Cardiology

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

Dual antiplatelet therapy (DAPT) with clopidogrel-aspirin given within 72 hours of a mild ischemic stroke or a high-risk transient ischemic attack (TIA) shows a greater risk reduction for new stroke than aspirin alone, although with a higher bleeding risk.

METHODOLOGY:

• The INSPIRES, a double-blind, placebo-controlled trial, involved patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
• A total of 6100 patients were randomly assigned to receive clopidogrel plus aspirin or matching clopidogrel placebo plus aspirin within 72 hours after symptom onset.
• The occurrence of any new stroke (ischemic or hemorrhagic) within 90 days was the primary efficacy outcome.
• The primary safety outcome was moderate to severe bleeding, also assessed within 90 days.

TAKEAWAY:

• Within 24 hours of symptom onset, 12.8% of patients were assigned to each treatment group, and the remaining 87.2% were assigned within the time window of 24-72 hours.
• (7.3% vs 9.2%; marginal estimated hazard ratio [HR], 0.79; P =.008).
• The risk of a composite cardiovascular event and ischemic stroke were also 20%-25% lower with aspirin-clopidogrel combo vs aspirin alone.
• Moderate to severe bleeding was low in both groups (<1%), but the risk was double in patients who received DAPT vs aspirin alone (HR, 2.08; P =.03).

IN PRACTICE:

In an accompanying editorial, Anthony S. Kim, MD from the UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, commented, “The current trial provides evidence to support expanding the time window for dual antiplatelet therapy to 72 hours.” He also warned against administering DAPT to “patients with heightened bleeding risks, such as those with a history of cerebral or systemic hemorrhage.”

SOURCE:

Yilong Wang, MD, PhD, who held positions in the Department of Neurology, Beijing Tiantan Hospital, and several other institutions, was the corresponding author of this study. This study was published online December 28 in the New England Journal of Medicine.

LIMITATIONS:

• Patients with stroke of presumed cardioembolic origin, those with moderate or severe stroke, and those who had undergone thrombolysis or thrombectomy were excluded from this study.
• Of the enrolled participants, 98.5% belonged to the Han Chinese ethnic group.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the National Key R&D Program of China, and other sources. Some authors declared receiving grants or contracts or serving as consultants in various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Light physical activity during childhood may lower blood cholesterol levels more effectively than moderate to vigorous physical activity, regardless of body fat mass.

METHODOLOGY:

• Researchers analyzed the data of 792 children (58% females) from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort.
• The measures included accelerometer-based sedentary time, light physical activity, and moderate to vigorous physical activity at ages 11, 15, and 24 years.
• The children had complete measurements of fasting high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol levels at ages 15 , 17, and 24 years.
• Data also included measures of body mass, composition (fat and lean mass), insulin resistance, inflammation, and other cardiometabolic, socioeconomic, and lifestyle factors.
• The researchers conducted two types of analyses: Mediation path, to examine how fat and lean body mass affected longitudinal associations of activity level with blood lipids over 13 years, and temporal path, to look at temporal relationships between activity and lipid levels at ages 15 and 24 years only.

TAKEAWAY:

• Higher cumulative light physical activity from childhood through young adulthood was associated with a fivefold to eightfold decrease in total cholesterol, while total body fat mass decreased the impact of light physical activity on total cholesterol by 6%.
• Higher cumulative moderate to vigorous physical activity over 13 years led to a modest decrease in total cholesterol, an effect reduced to nonsignificance by the presence of higher fat mass.
• More cumulative sedentary time was associated with increasing total cholesterol.

IN PRACTICE:

“Light physical activity provides an opportunity for persons with obesity to follow a path to potentially benefit from the lipid-lowering effect of mild exercise,» wrote the author.

SOURCE:

Andrew O. Agbaje, from the Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland, conducted this study. It was published online December 14, 2023, in the Journal of Clinical Endocrinology and Metabolism.

LIMITATIONS:

The study included mostly White participants, so the findings might not apply to diverse racial and ethnic groups. The accelerometer data were gathered using a 60-second epoch, a duration known to underestimate moderate to vigorous physical activity in pediatric populations. There were no measures of fasting plasma lipids at age 11 years. The study also lacked data on participants’ dietary habits, alcohol intake, and menstrual cycle.

DISCLOSURES:

The ALSPAC UK birth cohort is funded by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. The author is funded by multiple foundations. No conflicts of interest were reported.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.