into an ambulance. I wanted to go with them, but the woman’s friend needed to get in, so there wasn’t enough room.

And then they were gone, and I was just standing there.

A police officer put his arm around me. He said, “Doc, you’re amazing. What do you need? Where can I take you?”

I said, “Take me? My wife is waiting for me at mile 17.”

I took off and ran. When I got to my wife and kids, they were so worried. We all wear tracking devices, and they could see that I had stopped for more than 20 minutes.

I fell into my wife’s arms and told her what had happened. I was crying. “I don’t know what to do. I need to get to the hospital.”

And she said, “No, you need to go finish the race.”

So, I did. It was painful because of the cramps, but I was numb at that point. I was thinking about the woman the whole way. My time was 5 hours and 20 minutes.

As soon as I finished, I went to every police officer I could find, but nobody knew anything. Suddenly, I remembered my cousin. He had previously been the head of EMS for New York City. I called him. “Abdo, it’s Ted, you’ve got to do me a favor.”

“What?” he said. “Are you delirious from running the marathon?”

I told him what I needed. He called me back 5 minutes later and said, “Ted, what’d you do? Everybody wants to know who you are and where you are! The woman just went out again at New York Cornell. But they got her back, and they’re bringing her up to the cath lab.”

After every marathon that I run, we host a big party at our house. My family and friends and neighbors all celebrate while I’m dying on the couch. That night, my daughter told everyone the story of what happened.

But I was still not right. Still thinking about the malpractice suit.

Yes, I just did something great. But I’d recently been called the worst physician in the world. The distraction of the marathon was gone, and I was back to thinking, What am I going to do with my life? Who’s ever going to want to see me again? I’m a pariah.

Everybody said, “Ted, what happened a month ago isn’t you. What happened today was you.”

I told them to leave it alone, but my daughter and my neighbor started calling people anyway. The next day I got a call from the local newspaper. It was the same journalist who had written about me from the trial. I told him I didn’t want to talk. I was actually pretty nasty.

But my wife said, “Ted, what are you doing? That guy was trying to help you.” So, I called back and apologized.

“Dr. Strange, we knew that story wasn’t right,” he said. “We have to write this story.”

After the article came out, I started getting more calls from the media. Channel 7 News and CBS News did segments. The New York Knicks invited us to a game and presented me with a watch. It was incredible. But I was also really embarrassed by it.

People started calling me a hero. I’m not a hero. I just did what I’m supposed to do, what I’m trained to do. Shame on me if I don’t do that. Good guy and hopefully good physician, sure, but not a hero.

I also give credit to the City of New York Police Department, the FDNY, and the volunteers. Without them, I couldn’t have done what I did. It was a true team effort.

A few weeks later, the woman went home to Minnesota. She’ll never run a marathon again, but she’s still alive to this day. It turned out she had a single lesion called the “widow-maker” lesion. She was in perfect health and had just completed an ultramarathon a few months before; but she had a genetic predisposition. She still calls me every December to thank me for another Christmas.

There’s more.

One year after this whole thing, almost to the date, I got a call from my attorney. “The court just threw out the malpractice verdict,” he said. “You didn’t do anything wrong.”

I’m a man of faith. And I believe all this happened for a reason. Maybe God was sending me a message, and that’s why I heard a call for help on 59th Street in my 25th marathon among millions of people in a crowd.

I ran the marathon the next year. And when I got to that spot, I stopped and reflected. Nobody knew why I was standing there, but I knew. To this day, I could take you to that spot.

I turn 65 next July, and I plan to keep on running the race.
 

Dr. Strange is chair of medicine at Staten Island University Hospital, associate ambulatory physician executive of the Staten Island Region, and an internal medicine and geriatric medicine physician with Northwell Health.

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

I was running my 25th New York City Marathon. It was 2018, and I almost pulled out of running that year. I wasn’t myself, and maybe that’s an understatement.

A month earlier, I had been involved in a malpractice case. I was found liable for $10 million. My colleagues didn’t think I had done anything wrong, but the jury did. And the local newspapers made me look like a villain.

I was devastated. But my priest, my friends, and my family all told me, “You can’t quit.” So, I decided to run for them.

I started on the Verrazzano-Narrows Bridge that morning with some friends from work. I usually listen to music as I’m running, but I didn’t that year. I was just in my zone, enjoying the crowds. They’re huge. Millions of people on the streets.

I was running well. I did half the race in an hour and 57 minutes. My family always meets me at mile 17, and I was almost there. I had reached 59th Street and was about to make the turn onto First Avenue.

That’s one of the noisiest places in the marathon. There’s a kind of tunnel, and with the crowd and the throng of runners, it’s incredibly loud. But somehow, I heard somebody yell, “Help!”

Now, how I heard that, I don’t know. And if I’d been listening to music like I always do, no way I would’ve heard it. I could swear it was an angel on my shoulder that said, “Turn around, dummy. You’ve got a person that needs your help to your left.”

I turned around and about 30 feet behind me, I saw a woman waving her hands and a runner on the ground. I thought, Somebody fainted. I pushed through the crowd to get to them. The woman was crying, saying, “My friend went down to tie her shoe and she fell back. I think she’s seizing or something.”

I got down and tried to wake the other woman up. I lifted her legs up. But I quickly realized there was more to the story. I felt for pulses and couldn’t feel them. I screamed for a defibrillator and started to do CPR.

Some volunteers and police started coming toward us. The police officers looked at me like, What’s this guy doing? I explained that I was a physician, and one of them began helping me with the CPR. As we did that, someone brought a defibrillator.

Meanwhile, runners were going past, almost over us. The police officers were trying to create a barrier.

The machine gave the woman a shock, but we didn’t get a response, so we resumed CPR. At that point, my legs began to cramp so badly I couldn’t go on. So the police officer took over, and I yelled, “I need an ambu bag!” Somebody brought one, and I started giving her oxygen.

At that point, a paramedic team arrived with a bigger defibrillator. We shocked her again. And again. That time we got results, but she quickly went out again. The fourth time, we got her heart back and she started breathing on her own.

We finally got her into an ambulance. I wanted to go with them, but the woman’s friend needed to get in, so there wasn’t enough room.

And then they were gone, and I was just standing there.

A police officer put his arm around me. He said, “Doc, you’re amazing. What do you need? Where can I take you?”

I said, “Take me? My wife is waiting for me at mile 17.”

I took off and ran. When I got to my wife and kids, they were so worried. We all wear tracking devices, and they could see that I had stopped for more than 20 minutes.

I fell into my wife’s arms and told her what had happened. I was crying. “I don’t know what to do. I need to get to the hospital.”

And she said, “No, you need to go finish the race.”

So, I did. It was painful because of the cramps, but I was numb at that point. I was thinking about the woman the whole way. My time was 5 hours and 20 minutes.

As soon as I finished, I went to every police officer I could find, but nobody knew anything. Suddenly, I remembered my cousin. He had previously been the head of EMS for New York City. I called him. “Abdo, it’s Ted, you’ve got to do me a favor.”

“What?” he said. “Are you delirious from running the marathon?”

I told him what I needed. He called me back 5 minutes later and said, “Ted, what’d you do? Everybody wants to know who you are and where you are! The woman just went out again at New York Cornell. But they got her back, and they’re bringing her up to the cath lab.”

After every marathon that I run, we host a big party at our house. My family and friends and neighbors all celebrate while I’m dying on the couch. That night, my daughter told everyone the story of what happened.

But I was still not right. Still thinking about the malpractice suit.

Yes, I just did something great. But I’d recently been called the worst physician in the world. The distraction of the marathon was gone, and I was back to thinking, What am I going to do with my life? Who’s ever going to want to see me again? I’m a pariah.

Everybody said, “Ted, what happened a month ago isn’t you. What happened today was you.”

I told them to leave it alone, but my daughter and my neighbor started calling people anyway. The next day I got a call from the local newspaper. It was the same journalist who had written about me from the trial. I told him I didn’t want to talk. I was actually pretty nasty.

But my wife said, “Ted, what are you doing? That guy was trying to help you.” So, I called back and apologized.

“Dr. Strange, we knew that story wasn’t right,” he said. “We have to write this story.”

After the article came out, I started getting more calls from the media. Channel 7 News and CBS News did segments. The New York Knicks invited us to a game and presented me with a watch. It was incredible. But I was also really embarrassed by it.

People started calling me a hero. I’m not a hero. I just did what I’m supposed to do, what I’m trained to do. Shame on me if I don’t do that. Good guy and hopefully good physician, sure, but not a hero.

I also give credit to the City of New York Police Department, the FDNY, and the volunteers. Without them, I couldn’t have done what I did. It was a true team effort.

A few weeks later, the woman went home to Minnesota. She’ll never run a marathon again, but she’s still alive to this day. It turned out she had a single lesion called the “widow-maker” lesion. She was in perfect health and had just completed an ultramarathon a few months before; but she had a genetic predisposition. She still calls me every December to thank me for another Christmas.

There’s more.

One year after this whole thing, almost to the date, I got a call from my attorney. “The court just threw out the malpractice verdict,” he said. “You didn’t do anything wrong.”

I’m a man of faith. And I believe all this happened for a reason. Maybe God was sending me a message, and that’s why I heard a call for help on 59th Street in my 25th marathon among millions of people in a crowd.

I ran the marathon the next year. And when I got to that spot, I stopped and reflected. Nobody knew why I was standing there, but I knew. To this day, I could take you to that spot.

I turn 65 next July, and I plan to keep on running the race.
 

Dr. Strange is chair of medicine at Staten Island University Hospital, associate ambulatory physician executive of the Staten Island Region, and an internal medicine and geriatric medicine physician with Northwell Health.

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

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

PHILADELPHIA – The first in-human study of a gene therapy designed to reduce low-density lipoprotein cholesterol has shown a signal that the treatment works in a small group of patients with heterozygous familial hypercholesterolemia (HeFH).

While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.

“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”

The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.

Lipid nanoparticle

VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.

“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.

Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.

They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.

Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.

Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”

Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
 

Safety outcomes

Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.

He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”

The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
 

First, do no harm

Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.

“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”

She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”

Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”

Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.

PHILADELPHIA – The first in-human study of a gene therapy designed to reduce low-density lipoprotein cholesterol has shown a signal that the treatment works in a small group of patients with heterozygous familial hypercholesterolemia (HeFH).

While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.

“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”

The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.

Lipid nanoparticle

VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.

“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.

Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.

They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.

Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.

Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”

Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
 

Safety outcomes

Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.

He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”

The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
 

First, do no harm

Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.

“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”

She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”

Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”

Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.

PHILADELPHIA – The first in-human study of a gene therapy designed to reduce low-density lipoprotein cholesterol has shown a signal that the treatment works in a small group of patients with heterozygous familial hypercholesterolemia (HeFH).

While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.

“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”

The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.

Lipid nanoparticle

VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.

“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.

Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.

They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.

Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.

Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”

Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
 

Safety outcomes

Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.

He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”

The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
 

First, do no harm

Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.

“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”

She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”

Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”

Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.

TOPLINE:

Exposure to air pollutants is linked to emergency hospital admissions for stroke shortly after the exposure, with the risk being pronounced in men and individuals aged less than 65 years.

METHODOLOGY:

• Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
• The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
• Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
• Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.

TAKEAWAY:

• Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
• Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
• Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.

IN PRACTICE:

“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.

SOURCE:

The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.

LIMITATIONS:

• Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
• There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.

DISCLOSURES:

This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.

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

TOPLINE:

Exposure to air pollutants is linked to emergency hospital admissions for stroke shortly after the exposure, with the risk being pronounced in men and individuals aged less than 65 years.

METHODOLOGY:

• Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
• The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
• Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
• Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.

TAKEAWAY:

• Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
• Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
• Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.

IN PRACTICE:

“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.

SOURCE:

The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.

LIMITATIONS:

• Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
• There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.

DISCLOSURES:

This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.

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

TOPLINE:

Exposure to air pollutants is linked to emergency hospital admissions for stroke shortly after the exposure, with the risk being pronounced in men and individuals aged less than 65 years.

METHODOLOGY:

• Limited studies have investigated the association between hourly exposure to air pollutants and specific stroke subtypes, especially in regions with moderate to high levels of air pollution.
• The multicenter case-crossover study evaluated the association between hourly exposure to air pollution and stroke among 86,635 emergency admissions for stroke across 10 hospitals in 3 cities.
• Of 86,635 admissions, 79,478 were admitted for ischemic stroke, 3,122 for hemorrhagic stroke, and 4,035 for undetermined type of stroke.
• Hourly levels of fine particulate matter (PM2.5), respirable PM (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected from the China National Environmental Monitoring Center.

TAKEAWAY:

• Exposure to NO2 and SO2 increased the risk for emergency admission for stroke shortly after exposure by 3.34% (95% confidence interval, 1.41%-5.31%) and 2.81% (95% CI, 1.15%-4.51%), respectively.
• Among men, exposure to PM2.5 and PM10 increased the risk for emergency admission for stroke by 3.40% (95% CI, 1.21%-5.64%) and 4.33% (95% CI, 2.18%-6.53%), respectively.
• Among patients aged less than 65 years, exposure to PM10 and NO2 increased the risk for emergency admissions for stroke shortly after exposure by 4.88% (95% CI, 2.29%-7.54%) and 5.59% (95% CI, 2.34%-8.93%), respectively.

IN PRACTICE:

“These variations in susceptibility highlight the importance of implementing effective health protection measures to reduce exposure to air pollution and mitigate the risk of stroke in younger and male populations,” wrote the authors.

SOURCE:

The study was led by Xin Lv, MD, department of epidemiology and biostatistics, School of Public Health, Capital Medical University, Beijing. It was published online in the journal Stroke.

LIMITATIONS:

• Using data from the nearest monitoring site to the hospital address may lead to localized variations in pollution concentrations when assessing exposure.
• There may be a possibility of residual confounding resulting from time-varying lifestyle-related factors.

DISCLOSURES:

This study was supported by the Zhejiang Provincial Project for Medical Research and Health Sciences. No disclosures were reported.

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

PHILADELPHIA – Reducing albuminuria is a key mediator of the way finerenone (Kerendia, Bayer) reduces adverse renal and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD), based on findings from two novel mediation analyses run on data from more than 12,000 people included in the two finerenone pivotal trials.

Results from these analyses showed that the reduction in urine albumin-to-creatinine ratio (UACR) linked to finerenone treatment mediated 84% of the kidney protection and 37% of the cardiovascular event protection that finerenone treatment produced in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. FIDELIO-DKD, which had protection against adverse kidney outcomes as its primary endpoint, supplied the data that led to finerenone’s approval in 2021 by the U.S. Food and Drug Administration for treating people with type 2 diabetes and CKD.

The findings of the mediation analyses underscore the important role that albuminuria plays in the nephropathy and related comorbidities associated with type 2 diabetes and CKD and highlight the importance of ongoing monitoring of albuminuria to guide treatments aimed at minimizing this pathology, said Rajiv Agarwal, MD, who presented a poster on the mediation analyses at Kidney Week 2023, organized by the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

“My hope is that this [report] heightens awareness of UACR” as an important marker of both CKD and of the response by patients with CKD to their treatment, said Dr. Agarwal, a nephrologist and professor at Indiana University in Indianapolis.

“Only about half of people with type 2 diabetes get their UACR measured even though every guideline says measure UACR in people with diabetes. Our findings say that UACR is important not just for CKD diagnosis but also to give feedback” on whether management is working, Dr. Agarwal said in an interview.
 

Incorporate UACR into clinical decision-making

“My hope is that clinicians will look at UACR as something they should incorporate into clinical decision-making. I measure UACR in my patients [with CKD and type 2 diabetes] at every visit; it’s so inexpensive. Albuminuria is not a good sign. If it’s not reduced in a patient by at least 30% [the recommended minimum reduction by the American Diabetes Association for people who start with a UACR of at least 300 mg/g] clinicians should think of what else they could do to lower albuminuria”: Reduce salt intake, improve blood pressure control, make sure the patient is adherent to treatments, and add additional treatments, Dr. Agarwal advised.

Mitchel L. Zoler/MDedge News

Multiple efforts are now underway or will soon start to boost the rate at which at-risk people get their UACR measured, noted Leslie A. Inker, MD, in a separate talk during Kidney Week. These efforts include the National Kidney Foundation’s CKD Learning Collaborative, which aims to improve clinician awareness of CKD and improve routine testing for CKD. Early results during 2023 from this program in Missouri showed a nearly 8–percentage point increase in the screening rate for UACR levels in at-risk people, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston.

A second advance was introduction in 2018 of the “kidney profile” lab order by the American College of Clinical Pathology that allows clinicians to order as a single test both an estimated glomerular filtration rate (eGFR) and a UACR.

Also, the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance have both taken steps to encourage UACR ordering. The NCQA established a new Healthcare Effectiveness Data and Information Set performance measure for U.S. physicians starting in 2023 that will track measurement of UACR and eGFR in people with diabetes. CMS also has made assessment of kidney health a measure of care quality in programs effective in 2023 and 2024, Dr. Inker noted.
 

Most subjects had elevated UACRs

The study run by Dr. Agarwal and his associates used data from 12,512 of the more than 13,000 people enrolled in either FIDELITY-DKD or FIGARO-DKD who had UACR measurements recorded at baseline, at 4 months into either study, or both. Their median UACR at the time they began on finerenone or placebo was 514 mg/g, with 67% having a UACR of at least 300 mg/g (macroalbuminuria) and 31% having a UACR of 30-299 mg/g (microalbuminuria). By design, virtually all patients in these two trials were on a renin-angiotensin system inhibitor (either an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker), but given the time period when the two trials enrolled participants (during 2015-2018) only 7% of those enrolled were on a sodium-glucose cotransporter 2 inhibitor and only 7% were on a glucagonlike peptide–1 receptor agonist.

Four months after treatment began, 53% of those randomized to finerenone treatment and 27% of those in the placebo arm had their UACR reduced by at least 30% from baseline, the cutpoint chosen by Dr. Agarwal based on the American Diabetes Association guideline.

Kaplan-Meier analyses showed that the incidence of the primary kidney outcome – kidney failure, a sustained ≥ 57% decrease in eGFR from baseline, or kidney death – showed close correlation with at least a 30% reduction in UACR regardless of whether the patients in this subgroup received finerenone or placebo.

A different correlation was found in those with a less than 30% reduction in their UACR from baseline to 4 months, regardless of whether this happened on finerenone or placebo. People in the two finerenone trials who had a lesser reduction from baseline in their UACR also had a significantly higher rate of adverse kidney outcomes whether they received finerenone or placebo.

84% of finerenone’s kidney benefit linked to lowering of UACR

The causal-mediation analysis run by Dr. Agarwal quantified this observation, showing that 84% of finerenone’s effect on the kidney outcome was mediated by the reduction in UACR.

“It seems like the kidney benefit [from finerenone] travels through the level of albuminuria. This has broad implications for treatment of people with type 2 diabetes and CKD,” he said.

The link with reduction in albuminuria was weaker for the primary cardiovascular disease outcome: CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The strongest effect on this outcome was only seen in Kaplan-Meier analysis in those on finerenone who had at least a 30% reduction in their UACR. Those on placebo and with a similarly robust 4-month reduction in UACR showed a much more modest cardiovascular benefit that resembled those on either finerenone or placebo who had a smaller, less than 30% UACR reduction. The mediation analysis of these data showed that UACR reduction accounted for about 37% of the observed cardiovascular benefit seen during the trials.

“The effect of UACR is much stronger for the kidney outcomes,” summed up Dr. Agarwal. The results suggest that for cardiovascular outcomes finerenone works through factors other than lowering of UACR, but he admitted that no one currently knows what those other factors might be.
 

Treat aggressively to lower UACR by 30%

“I wouldn’t stop finerenone treatment in people who do not get a 30% reduction in their UACR” because these analyses suggest that a portion of the overall benefits from finerenone occurs via other mechanisms, he said. But in patients whose UACR is not reduced by at least 30% “be more aggressive on other measures to reduce UACR,” he advised.

The mediation analyses he ran are “the first time this has been done in nephrology,” producing a “groundbreaking” analysis and finding, Dr. Agarwal said. He also highlighted that the findings primarily relate to the importance of controlling UACR rather than an endorsement of finerenone as the best way to achieve this.

“All I care about is that people think about UACR as a modifiable risk factor. It doesn’t have to be treated with finerenone. It could be a renin-angiotensin system inhibitor, it could be chlorthalidone [a thiazide diuretic]. It just happened that we had a large dataset of people treated with finerenone or placebo.”

He said that future mediation analyses should look at the link between outcomes and UACR reductions produced by agents from the classes of sodium-glucose cotransporter 2 inhibitors and the glucagonlike peptide–1 receptor agonists.

FIDELIO-DKD and FIGARO-DKD were both sponsored by Bayer, the company that markets finerenone. Dr. Agarwal has received personal fees and nonfinancial support from Bayer. He has also received personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma, and he is a member of data safety monitoring committees for Chinook and Vertex. Dr. Inker is a consultant to Diamtrix, and her department receives research funding from Chinook, Omeros, Reata, and Tricida.

PHILADELPHIA – Reducing albuminuria is a key mediator of the way finerenone (Kerendia, Bayer) reduces adverse renal and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD), based on findings from two novel mediation analyses run on data from more than 12,000 people included in the two finerenone pivotal trials.

Results from these analyses showed that the reduction in urine albumin-to-creatinine ratio (UACR) linked to finerenone treatment mediated 84% of the kidney protection and 37% of the cardiovascular event protection that finerenone treatment produced in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. FIDELIO-DKD, which had protection against adverse kidney outcomes as its primary endpoint, supplied the data that led to finerenone’s approval in 2021 by the U.S. Food and Drug Administration for treating people with type 2 diabetes and CKD.

The findings of the mediation analyses underscore the important role that albuminuria plays in the nephropathy and related comorbidities associated with type 2 diabetes and CKD and highlight the importance of ongoing monitoring of albuminuria to guide treatments aimed at minimizing this pathology, said Rajiv Agarwal, MD, who presented a poster on the mediation analyses at Kidney Week 2023, organized by the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

“My hope is that this [report] heightens awareness of UACR” as an important marker of both CKD and of the response by patients with CKD to their treatment, said Dr. Agarwal, a nephrologist and professor at Indiana University in Indianapolis.

“Only about half of people with type 2 diabetes get their UACR measured even though every guideline says measure UACR in people with diabetes. Our findings say that UACR is important not just for CKD diagnosis but also to give feedback” on whether management is working, Dr. Agarwal said in an interview.
 

Incorporate UACR into clinical decision-making

“My hope is that clinicians will look at UACR as something they should incorporate into clinical decision-making. I measure UACR in my patients [with CKD and type 2 diabetes] at every visit; it’s so inexpensive. Albuminuria is not a good sign. If it’s not reduced in a patient by at least 30% [the recommended minimum reduction by the American Diabetes Association for people who start with a UACR of at least 300 mg/g] clinicians should think of what else they could do to lower albuminuria”: Reduce salt intake, improve blood pressure control, make sure the patient is adherent to treatments, and add additional treatments, Dr. Agarwal advised.

Mitchel L. Zoler/MDedge News

Multiple efforts are now underway or will soon start to boost the rate at which at-risk people get their UACR measured, noted Leslie A. Inker, MD, in a separate talk during Kidney Week. These efforts include the National Kidney Foundation’s CKD Learning Collaborative, which aims to improve clinician awareness of CKD and improve routine testing for CKD. Early results during 2023 from this program in Missouri showed a nearly 8–percentage point increase in the screening rate for UACR levels in at-risk people, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston.

A second advance was introduction in 2018 of the “kidney profile” lab order by the American College of Clinical Pathology that allows clinicians to order as a single test both an estimated glomerular filtration rate (eGFR) and a UACR.

Also, the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance have both taken steps to encourage UACR ordering. The NCQA established a new Healthcare Effectiveness Data and Information Set performance measure for U.S. physicians starting in 2023 that will track measurement of UACR and eGFR in people with diabetes. CMS also has made assessment of kidney health a measure of care quality in programs effective in 2023 and 2024, Dr. Inker noted.
 

Most subjects had elevated UACRs

The study run by Dr. Agarwal and his associates used data from 12,512 of the more than 13,000 people enrolled in either FIDELITY-DKD or FIGARO-DKD who had UACR measurements recorded at baseline, at 4 months into either study, or both. Their median UACR at the time they began on finerenone or placebo was 514 mg/g, with 67% having a UACR of at least 300 mg/g (macroalbuminuria) and 31% having a UACR of 30-299 mg/g (microalbuminuria). By design, virtually all patients in these two trials were on a renin-angiotensin system inhibitor (either an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker), but given the time period when the two trials enrolled participants (during 2015-2018) only 7% of those enrolled were on a sodium-glucose cotransporter 2 inhibitor and only 7% were on a glucagonlike peptide–1 receptor agonist.

Four months after treatment began, 53% of those randomized to finerenone treatment and 27% of those in the placebo arm had their UACR reduced by at least 30% from baseline, the cutpoint chosen by Dr. Agarwal based on the American Diabetes Association guideline.

Kaplan-Meier analyses showed that the incidence of the primary kidney outcome – kidney failure, a sustained ≥ 57% decrease in eGFR from baseline, or kidney death – showed close correlation with at least a 30% reduction in UACR regardless of whether the patients in this subgroup received finerenone or placebo.

A different correlation was found in those with a less than 30% reduction in their UACR from baseline to 4 months, regardless of whether this happened on finerenone or placebo. People in the two finerenone trials who had a lesser reduction from baseline in their UACR also had a significantly higher rate of adverse kidney outcomes whether they received finerenone or placebo.

84% of finerenone’s kidney benefit linked to lowering of UACR

The causal-mediation analysis run by Dr. Agarwal quantified this observation, showing that 84% of finerenone’s effect on the kidney outcome was mediated by the reduction in UACR.

“It seems like the kidney benefit [from finerenone] travels through the level of albuminuria. This has broad implications for treatment of people with type 2 diabetes and CKD,” he said.

The link with reduction in albuminuria was weaker for the primary cardiovascular disease outcome: CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The strongest effect on this outcome was only seen in Kaplan-Meier analysis in those on finerenone who had at least a 30% reduction in their UACR. Those on placebo and with a similarly robust 4-month reduction in UACR showed a much more modest cardiovascular benefit that resembled those on either finerenone or placebo who had a smaller, less than 30% UACR reduction. The mediation analysis of these data showed that UACR reduction accounted for about 37% of the observed cardiovascular benefit seen during the trials.

“The effect of UACR is much stronger for the kidney outcomes,” summed up Dr. Agarwal. The results suggest that for cardiovascular outcomes finerenone works through factors other than lowering of UACR, but he admitted that no one currently knows what those other factors might be.
 

Treat aggressively to lower UACR by 30%

“I wouldn’t stop finerenone treatment in people who do not get a 30% reduction in their UACR” because these analyses suggest that a portion of the overall benefits from finerenone occurs via other mechanisms, he said. But in patients whose UACR is not reduced by at least 30% “be more aggressive on other measures to reduce UACR,” he advised.

The mediation analyses he ran are “the first time this has been done in nephrology,” producing a “groundbreaking” analysis and finding, Dr. Agarwal said. He also highlighted that the findings primarily relate to the importance of controlling UACR rather than an endorsement of finerenone as the best way to achieve this.

“All I care about is that people think about UACR as a modifiable risk factor. It doesn’t have to be treated with finerenone. It could be a renin-angiotensin system inhibitor, it could be chlorthalidone [a thiazide diuretic]. It just happened that we had a large dataset of people treated with finerenone or placebo.”

He said that future mediation analyses should look at the link between outcomes and UACR reductions produced by agents from the classes of sodium-glucose cotransporter 2 inhibitors and the glucagonlike peptide–1 receptor agonists.

FIDELIO-DKD and FIGARO-DKD were both sponsored by Bayer, the company that markets finerenone. Dr. Agarwal has received personal fees and nonfinancial support from Bayer. He has also received personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma, and he is a member of data safety monitoring committees for Chinook and Vertex. Dr. Inker is a consultant to Diamtrix, and her department receives research funding from Chinook, Omeros, Reata, and Tricida.

PHILADELPHIA – Reducing albuminuria is a key mediator of the way finerenone (Kerendia, Bayer) reduces adverse renal and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD), based on findings from two novel mediation analyses run on data from more than 12,000 people included in the two finerenone pivotal trials.

Results from these analyses showed that the reduction in urine albumin-to-creatinine ratio (UACR) linked to finerenone treatment mediated 84% of the kidney protection and 37% of the cardiovascular event protection that finerenone treatment produced in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. FIDELIO-DKD, which had protection against adverse kidney outcomes as its primary endpoint, supplied the data that led to finerenone’s approval in 2021 by the U.S. Food and Drug Administration for treating people with type 2 diabetes and CKD.

The findings of the mediation analyses underscore the important role that albuminuria plays in the nephropathy and related comorbidities associated with type 2 diabetes and CKD and highlight the importance of ongoing monitoring of albuminuria to guide treatments aimed at minimizing this pathology, said Rajiv Agarwal, MD, who presented a poster on the mediation analyses at Kidney Week 2023, organized by the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

“My hope is that this [report] heightens awareness of UACR” as an important marker of both CKD and of the response by patients with CKD to their treatment, said Dr. Agarwal, a nephrologist and professor at Indiana University in Indianapolis.

“Only about half of people with type 2 diabetes get their UACR measured even though every guideline says measure UACR in people with diabetes. Our findings say that UACR is important not just for CKD diagnosis but also to give feedback” on whether management is working, Dr. Agarwal said in an interview.
 

Incorporate UACR into clinical decision-making

“My hope is that clinicians will look at UACR as something they should incorporate into clinical decision-making. I measure UACR in my patients [with CKD and type 2 diabetes] at every visit; it’s so inexpensive. Albuminuria is not a good sign. If it’s not reduced in a patient by at least 30% [the recommended minimum reduction by the American Diabetes Association for people who start with a UACR of at least 300 mg/g] clinicians should think of what else they could do to lower albuminuria”: Reduce salt intake, improve blood pressure control, make sure the patient is adherent to treatments, and add additional treatments, Dr. Agarwal advised.

Mitchel L. Zoler/MDedge News

Multiple efforts are now underway or will soon start to boost the rate at which at-risk people get their UACR measured, noted Leslie A. Inker, MD, in a separate talk during Kidney Week. These efforts include the National Kidney Foundation’s CKD Learning Collaborative, which aims to improve clinician awareness of CKD and improve routine testing for CKD. Early results during 2023 from this program in Missouri showed a nearly 8–percentage point increase in the screening rate for UACR levels in at-risk people, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston.

A second advance was introduction in 2018 of the “kidney profile” lab order by the American College of Clinical Pathology that allows clinicians to order as a single test both an estimated glomerular filtration rate (eGFR) and a UACR.

Also, the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance have both taken steps to encourage UACR ordering. The NCQA established a new Healthcare Effectiveness Data and Information Set performance measure for U.S. physicians starting in 2023 that will track measurement of UACR and eGFR in people with diabetes. CMS also has made assessment of kidney health a measure of care quality in programs effective in 2023 and 2024, Dr. Inker noted.
 

Most subjects had elevated UACRs

The study run by Dr. Agarwal and his associates used data from 12,512 of the more than 13,000 people enrolled in either FIDELITY-DKD or FIGARO-DKD who had UACR measurements recorded at baseline, at 4 months into either study, or both. Their median UACR at the time they began on finerenone or placebo was 514 mg/g, with 67% having a UACR of at least 300 mg/g (macroalbuminuria) and 31% having a UACR of 30-299 mg/g (microalbuminuria). By design, virtually all patients in these two trials were on a renin-angiotensin system inhibitor (either an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker), but given the time period when the two trials enrolled participants (during 2015-2018) only 7% of those enrolled were on a sodium-glucose cotransporter 2 inhibitor and only 7% were on a glucagonlike peptide–1 receptor agonist.

Four months after treatment began, 53% of those randomized to finerenone treatment and 27% of those in the placebo arm had their UACR reduced by at least 30% from baseline, the cutpoint chosen by Dr. Agarwal based on the American Diabetes Association guideline.

Kaplan-Meier analyses showed that the incidence of the primary kidney outcome – kidney failure, a sustained ≥ 57% decrease in eGFR from baseline, or kidney death – showed close correlation with at least a 30% reduction in UACR regardless of whether the patients in this subgroup received finerenone or placebo.

A different correlation was found in those with a less than 30% reduction in their UACR from baseline to 4 months, regardless of whether this happened on finerenone or placebo. People in the two finerenone trials who had a lesser reduction from baseline in their UACR also had a significantly higher rate of adverse kidney outcomes whether they received finerenone or placebo.

84% of finerenone’s kidney benefit linked to lowering of UACR

The causal-mediation analysis run by Dr. Agarwal quantified this observation, showing that 84% of finerenone’s effect on the kidney outcome was mediated by the reduction in UACR.

“It seems like the kidney benefit [from finerenone] travels through the level of albuminuria. This has broad implications for treatment of people with type 2 diabetes and CKD,” he said.

The link with reduction in albuminuria was weaker for the primary cardiovascular disease outcome: CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The strongest effect on this outcome was only seen in Kaplan-Meier analysis in those on finerenone who had at least a 30% reduction in their UACR. Those on placebo and with a similarly robust 4-month reduction in UACR showed a much more modest cardiovascular benefit that resembled those on either finerenone or placebo who had a smaller, less than 30% UACR reduction. The mediation analysis of these data showed that UACR reduction accounted for about 37% of the observed cardiovascular benefit seen during the trials.

“The effect of UACR is much stronger for the kidney outcomes,” summed up Dr. Agarwal. The results suggest that for cardiovascular outcomes finerenone works through factors other than lowering of UACR, but he admitted that no one currently knows what those other factors might be.
 

Treat aggressively to lower UACR by 30%

“I wouldn’t stop finerenone treatment in people who do not get a 30% reduction in their UACR” because these analyses suggest that a portion of the overall benefits from finerenone occurs via other mechanisms, he said. But in patients whose UACR is not reduced by at least 30% “be more aggressive on other measures to reduce UACR,” he advised.

The mediation analyses he ran are “the first time this has been done in nephrology,” producing a “groundbreaking” analysis and finding, Dr. Agarwal said. He also highlighted that the findings primarily relate to the importance of controlling UACR rather than an endorsement of finerenone as the best way to achieve this.

“All I care about is that people think about UACR as a modifiable risk factor. It doesn’t have to be treated with finerenone. It could be a renin-angiotensin system inhibitor, it could be chlorthalidone [a thiazide diuretic]. It just happened that we had a large dataset of people treated with finerenone or placebo.”

He said that future mediation analyses should look at the link between outcomes and UACR reductions produced by agents from the classes of sodium-glucose cotransporter 2 inhibitors and the glucagonlike peptide–1 receptor agonists.

FIDELIO-DKD and FIGARO-DKD were both sponsored by Bayer, the company that markets finerenone. Dr. Agarwal has received personal fees and nonfinancial support from Bayer. He has also received personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Vifor Pharma, and he is a member of data safety monitoring committees for Chinook and Vertex. Dr. Inker is a consultant to Diamtrix, and her department receives research funding from Chinook, Omeros, Reata, and Tricida.

PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.

“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.

AHA/Scott Morgan

Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.

They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.

Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
 

Trial results

The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*

He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).

The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.

The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”

Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
 

‘Novel’ for an AI trial

“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”

AHA/Scott Morgan

Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”

He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”

However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.

Dr. Lin and Dr. Nallamothu have no relevant disclosures.

*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.

PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.

“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.

AHA/Scott Morgan

Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.

They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.

Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
 

Trial results

The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*

He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).

The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.

The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”

Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
 

‘Novel’ for an AI trial

“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”

AHA/Scott Morgan

Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”

He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”

However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.

Dr. Lin and Dr. Nallamothu have no relevant disclosures.

*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.

PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.

“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.

AHA/Scott Morgan

Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.

They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.

Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
 

Trial results

The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*

He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).

The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.

The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”

Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
 

‘Novel’ for an AI trial

“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”

AHA/Scott Morgan

Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”

He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”

However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.

Dr. Lin and Dr. Nallamothu have no relevant disclosures.

*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.

Sit less, move more. Or stand more. Or sleep more.

Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health. 

The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time. 

“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.

The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death. 

In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting. 

A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin. 

Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers. 

The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”  

Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
 

Limitations

Because the study was observational, results can’t be used to infer causality.

“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.

The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said. 

One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.

What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
 

Impact on patient care

That said, the results could help tailor recommendations for patients, Dr. Blodgett said.

If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion. 

More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most. 

You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them. 

Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.

The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice. 

“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.

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

Sit less, move more. Or stand more. Or sleep more.

Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health. 

The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time. 

“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.

The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death. 

In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting. 

A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin. 

Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers. 

The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”  

Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
 

Limitations

Because the study was observational, results can’t be used to infer causality.

“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.

The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said. 

One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.

What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
 

Impact on patient care

That said, the results could help tailor recommendations for patients, Dr. Blodgett said.

If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion. 

More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most. 

You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them. 

Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.

The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice. 

“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.

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

Sit less, move more. Or stand more. Or sleep more.

Replacing 30 minutes of sitting a day with equal time standing or even sleeping could improve obesity markers like body weight and waist circumference, according to a new cross-sectional study investigating the impact of movement behavior on cardiometabolic health. 

The findings suggest that, while higher-intensity activity may confer benefits sooner, adding more light activity or more standing, or even going to bed earlier, could improve heart health measures over time. 

“Our study highlights that replacing sedentary behavior with any other behavior can be beneficial,” said study author Joanna M. Blodgett, PhD, a researcher at University College London’s Institute of Sport, Exercise and Health, and department of targeted intervention.

The study builds on a large and growing body of evidence that movement behaviors impact cardiometabolic health. Increasing physical activity to 150 minutes a week has been shown to reduce the risk for cardiovascular disease by 17% and type 2 diabetes by 26%. Other studies suggest that even modest increases in physical activity can be beneficial. A prospective study published in October found that even short activity bouts of a few minutes a day may lower risks for heart attack, stroke, and early death. 

In the new study, researchers analyzed data from six studies and more than 15,000 participants, ranking behaviors according to their association with heart health. Moderate-to-vigorous activity was linked to the greatest benefit, followed by light activity, standing, sleeping, and finally – dead last on the list – sitting. 

A thigh-worn device tracked participants’ activity throughout the day, and six measures gauged heart health: body mass index (BMI), waist circumference, HDL cholesterol, total-cholesterol-to-HDL ratio, triglycerides, and glycated hemoglobin. 

Researchers modeled what would happen if people swapped various amounts of one activity for another every day for a week. Replacing just 4-13 minutes of sitting with moderate to vigorous activity improved heart health markers. 

The cardiovascular demands of regular intense activity like running, cycling, dancing, or playing sports – even in small bouts – strengthen the heart and improve blood flow throughout the body, Dr. Blodgett said. “This can lower cholesterol, blood pressure, and resting heart rate.”  

Even if adding moderate to vigorous activity is not an option, the findings suggest that people can still see benefits by replacing sitting with virtually any other activity – walking, standing, even sleeping.
 

Limitations

Because the study was observational, results can’t be used to infer causality.

“We cannot directly lean on the study results to guide prescriptions for particular exercise or lifestyle changes,” said Matthew Tomey, MD, a cardiologist with the Mount Sinai Health System, New York, who was not involved with the study. An interventional trial would be needed to confirm the findings.

The finding that sleep was better for participants than sitting is a good example. The benefits of replacing sitting with sleep were “clear” for adiposity measures like BMI and waist circumference, but negligible for blood markers such as cholesterol, triglycerides, and blood glucose, Dr. Blodgett said. 

One explanation: “The negative impact of sitting on these obesity measures is likely due to related unhealthy behaviors like snacking rather than the physiological benefits of sleep itself,” Dr. Blodgett said.

What’s more, study participants were relatively young, healthy, and active. The average age was 54, and they averaged nearly 8 hours of sleep, 10 hours of sitting, 3 hours of standing, 1.5 hours of light activity, and more than an hour of moderate to vigorous activity per day. So it’s difficult to draw conclusions about patients who don’t fit those metrics.
 

Impact on patient care

That said, the results could help tailor recommendations for patients, Dr. Blodgett said.

If a patient is struggling to exercise or is unable to exercise because of health or ability restrictions, you could help them find ways to add a lighter activity to their day, such as taking the stairs or walking briskly to catch the bus. Even swapping a regular desk for a standing one, or going to bed 30 minutes earlier, could be a more practical and effective suggestion. 

More than that: The research could be used to educate patients on the power of small changes. It shows that shifting daily habits even in small ways can make a difference, and people who are the least active stand to benefit the most. 

You can also remind patients that moderate or vigorous activity doesn’t need to happen at the gym. It could be lawn work, taking a walk, or moving heavy boxes. In fact, many activities can be “moderate” or even “vigorous” depending on the effort put into them. 

Share this rule of thumb: “An activity is classified as moderate intensity if you can talk but not sing while doing it, and an activity is generally considered vigorous intensity if you can’t say more than a few words without stopping to breathe,” Dr. Blodgett said.

The study also has implications for the potential of wearable activity trackers to monitor progress. Combining objective activity data with results from studies like this, and longer prospective studies, could help inform more helpful advice. 

“Ultimately, this research helps move us closer to more personalized guidance of how changing behaviors can improve your health,” Dr. Blodgett said.

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

Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.

That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”

Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.

“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.

The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.

Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.

It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”

Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
 

Love as medicine

The healing power of love may sound like pseudoscience, but more and more research backs the health benefits of connection and the hazards of isolation.

Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”

“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.

Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.

In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.

He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”

One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.

“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”

“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.

In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”

Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
 

Future

Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”

He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”

The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”

Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.

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

Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.

That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”

Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.

“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.

The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.

Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.

It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”

Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
 

Love as medicine

The healing power of love may sound like pseudoscience, but more and more research backs the health benefits of connection and the hazards of isolation.

Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”

“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.

Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.

In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.

He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”

One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.

“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”

“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.

In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”

Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
 

Future

Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”

He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”

The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”

Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.

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

Those who embrace lifestyle medicine are familiar with the slogan Dean Ornish, MD, likes to use: Eat well, move more, stress less, love more.

That last one, love, was the renowned physician and author’s focus at the recent American College of Lifestyle Medicine Conference in Denver. That’s because love – essentially the support, connectedness, and caring that patients feel when they join a lifestyle-change program – is “where healing occurs at the deepest level.”

Indeed, social connectedness is emerging as a vital pillar in the burgeoning field of lifestyle medicine, a specialty that uses lifestyle interventions to treat chronic conditions. About 300 lifestyle medicine programs are now integrated into residencies in medical schools across the country, up from a handful just 5 years ago, said Meagan Grega, MD, the conference chair.

“The energy and growth in American lifestyle medicine is unparalleled by anything else I see in the health care world right now,” said Dr. Grega, a family physician for 25 years in eastern Pennsylvania.

The field applies volumes of research, from the 1990s to today, demonstrating the healing effects of lifestyle changes. Dr. Ornish’s Preventive Medicine Research Institute has published research on small changes (like pomegranate juice helping blood flow in the heart) and huge ones: Coronary heart patients reversed the narrowing of arteries without lipid-lowering drugs after 1 year of lifestyle changes, including a vegetarian diet, aerobic exercise, stress management, and group support.

Ranking alongside bedrocks such as healthy diet, sleep, exercise, and stress management is positive social connection. That part, the “love more” part, often draws skepticism but is vital, said Dr. Ornish, who is sometimes referred to as the father of lifestyle medicine.

It’s “invariably the part that’s the most meaningful – that sense of connection to community that can come when you bring total strangers together,” Dr. Ornish said. “The ‘love more’ part, in many ways, is not only as important, but in some ways even more because everything really flows from that.”

Patients in a support group, who can “let down their emotional defenses and talk openly and authentically,” are much more likely to make and maintain healthy changes, Dr. Ornish said.
 

Love as medicine

The healing power of love may sound like pseudoscience, but more and more research backs the health benefits of connection and the hazards of isolation.

Mounting evidence links loneliness and isolation with a range of health issues, from mood disorders such as depression to chronic conditions such as cardiovascular disease. What’s more, data suggest that loneliness and social isolation in the United States are on the rise, and the COVID pandemic made that more clear. In May 2023, Surgeon General Vivek Murthy, MD, called loneliness, isolation, and lack of connection in the United States a “public health crisis.”

“Good relationships keep us happier and healthier,” said Robert Waldinger, MD, a psychiatrist at Massachusetts General Hospital, Boston.

Dr. Waldinger, who was not affiliated with the conference, is head of the Harvard Study of Adult Development, one of the longest studies of adult life. Beginning in 1938, the study has tracked 724 people plus more than 1,300 of their descendants and found that embracing community and close relationships helps us live longer and be happier.

In the study, the people who were most satisfied with their relationships at age 50 years were the healthiest at age 80 years. Knowing you have someone to rely on protects the brain: “Those people’s memories stay sharper longer,” Dr. Waldinger said.

He draws a distinction between connection and love. “Love is, I think, more of a feeling,” Dr. Waldinger noted. “Connection is a feeling, but it’s also an activity.”

One in five Americans say they’re lonely, he said, “and loneliness is a stressor.” People who are isolated don’t sleep as well, he added. Their health declines earlier in midlife, brain function slips sooner, and their lives are shorter.

“You don’t have anyone to complain to,” he said. If you do, “you can feel your body start to calm down.” Those without social connections may stay in a low-level “fight-or-flight mode.”

“What we think happens is that you have low levels of inflammation chronically, and those can gradually break down body systems.” Moreover, higher rates of cardiac reactivity, for instance, a racing heartbeat when upset, can lead to high blood pressure and lower immune function.

In his talk, Dr. Ornish said, “Anger is that one emotion that has consistently been shown to make heart disease worse.”

Helping people in those straits is gratifying, Dr. Ornish said. “If we can work with people as lifestyle medicine practitioners when they’re suffering, there’s an opportunity for transformation.”
 

Future

Of course, that can be easier said than done. Dr. Ornish relayed a patient’s typical reaction to a lifestyle program: “This is kind of weird stuff. Like, I get diet. But a plant-based diet, really? Meditation? Loving more? Really?”

He told the conference, “Part of our job as lifestyle medicine practitioners is to spend a little extra time with them. It doesn’t even take that much time. And to really help them understand what brings them a sense of hope and meaning and purpose.”

The results can be motivating. “Most people feel so much better so quickly,” Dr. Ornish said. “It reframes the reason for change from fear of dying to joy of living.”

Dr. Grega, for one, is optimistic for the future, citing survey results showing that 95% of medical students think that they›d be better counselors with lifestyle training. ‘They passionately want this type of thing,” she said.

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

Cardiovascular disease is the most common cause of death in people living with type 2 diabetes (T2D). It is true that patient prognoses have improved with the use of metformin and by addressing cardiovascular risk factors. But the new oral antidiabetic drugs, SGLT2 (sodium glucose cotransporter-2) inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1Ra) offer fresh therapeutic approaches. Several recent controlled studies and meta-analyses have demonstrated the possibility of a cardioprotective and nephroprotective effect, even in patients without diabetes, especially with regard to SGLT2 inhibitors.

A cohort of more than 2 million patients with T2D

What about in the real world, far away from the ideal conditions of randomized trials? Could combining SGLT2 inhibitors with GLP-1R agonists be even more effective?

These are the questions answered by a large retrospective cohort study in which 2.2 million patients with T2D receiving insulin were initially enrolled and monitored at 85 specialist centers spread throughout three countries (Denmark, the United Kingdom, and the United States).

Three groups were formed from this cohort according to whether they received monotherapy or combination treatments: SGLT2i (n = 143,600), GLP-1Ra (n = 186,841), and SGLT2i + GLP-1Ra (n = 108,5040). A control group received none of these treatments.

Propensity score matching took into account the following relevant variables: age, sex, ischemic heart disease, hypertension, chronic kidney disease, heart failure, and glycated hemoglobin. The data was analyzed using the Cox’s proportional hazards model, with follow-up at 5 years.
 

Real-world benefits – Even better when combined

The inter-group comparison suggests that oral antidiabetic agents are effective when taking into account three major events:

All-cause mortality: SGLT2i (hazard ratio, 0.49; confidence interval 95% 0.48-0.50); GLP-1Ra (HR, 0.47; CI 95% 0.46-0.48); SGLT2i + GLP-1Ra (HR, 0.25; CI 95% 0.24-0.26).

Admissions rate: respectively HR: 0.73 (0.72-0.74); 0.69 (0.68-0.69); 0.60 (0.59-0.61).

Myocardial infarction rate: respectively HR: 0.75 (0.72-0.78); 0.70 (0.68-0.73); 0.63 (0.60-0.66).

A complementary sub-analysis also revealed a more significant reduction in all-cause mortality in the event of exposure to the combination of two antidiabetic drugs versus SGLT2i alone (HR, 0.53 [0.50-0.55]) and GLP-1Ra as monotherapy (HR, 0.56 [0.54-0.59]).

This real-world retrospective cohort study involves a large sample size: more than 400,000 patients with T2D treated with new oral antidiabetic drugs and as many control patients. It suggests that SGLT2 inhibitors and GLP-1R agonists have a significant effect on overall mortality, as well as on the risk of myocardial infarction and the admissions rate. Yes, it is retrospective, but its findings are in line with those from the most recent and conclusive randomized trials that suggest a cardio- and nephroprotective effect, at least with regard to SGLT2 inhibitors.

This article was translated from JIM and a version appeared on Medscape.com.

Cardiovascular disease is the most common cause of death in people living with type 2 diabetes (T2D). It is true that patient prognoses have improved with the use of metformin and by addressing cardiovascular risk factors. But the new oral antidiabetic drugs, SGLT2 (sodium glucose cotransporter-2) inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1Ra) offer fresh therapeutic approaches. Several recent controlled studies and meta-analyses have demonstrated the possibility of a cardioprotective and nephroprotective effect, even in patients without diabetes, especially with regard to SGLT2 inhibitors.

A cohort of more than 2 million patients with T2D

What about in the real world, far away from the ideal conditions of randomized trials? Could combining SGLT2 inhibitors with GLP-1R agonists be even more effective?

These are the questions answered by a large retrospective cohort study in which 2.2 million patients with T2D receiving insulin were initially enrolled and monitored at 85 specialist centers spread throughout three countries (Denmark, the United Kingdom, and the United States).

Three groups were formed from this cohort according to whether they received monotherapy or combination treatments: SGLT2i (n = 143,600), GLP-1Ra (n = 186,841), and SGLT2i + GLP-1Ra (n = 108,5040). A control group received none of these treatments.

Propensity score matching took into account the following relevant variables: age, sex, ischemic heart disease, hypertension, chronic kidney disease, heart failure, and glycated hemoglobin. The data was analyzed using the Cox’s proportional hazards model, with follow-up at 5 years.
 

Real-world benefits – Even better when combined

The inter-group comparison suggests that oral antidiabetic agents are effective when taking into account three major events:

All-cause mortality: SGLT2i (hazard ratio, 0.49; confidence interval 95% 0.48-0.50); GLP-1Ra (HR, 0.47; CI 95% 0.46-0.48); SGLT2i + GLP-1Ra (HR, 0.25; CI 95% 0.24-0.26).

Admissions rate: respectively HR: 0.73 (0.72-0.74); 0.69 (0.68-0.69); 0.60 (0.59-0.61).

Myocardial infarction rate: respectively HR: 0.75 (0.72-0.78); 0.70 (0.68-0.73); 0.63 (0.60-0.66).

A complementary sub-analysis also revealed a more significant reduction in all-cause mortality in the event of exposure to the combination of two antidiabetic drugs versus SGLT2i alone (HR, 0.53 [0.50-0.55]) and GLP-1Ra as monotherapy (HR, 0.56 [0.54-0.59]).

This real-world retrospective cohort study involves a large sample size: more than 400,000 patients with T2D treated with new oral antidiabetic drugs and as many control patients. It suggests that SGLT2 inhibitors and GLP-1R agonists have a significant effect on overall mortality, as well as on the risk of myocardial infarction and the admissions rate. Yes, it is retrospective, but its findings are in line with those from the most recent and conclusive randomized trials that suggest a cardio- and nephroprotective effect, at least with regard to SGLT2 inhibitors.

This article was translated from JIM and a version appeared on Medscape.com.

Cardiovascular disease is the most common cause of death in people living with type 2 diabetes (T2D). It is true that patient prognoses have improved with the use of metformin and by addressing cardiovascular risk factors. But the new oral antidiabetic drugs, SGLT2 (sodium glucose cotransporter-2) inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1Ra) offer fresh therapeutic approaches. Several recent controlled studies and meta-analyses have demonstrated the possibility of a cardioprotective and nephroprotective effect, even in patients without diabetes, especially with regard to SGLT2 inhibitors.

A cohort of more than 2 million patients with T2D

What about in the real world, far away from the ideal conditions of randomized trials? Could combining SGLT2 inhibitors with GLP-1R agonists be even more effective?

These are the questions answered by a large retrospective cohort study in which 2.2 million patients with T2D receiving insulin were initially enrolled and monitored at 85 specialist centers spread throughout three countries (Denmark, the United Kingdom, and the United States).

Three groups were formed from this cohort according to whether they received monotherapy or combination treatments: SGLT2i (n = 143,600), GLP-1Ra (n = 186,841), and SGLT2i + GLP-1Ra (n = 108,5040). A control group received none of these treatments.

Propensity score matching took into account the following relevant variables: age, sex, ischemic heart disease, hypertension, chronic kidney disease, heart failure, and glycated hemoglobin. The data was analyzed using the Cox’s proportional hazards model, with follow-up at 5 years.
 

Real-world benefits – Even better when combined

The inter-group comparison suggests that oral antidiabetic agents are effective when taking into account three major events:

All-cause mortality: SGLT2i (hazard ratio, 0.49; confidence interval 95% 0.48-0.50); GLP-1Ra (HR, 0.47; CI 95% 0.46-0.48); SGLT2i + GLP-1Ra (HR, 0.25; CI 95% 0.24-0.26).

Admissions rate: respectively HR: 0.73 (0.72-0.74); 0.69 (0.68-0.69); 0.60 (0.59-0.61).

Myocardial infarction rate: respectively HR: 0.75 (0.72-0.78); 0.70 (0.68-0.73); 0.63 (0.60-0.66).

A complementary sub-analysis also revealed a more significant reduction in all-cause mortality in the event of exposure to the combination of two antidiabetic drugs versus SGLT2i alone (HR, 0.53 [0.50-0.55]) and GLP-1Ra as monotherapy (HR, 0.56 [0.54-0.59]).

This real-world retrospective cohort study involves a large sample size: more than 400,000 patients with T2D treated with new oral antidiabetic drugs and as many control patients. It suggests that SGLT2 inhibitors and GLP-1R agonists have a significant effect on overall mortality, as well as on the risk of myocardial infarction and the admissions rate. Yes, it is retrospective, but its findings are in line with those from the most recent and conclusive randomized trials that suggest a cardio- and nephroprotective effect, at least with regard to SGLT2 inhibitors.

This article was translated from JIM and a version appeared on Medscape.com.