Lipid Disorders

A new strategy for the management of atherosclerotic plaque as a source of major adverse cardiac events is needed with the focus shifting from the flow-limiting coronary artery luminal lesions to the overall atherosclerotic burden, be it obstructive or nonobstructive, according to a review article.

The article, by Peter H. Stone, MD, and Peter Libby, MD, Brigham and Women’s Hospital, Boston, and William E. Boden, MD, Boston University School of Medicine, was published online in JAMA Cardiology.  

The review explored new data from vascular biology, atherosclerosis imaging, natural history outcome studies, and large-scale clinical trials that support what the authors refer to as “The Plaque Hypothesis” – the idea that major adverse cardiac events such as myocardial infarction and cardiac death are triggered by destabilization of vulnerable plaque, which may be obstructive or nonobstructive.

“We need to consider embracing a new management strategy that directs our diagnostic and management focus to evaluate the entire length of the atheromatous coronary artery and broaden the target of our therapeutic intervention to include all regions of the plaque (both flow-limiting and non–flow-limiting), even those that are distant from the presumed ischemia-producing obstruction,” the authors concluded.

Dr. Stone explained to this news organization that, for several decades, the medical community has focused on plaques causing severe obstruction of coronary arteries as being responsible for major adverse cardiac events. This approach – known as the Ischemia Hypothesis – has been the accepted strategy for many years, with all guidelines advising the identification of the stenoses that cause the most obstruction for treatment with stenting.

However, the authors pointed out that a number of studies have now suggested that, while these severe obstructive stenoses cause angina, they do not seem to be responsible for the hard events of MI, acute coronary syndrome (ACS), and cardiac death. 

Several studies including the COURAGE trial and BARI-2D, and the recent ISCHEMIA trial have all failed to show a reduction in these hard endpoints by intervening on these severe obstructive lesions, Dr. Stone noted. 

“We present evidence for a new approach – that it is the composition and vascular biology of the atherosclerotic plaques that cause MI, ACS, and cardiac death, rather than simply how obstructive they are,” he said.  

Dr. Stone pointed out that plaque seen on a coronary angiogram looks at only the lumen of the artery, but plaque is primarily based in the wall of the artery, and if that plaque is inflamed it can easily be the culprit responsible for adverse events even without encroaching into the lumen.

“Our paper describes many factors which can cause plaques to destabilize and cause an ACS. These include anatomical, biochemical, and biomechanical features that together cause plaque rupture or erosion and precipitate a clinical event. It is not sufficient to just look for obstructive plaques on a coronary angiogram,” he said. “We are barking up the wrong tree. We need to look for inflamed plaque in the whole wall of the coronary arteries.”

The authors described different factors that identify a plaque at high risk of destabilization. These include a large area of vulnerable plaque, a thin-cap atheroma, a severe inflamed core, macrocalcifications, a large plaque burden, and a physical profile that would encourage a thrombus to become trapped.  

“Atherosclerotic plaques are very heterogeneous and complex structures and it is not just the mountain peaks but also the lower foothills that can precipitate a flow-limiting obstruction,” Dr. Stone noted. 

“The slope of the mountain is probably very important in the ability for a thrombus to form. If the slope is gradual there isn’t a problem. But if the slope is jagged with sharp edges this can cause a thrombus to become trapped. We need to look at the entirety of plaque and all its risk features to identify the culprit areas that could cause MI or cardiac death. These are typically not the obstructive plaques we have all been fixated on for many years,” he added. 

“We need to focus on plaque heterogeneity. Once plaque is old and just made up of scar tissue which is not inflamed it does not cause much [of] a problem – we can probably just leave it alone. Some of these obstructive plaques may cause some angina but many do not cause major cardiac events unless they have other high-risk features,” he said. 

“Cardiac events are still caused by obstruction of blood flow but that can be an abrupt process where a thrombus attaches itself to an area of destabilized plaque. These areas of plaque were not necessarily obstructing to start with. We believe that this is the explanation behind the observation that 50% of all people who have an MI (half of which are fatal) do not have symptoms beforehand,” Dr. Stone commented. 

Because these areas of destabilized plaque do not cause symptoms, he believes that vast populations of people with established cardiovascular risk factors should undergo screening. “At the moment we wait for people to experience chest pain or to have an MI – that is far too little too late.” 

To identify these areas of high-risk plaques, imaging techniques looking inside the artery wall are needed such as intravascular ultrasound. However, this is an invasive procedure, and the noninvasive coronary CT angiography also gives a good picture, so it is probably the best way to begin as a wider screening modality, with more invasive screening methods then used in those found to be at risk, Dr. Stone suggested.  

Plaques that are identified as likely to destabilize can be treated with percutaneous coronary intervention and stenting.  

While systemic therapies are useful, those currently available are not sufficient, Dr. Stone noted. For example, there are still high levels of major cardiac events in patients treated with the PCSK9 inhibitors, which bring about very large reductions in LDL cholesterol. “These therapies are beneficial, but they are not enough on their own. So, these areas of unstable plaque would need to be treated with stenting or something similar. We believe that the intervention of stenting is good but at present it is targeted at the wrong areas,” he stated.  

“Clearly what we’ve been doing – stenting only obstructive lesions – does not reduce hard clinical events. Imaging methods have improved so much in recent years that we can now identify high-risk areas of plaque. This whole field of studying the vulnerable plaque has been ongoing for many years, but it is only recently that imaging methods have become good enough to identify plaques at risk. This field is now coming of age,” he added.

The next steps are to start identifying these plaques in larger populations, more accurately characterizing those at the highest risk, and then performing randomized trials of preemptive intervention in those believed to be at highest risk, and follow up for clinical events, Dr. Stone explained.  

Advances in detecting unstable plaque may also permit early evaluation of novel therapeutics and gauge the intensity of lifestyle and disease-modifying pharmacotherapy, the authors suggested.

This work was supported in part by the National Heart, Lung, and Blood Institute, the American Heart Association, the RRM Charitable Fund, the Simard Fund, and the Schaubert Family. Dr. Libby is an unpaid consultant to or involved in clinical trials with Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, MedImmune, Merck, Norvo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, MedImmune, Moderna, Novartis, PlaqueTec, TenSixteen Bio, Soley Thereapeutics, and XBiotech.

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

A new strategy for the management of atherosclerotic plaque as a source of major adverse cardiac events is needed with the focus shifting from the flow-limiting coronary artery luminal lesions to the overall atherosclerotic burden, be it obstructive or nonobstructive, according to a review article.

The article, by Peter H. Stone, MD, and Peter Libby, MD, Brigham and Women’s Hospital, Boston, and William E. Boden, MD, Boston University School of Medicine, was published online in JAMA Cardiology.  

The review explored new data from vascular biology, atherosclerosis imaging, natural history outcome studies, and large-scale clinical trials that support what the authors refer to as “The Plaque Hypothesis” – the idea that major adverse cardiac events such as myocardial infarction and cardiac death are triggered by destabilization of vulnerable plaque, which may be obstructive or nonobstructive.

“We need to consider embracing a new management strategy that directs our diagnostic and management focus to evaluate the entire length of the atheromatous coronary artery and broaden the target of our therapeutic intervention to include all regions of the plaque (both flow-limiting and non–flow-limiting), even those that are distant from the presumed ischemia-producing obstruction,” the authors concluded.

Dr. Stone explained to this news organization that, for several decades, the medical community has focused on plaques causing severe obstruction of coronary arteries as being responsible for major adverse cardiac events. This approach – known as the Ischemia Hypothesis – has been the accepted strategy for many years, with all guidelines advising the identification of the stenoses that cause the most obstruction for treatment with stenting.

However, the authors pointed out that a number of studies have now suggested that, while these severe obstructive stenoses cause angina, they do not seem to be responsible for the hard events of MI, acute coronary syndrome (ACS), and cardiac death. 

Several studies including the COURAGE trial and BARI-2D, and the recent ISCHEMIA trial have all failed to show a reduction in these hard endpoints by intervening on these severe obstructive lesions, Dr. Stone noted. 

“We present evidence for a new approach – that it is the composition and vascular biology of the atherosclerotic plaques that cause MI, ACS, and cardiac death, rather than simply how obstructive they are,” he said.  

Dr. Stone pointed out that plaque seen on a coronary angiogram looks at only the lumen of the artery, but plaque is primarily based in the wall of the artery, and if that plaque is inflamed it can easily be the culprit responsible for adverse events even without encroaching into the lumen.

“Our paper describes many factors which can cause plaques to destabilize and cause an ACS. These include anatomical, biochemical, and biomechanical features that together cause plaque rupture or erosion and precipitate a clinical event. It is not sufficient to just look for obstructive plaques on a coronary angiogram,” he said. “We are barking up the wrong tree. We need to look for inflamed plaque in the whole wall of the coronary arteries.”

The authors described different factors that identify a plaque at high risk of destabilization. These include a large area of vulnerable plaque, a thin-cap atheroma, a severe inflamed core, macrocalcifications, a large plaque burden, and a physical profile that would encourage a thrombus to become trapped.  

“Atherosclerotic plaques are very heterogeneous and complex structures and it is not just the mountain peaks but also the lower foothills that can precipitate a flow-limiting obstruction,” Dr. Stone noted. 

“The slope of the mountain is probably very important in the ability for a thrombus to form. If the slope is gradual there isn’t a problem. But if the slope is jagged with sharp edges this can cause a thrombus to become trapped. We need to look at the entirety of plaque and all its risk features to identify the culprit areas that could cause MI or cardiac death. These are typically not the obstructive plaques we have all been fixated on for many years,” he added. 

“We need to focus on plaque heterogeneity. Once plaque is old and just made up of scar tissue which is not inflamed it does not cause much [of] a problem – we can probably just leave it alone. Some of these obstructive plaques may cause some angina but many do not cause major cardiac events unless they have other high-risk features,” he said. 

“Cardiac events are still caused by obstruction of blood flow but that can be an abrupt process where a thrombus attaches itself to an area of destabilized plaque. These areas of plaque were not necessarily obstructing to start with. We believe that this is the explanation behind the observation that 50% of all people who have an MI (half of which are fatal) do not have symptoms beforehand,” Dr. Stone commented. 

Because these areas of destabilized plaque do not cause symptoms, he believes that vast populations of people with established cardiovascular risk factors should undergo screening. “At the moment we wait for people to experience chest pain or to have an MI – that is far too little too late.” 

To identify these areas of high-risk plaques, imaging techniques looking inside the artery wall are needed such as intravascular ultrasound. However, this is an invasive procedure, and the noninvasive coronary CT angiography also gives a good picture, so it is probably the best way to begin as a wider screening modality, with more invasive screening methods then used in those found to be at risk, Dr. Stone suggested.  

Plaques that are identified as likely to destabilize can be treated with percutaneous coronary intervention and stenting.  

While systemic therapies are useful, those currently available are not sufficient, Dr. Stone noted. For example, there are still high levels of major cardiac events in patients treated with the PCSK9 inhibitors, which bring about very large reductions in LDL cholesterol. “These therapies are beneficial, but they are not enough on their own. So, these areas of unstable plaque would need to be treated with stenting or something similar. We believe that the intervention of stenting is good but at present it is targeted at the wrong areas,” he stated.  

“Clearly what we’ve been doing – stenting only obstructive lesions – does not reduce hard clinical events. Imaging methods have improved so much in recent years that we can now identify high-risk areas of plaque. This whole field of studying the vulnerable plaque has been ongoing for many years, but it is only recently that imaging methods have become good enough to identify plaques at risk. This field is now coming of age,” he added.

The next steps are to start identifying these plaques in larger populations, more accurately characterizing those at the highest risk, and then performing randomized trials of preemptive intervention in those believed to be at highest risk, and follow up for clinical events, Dr. Stone explained.  

Advances in detecting unstable plaque may also permit early evaluation of novel therapeutics and gauge the intensity of lifestyle and disease-modifying pharmacotherapy, the authors suggested.

This work was supported in part by the National Heart, Lung, and Blood Institute, the American Heart Association, the RRM Charitable Fund, the Simard Fund, and the Schaubert Family. Dr. Libby is an unpaid consultant to or involved in clinical trials with Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, MedImmune, Merck, Norvo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, MedImmune, Moderna, Novartis, PlaqueTec, TenSixteen Bio, Soley Thereapeutics, and XBiotech.

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

A new strategy for the management of atherosclerotic plaque as a source of major adverse cardiac events is needed with the focus shifting from the flow-limiting coronary artery luminal lesions to the overall atherosclerotic burden, be it obstructive or nonobstructive, according to a review article.

The article, by Peter H. Stone, MD, and Peter Libby, MD, Brigham and Women’s Hospital, Boston, and William E. Boden, MD, Boston University School of Medicine, was published online in JAMA Cardiology.  

The review explored new data from vascular biology, atherosclerosis imaging, natural history outcome studies, and large-scale clinical trials that support what the authors refer to as “The Plaque Hypothesis” – the idea that major adverse cardiac events such as myocardial infarction and cardiac death are triggered by destabilization of vulnerable plaque, which may be obstructive or nonobstructive.

“We need to consider embracing a new management strategy that directs our diagnostic and management focus to evaluate the entire length of the atheromatous coronary artery and broaden the target of our therapeutic intervention to include all regions of the plaque (both flow-limiting and non–flow-limiting), even those that are distant from the presumed ischemia-producing obstruction,” the authors concluded.

Dr. Stone explained to this news organization that, for several decades, the medical community has focused on plaques causing severe obstruction of coronary arteries as being responsible for major adverse cardiac events. This approach – known as the Ischemia Hypothesis – has been the accepted strategy for many years, with all guidelines advising the identification of the stenoses that cause the most obstruction for treatment with stenting.

However, the authors pointed out that a number of studies have now suggested that, while these severe obstructive stenoses cause angina, they do not seem to be responsible for the hard events of MI, acute coronary syndrome (ACS), and cardiac death. 

Several studies including the COURAGE trial and BARI-2D, and the recent ISCHEMIA trial have all failed to show a reduction in these hard endpoints by intervening on these severe obstructive lesions, Dr. Stone noted. 

“We present evidence for a new approach – that it is the composition and vascular biology of the atherosclerotic plaques that cause MI, ACS, and cardiac death, rather than simply how obstructive they are,” he said.  

Dr. Stone pointed out that plaque seen on a coronary angiogram looks at only the lumen of the artery, but plaque is primarily based in the wall of the artery, and if that plaque is inflamed it can easily be the culprit responsible for adverse events even without encroaching into the lumen.

“Our paper describes many factors which can cause plaques to destabilize and cause an ACS. These include anatomical, biochemical, and biomechanical features that together cause plaque rupture or erosion and precipitate a clinical event. It is not sufficient to just look for obstructive plaques on a coronary angiogram,” he said. “We are barking up the wrong tree. We need to look for inflamed plaque in the whole wall of the coronary arteries.”

The authors described different factors that identify a plaque at high risk of destabilization. These include a large area of vulnerable plaque, a thin-cap atheroma, a severe inflamed core, macrocalcifications, a large plaque burden, and a physical profile that would encourage a thrombus to become trapped.  

“Atherosclerotic plaques are very heterogeneous and complex structures and it is not just the mountain peaks but also the lower foothills that can precipitate a flow-limiting obstruction,” Dr. Stone noted. 

“The slope of the mountain is probably very important in the ability for a thrombus to form. If the slope is gradual there isn’t a problem. But if the slope is jagged with sharp edges this can cause a thrombus to become trapped. We need to look at the entirety of plaque and all its risk features to identify the culprit areas that could cause MI or cardiac death. These are typically not the obstructive plaques we have all been fixated on for many years,” he added. 

“We need to focus on plaque heterogeneity. Once plaque is old and just made up of scar tissue which is not inflamed it does not cause much [of] a problem – we can probably just leave it alone. Some of these obstructive plaques may cause some angina but many do not cause major cardiac events unless they have other high-risk features,” he said. 

“Cardiac events are still caused by obstruction of blood flow but that can be an abrupt process where a thrombus attaches itself to an area of destabilized plaque. These areas of plaque were not necessarily obstructing to start with. We believe that this is the explanation behind the observation that 50% of all people who have an MI (half of which are fatal) do not have symptoms beforehand,” Dr. Stone commented. 

Because these areas of destabilized plaque do not cause symptoms, he believes that vast populations of people with established cardiovascular risk factors should undergo screening. “At the moment we wait for people to experience chest pain or to have an MI – that is far too little too late.” 

To identify these areas of high-risk plaques, imaging techniques looking inside the artery wall are needed such as intravascular ultrasound. However, this is an invasive procedure, and the noninvasive coronary CT angiography also gives a good picture, so it is probably the best way to begin as a wider screening modality, with more invasive screening methods then used in those found to be at risk, Dr. Stone suggested.  

Plaques that are identified as likely to destabilize can be treated with percutaneous coronary intervention and stenting.  

While systemic therapies are useful, those currently available are not sufficient, Dr. Stone noted. For example, there are still high levels of major cardiac events in patients treated with the PCSK9 inhibitors, which bring about very large reductions in LDL cholesterol. “These therapies are beneficial, but they are not enough on their own. So, these areas of unstable plaque would need to be treated with stenting or something similar. We believe that the intervention of stenting is good but at present it is targeted at the wrong areas,” he stated.  

“Clearly what we’ve been doing – stenting only obstructive lesions – does not reduce hard clinical events. Imaging methods have improved so much in recent years that we can now identify high-risk areas of plaque. This whole field of studying the vulnerable plaque has been ongoing for many years, but it is only recently that imaging methods have become good enough to identify plaques at risk. This field is now coming of age,” he added.

The next steps are to start identifying these plaques in larger populations, more accurately characterizing those at the highest risk, and then performing randomized trials of preemptive intervention in those believed to be at highest risk, and follow up for clinical events, Dr. Stone explained.  

Advances in detecting unstable plaque may also permit early evaluation of novel therapeutics and gauge the intensity of lifestyle and disease-modifying pharmacotherapy, the authors suggested.

This work was supported in part by the National Heart, Lung, and Blood Institute, the American Heart Association, the RRM Charitable Fund, the Simard Fund, and the Schaubert Family. Dr. Libby is an unpaid consultant to or involved in clinical trials with Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, MedImmune, Merck, Norvo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, MedImmune, Moderna, Novartis, PlaqueTec, TenSixteen Bio, Soley Thereapeutics, and XBiotech.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Metabolic syndrome is associated with a significantly increased risk for gout in young men, but the risk can be mitigated by improvement in individual components of the syndrome, based on data from a pair of population-based studies totaling more than 4 million individuals.

Gout remains the most common type of inflammatory arthritis in men, and the rate has been rising among younger adults, Yeonghee Eun, MD, PhD, of Sungkyunkwan University, Seoul, South Korea, and colleagues wrote. An increasing body of evidence suggests a link between gout and metabolic syndrome (MetS), but large studies have been lacking, especially in younger adults.

In a study published in Frontiers in Medicine, the researchers reviewed data from 3,569,104 men aged 20-39 years who underwent a health checkup between 2009 and 2012 in South Korea, based on the Korean National Health Insurance Service. The primary outcome of incident gout was identified using claims data. The mean age of the participants was 31.5 years.

Over a mean follow-up of 7.4 years, the incidence of gout was 3.36 per 1,000 person-years. The risk of developing gout was more than twice as high among individuals who met MetS criteria than in those who did not (adjusted hazard ratio, 2.44).

MetS was defined as the presence of at least two of the following components: hypertriglyceridemia, abdominal obesity, reduced HDL cholesterol, elevated blood pressure, and elevated fasting glucose.

Overall, individuals with all five MetS components had a fivefold increase in gout risk, compared with people who did not have MetS (aHR, 5.24). In an analysis of each component of MetS, hypertriglyceridemia and abdominal obesity showed the strongest association with gout (aHRs of 2.08 and 2.33, respectively).

The impact of MetS on risk of incident gout was greater in younger participants, which suggests that the management of MetS in young people should be emphasized, the researchers said.

In a further analysis of body mass index subgroups, MetS had the greatest impact on gout risk for individuals who were underweight (aHR, 3.82). “In particular, in the underweight group, the risk of gout increased 10-fold when abdominal obesity was present,” the researchers said.

The study was limited by several factors including potential selection bias and potential overestimation of gout incidence because of the use of diagnostic codes, the researchers noted. Other limitations included lack of control for nutritional or dietary risk factors and the inability to include cases that occurred after the study period.

However, findings were strengthened by the large number of participants with MetS who were underweight or normal weight, the researchers wrote. More research on the mechanism of action is needed, but the data suggest that MetS is a key risk factor in the development of gout in young men.

In a second study, published in Arthritis & Rheumatology, Dr. Eun and colleagues examined associations between MetS changes and incident gout in young men. Although previous studies have shown that changes in MetS status can alter the risk of cardiovascular events, atrial fibrillation, end-stage renal disease, and all-cause mortality, the impact of these changes on gout has not been well studied, they said. The researchers used the same study cohort, the National Health Insurance Service database in South Korea. They reviewed data from 1,293,166 individuals aged 20-39 years. Of these, 18,473 were diagnosed with gout for an incidence rate 3.36/1,000 person-years. The researchers compared gout incidence for men who met criteria for MetS at three health checkups and those without MetS.

Overall, patients with MetS at all three checkups had a nearly fourfold higher risk of gout than those who never had MetS, with an adjusted hazard ratio of 3.82, the researchers wrote. The development of MetS over the study period more than doubled the risk of gout, but recovery from MetS reduced incident gout risk by approximately 50% (aHR, 0.52).

In findings similar to the Frontiers in Medicine study, the greatest associations with gout were noted for changes in elevated triglycerides and changes in abdominal obesity; aHRs for development and recovery for elevated triglycerides were 1.74 and 0.56, respectively, and for abdominal obesity, 1.94 and 0.69, respectively.

More research is needed to explore the mechanism by which both abdominal obesity and elevated triglycerides drive the development of gout, the researchers wrote in their discussion.

Also similar to the Frontiers study, the associations among changes in MetS and incident gout were greater for the youngest participants (in their 20s) and in the underweight or normal weight BMI groups.

Limitations of the second study included possible selection bias because of the study population of workplace employees who participated in regular health checks and the lack of data on women or on men aged 40 years and older, the researchers noted. Other limitations included possible misclassification of MetS because of varying health checkup results and drug claims, and lack of data on serum urate, which prevented assessment of hyperuricemia as a cause of gout.

However, the results were strengthened by the large sample size and suggest that MetS is a modifiable risk factor for gout, the researchers concluded.

Neither of the studies received outside funding. The researchers had no financial conflicts to disclose.

Metabolic syndrome is associated with a significantly increased risk for gout in young men, but the risk can be mitigated by improvement in individual components of the syndrome, based on data from a pair of population-based studies totaling more than 4 million individuals.

Gout remains the most common type of inflammatory arthritis in men, and the rate has been rising among younger adults, Yeonghee Eun, MD, PhD, of Sungkyunkwan University, Seoul, South Korea, and colleagues wrote. An increasing body of evidence suggests a link between gout and metabolic syndrome (MetS), but large studies have been lacking, especially in younger adults.

In a study published in Frontiers in Medicine, the researchers reviewed data from 3,569,104 men aged 20-39 years who underwent a health checkup between 2009 and 2012 in South Korea, based on the Korean National Health Insurance Service. The primary outcome of incident gout was identified using claims data. The mean age of the participants was 31.5 years.

Over a mean follow-up of 7.4 years, the incidence of gout was 3.36 per 1,000 person-years. The risk of developing gout was more than twice as high among individuals who met MetS criteria than in those who did not (adjusted hazard ratio, 2.44).

MetS was defined as the presence of at least two of the following components: hypertriglyceridemia, abdominal obesity, reduced HDL cholesterol, elevated blood pressure, and elevated fasting glucose.

Overall, individuals with all five MetS components had a fivefold increase in gout risk, compared with people who did not have MetS (aHR, 5.24). In an analysis of each component of MetS, hypertriglyceridemia and abdominal obesity showed the strongest association with gout (aHRs of 2.08 and 2.33, respectively).

The impact of MetS on risk of incident gout was greater in younger participants, which suggests that the management of MetS in young people should be emphasized, the researchers said.

In a further analysis of body mass index subgroups, MetS had the greatest impact on gout risk for individuals who were underweight (aHR, 3.82). “In particular, in the underweight group, the risk of gout increased 10-fold when abdominal obesity was present,” the researchers said.

The study was limited by several factors including potential selection bias and potential overestimation of gout incidence because of the use of diagnostic codes, the researchers noted. Other limitations included lack of control for nutritional or dietary risk factors and the inability to include cases that occurred after the study period.

However, findings were strengthened by the large number of participants with MetS who were underweight or normal weight, the researchers wrote. More research on the mechanism of action is needed, but the data suggest that MetS is a key risk factor in the development of gout in young men.

In a second study, published in Arthritis & Rheumatology, Dr. Eun and colleagues examined associations between MetS changes and incident gout in young men. Although previous studies have shown that changes in MetS status can alter the risk of cardiovascular events, atrial fibrillation, end-stage renal disease, and all-cause mortality, the impact of these changes on gout has not been well studied, they said. The researchers used the same study cohort, the National Health Insurance Service database in South Korea. They reviewed data from 1,293,166 individuals aged 20-39 years. Of these, 18,473 were diagnosed with gout for an incidence rate 3.36/1,000 person-years. The researchers compared gout incidence for men who met criteria for MetS at three health checkups and those without MetS.

Overall, patients with MetS at all three checkups had a nearly fourfold higher risk of gout than those who never had MetS, with an adjusted hazard ratio of 3.82, the researchers wrote. The development of MetS over the study period more than doubled the risk of gout, but recovery from MetS reduced incident gout risk by approximately 50% (aHR, 0.52).

In findings similar to the Frontiers in Medicine study, the greatest associations with gout were noted for changes in elevated triglycerides and changes in abdominal obesity; aHRs for development and recovery for elevated triglycerides were 1.74 and 0.56, respectively, and for abdominal obesity, 1.94 and 0.69, respectively.

More research is needed to explore the mechanism by which both abdominal obesity and elevated triglycerides drive the development of gout, the researchers wrote in their discussion.

Also similar to the Frontiers study, the associations among changes in MetS and incident gout were greater for the youngest participants (in their 20s) and in the underweight or normal weight BMI groups.

Limitations of the second study included possible selection bias because of the study population of workplace employees who participated in regular health checks and the lack of data on women or on men aged 40 years and older, the researchers noted. Other limitations included possible misclassification of MetS because of varying health checkup results and drug claims, and lack of data on serum urate, which prevented assessment of hyperuricemia as a cause of gout.

However, the results were strengthened by the large sample size and suggest that MetS is a modifiable risk factor for gout, the researchers concluded.

Neither of the studies received outside funding. The researchers had no financial conflicts to disclose.

Metabolic syndrome is associated with a significantly increased risk for gout in young men, but the risk can be mitigated by improvement in individual components of the syndrome, based on data from a pair of population-based studies totaling more than 4 million individuals.

Gout remains the most common type of inflammatory arthritis in men, and the rate has been rising among younger adults, Yeonghee Eun, MD, PhD, of Sungkyunkwan University, Seoul, South Korea, and colleagues wrote. An increasing body of evidence suggests a link between gout and metabolic syndrome (MetS), but large studies have been lacking, especially in younger adults.

In a study published in Frontiers in Medicine, the researchers reviewed data from 3,569,104 men aged 20-39 years who underwent a health checkup between 2009 and 2012 in South Korea, based on the Korean National Health Insurance Service. The primary outcome of incident gout was identified using claims data. The mean age of the participants was 31.5 years.

Over a mean follow-up of 7.4 years, the incidence of gout was 3.36 per 1,000 person-years. The risk of developing gout was more than twice as high among individuals who met MetS criteria than in those who did not (adjusted hazard ratio, 2.44).

MetS was defined as the presence of at least two of the following components: hypertriglyceridemia, abdominal obesity, reduced HDL cholesterol, elevated blood pressure, and elevated fasting glucose.

Overall, individuals with all five MetS components had a fivefold increase in gout risk, compared with people who did not have MetS (aHR, 5.24). In an analysis of each component of MetS, hypertriglyceridemia and abdominal obesity showed the strongest association with gout (aHRs of 2.08 and 2.33, respectively).

The impact of MetS on risk of incident gout was greater in younger participants, which suggests that the management of MetS in young people should be emphasized, the researchers said.

In a further analysis of body mass index subgroups, MetS had the greatest impact on gout risk for individuals who were underweight (aHR, 3.82). “In particular, in the underweight group, the risk of gout increased 10-fold when abdominal obesity was present,” the researchers said.

The study was limited by several factors including potential selection bias and potential overestimation of gout incidence because of the use of diagnostic codes, the researchers noted. Other limitations included lack of control for nutritional or dietary risk factors and the inability to include cases that occurred after the study period.

However, findings were strengthened by the large number of participants with MetS who were underweight or normal weight, the researchers wrote. More research on the mechanism of action is needed, but the data suggest that MetS is a key risk factor in the development of gout in young men.

In a second study, published in Arthritis & Rheumatology, Dr. Eun and colleagues examined associations between MetS changes and incident gout in young men. Although previous studies have shown that changes in MetS status can alter the risk of cardiovascular events, atrial fibrillation, end-stage renal disease, and all-cause mortality, the impact of these changes on gout has not been well studied, they said. The researchers used the same study cohort, the National Health Insurance Service database in South Korea. They reviewed data from 1,293,166 individuals aged 20-39 years. Of these, 18,473 were diagnosed with gout for an incidence rate 3.36/1,000 person-years. The researchers compared gout incidence for men who met criteria for MetS at three health checkups and those without MetS.

Overall, patients with MetS at all three checkups had a nearly fourfold higher risk of gout than those who never had MetS, with an adjusted hazard ratio of 3.82, the researchers wrote. The development of MetS over the study period more than doubled the risk of gout, but recovery from MetS reduced incident gout risk by approximately 50% (aHR, 0.52).

In findings similar to the Frontiers in Medicine study, the greatest associations with gout were noted for changes in elevated triglycerides and changes in abdominal obesity; aHRs for development and recovery for elevated triglycerides were 1.74 and 0.56, respectively, and for abdominal obesity, 1.94 and 0.69, respectively.

More research is needed to explore the mechanism by which both abdominal obesity and elevated triglycerides drive the development of gout, the researchers wrote in their discussion.

Also similar to the Frontiers study, the associations among changes in MetS and incident gout were greater for the youngest participants (in their 20s) and in the underweight or normal weight BMI groups.

Limitations of the second study included possible selection bias because of the study population of workplace employees who participated in regular health checks and the lack of data on women or on men aged 40 years and older, the researchers noted. Other limitations included possible misclassification of MetS because of varying health checkup results and drug claims, and lack of data on serum urate, which prevented assessment of hyperuricemia as a cause of gout.

However, the results were strengthened by the large sample size and suggest that MetS is a modifiable risk factor for gout, the researchers concluded.

Neither of the studies received outside funding. The researchers had no financial conflicts to disclose.

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

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

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

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

New more aggressive targets for blood pressure and lipids are among the changes to the annual American Diabetes Association (ADA) Standards of Care in Diabetes – 2023.

The document, long considered the gold standard for care of the more than 100 million Americans living with diabetes and prediabetes, was published as a supplement in Diabetes Care. The guidelines are also accessible to doctors via an app; last year’s standards were accessed more than 4 million times.

The standards now advise a blood pressure target for people with diabetes of less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol targets of below 70 mg/dL or no greater than 55 mg/dL, depending on the individual’s cardiovascular risk.

Courtesy Joslin Diabetes Center

“In this year’s version of the ADA Standards of Care – the longstanding guidelines for diabetes management globally – you’ll see information that really speaks to how we can more aggressively treat diabetes and reduce complications in a variety of different ways,” ADA Chief Scientific and Medical Officer Robert A. Gabbay, MD, PhD, said in an interview.

Other changes for 2023 include a new emphasis on weight loss as a goal of therapy for type 2 diabetes; guidance for screening and assessing peripheral arterial disease in an effort to prevent amputations; use of finerenone in people with diabetes and chronic kidney disease; use of approved point-of-care A1c tests; and guidance on screening for food insecurity, along with an elevated role for community health workers.

“The management of type 2 diabetes is not just about glucose,” Dr. Gabbay emphasized, noting that the ADA Standards have increasingly focused on cardiorenal risk as well as weight management. “We need to think about all those things, not just one. We have better tools now that have been helpful in being able to move forward with this.”
 

New targets in cardiovascular disease and risk management

As it has been for the past 6 years, the section on cardiovascular disease and risk management is also endorsed by the American College of Cardiology.

The new definition of hypertension in people with diabetes is ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic blood pressure, repeated on two measurements at different times. Among individuals with established cardiovascular disease, hypertension can be diagnosed with one measurement of ≥ 180/110 mm Hg.

The goal of treatment is now less than 130/80 mm Hg if it can be reached safely.

In 2012, easing of the systolic target to 140 mm Hg by the ADA caused some controversy.

But, as Dr. Gabbay explained: “The evidence wasn’t there 10 years ago. We stuck to the evidence at that time, although there was a belief that lower was better. Over the past decade, a number of studies have made it quite clear that there is benefit to a lower target. That’s why we staked out the ground on this.”

The new Standards of Care also has new lipid targets. For people with diabetes aged 40-75 years at increased cardiovascular risk, including those with one or more atherosclerotic risk factors, high-intensity statin therapy is recommended to reduce LDL cholesterol by 50% or more from baseline and to a target of less than 70 mg/dL, in contrast to the previous target of 100 mg/dL.  

To achieve that goal, the document advises to consider adding ezetimibe or a PCSK9 inhibitor to maximally tolerated statin therapy.

For people with diabetes aged 40-75 who have established cardiovascular disease, treatment with high-intensity statin therapy is recommended with the target of a 50% or greater reduction from baseline and an LDL cholesterol level of 55 mg/dL or lower, in contrast to the previous 70 mg/dL.

“That is a lower goal than previously recommended, and based on strong evidence in the literature,” Dr. Gabbay noted.

Here, a stronger recommendation is made for ezetimibe or a PCSK9 inhibitor added to maximal statins.

And for people with diabetes older than 75 years, those already on statins should continue taking them. For those who aren’t, it may be reasonable to initiate moderate-intensity statin therapy after discussion of the benefits and risks.

Another new recommendation based on recent trial data is use of a sodium–glucose cotransporter 2 (SGLT2) inhibitor in people with diabetes and heart failure with preserved, as well as reduced, ejection fraction.
 

Kidney disease guidance updated: SGLT2 inhibitors, finerenone

Another recommendation calls for the addition of finerenone for people with type 2 diabetes who have chronic kidney disease (CKD) with albuminuria and have been treated with the maximum tolerated doses of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to improve cardiovascular outcomes as well as reduce the risk of CKD progression.

The threshold for initiating an SGLT2 inhibitor for kidney protection has changed to an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m² and urinary albumin ≥ 200 mg/g creatinine (previously ≥ 25 mL/min/1.73 m² and ≥ 300 mg/g, respectively). An SGLT2 inhibitor may also be beneficial in people with a urinary albumin of normal to ≥ 200 mg/g creatinine, but supporting data have not yet been published.

Referral to a nephrologist is advised for individuals with increasing urinary albumin levels or continued decreasing eGFR or eGFR < 30 mL/min/1.73 m².
 

Weight loss, point-of-care testing, food insecurity assessment 

Other changes for 2023 include fresh emphasis on supporting weight loss of up to 15% with the new twincretin tirzepatide (Mounjaro) – approved in the United States in May for type 2 diabetes – added as a glucose-lowering drug with weight loss potential.

A novel section was added with guidance for peripheral arterial disease screening.

And a new recommendation advises use of point-of-care A1c testing for diabetes screening and diagnosis using only tests approved by the Food and Drug Administration.

Also introduced for 2023 is guidance to use community health workers to support the management of diabetes and cardiovascular risk factors, particularly in underserved areas and health systems.

“Community health workers can be a link to help people navigate and engage with the health system for better outcomes,” said Dr. Gabbay.

He added that these professionals are among those who can also assist with screening for food insecurity, another new recommendation. “We talk about screening for food insecurity and tools to use. That shouldn’t be something only dietitians do.”

Dr. Gabbay said he’d like to see more clinicians partner with community health workers. “We’d like to see more of that ... They should be considered part of the health care team,” he said.

Dr. Gabbay has reported serving on advisory boards for Lark, Health Reveal, Sweetch, StartUp Health, Vida Health, and Onduo.

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

The randomized, placebo-controlled CLEAR Outcomes trial has shown a significant reduction in risk for a composite cardiovascular (CV) endpoint among its patients treated with the lipid-lowering agent bempedoic acid (Nexletol), the drug’s owner, Esperion, announced today.

The trial marks the first time an ATP-citrate lyase inhibitor has shown significant and “clinically meaningful” benefit for patients not adequately managed with standard lipid-modifying agents, Esperion president and CEO Sheldon Koenig said in a press release.

The brief statement provided only top-line results, without P values or other evidence of the magnitude of benefit in the active-therapy group. The company expects to present more complete results “at a key medical conference in the first quarter of 2023.”

CLEAR Outcomes had entered 14,014 patients with a history of or at high risk for CV disease events, elevated low-density lipoprotein cholesterol (LDL-C) levels, and demonstrated intolerance to at least two statins.

They were randomly assigned to bempedoic acid 180 mg once daily or placebo and followed for the primary endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial, conducted in 32 countries, launched in December 2016.  

Bempedoic acid is currently approved for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease on maximally tolerated statins who require additional LDL-C lowering, the company states.

Concomitant use of bempedoic acid with simvastatin or pravastatin, the press release says, may lead to increased statin concentrations and risk for “simvastatin- or pravastatin-related myopathy.” Therefore, “use with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided.”

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

The randomized, placebo-controlled CLEAR Outcomes trial has shown a significant reduction in risk for a composite cardiovascular (CV) endpoint among its patients treated with the lipid-lowering agent bempedoic acid (Nexletol), the drug’s owner, Esperion, announced today.

The trial marks the first time an ATP-citrate lyase inhibitor has shown significant and “clinically meaningful” benefit for patients not adequately managed with standard lipid-modifying agents, Esperion president and CEO Sheldon Koenig said in a press release.

The brief statement provided only top-line results, without P values or other evidence of the magnitude of benefit in the active-therapy group. The company expects to present more complete results “at a key medical conference in the first quarter of 2023.”

CLEAR Outcomes had entered 14,014 patients with a history of or at high risk for CV disease events, elevated low-density lipoprotein cholesterol (LDL-C) levels, and demonstrated intolerance to at least two statins.

They were randomly assigned to bempedoic acid 180 mg once daily or placebo and followed for the primary endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial, conducted in 32 countries, launched in December 2016.  

Bempedoic acid is currently approved for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease on maximally tolerated statins who require additional LDL-C lowering, the company states.

Concomitant use of bempedoic acid with simvastatin or pravastatin, the press release says, may lead to increased statin concentrations and risk for “simvastatin- or pravastatin-related myopathy.” Therefore, “use with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided.”

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

The randomized, placebo-controlled CLEAR Outcomes trial has shown a significant reduction in risk for a composite cardiovascular (CV) endpoint among its patients treated with the lipid-lowering agent bempedoic acid (Nexletol), the drug’s owner, Esperion, announced today.

The trial marks the first time an ATP-citrate lyase inhibitor has shown significant and “clinically meaningful” benefit for patients not adequately managed with standard lipid-modifying agents, Esperion president and CEO Sheldon Koenig said in a press release.

The brief statement provided only top-line results, without P values or other evidence of the magnitude of benefit in the active-therapy group. The company expects to present more complete results “at a key medical conference in the first quarter of 2023.”

CLEAR Outcomes had entered 14,014 patients with a history of or at high risk for CV disease events, elevated low-density lipoprotein cholesterol (LDL-C) levels, and demonstrated intolerance to at least two statins.

They were randomly assigned to bempedoic acid 180 mg once daily or placebo and followed for the primary endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial, conducted in 32 countries, launched in December 2016.  

Bempedoic acid is currently approved for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease on maximally tolerated statins who require additional LDL-C lowering, the company states.

Concomitant use of bempedoic acid with simvastatin or pravastatin, the press release says, may lead to increased statin concentrations and risk for “simvastatin- or pravastatin-related myopathy.” Therefore, “use with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided.”

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

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

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

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

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

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

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

Automated alerts to aid clinical decision-making are designed with the best of intentions but can be easy to ignore or overlook. But a randomized trial testing such electronic alerts or “nudges” for promoting statin prescribing may have identified a few design features that help their success, researchers say.

In the trial’s primary finding, for example, reminders displayed to primary care physicians in the electronic health record worked best when the system also reached out to the patient.

Ariel Skelley/DigitalVision/Getty Images

Reminders sent only to the clinician also boosted statin prescribing, but not as well, and nudging only the patient didn’t work at all, compared to a nudge-free usual care approach. The patient-only nudges consisted of text messages explaining why a statin prescription may figure in their upcoming appointment.
 

Nudge trustworthiness

Importantly, the clinician nudges were more than simply reminders to consider a statin prescription, Mitesh S. Patel, MD, MBA, Ascension Health, St. Louis, told this news organization. They also displayed the patient’s atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and explained why a statin may be appropriate. He thinks that information, often left out of such clinical decision support alerts, increases physician trust in them.

In another key feature, Dr. Patel said, the EHR nudges themselves were actionable – that is, they were functional in ways that streamlined the prescribing process. In particular, they include checkbox shortcuts to prescribing statins at appropriate patient-specific dosages, making the entire process “faster and easier,” said Dr. Patel, who is senior author on the study published in JAMA Cardiology with lead author Srinath Adusumalli, MD, University of Pennsylvania, Philadelphia.

The timing may matter as well, he observed. In previous iterations of the study’s EHR nudge system, the nudge would appear “when you open the chart,” he said. “Now, it’s when you go to the orders section, which is when you’re going to be in the mindset of ordering prescriptions and tests.”

Prescription rates were higher with the doctor-patient nudges than with the doctor-only approach, Dr. Patel speculates, largely because the decision process for initiating statins is shared. “The most effective intervention is going to recognize that and try to bring the two groups together.”
 

Two text messages

The trial, with 158 participating physicians in 28 primary care practices, randomly assigned 4,131 patients to three intervention groups and one control group. Nudges were sent only to the physician, only to the patient, or to both physician and patient; and there was a no-nudge usual-care group.

Patient nudges consisted of two text messages, one 4 days and another 15 minutes before the appointment, announcing that prescription of a statin “to reduce the chance of a heart attack” would be discussed with the physician, the report states.

Statins are grossly underprescribed nationally, it notes, and that was reflected in prescription rates seen during the study’s initial 12-month, no-intervention period of observation. Rates ranged from only 4.7% up to 6% of patients across the four assignment groups.

During the subsequent 6-month intervention period, however, the rates climbed in the doctor-only and doctor-plus-patient nudge groups compared with usual care, by 5.5 (P = .01) and 7.2 (P = .001) absolute percentage points, respectively.

The overall cohort’s mean age was 65.5. About half were male, 29% were Black, 66% were White, and 22.6% already had a cardiovascular disease diagnosis. The analysis was adjusted for calendar month and preintervention statin prescribing rates. Further adjustment for demographics, insurance type, household income, and comorbidities yielded results similar to the primary analysis, the report states.
 

The results in context

“Although the differences in the combined clinician and patient and clinician-only arms were small, this outcome needs to be interpreted in the context of the population in which the study was performed,” an editorial accompanying the published report states.

For example, “the majority of untreated patients were candidates for primary, not secondary, prevention, making this group of patients particularly challenging for seeing large effect sizes of interventions.”

Moreover, “There was a high baseline prescription rate of statins in the statin-eligible population (approximately 70%) and a high rate of already established patients,” write Faraz S. Ahmad, MD, and Stephen D. Persell, MD, of Northwestern University, Chicago.

Among the approximately 30% of patients who had not previously been prescribed statins, the true target of the nudge interventions, the published trial report states, about 98% were not seeing the physician for the first time.

So “this may not have been the first opportunity to discuss statins,” they write. “It is possible that many of these patients were resistant to statins in the past, which could have created a ceiling effect for prescribing rates.”

Dr. Patel reports owning and receiving personal fees from Catalyst Health and serving on an advisory board for and receiving personal fees from Humana. Dr. Adusumalli reports having been employed by CVS Health. Dr. Ahmad reports receiving consulting fees from Teladoc Livongo and Pfizer. Dr. Persell discloses receiving grants from Omron Healthcare.

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

Automated alerts to aid clinical decision-making are designed with the best of intentions but can be easy to ignore or overlook. But a randomized trial testing such electronic alerts or “nudges” for promoting statin prescribing may have identified a few design features that help their success, researchers say.

In the trial’s primary finding, for example, reminders displayed to primary care physicians in the electronic health record worked best when the system also reached out to the patient.

Ariel Skelley/DigitalVision/Getty Images

Reminders sent only to the clinician also boosted statin prescribing, but not as well, and nudging only the patient didn’t work at all, compared to a nudge-free usual care approach. The patient-only nudges consisted of text messages explaining why a statin prescription may figure in their upcoming appointment.
 

Nudge trustworthiness

Importantly, the clinician nudges were more than simply reminders to consider a statin prescription, Mitesh S. Patel, MD, MBA, Ascension Health, St. Louis, told this news organization. They also displayed the patient’s atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and explained why a statin may be appropriate. He thinks that information, often left out of such clinical decision support alerts, increases physician trust in them.

In another key feature, Dr. Patel said, the EHR nudges themselves were actionable – that is, they were functional in ways that streamlined the prescribing process. In particular, they include checkbox shortcuts to prescribing statins at appropriate patient-specific dosages, making the entire process “faster and easier,” said Dr. Patel, who is senior author on the study published in JAMA Cardiology with lead author Srinath Adusumalli, MD, University of Pennsylvania, Philadelphia.

The timing may matter as well, he observed. In previous iterations of the study’s EHR nudge system, the nudge would appear “when you open the chart,” he said. “Now, it’s when you go to the orders section, which is when you’re going to be in the mindset of ordering prescriptions and tests.”

Prescription rates were higher with the doctor-patient nudges than with the doctor-only approach, Dr. Patel speculates, largely because the decision process for initiating statins is shared. “The most effective intervention is going to recognize that and try to bring the two groups together.”
 

Two text messages

The trial, with 158 participating physicians in 28 primary care practices, randomly assigned 4,131 patients to three intervention groups and one control group. Nudges were sent only to the physician, only to the patient, or to both physician and patient; and there was a no-nudge usual-care group.

Patient nudges consisted of two text messages, one 4 days and another 15 minutes before the appointment, announcing that prescription of a statin “to reduce the chance of a heart attack” would be discussed with the physician, the report states.

Statins are grossly underprescribed nationally, it notes, and that was reflected in prescription rates seen during the study’s initial 12-month, no-intervention period of observation. Rates ranged from only 4.7% up to 6% of patients across the four assignment groups.

During the subsequent 6-month intervention period, however, the rates climbed in the doctor-only and doctor-plus-patient nudge groups compared with usual care, by 5.5 (P = .01) and 7.2 (P = .001) absolute percentage points, respectively.

The overall cohort’s mean age was 65.5. About half were male, 29% were Black, 66% were White, and 22.6% already had a cardiovascular disease diagnosis. The analysis was adjusted for calendar month and preintervention statin prescribing rates. Further adjustment for demographics, insurance type, household income, and comorbidities yielded results similar to the primary analysis, the report states.
 

The results in context

“Although the differences in the combined clinician and patient and clinician-only arms were small, this outcome needs to be interpreted in the context of the population in which the study was performed,” an editorial accompanying the published report states.

For example, “the majority of untreated patients were candidates for primary, not secondary, prevention, making this group of patients particularly challenging for seeing large effect sizes of interventions.”

Moreover, “There was a high baseline prescription rate of statins in the statin-eligible population (approximately 70%) and a high rate of already established patients,” write Faraz S. Ahmad, MD, and Stephen D. Persell, MD, of Northwestern University, Chicago.

Among the approximately 30% of patients who had not previously been prescribed statins, the true target of the nudge interventions, the published trial report states, about 98% were not seeing the physician for the first time.

So “this may not have been the first opportunity to discuss statins,” they write. “It is possible that many of these patients were resistant to statins in the past, which could have created a ceiling effect for prescribing rates.”

Dr. Patel reports owning and receiving personal fees from Catalyst Health and serving on an advisory board for and receiving personal fees from Humana. Dr. Adusumalli reports having been employed by CVS Health. Dr. Ahmad reports receiving consulting fees from Teladoc Livongo and Pfizer. Dr. Persell discloses receiving grants from Omron Healthcare.

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

Automated alerts to aid clinical decision-making are designed with the best of intentions but can be easy to ignore or overlook. But a randomized trial testing such electronic alerts or “nudges” for promoting statin prescribing may have identified a few design features that help their success, researchers say.

In the trial’s primary finding, for example, reminders displayed to primary care physicians in the electronic health record worked best when the system also reached out to the patient.

Ariel Skelley/DigitalVision/Getty Images

Reminders sent only to the clinician also boosted statin prescribing, but not as well, and nudging only the patient didn’t work at all, compared to a nudge-free usual care approach. The patient-only nudges consisted of text messages explaining why a statin prescription may figure in their upcoming appointment.
 

Nudge trustworthiness

Importantly, the clinician nudges were more than simply reminders to consider a statin prescription, Mitesh S. Patel, MD, MBA, Ascension Health, St. Louis, told this news organization. They also displayed the patient’s atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and explained why a statin may be appropriate. He thinks that information, often left out of such clinical decision support alerts, increases physician trust in them.

In another key feature, Dr. Patel said, the EHR nudges themselves were actionable – that is, they were functional in ways that streamlined the prescribing process. In particular, they include checkbox shortcuts to prescribing statins at appropriate patient-specific dosages, making the entire process “faster and easier,” said Dr. Patel, who is senior author on the study published in JAMA Cardiology with lead author Srinath Adusumalli, MD, University of Pennsylvania, Philadelphia.

The timing may matter as well, he observed. In previous iterations of the study’s EHR nudge system, the nudge would appear “when you open the chart,” he said. “Now, it’s when you go to the orders section, which is when you’re going to be in the mindset of ordering prescriptions and tests.”

Prescription rates were higher with the doctor-patient nudges than with the doctor-only approach, Dr. Patel speculates, largely because the decision process for initiating statins is shared. “The most effective intervention is going to recognize that and try to bring the two groups together.”
 

Two text messages

The trial, with 158 participating physicians in 28 primary care practices, randomly assigned 4,131 patients to three intervention groups and one control group. Nudges were sent only to the physician, only to the patient, or to both physician and patient; and there was a no-nudge usual-care group.

Patient nudges consisted of two text messages, one 4 days and another 15 minutes before the appointment, announcing that prescription of a statin “to reduce the chance of a heart attack” would be discussed with the physician, the report states.

Statins are grossly underprescribed nationally, it notes, and that was reflected in prescription rates seen during the study’s initial 12-month, no-intervention period of observation. Rates ranged from only 4.7% up to 6% of patients across the four assignment groups.

During the subsequent 6-month intervention period, however, the rates climbed in the doctor-only and doctor-plus-patient nudge groups compared with usual care, by 5.5 (P = .01) and 7.2 (P = .001) absolute percentage points, respectively.

The overall cohort’s mean age was 65.5. About half were male, 29% were Black, 66% were White, and 22.6% already had a cardiovascular disease diagnosis. The analysis was adjusted for calendar month and preintervention statin prescribing rates. Further adjustment for demographics, insurance type, household income, and comorbidities yielded results similar to the primary analysis, the report states.
 

The results in context

“Although the differences in the combined clinician and patient and clinician-only arms were small, this outcome needs to be interpreted in the context of the population in which the study was performed,” an editorial accompanying the published report states.

For example, “the majority of untreated patients were candidates for primary, not secondary, prevention, making this group of patients particularly challenging for seeing large effect sizes of interventions.”

Moreover, “There was a high baseline prescription rate of statins in the statin-eligible population (approximately 70%) and a high rate of already established patients,” write Faraz S. Ahmad, MD, and Stephen D. Persell, MD, of Northwestern University, Chicago.

Among the approximately 30% of patients who had not previously been prescribed statins, the true target of the nudge interventions, the published trial report states, about 98% were not seeing the physician for the first time.

So “this may not have been the first opportunity to discuss statins,” they write. “It is possible that many of these patients were resistant to statins in the past, which could have created a ceiling effect for prescribing rates.”

Dr. Patel reports owning and receiving personal fees from Catalyst Health and serving on an advisory board for and receiving personal fees from Humana. Dr. Adusumalli reports having been employed by CVS Health. Dr. Ahmad reports receiving consulting fees from Teladoc Livongo and Pfizer. Dr. Persell discloses receiving grants from Omron Healthcare.

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

Visceral adipose tissue is significantly reduced with the green Mediterranean diet (MED), which consists of polyphenols and reduced red meat intake, according to a new analysis of the 18-month Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed (DIRECT-PLUS) trial.

The new results indicate that the green Mediterranean diet lowered visceral fat by twice as much as the standard Mediterranean diet (14% vs. 7%), reported Iris Shai, PhD, of Ben-Gurion University of the Negev in Be’er Sheva, Israel, and colleagues.

“This study may suggest an improved dietary protocol for treating visceral adiposity,” the authors wrote in their article, published recently in BMC Medicine.

“A healthy lifestyle is a strong basis for any weight-loss program. We learned from the results of our experiment that the quality of food is no less important than the number of calories consumed and the goal today is to understand the mechanisms of various nutrients, for example, positive ones such as the polyphenols, and negative ones such as empty carbohydrates and processed red meat, on the pace of fat cell differentiation and their aggregation in the viscera,” Dr. Shai said in a press release from Ben‐Gurion University.

“A 14% reduction in visceral fat is a dramatic achievement for making simple changes to your diet and lifestyle. Weight loss is an important goal only if it is accompanied by impressive results in reducing adipose tissue,” added coauthor Hila Zelicha, RD, PhD, also of Ben‐Gurion University of the Negev.

Previous randomized controlled trials have shown that dietary changes with a higher polyphenol content tend to produce better cardiometabolic outcomes and appear to mobilize particular ectopic fat depots, the researchers noted.

The main results of the DIRECT-PLUS trial were published in 2020 in Heart. Almost 300 participants with abdominal obesity/dyslipidemia were randomized to one of three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean diet, and the so-called green Mediterranean diet. The mean age of participants was 51 years, and men comprised 88% of the study cohort.

Participants in both Mediterranean diet groups ate 28 grams/day of walnuts, which accounted for about 440 mg/day of polyphenols. Participants in the green Mediterranean group also ate 100 grams/day of frozen cubes of a Wolffia globosa (duckweed strain) plant green shake, and three to four cups/day of green tea, which contributed to consumption of 800 mg/day of polyphenols, and decreased red meat consumption.

Both the green and standard Mediterranean diet groups achieved similar weight loss (–6.2 kg and –5.4 kg) compared with the HDG group (–1.5 kg; P < .001). However, the green Mediterranean diet group had a greater reduction in waist circumference (–8.6 cm) than the standard Mediterranean diet group (–6.8 cm; P = .033) and HDG group (–4.3 cm; P < .001). Stratification by gender showed these differences were significant only among men.

Explaining the rationale for the study, the researchers noted that visceral adipose tissue accumulation is a key factor that differentiates metabolic healthy and unhealthy obese individuals, is closely related to the development of multiple cardiovascular risk factors, including hypertension, dyslipidemia, and type 2 diabetes, and is an independent marker of mortality.

Now, their latest data show the green Mediterranean diet group lost approximately twice as much visceral adipose tissue compared with the standard Mediterranean diet and HDG groups (−14.1%, −6.0%, and − 4.2%; P < .05 independent of weight loss, sex, waist circumference, or age).

Lower red meat consumption, greater dietary consumption of walnuts, Wolffia globosa, and green tea, increased urine urolithin A polyphenol, and elevated total plasma polyphenols were significantly associated with greater visceral adipose tissue loss (P < .05, multivariate models).

“A green Mediterranean diet enriched with polyphenols and decreased red meat consumption might serve as an improved version of the Mediterranean diet for targeted VAT reduction. Future studies are needed to explore the exact mechanisms of specific polyphenol-rich foods on visceral adiposity,” the study authors concluded.

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

Visceral adipose tissue is significantly reduced with the green Mediterranean diet (MED), which consists of polyphenols and reduced red meat intake, according to a new analysis of the 18-month Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed (DIRECT-PLUS) trial.

The new results indicate that the green Mediterranean diet lowered visceral fat by twice as much as the standard Mediterranean diet (14% vs. 7%), reported Iris Shai, PhD, of Ben-Gurion University of the Negev in Be’er Sheva, Israel, and colleagues.

“This study may suggest an improved dietary protocol for treating visceral adiposity,” the authors wrote in their article, published recently in BMC Medicine.

“A healthy lifestyle is a strong basis for any weight-loss program. We learned from the results of our experiment that the quality of food is no less important than the number of calories consumed and the goal today is to understand the mechanisms of various nutrients, for example, positive ones such as the polyphenols, and negative ones such as empty carbohydrates and processed red meat, on the pace of fat cell differentiation and their aggregation in the viscera,” Dr. Shai said in a press release from Ben‐Gurion University.

“A 14% reduction in visceral fat is a dramatic achievement for making simple changes to your diet and lifestyle. Weight loss is an important goal only if it is accompanied by impressive results in reducing adipose tissue,” added coauthor Hila Zelicha, RD, PhD, also of Ben‐Gurion University of the Negev.

Previous randomized controlled trials have shown that dietary changes with a higher polyphenol content tend to produce better cardiometabolic outcomes and appear to mobilize particular ectopic fat depots, the researchers noted.

The main results of the DIRECT-PLUS trial were published in 2020 in Heart. Almost 300 participants with abdominal obesity/dyslipidemia were randomized to one of three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean diet, and the so-called green Mediterranean diet. The mean age of participants was 51 years, and men comprised 88% of the study cohort.

Participants in both Mediterranean diet groups ate 28 grams/day of walnuts, which accounted for about 440 mg/day of polyphenols. Participants in the green Mediterranean group also ate 100 grams/day of frozen cubes of a Wolffia globosa (duckweed strain) plant green shake, and three to four cups/day of green tea, which contributed to consumption of 800 mg/day of polyphenols, and decreased red meat consumption.

Both the green and standard Mediterranean diet groups achieved similar weight loss (–6.2 kg and –5.4 kg) compared with the HDG group (–1.5 kg; P < .001). However, the green Mediterranean diet group had a greater reduction in waist circumference (–8.6 cm) than the standard Mediterranean diet group (–6.8 cm; P = .033) and HDG group (–4.3 cm; P < .001). Stratification by gender showed these differences were significant only among men.

Explaining the rationale for the study, the researchers noted that visceral adipose tissue accumulation is a key factor that differentiates metabolic healthy and unhealthy obese individuals, is closely related to the development of multiple cardiovascular risk factors, including hypertension, dyslipidemia, and type 2 diabetes, and is an independent marker of mortality.

Now, their latest data show the green Mediterranean diet group lost approximately twice as much visceral adipose tissue compared with the standard Mediterranean diet and HDG groups (−14.1%, −6.0%, and − 4.2%; P < .05 independent of weight loss, sex, waist circumference, or age).

Lower red meat consumption, greater dietary consumption of walnuts, Wolffia globosa, and green tea, increased urine urolithin A polyphenol, and elevated total plasma polyphenols were significantly associated with greater visceral adipose tissue loss (P < .05, multivariate models).

“A green Mediterranean diet enriched with polyphenols and decreased red meat consumption might serve as an improved version of the Mediterranean diet for targeted VAT reduction. Future studies are needed to explore the exact mechanisms of specific polyphenol-rich foods on visceral adiposity,” the study authors concluded.

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

Visceral adipose tissue is significantly reduced with the green Mediterranean diet (MED), which consists of polyphenols and reduced red meat intake, according to a new analysis of the 18-month Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed (DIRECT-PLUS) trial.

The new results indicate that the green Mediterranean diet lowered visceral fat by twice as much as the standard Mediterranean diet (14% vs. 7%), reported Iris Shai, PhD, of Ben-Gurion University of the Negev in Be’er Sheva, Israel, and colleagues.

“This study may suggest an improved dietary protocol for treating visceral adiposity,” the authors wrote in their article, published recently in BMC Medicine.

“A healthy lifestyle is a strong basis for any weight-loss program. We learned from the results of our experiment that the quality of food is no less important than the number of calories consumed and the goal today is to understand the mechanisms of various nutrients, for example, positive ones such as the polyphenols, and negative ones such as empty carbohydrates and processed red meat, on the pace of fat cell differentiation and their aggregation in the viscera,” Dr. Shai said in a press release from Ben‐Gurion University.

“A 14% reduction in visceral fat is a dramatic achievement for making simple changes to your diet and lifestyle. Weight loss is an important goal only if it is accompanied by impressive results in reducing adipose tissue,” added coauthor Hila Zelicha, RD, PhD, also of Ben‐Gurion University of the Negev.

Previous randomized controlled trials have shown that dietary changes with a higher polyphenol content tend to produce better cardiometabolic outcomes and appear to mobilize particular ectopic fat depots, the researchers noted.

The main results of the DIRECT-PLUS trial were published in 2020 in Heart. Almost 300 participants with abdominal obesity/dyslipidemia were randomized to one of three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean diet, and the so-called green Mediterranean diet. The mean age of participants was 51 years, and men comprised 88% of the study cohort.

Participants in both Mediterranean diet groups ate 28 grams/day of walnuts, which accounted for about 440 mg/day of polyphenols. Participants in the green Mediterranean group also ate 100 grams/day of frozen cubes of a Wolffia globosa (duckweed strain) plant green shake, and three to four cups/day of green tea, which contributed to consumption of 800 mg/day of polyphenols, and decreased red meat consumption.

Both the green and standard Mediterranean diet groups achieved similar weight loss (–6.2 kg and –5.4 kg) compared with the HDG group (–1.5 kg; P < .001). However, the green Mediterranean diet group had a greater reduction in waist circumference (–8.6 cm) than the standard Mediterranean diet group (–6.8 cm; P = .033) and HDG group (–4.3 cm; P < .001). Stratification by gender showed these differences were significant only among men.

Explaining the rationale for the study, the researchers noted that visceral adipose tissue accumulation is a key factor that differentiates metabolic healthy and unhealthy obese individuals, is closely related to the development of multiple cardiovascular risk factors, including hypertension, dyslipidemia, and type 2 diabetes, and is an independent marker of mortality.

Now, their latest data show the green Mediterranean diet group lost approximately twice as much visceral adipose tissue compared with the standard Mediterranean diet and HDG groups (−14.1%, −6.0%, and − 4.2%; P < .05 independent of weight loss, sex, waist circumference, or age).

Lower red meat consumption, greater dietary consumption of walnuts, Wolffia globosa, and green tea, increased urine urolithin A polyphenol, and elevated total plasma polyphenols were significantly associated with greater visceral adipose tissue loss (P < .05, multivariate models).

“A green Mediterranean diet enriched with polyphenols and decreased red meat consumption might serve as an improved version of the Mediterranean diet for targeted VAT reduction. Future studies are needed to explore the exact mechanisms of specific polyphenol-rich foods on visceral adiposity,” the study authors concluded.

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

LAS VEGAS – The delay in the diagnosis of hidradenitis suppurativa (HS) often ranges from 7 to 10 years, which results in increased morbidity and disease severity, and an extended impact on quality of life, Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.

Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.

Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.

For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.

Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.

For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.

To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.

His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.

Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
 

Don’t forget lifestyle

Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.

In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
 

Consider comorbidities

Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.

Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
 

Medical management

Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.

Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.

When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.

Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.

However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.

Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.

Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.

If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
 

Surgical solutions

For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.

“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.

When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.

In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.

Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.

LAS VEGAS – The delay in the diagnosis of hidradenitis suppurativa (HS) often ranges from 7 to 10 years, which results in increased morbidity and disease severity, and an extended impact on quality of life, Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.

Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.

Wikimedia Commons/Creative Commons Attribution-Share Alike 4.0 International

Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.

Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.

For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.

Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.

For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.

To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.

His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.

Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
 

Don’t forget lifestyle

Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.

In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
 

Consider comorbidities

Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.

Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
 

Medical management

Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.

Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.

When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.

Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.

However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.

Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.

Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.

If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
 

Surgical solutions

For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.

“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.

When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.

In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.

Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.

LAS VEGAS – The delay in the diagnosis of hidradenitis suppurativa (HS) often ranges from 7 to 10 years, which results in increased morbidity and disease severity, and an extended impact on quality of life, Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.

Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.

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Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.

Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.

For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.

Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.

For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.

To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.

His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.

Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
 

Don’t forget lifestyle

Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.

In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
 

Consider comorbidities

Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.

Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
 

Medical management

Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.

Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.

When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.

Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.

However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.

Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.

Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.

If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
 

Surgical solutions

For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.

“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.

When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.

In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.

Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.

CHICAGO – A single chest x-ray could predict a patient’s 10-year risk of dying from a heart attack or stroke, say researchers who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.

Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.

The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
 

Not all data points available in EHR

But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.

Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.

The researchers trained a deep-learning model with single chest x-rays only.

They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.

Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.

They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.

“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
 

Tested against independent group

They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.

Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.

There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).

Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.

They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).

Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.

“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.

“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.

David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.

“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”

He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.

Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.

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

CHICAGO – A single chest x-ray could predict a patient’s 10-year risk of dying from a heart attack or stroke, say researchers who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.

Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.

The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
 

Not all data points available in EHR

But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.

Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.

The researchers trained a deep-learning model with single chest x-rays only.

They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.

Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.

They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.

“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
 

Tested against independent group

They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.

Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.

There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).

Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.

They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).

Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.

“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.

“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.

David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.

“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”

He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.

Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.

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

CHICAGO – A single chest x-ray could predict a patient’s 10-year risk of dying from a heart attack or stroke, say researchers who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.

Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.

The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
 

Not all data points available in EHR

But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.

Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.

The researchers trained a deep-learning model with single chest x-rays only.

They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.

Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.

They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.

“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
 

Tested against independent group

They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.

Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.

There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).

Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.

They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).

Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.

“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.

“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.

David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.

“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”

He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.

Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.

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