European Society of Cardiology Congress 2021

Links between mental health disorders and organ system disease have long been known. However, a recent study published in 

 found that men with heart failure died with greater frequency if they had severe depression, bipolar disorder, or schizophrenia. We know that people with serious mental health conditions develop high blood pressure, diabetes and have myocardial infarctions at younger ages than the general population. What we didn’t know is how mental health interacts with heart failure.

The study looked at over 20,000 patients with heart failure seen at Duke University. After entering the study, patients were followed to 7 years at which time it was discovered that men with severe mental illness were 36% more likely to die from any cause than those with normal mental health. In addition to increased mortality the study showed that people with severe mental health conditions were diagnosed with heart failure up to 7 years earlier than those without. The lead author of the Duke study, Christoffer Polcwiartek, MD, states,

“Doctors and heart failure specialists need to become more aware of mental health disorders among their patients and take early preventive steps.”

Polcwiartek further suggest that bringing cardiologists, general practitioners, and psychiatrists together is the best way to reduce the burden of heart failure in patients navigating the mental health system.

Current guidelines for heart failure recommend screening for depression but not more severe forms of mental illness. When other more severe forms of mental illness are discovered, special effort should be made to minimize the possibility of early-onset heart failure which could lead to increased short- and long-term mortality.

The study and its recommendations received a strong endorsement from clinical psychologist James Blumenthal, PhD, a professor of psychiatry at Duke University, who was not involved in the study. Blumenthal states, 

“This is an important study that suggests doctors need to evaluate patients' mental health status in addition to evaluating more traditional heart failure risk factors.”

Blumenthal goes on to suggest that, although this study shines a light on a troubling association between mental health and heart failure, many questions remain. It is still unknown why men with severe mental health problems are more likely to die from heart failure while women are not. From the point of view of the mental health specialist, it could be that mental health conditions in patients with cardiovascular disease may be underrecognized and undertreated. In response to this study, the American Heart Association released a 

 calling for the routine assessment of the mental well-being of all heart patients. The emphasis of the statement was on promoting clinician awareness and the concept of holistic treatment rather than a disease-centered model.

As specialists, cardiologists may fall prey to missing the trees for the forest. They train to focus on the cardiovascular system but failing to recognize the mind-body connection is a disservice to our patients. It is quite possible that, with regular screening and modifications to the treatment plan, cardiac patients with mental health conditions can live long full lives. More research is needed to determine the underpinnings of these data but in the meantime, the focus brought, especially to men with heart disease and severe depression, bipolar disease, or schizophrenia, can only stimulate further investigation and innovation in this area.

Not knowing all the answers is a frustrating but necessary position. The American Heart Association recognizes that having questions is the basis for finding answers to those questions. Now we know that men with severe mental health problems are at significantly higher risk of dying from heart failure. As clinicians, we must treat the whole patient at every visit truly winning for both hearts and minds.

Articles

Gregory Weiss, MD, reflects on recent data and an AHA statement related to mental health and increased risk of mortality among patients with heart failure with mental health disorders.

Troubled Minds, Broken Hearts: The Link Between Mental Health and Heart Failure

The news surrounding the US Preventive Services Task Force related to their 

 in prevention of cardiovascular disease was a surprise to many in cardiology, but not because it was unexpected. In fact, many were taken aback by how long it had taken for the Task Force to address aspirin use in the wake of data refuting its benefit dating back to the early 2000s.

Released on October 12, the draft evidence review details more than a dozen randomized clinical trials used in support of their new recommendations, which considers use of low-dose aspirin for primary prevention inappropriate for most patients but underlines the benefit of the approach for secondary prevention. While cardiologists and other clinicians have been aware of the lack of net benefit associated with aspirin use for years, the reality is that many patients are ignorant to the stance change surrounding aspirin, which has been a staple in medicine cabinets for decades. Now, the priority transitions to educating patients about those still stand to benefit from use of aspirin, including those with a history of myocardial infarction, stent implantation or bypass surgery, stroke, or peripheral artery disease.

For more perspective from a practicing cardiologist, 

 reached out to editorial advisory board chief Guy Mintz, MD, director of Cardiovascular Health and Lipidology at the Sandra Atlas Bass Heart Hospital at North Shore University Hospital and co-director of the Lipid Center, to learn how he believes the news will impact patients and clinicians.

Guy Mintz, MD, on Aspirin Guidelines for Primary and Secondary Prevention

Where does aspirin fit into treatment algorithms of your patients?

I think that's a great question. It's important for us as clinicians to sort out who really benefits from aspirin therapy. So, the first group is secondary prevention: those patients that have had coronary artery disease, whether it's a stent, an angioplasty, a heart attack, or coronary artery bypass surgery or stroke—that's secondary prevention, those people clearly benefit from aspirin therapy.

The issue, with regard to the new guidelines, circles around primary prevention patients, patients that may be at high risk for heart disease, but don't have heart disease. The question is: is there a role for aspirin therapy? Now, aspirin does work. It's a blood thinner and works by interfering with the platelets, but in various groups, you have increased risk for bleeding.

So, the benefit from aspirin is outweighed by the risk of bleeding and the costs associated with gastrointestinal hemorrhage, and so on, so forth. So, the guidelines came out and said, if you have cardiac risk factors and you're below the age of 60, you should talk to your physician about what role aspirin could play. If you're above the age 60 or above and have not been on aspirin therapy, you shouldn't be on aspirin therapy because the risk of bleeding can increase.

When we look back in time, we've been using aspirin, you know, forever. In terms of cardiac prevention, the famous saying goes "An aspirin a day keeps the doctor away". Well back down in 1988, when they had the Physicians Health Study, which actually was an aspirin every other day, it reduced heart attacks in healthy physicians. That's all we had back then. Now, fast-forward to where we are now, and we have very potent medications to lower cholesterol. Statins are main group we use for lowering cholesterol because they not only lower cholesterol, but they also stabilize plaque, they have anti-inflammatory benefits. Beyond the cholesterol-lowering effects, we have lower guidelines for controlling blood pressure and more effective medications for blood pressure control. We have medications for diabetes that low blood sugar, but they also lower cardiovascular events. So, medicine has advanced, and we have many different tools in our toolbox. When you put all these tools in the toolbox, and you lower a patient's risk, the need for aspirin therapy becomes smaller and smaller in that group. So, I think that's where the guidelines are coming from here.

How prevalent do you think current aspirin use is among older patients?

I think it's very prevalent and many patients are taking aspirin without a doctor's knowledge, they just decided "that's kind of the way I was brought up, but that's what I heard". And some doctors may not even have that on their list of medications for the individual patient. So, I think this guideline coming out has certainly proved to be important to move patients back to having discussions with their physicians, because I can tell you since the news broke, we've had 50, 60, 70 patients who have called within the last two days asking, "Should I be on the aspirin? Should I not be on aspirin, but I've been on aspirin for 25 years?" And I like to say we don't do phone medicine, because it's truly an individual assessment based on the patient's risk.

If you have a diabetic patient with peripheral arterial disease, that may be someone that should be on aspirin therapy. So, it's not like as quick as just saying yes or no, on the telephone, we need to really assess the risk. So, there are many patients on aspirin therapy, in practices that we don't even know they're on aspirin therapy. I think this really serves as a wakeup call to educate the patients and educate some physicians as well, should a patient be on aspirin or should they really have all their other risk factors negated, should they be on lipid lowering therapy or enhanced lipid lowering therapy, should they be on better antihypertensive therapy? So, I think that's really where the wakeup call comes in, where the patient could come in and get their cardiovascular risk re-evaluated.

Do you foresee a world where aspirin no longer has a role in secondary prevention or is aspirin always going to be in the back of the medicine cabinet?

 That's a great question. So, when you look at what contributes to plaque or cholesterol instability within the arteries, part of that process is inflammation. Aspirin has an anti-inflammatory benefit that was actually shown in the subsequent analysis of the Physicians Health Study data. In the 1990s, they developed a high sensitivity C-reactive protein and they showed that those physicians that were "healthy” but had a higher high sensitivity C-reactive protein were more likely to go on and have a myocardial infarction. So, in terms of secondary prevention, aspirin plays a role from an anti-inflammatory benefit. When the plaque starts to rupture and platelets want to start attaching to each other, aspirin can interfere with that process. If you look at some of the newer data with rivaroxaban, they have an anticoagulant and with a dose of 2.5 milligrams twice a day and low dose aspirin at 81 milligrams per day, they had a 24% reduction in clinical events.

So, as we get more sophisticated understanding what upsets the milieu of the plaque, there's a role for antiplatelet therapy, there's a role for anti-thrombotic therapy, there's a role, as we develop newer agents, for anti-inflammatory benefit to protect patients as well, in terms of secondary prevention. We also know from primary prevention that patients with inflammatory disease such as lupus, or psoriasis, or HIV, even Crohn's disease, causes increased risk of cardiovascular disease due to increase inflammatory effect.

At this time, I don't really see aspirin going out the door for secondary prevention. So, I do think we can stick to the motto, "An Aspirin a day will keep the doctor away, for some people". But I think it's important for patients not to just take it because they think it's the right thing to do. I think maybe down the road, there'll be a better antiplatelet agent than aspirin or something comprehensive, but I think we're understanding more about the processes of preventing secondary events and certainly we'll learn more about preventing primary prevents. On the primary side, it's always about the risk factors. So, it's exciting times in cardiology. Knowledge is power and I think patients now are seeking out more knowledge on this particular topic.

In a Q&A, Guy Mintz, MD, provides perspective on the USPSTF draft recommendations surrounding aspirin for primary and secondary prevention, how the role of aspirin has evolved in recent decades, and how the news has caused a surge of questions in his practice.

Aspirin's Role in Cardiovascular Prevention With Guy Mintz, MD

Patrick Campbell is the senior editor of Practical Cardiology, as well as its sister publication Endocrinology Network. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. In his free time, he enjoys traveling, sports, and exploring the great outdoors. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

New research is underlying the potential impact of mobile technology in helping patients achieve 

The study, which was led by investigators at the University of California, San Francisco (UCSF), provides evidence suggesting use of mobile technology resulted in 84% of users with stage 2 hypertension reducing blood pressure at 3 years and also indicate increased engagement with technology was associated with lower risk of experiencing very high blood pressure.

“This is the first peer-reviewed, published study reporting the long-term experience of a digital health application for blood pressure management, with a magnitude of association that is clinically meaningful,” said lead investigator Alexis Beatty, MD, MAS, a cardiologist and associate professor at UCSF, 

. “The level of engagement is something I have not seen in other digital hypertension management programs. Sustained engagement and decreases in systolic blood pressure of more than 20 mmHg could reduce a person’s chances of heart attack, stroke, kidney disease, and death.”

As the integration of technology into cardiology continues, Beatty and a team of colleagues sought to further understand how use of mobile self-management programs might influence long-term blood pressure control among patients with elevated blood pressure. Using a cohort of individuals enrolled in an employer-sponsored health insurance program, investigators designed their study to assess whether use of the Hello Heart hypertension self-management program, which includes a blood pressure monitor and connected smartphone application, over a long-term period.

Individuals enrolled in the health plan with either a diagnosis of elevated blood pressure or hypertension or a pharmacy claim for medication for treatment or management of hypertension were invited to participate in the study. With a study period ranging from January 1, 2015, through July 1, 2020, investigators identified 28,189 adults meeting inclusion criteria for the study, which required an individual to record at least 2 blood pressure measurements in the app during the study period.

For the purpose of analysis, median systolic and diastolic blood pressures were recorded during the first week, after 2 weeks, and again 4 (weeks 3-4), 6 (weeks 5-6), 12 (weeks 11-12), 26 (weeks 24-27), 52 (weeks 48-55), 104 (weeks 96-111), and 155 (weeks 148-163) weeks after the first reading. The primary outcome of interest for the study was changes in systolic and diastolic blood pressure over time. The exposure of interest for the study was program engagement, which investigators defined as the average number of application sessions. Based on engagement levels relative to the rest of the cohort, patients were placed into groups defined by low, medium, and high engagement.

The study cohort had a median age of 51 (IQR, 43-58) years, 40.4% were women, and the median systolic and diastolic blood pressure measurements at baseline were 129.5 (IQR, 120.5-139.6) mmHg and 81.7 (IQR, 75.7-88.4) mmHg, respectively. The mean number of blood pressure measurements per week ranged from a median of 1.3 (IQR, 0.6-2.8) in the low-engagement group to 2.8 (IQR, 1.5-5.3) in the high-engagement group.

Upon analysis, results indicated median systolic blood pressure improved at least 1 category for 495 of 934 participants (53.0%) with baseline elevated BP, 673 of 966 (69.7%) with baseline stage 1 hypertension, and 920 of 1075 (85.7%) with baseline stage 2 hypertension at 1 year. Among individuals enrolled in the program for 3 years, the mean reduction in systolic blood pressure was 7.2 (SEM, 0.4) mmHg among those with elevated blood pressure, 12.2 (SEM, 0.7) mmHg among those with stage 1 hypertension, and 20.9 (SEM, 1.7) mmHg, among those with stage 2 hypertension when compared to baseline measurements.

Further analysis indicated greater engagement was associated with lower systolic blood pressure over time, even after adjustment for age, gender, depression, anxiety, diabetes, high cholesterol, smoking, area deprivation index rank, and US region. Investigators also pointed out greater engagement was associated with a lower risk of very high blood pressure, with increased incidence seen among the low-engagement group (1.42%, [95% CI, 1.26%-1.59%]) compared with the medium-engagement group (0.79%, [95% CI, 0.71%-0.87%]; 

 <.001) and the high-engagement group (0.53%, [95% CI, 0.45%-0.60%]; 

Assessment of Hypertension Control Among Adults Participating in a Mobile Technology Blood Pressure Self-Management Program

New research suggests use of mobile technology could help improve blood pressure over a long-term period, with greater engagement with the technology associated with greater improvements in blood pressure. 

Mobile Blood Pressure App Shows Promise in First-of-Its-Kind, Long-Term Study

This article was originally published on 

A new study from Israel is providing clinicians with further insight into the risk of myocarditis associated with COVID-19 vaccines. 

A study assessing the risk associated with the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in Israel, results of the study provide insight into the apparent risk of myocarditis according to dose number and other factors. A team of investigators, led by Dror Mevorach, MD, Hadassah Hebrew University Medical Center, observed the incidence of myocarditis, while considered low, increased after receipt of COVID-19 vaccination, particularly after the second dose in young male recipients. 

A retrospective review of data on presumptive cases of myocarditis was performed, with medical records obtained from the Ministry of Health database in Israel. Data was obtained from December 2020 - May 2021.

Criteria for myocarditis was adapted using the case definition of the Bright Collaboration and classified as definitive, probably, possible, having insufficient data, or having an alternative diagnosis. Investigators used descriptive frequencies, percentages, means, and standard deviations to characterize cases of myocarditis according to age, sex, time elapsed since vaccination, length of hospital stay, and clinical outcome.

Additionally, investigators analyzed the occurrence of myocarditis through computing the risk difference for the comparison of myocarditis incidence after the first and second vaccine doses, at 21 days apart.

Then, they calculated the standardized incidence ratio of the observed-to-expected incidence within 21 days following the first dose and 30 days after the second dose. Further, they calculated the rate ratio 30 days after the second dose, in comparison to unvaccinated patients.

In Israel, a total of 9,289,765 were included in the surveillance period, with 5,125,635 receiving 2 doses. The data show 304 people had symptoms of myocarditis reported to the Isreali Ministry of Health.

After ruling out 21 cases due to alternative diagnosis, a total of 283 cases confirmed the diagnosis of myocarditis. Of these cases, 142 cases occurred after vaccination, with 136 of these diagnoses proving to be definite or probably myocarditis.

Additionally, clinical presentation was deemed to be mild in 129 recipients of the vaccine, while 1 person with fulminant myocarditis died.

Data show the overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval, 1.33 - 2.19), showing an overall risk difference of 3.19 (95% CI, 2.37 - 4.02) among men and 0.39 (95% CI, 0.10 - 0.68) among women.

They noticed the highest difference was among male patients between 16 - 19 years of age, at a difference of 13.73 (95% CI, 8.11 - 19.46).

Furthermore, the standardized incidence ratio of myocarditis after the second dose of vaccine was 5.34 (95% CI, 4.48 - 6.40). Among males, the standardized incidence ratio was highest in those aged 16 - 19 years at 13.60 (95% CI, 9.30 - 19.20).

Investigators observed fully vaccinated recipients, compared to unvaccinated patients, had a rate ratio 30 days after the second vaccine dose of 2.35 (95% CI, 1.10 - 5.02). It was seen to be highest in males between 16 - 19 years old at 8.96 (95% CI, 4.50 - 17.83).

Investigators noted the incidence of myocarditis was shown to decline as the number of newly vaccinated persons decreased over time, suggesting the possibility of a causal relationship between myocarditis and vaccination.

“The mechanism of vaccine-induced myocarditis is not known but may be related to the active component of the vaccine, the mRNA sequence that codes for the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or to the immune response that follows vaccination,” investigators wrote.

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel

An analysis of more than 9 million patients, including more than 5 million receiving both doses, provides insight into the risks of myocarditis associated with the BNT162b2 COVID-19 vaccine.

Israeli Study Details Myocarditis Risk Associated with Pfizer COVID-19 Vaccine

An analysis of data from more than 2.1 million mothers suggests preterm delivery was associated with a 1.6-fold increase in risk of new-onset chronic 

An analysis of women with a singleton delivery in Sweden from 1973 through 2015, results of the study provide insight into the apparent increase of hypertension associated with preterm delivery in this patient population and also stratified according to weeks of gestation at delivery.

“Preterm delivery should now be recognized as a risk factor for hypertension across the life course. Women with a history of preterm delivery need early preventive evaluation and long-term risk reduction and monitoring for hypertension,” wrote investigators.

With an interest in further investigating associations of preterm delivery with long-term cardiometabolic disorders, a trio of clinicians from Icahn School of Medicine at Mount Sinai led by Casey Crump designed the current study as a national cohort study leveraging data from the Swedish Medical Birth Register. Using the register, which contains prenatal and birth information for deliveries in Sweden dating back to 1973, investigators sought to identify all singleton deliveries occurring from 1973-2015 for inclusion in their analysis.

Investigators noted singleton deliveries were selected to improve internal comparability and women with preexisting hypertension were excluded from the analysis. In total, 2,195,989 women with 4,308,286 deliveries were identified for inclusion. Of these, 351,189 (16.0%) went on to be diagnosed with hypertension during the follow-up period, which included 46.1 million person-years of follow-up.

The primary outcome of interest for the study was new-onset chronic hypertension, which was identified from primary care, specialty outpatient, and inpatient diagnoses using administrative data. Investigators noted plans to use Cox proportional hazards regression adjusted for preeclampsia, other hypertensive disorders of pregnancy, and other maternal factors to determine hazard ratios. Additionally, cosibling analyses were used to assess for potential confounding by shared familial factors.

Upon analysis, preterm delivery was associated with an increased risk for diagnosis of hypertension was observed within 10 years of delivery. Further analysis indicated this risk was greatest among those giving birth at 22-27 weeks (aHR, 2.23 [95% CI, 1.98-2.52]) of gestation followed by those giving birth at 28-33 weeks (aHR, 1.85 [95% CI, 1.74-1.97]), 34-36 weeks (aHR, 1.55 [95% CI, 1.48-1.63]), and 37-38 weeks (aHR, 1.26 [95% CI, 1.22-1.30]) compared with full-term delivery, which was defined as 39-41 weeks of gestation.

When examining risk beyond 10 years, results indicated the apparent risks decreased but remained significant at 10-19 years (aHR, 1.40 [95% CI, 1.36-1.44]), 20-29 years (aHR, 1.20 [95% CI, 1.18-1.23]), and 30-43 years (aHR, 1.12 [95% CI, 1.10-1.14]) after delivery. Additionally, cosibling analyses determined the findings were not explained by shared determinants of preterm delivery and hypertension within families.

“To our knowledge, this is the largest study to date of preterm delivery in relation to future risks of hypertension and the first to assess for potential confounding by shared familial factors using a cosibling design,” added investigators.

Preterm Delivery and Long-term Risk of Hypertension in Women

An analysis of more than 4 million singleton deliveries from more than 2.1 million women provides insight into the apparent increase in risk associated with preterm delivery.

Preterm Delivery Associated with 1.6-Fold Increase in Risk of Hypertension Later in Life

An analysis of data from more than 400 women included in a major study is detailing the insight provided by changes in patterns of menstrual cycle length over the menopause transition on risk of atherosclerosis in aging women.

The study, which leveraged data from women within the Study of Women’s Health Across the Nation (SWAN) Daily Hormone Study (DHS), identified 3 distinct trajectories of cycle length and described their associations with postmenopausal carotid intima-media thickness and brachial-ankle pulse wave velocity.

“Menopause is not just a click of a button. It’s a multistage transition where women experience many changes that could put them at higher risk for cardiovascular disease. Change in cycle length, which is linked to hormone levels, is a simple metric that might tell us who is more at risk,” Samar El Khoudary, PhD, associate professor of epidemiology at Pitt’s Graduate School of Public Health, in a 

statement from the North American Menopause Society (NAMS

As organizations and institutions push to improve the cardiovascular care of women, identifying potential risk factors for cardiovascular disease stand to have a major potential impact on a societal level. With this in mind, El Khoudary and colleagues sought to assess whether trajectories of menstrual cycle length were associated with markers of subclinical atherosclerosis.

Briefly, the SWAN study, which was co-sponsored by the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the National Institutes of Health (NIH), designed with the intent of collecting data related to potential physical, biological, psychological, and social changes during their transition to menopause. The SWAN DHS study is a subsidy of the SWAN study and recorded additional data, such as vasomotor menopausal symptoms in daily diaries for 12-50 days.

From SWAN DHS, investigators identified 428 women with 1,808 cycles over the menopause transition for inclusion in the current study. To be included in the study, women needed to have an observed date of final menstrual period, have recorded cycle lengths from 2 or more annual menstrual cycles, and have measurements of postmenopausal carotid intimal-media thickness and/or brachial-ankle pulse wave velocity.

The study population had a mean age of 45.1±2.3 years at baseline visit and the mean number of menstrual cycles recorded was 4.22±1.91 cycles. Of the 428 included, 263 had carotid intimal-media thickness and 213 had brachial-ankle pulse wave velocity measured after the transition to menopause. Investigators pointed out carotid intimal-media thickness was measured a mean of 13.88±0.42 years after the baseline visit and brachial-ankle pulse wave velocity was measured a mean of 15.25±0.7 years after the baseline visit.

When assessing patterns of cycle length, investigates identified 3 distinct trajectories. In total, 62.1% were considered to have stable cycle length, 21.8% experienced a late increase in cycle length, and 16.2% experienced an early increase in cycle length. Investigators defined stable as no chances in length over the menopause transition, late increase was defined as a late increase 2 years before the final menstrual period, and early increase was defined as an increase 5 years before final menstrual period.

Results of the investigators’ analysis, which were adjusted for race, concurrent age, socioeconomic status, physical activity level, and premenopausal cardiovascular risk profile, suggested women with a late-increase pattern had significantly lower postmenopausal carotid intima-media thickness (0.72 mm) and brachial-ankle pulse wave velocity (1392 cm/s) than those in the stable group (0.77 mm and 1508 cm/s, respectively).

“These findings are important because they show that we cannot treat women as one group: Women have different menstrual cycle trajectories over the menopause transition, and this trajectory seems to be a marker of vascular health,” said El Khoudary. “This information adds to the toolkit that we are developing for clinicians who care for women in midlife to assess cardiovascular disease risk and brings us closer to personalizing prevention strategies.”

Patterns of menstrual cycle length over the menopause transition are associated with subclinical atherosclerosis after menopause

In an analysis of SWAN data, investigators found changes in menstrual cycle length within the 5 years preceding a woman's final menstrual period was associated with changes in carotid intima-media thickness and brachial-ankle pulse wave velocity.

Changes in Menstrual Cycle Length Prior to Menopause Could Help Predict Risk of Atherosclerosis

The role of advanced practice providers (APPs) has undergone a revolution in recent decades. Once relegated to an undefined role in the care of patients, APPs have become a critical part of care across nearly every specialty in medicine, particularly cardiology.

With an interest in recognizing the evolution of the role of APPs and spotlighting National Physician Assistant Week, 

 reached out to Viet Le, PA-C, a researcher and physician assistant with Intermountain Healthcare and president of the Association of Physician Assistants in Cardiology (APAC), for his perspective on the role of PAs in cardiology and the importance of awareness holidays, such as National Physician Assistant Week.



Q&A on National Physician Assitant Week with Viet Le, PA-C


How important are awareness holidays for educating the general public and other clinicians around the evolving role of physician's assistants and various disciplines?

: I think they're very important, in particular, for the PA profession. While it's been around nearly 50 years, it's not as widespread as your traditional professions such as nursing and or physicians. I think when you say physician patients, whether right or wrong, they have an image of who that is and what they do as a role. Same with the nursing profession, they come with implicit bias whether that is what they've learned from TV or another type of media, but I think these specific days of recognition are important for us to be able to teach not only the lay public, but our colleagues about what our training is, what we do, and how we fit into that team-based care.

So, I think it's very important and will continue to be so until you see PAs, and nurse practitioners and PharmDs, these recognition days kind of roll forward to a point where when you hear PA, you immediately know what that means. Still, 17 years later in practice, I find myself still educating patients and colleagues, what my scope of practice is, what my training is, and then what I can do for them as well as my patients.

How much has the role of the PA in cardiology evolved during your time in the field?

 Well, I think it's changed quite a bit. So, it's been around 50 plus years, but even the last 17 years has seen a huge surge in PAs practicing in specialties and cardiology is one of those areas. Especially as we've recognized the depth and breadth of specialties within cardiology itself—I mean, we have EP, we have heart failure, we have interventional, noninvasive imaging, we're breaking down into lipids now and, and preventive cardiology. So, there's a lot of areas and not any single physician can manage all the other parts within the moving parts within cardiology, let alone subspecialty care.

So, with team-based practice, what we've seen is within my 17 years is that it's percolated. The federal portion of it, the national certification, has really stayed the same. It's the state laws that have evolved. With the state evolution has come evolution within health systems, because, ultimately, it's the private provider credentialing that dictates what I do within those facilities, regardless of what the state law says.

The things that I've seen are more prescription, more supervision by case nurse practitioners on stress tests, we oversee imaging, you are starting to see advanced practice providers such as PAs overseeing tests and reading the tests initially before having someone else read them over—I would say similar to how family practice physicians pre-read x-rays and specialty diagnostics, we're doing the same thing before they move on to the radiologist or the cardiovascular imager, etc.

I find myself ordering more tests. As my physician partners have found themselves busier and as we've worked together, they've seen my experience and I read those or order those etc. I'm ordering more or prescribing more specialty medications that traditionally you'd say a family practice would leave to cardiology. Well, in the same way, cardiology attendings are also kind of filtering that and it percolates down to the advanced practice providers in terms of managing and initiating medications that are really specialty-based.

The other evolution that you're seeing within my practice is I'm starting to see PAs first assisting at a higher level: they're harvesting veins, they may be starting the sternotomy, but they're not doing the meat, so to speak, of the surgery, but didn't really in that first assist role. So, we are really being the teammate and those extra set of hands that our physician partners require, both procedurally and in terms of management of very complex diseases with patients.

What's it like for you when your organization also recognizes the advancement of PAs in practice and the evolving roles of advanced practice providers?



It's a complex question, because, for me, we've seen a lot of changes recently within Intermountain. My first role within Intermountain was actually as an affiliated provider, meaning I was not employed by Intermountain, but I was within the Intermountain hospitals working for private practice groups.

At that time, advanced practice providers and specifically PAs were a novelty, so to speak, within the floors. I was rounding seeing patients on the floor and people would see me and, honestly, these are my nursing colleagues, etc., who thought I was a resident. And I just happened to be like, "What are you a five or six now? What are you doing still here?" and they didn't recognize that as a PA, I was rounding on patients, prescribing things, and ordering things.

So, the close approximate that folks had was that I was a resident or a fellow or something like that, but as Intermountain incorporated the lexicon of physician assistant, nurse practitioner, and now advanced practice provider, what that has done is actually given us an administrative voice. Rather than just these kind of Maverick providers within the system, we now actually have direct roles with direct lines of leadership and some dotted lines as well. What that has allowed us to do is, is be in triads, where we have nurses, physicians, and then advanced practice providers who are now helping to flesh out those roles of APPs, rather than just kind of randomly occurring in this clinic or that hospital.

There's an intention now for utilization of these APPs in practice and, even as early as 2012, when I came back to Intermountain, we developed an ad hoc and not very formalized, but it was structured within it was grassroots. We were APCs, advanced practice clinicians, and that was in 2012. That continued to grow and grow and we had a voice. We were starting to find ourselves at the table, either accidentally and/or because of our relationships with nursing directors and/or with physician directors, that we were invited to the table.

Now, it's intentioned. We have a place set aside rather than an invitation. It's now intentional that we have a place at the table. So, for me to have Intermountain recognize that really, I almost get emotional about it because it means that I'm recognized within the system. I'm not just an afterthought and a good afterthought that seems to provide excellent care. Now, it's intentional and there's a place at this table for us where we can help grow team-based care rather than just accidentally arrive at it.

Editor’s Note: This transcript has been edited for length and clarity.

To celebrate National Physician Assistant Week, we reached out to the president of the Association of Physician Assistants in Cardiology for his perspective on the holiday and to reflect on the evolving role of PAs in cardiology.

Recognizing the Role of PAs in Cardiology With Viet Le, PA-C

: A woman in her mid-40’s is sent from a nearby monoclonal antibody clinic to the ER for a syncopal episode. She denies any injury or prodromal chest pain, SOB, palpitations, or other complaints beyond the low-grade fever and cough she has been having for the past week.

: Vital signs are normal though the pulse is in the high 90’s. Exam is otherwise non-focal.

Computer Read: NSR at 94, long QT at 717.

Our latest case report from Brady Pregerson, MD, features a woman in her 40s sent from a monoclonal antibody clinic to the ER for a syncopal episode. Check out the EKG and try to determine the correct diagnosis!

Cardiology Case Report: Syncope and COVID-19

Results from an observational analysis of 3 European-based cohorts provide evidence suggesting iron deficiency in middle age was linked to increased risk of poor cardiovascular health later in life.

Designed with the intent of assessing the risks posed by iron deficiency in the general population, results of the study indicate patients with functional iron deficiency (FID) had a 24% greater risk of coronary heart disease, a 26% greater risk of cardiovascular mortality, and a 12% greater risk of all-cause mortality.

“This was an observational study and we cannot conclude that iron deficiency causes heart disease,” said lead investigator Benedikt Schrage, MD, of the University Heart and Vasculature Centre Hamburg, Germany, 

. “However, evidence is growing that there is a link and these findings provide the basis for further research to confirm the results.”

As data related to the effects of iron deficiency continue to grow, Schrage and a team of colleagues form multiple institutions in Europe sought to examine associations between absolute iron deficiency (AID)/FID with incident cardiovascular disease and mortality among the general population. To do so, the current study was designed as an observational analysis of data from within the KORA, Northern Sweden, and Tromsø cohort studies.

From this trio of study cohorts, investigators identified 12,164 individuals for inclusion in the current study. This cohort had a median age of 59 (IQR, 45-68) years, a median follow-up time of 13.3 years, and 45.2% were male. Of the 12,164 identified for inclusion 7296 (60%) had AID, 1989 (16.4%) had severe AID, 7825 had FID, and 4868 had no absolute iron deficiency. Of note, AID was defined as ferritin below 100 μg/L and severe AID as ferritin below 30 μg/L. FID was defined as ferritin above 100 μg/L or ferritin 100–299 μg/L and TSAT below 20%. Investigators planned to assess associations between iron deficiency and incident coronary heart disease, incident stroke, cardiovascular mortality, and all-cause mortality using Cox regression models.

During the course of the follow-up period, 2212 individuals died, including 573 from cardiovascular causes. A total of 1033 individuals were diagnosed with incident coronary heart disease and 766 were diagnosed with incident stroke during the follow-up.

In adjusted analysis, results suggested AID was not associated with all-cause mortality (HR, 1.08 [95% CI, 0.98-1.19]; 

=.12) cardiovascular mortality (HR, 1.22 [95% CI, 1.00-1.48]; 

=.05), or incident stroke (HR, 1.11 [95% CI, 0.94-1.31]; 

=.22), but was associated with increased risk of incident coronary heart disease (HR, 1.20 [95% CI, 1.04=1.39]; 

=.01). Further analysis suggested severe AID was associated with increased risk of all-cause mortality (HR, 1.28 [95% CI, 1.12-1.46]; 

<.01), but not cardiovascular mortality (HR, 1.01 [95% CI, 0.76-1.344]; 

=.95), incident coronary heart disease (HR, 1.22 [95% CI, 1.00-1.50]; 

=.05), or incident stroke (HR, 1.10 [95% CI, 0.87-1.40]; 

When assessing associations with FID, results indicated FID was significantly associated with all-cause mortality (HR, 1.12 [95% CI 1.01–1.24]; 

=.03),cardiovascular mortality (HR, 1.26 [95% CI 1.03–1.54] 

=.03), and incident coronary heart disease (HR, 1.24 [95% CI 1.07–1.43] 

 <.01), but not incident stroke (HR, 1.15 [95% CI, 0.97–1.36]; 

“This analysis suggests that if iron deficiency had been absent at baseline, about 5% of deaths, 12% of cardiovascular deaths, and 11% of new coronary heart disease diagnoses would not have occurred in the following decade,” Schrage added. “The study showed that iron deficiency was highly prevalent in this middle-aged population, with nearly two-thirds having functional iron deficiency. These individuals were more likely to develop heart disease and were also more likely to die during the next 13 years.”

Association of iron deficiency with incident cardiovascular diseases and mortality in the general population

Leveraging data from 3 European cohorts, investigators detail the risk of incident coronary heart disease and mortality associated with iron deficiency in the general population. 

Functional Iron Deficiency Linked to Increased Risk of Coronary Heart Disease, Cardiovascular Mortality

A systematic review and meta-analysis from Cedars-Sinai Medical Center is raising the alarm on the potential increase in risk of 

 among patients consuming omega-3 supplements.

With interest and use of both pharmaceutical- and consumer-grade omega-3 supplements at an all-time high, results of the study, which indicated patients consuming more than 1 gram of omega-3 fatty acids per day had a 49% increase in risk of AF, provide valuable insight for clinicians.

“Our goal was to bring clarity, answers and actionable information to the broader medical field and to patients,” said Christine Albert, MD, MPH, a professor of Cardiology and chair of the Department of Cardiology in the Smidt Heart Institute, in a 

. “In this instance, the results suggest that there may not be a straightforward answer to, ‘Is fish oil good or bad for atrial fibrillation?’ but instead, the answer may depend on the dose.”

With recent clinical trials producing results suggesting use of marine omega-3 fatty acid supplements could increase risk of AF, Albert and a team of colleagues conducted the current study to provide further clarity on the potential for arrhythmias associated with these agents. To do so, investigators designed a systematic review and meta-analysis with the intent of assessing this potential for increased risk using data obtained from the MEDLINE and Embase databases as well as a meta-analysis of randomized clinical trials published in 2019.

For inclusion in the analysis, randomized clinical trials needed to report results for AF, either as pre-specified outcome, adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year. For the purpose of analysis, investigators meta-analyzed HRs for reported AF outcomes within each trial using random-effects model with Knapp-Hartung adjustment and potential dose-response relationships were assessed with a meta-regression model.

In total, 4059 records were screening for inclusion. Of these, 7 were considered eligible for inclusion, including 5 that were previously included in the 2019 meta-analysis. A total of 81,210 patients were identified from the 7 trials, including 58,939 enrolled in trials testing low dose marina omega-3 fatty acids and 22,271 examining high doses of omega-3 fatty acids. The overall study cohort had a mean age of 65 years, 39% were female, and the average weighted follow-up was 4.9 years. Of note, low dose marine omega-3 fatty acids was considered 1 gram or less per day and high dose was considered more than 1 gram per day.

Results of the meta-analysis indicated use of marine omega-3 fatty acid supplements was associated with an increased risk of atrial fibrillation (HR, 1.25 [95% CI, 1.07-1.46]; 

=.013). When stratifying by dose, results indicated those receiving a high dose (HR, 1.49 [9545CI, 1.04-2.15]; 

=.042) appeared to be at a greater risk of AF than those receiving a low dose (HR, 1.12 [95% CI, 1.03-1.22]; 

=.024) when compared to those not receiving marine omega-3 fatty acid supplements (

 for interaction <.001). In meta-regression, results indicated the risk of AF increased 11% for every 1 gram increase of omega-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; 

“For patients, the risk of developing atrial fibrillation appears to be relatively small for those taking one gram or less of fish oil per day,” said Albert. “Taking more than one gram of fish oil per day is something you should only do following your doctors’ advice.”

Effect of Long-Term Marine Omega-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

A meta-analysis and systematic review of 7 RCTs suggests consuming more than 1 gram of marine omega-3 fatty acid supplements per day could increase a patient's risk of atrial fibrillation. 

Meta-Analysis Raises Questions Around Risk of Atrial Fibrillation Associated with Omega-3 Supplements

A new study is highlighting the disparities in cardiovascular care provided to women with 

A post hoc analysis of the REWIND trial, results demonstrate women were less likely to achieve treatment targets for cardiovascular management than their male counterparts and were less likely to receive guideline-directed medical therapies.

“Despite evidence of the benefits for managing cardiovascular risk factors (such as lowering blood pressure and cholesterol levels) in people with type 2 diabetes, an unacceptable proportion of affected women are not reaching recommended treatment targets”, said lead author Giulia Ferrannini, MD, from the Karolinska Institutet, Stockholm, Sweden, 

. “Cardiovascular disease is the leading killer of women, but it has never been more preventable and treatable. The reasons why women are not receiving the same standard of treatment as men are complex and require further investigation so that women with type 2 diabetes can be treated more effectively.”

With improving the cardiovascular care of women, especially those with diabetes, a major research focus in the community, Ferrannini and colleagues from Karolinska Institute, Population Health Research Institute, and Eli Lilly and Company performed the current study with the intent of assessing the topic through analysis of the REWIND trial. To do so, the current study was designed as an assessment of a subset of REWIND participants with baseline and follow-up data related to blood pressure, LDL-C, and HDL-C from within the REWIND trial.

Briefly, the REWIND trial was a multicenter, randomized, placebo-controlled trial conducted in 24 countries and enrolling more nearly 10,000 patients with type 2 diabetes and various levels of cardiovascular risk. The trial had a mean follow-up of 5.4 years and was designed to compare the effects of dulaglutide against placebo therapy with a primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The trial ultimately concluded dulaglutide was associated with a 12% lower risk of the primary composite outcome (HR, 0.88 [95% CI, 0.79-0.99]; 

Of the 9901 patients within the REWIND trial, 46.3% were women. Of note, men included in the study were more likely to have a history of cardiovascular disease than their female counterparts (41.4% vs 20.0%; 

 <.001). Upon analysis, results indicate the majority of women met clinically relevant treatment targets for blood pressure and cholesterol at baseline, but a smaller proportion of women were at target for ACE/ARB use (80% vs 83%), lipid control or statin use (73% vs 81%), or aspirin use (

Further analysis suggested women had a lower risk for all cardiovascular outcomes included in the study except for fatal or nonfatal stroke, which investigators pointed out was also observed in a subgroup of patients without a history of cardiovascular disease at baseline. Additionally, investigators pointed out women with a history of cardiovascular disease had a similar risk of stroke, heart failure hospitalization, all-cause mortality, and cardiovascular mortality compared to their male counterparts.

“It is important to consider all gender disparities that exist in the real-world setting that prevent women with diabetes to keep such advantage, including time to diagnosis, use of invasive revascularization procedures, and use of guideline-recommended treatments. Women with type 2 diabetes are at high cardiovascular risk and should not be neglected in its comprehensive management,” Ferrannini added.

This study, “Gender differences in cardiovascular risk, treatment, and outcomes: a post-hoc analysis from the REWIND trial,” was presented at EASD 2021.

A post hoc analysis of the REWIND trial suggests women with diabetes were less likely to achieve treatment targets and receive guideline-directed medical therapies than their male counterparts.

Study Highlights Need for More Comprehensive Cardiovascular Care in Women with Diabetes

Data from an analysis of patients within the SWEDEHEART registry suggests there were no differences in long-term survival between patients who did and did not undergo permanent pacemaker implantation following transcatheter aortic valve replacement (TAVR).

A look at data from patients who underwent transfemoral TAVR in Sweden from 2008-2018, results of the study provide insight into the effects of pacemaker implantation on survival over a period lasting up to 10 years, including a lack of significant difference observed in cardiovascular mortality, heart failure, and endocarditis between the groups.

“Our study contributes to understanding the impact of pacemaker implantation after transcatheter aortic valve replacement, which is becoming increasingly important as the use of this method expands to include younger and low-risk patients with a long life expectancy,” says Natalie Glaser, MD, PhD, study investigator and researcher at the Department of Molecular Medicine and Surgery at Karolinska Institutet, 

With previous studies producing uncertainty related to differences in outcomes observed with patients who underwent permanent pacemaker implantation after TAVR compared to their counterparts who did not receive a pacemaker, the current study was designed by Glaser and colleagues to fill this apparent knowledge gap. To do so, the current study was designed as an observational, population-based cohort study using data from the SWEDEHEART registry.

Pooling data from 8 sites performing TAVR in Sweden, investigators sought to identify a cohort containing all patients who underwent TAVR from 2008-2018. Using this data, investigators hoped to evaluate the unadjusted and multivariable-adjusted risks of all-cause mortality, cardiovascular death, heart failure hospitalizations, and endocarditis using Cox proportional hazards regression. For the purpose of analysis, the exposure of interest was defined as implantation of a permanent pacemaker or implantable cardioverter-defibrillator within 30 days of undergoing TAVR.

Incidence of cardiovascular mortality was considered the primary outcome of interest while heart failure hospitalization and endocarditis were considered secondary outcomes. Of note, the index date for the study was defined as 30 days after TAVR. Additionally, investigators noted the end of follow-up for all-cause mortality was March 20, 2020, and the end of follow-up for cardiovascular mortality, heart failure, and endocarditis was December 31, 2018.

From SWEDEHEART, investigators identified 4750 patients who underwent TAVR from 2008-2018. Of these, 124 were excluded because they died within 30 days, 465 were excluded due to having had a CIED prior to undergoing TAVR, 581 were excluded for nontransfemoral access, and 160 were excluded for undergoing valve-in-valve procedures. Of the 3420 included in the study population, 481 (14%) received a pacemaker following TAVR.

At 1, 5, and 10 years, the survival rates were 90.0%, 52.7%, and 10.9% in the pacemaker group and 92.7%, 53.8%, and 15.3% in the nonpacemaker group, respectively (HR: 1.03; 95% CI: 0.88-1.22; 

=.692). Further analysis indicated the cumulative incidence of heart failure at 1, 5, and 8 years was 6.6%, 21.1%, and 26.6% in the pacemaker group and 4.7%, 15.7%, and 20.5% in the nonpacemaker group, respectively. For endocarditis, the cumulative incidence rate at 1, 5, and 8 years was 1.8%, 3.8%, and 4.2% in the pacemaker group and 1.7%, 3.8%, and 4.2% in the nonpacemaker group, respectively.

In multivariable-adjusted analyses, investigators observed no significant difference in risk of cardiovascular mortality (HR, 0.91 [95% CI, 0.71-1.18]; 

=.611), heart failure (HR, 1.23 [95% CI: 0.92-1.63]; 

=.157), or endocarditis (HR, 0.90 [95% CI, 0.47-1.69]; 

“As the use of TAVR expands to younger and low-risk patients, studies including younger and low-risk patients with longer follow-up are needed to confirm the present findings in these patient populations,” wrote investigators.

Outcomes following permanent pacemaker implantation after transcatheter aortic valve replacement: SWEDEHEART observational study,

An analysis of patient outcomes for those undergoing transfemoral TAVR from 2008-2018 sugggests permanent pacemaker implantation was not associated with an increase in risk of cardiovascular mortality, heart failure, or endocarditis. 

Pacemaker Implantation Not Linked to Increased Mortality Following TAVR

Data from a matched-cohort study indicates 

 was associated increased odds of worsening diabetes in a national cohort of patients with 

Results of the study, which included data from 83,022 matched pairs of statin users and comparators, indicate statin initiation was associated with increased risk of diabetes progression, including an increase in the likelihood of initiating new therapies and experiencing glycemic events.

“The higher risk of diabetes progression associated with statin use may seem less consequential, at least in the short and intermediate term, than the cardiovascular benefits of statin use, especially when used for secondary prevention,” wrote investigators. “However, diabetes progression has long-term effects on quality of life and treatment burden, which warrant consideration when discussing the overall risk-benefit profile, especially when used for primary prevention.”

To further investigate potential links between statin therapy and increased insulin resistance, a team of investigators from the University of Texas Southwestern Medical Center conducted the current study with the intent of using data from the national Veterans Affairs Corporate DataWarehouse from 2003-2015. Using a validated algorithm, investigators sought to identify all patients with VA medical encounters and a diagnosis of diabetes from the aforementioned period and assess whether initiation of statin therapy was associated with progression of diabetes, which was defined as a composite of new insulin initiation, increase in the number of glucose-lowering medication classes, incidence of 5 or more measurements of blood glucose of 200 mg/dL or greater, or a new diagnosis of ketoacidosis or uncontrolled diabetes.

For inclusion in the study, patients needed to be at least 30 years of age or older, have at least 1 VA encounter, blood pressure and weight measurements, VA pharmacy dispensing data, and laboratory data, including g blood or serum glucose, creatinine, and LDL-C measurements. Investigators planned a total of 6 primary and secondary analyses, including analyses stratifying patients by presence of comorbidities and intensity of statin therapy. Of note, the exposure of interest for the study was treatment initiation with statins for those classified as statin users and treatment initiation with H2-blockers or portion pump inhibitors for those classified as comparators.

The investigators identified a cohort of 705,774 VA patients considered eligible for inclusion in the study, including 595,579 statin users. From this cohort, investigators identified 83,022 matched pairs of statin users and active comparators. This cohort had a mean age of 60.1 (SD, 11.6) years, 94.9% were men, and 68.2% were White.

Results of the investigators' analyses suggested statin users had significantly greater odds of diabetes progression compared with nonusers, with increased odds observed for increases in the number of glucose-lowering medication classes (OR, 1.41; 95% CI, 1.38- 1.43), new insulin starts (OR, 1.16; 95% CI, 1.12-1.19), presence of persistent hyperglycemia (OR, 1.13; 95% CI, 1.10-1.16), and new diagnosis of ketoacidosis or uncontrolled diabetes (OR, 1.24; 95% CI, 1.19-1.30).

Secondary analyses provided further insight into the potential effects of statin therapy on diabetes progression, with all secondary and sensitivity analyses indicating the odds of diabetes progression were consistently greater among statin users compared to nonusers. Investigators highlighted analyses demonstrating odds of diabetes progression were greater among statin users with no other comorbidities compared to the overall cohort and demonstrating more intensive cholesterol-lowering therapy was associated with the greatest odds of diabetes progression among statin users compared with nonusers.

Using data from more than 80k matched pairs of statin users and comparators, investigators from UT Southwestern Medical Center found initiation of statin therapy was associated with an increased likelihood of diabetes progression, including risk of hyperglycemia and ketoacidosis. 