Gregory M. Weiss, MD

Cardiovascular disease (CVD) remains the leading killer of both men and women across the world. While marquee risk factors such as hypertension, diabetes, and obesity enjoy entire disciplines of medicine there exists a multitude of other factors that contribute to long-term CV risk. 

Everyone knows how important sleep is. So much so that there are entire industries dedicated to facilitating our nightly quest for rest. Emerging evidence suggests that sleep patterns and disturbances may play a significant role in our long-term cardiovascular health as well.

Although there are quite a few sleep disorders, obstructive sleep apnea (OSA) is ubiquitous today with widespread obesity contributing to the disease burden significantly. It is estimated that nearly 1 billion people are affected by OSA worldwide.

 Sleep apnea is closely associated with the obesity hypoventilation syndrome marked by retained carbon dioxide and hypertension as well as cardiovascular disease.

 More recently OSA has been linked to coronary artery disease, stroke, and heart failure.

In addition to sleep apnea, researchers have identified other sleep disturbances that contribute to CVD. A reduction in slow wave sleep (SWS) appears associated with OSA and is independently related to increased sympathetic activity which in turn increases the risk of cardiovascular and metabolic diseases.

 In essence, lack of slow wave sleep, or deep sleep, leads to cardiovascular stress and risk.

In addition to the quality of sleep, the duration of sleep appears to play a role in CV risk as well. Evidence suggests that those who sleep too little and those who sleep too much have higher rates of CVD.1 In particular, sleep durations less than 6 hours and greater than 10 were associated with increased rates of hypertension.1

Ultimately, the quality and duration of sleep are closely linked. Factors such as diet, stress, alcohol intake, and body composition are important in determining how much restful sleep each of us gets. Sleep apnea represents a cluster of symptoms and sequelae that affect several body systems. Through obstruction, usually due to excessive soft tissue in the mouth and neck, hypoventilation, increased CO2, and increased blood acid leads to changes in cardiovascular set points. Blood pressure and blood glucose levels rise leading to microvascular damage and cardiovascular disease.

The US Preventative Services Task Force thought the problem of OSA severe enough to put forth a set of recommendations this year.

 The task force recommends that positive airway pressure devices be employed when indicated for OSA.

They further recommend screening in an effort to increase early detection and treatment.

 As with most conditions, especially ones that lead to cardiovascular disease, the earlier in the disease process treatment is started, the slower the progression to overt complications.

Sleep medicine is a discipline whose time has come. We are seeing clinicians from multiple disciplines choosing to enter this specialized field highlighting its newfound importance. In any case these reports shed important light on the link between healthy sleep and a healthy cardiovascular system. OSA, hypertension, daytime fatigue, and poor sleep go hand in hand. We now know that good sleep may just mean a healthier heart in the long run. As clinicians, especially primary care providers, we should screen our at-risk patients at every opportunity for sleep disturbances. Now, with an increasing number of clinicians choosing sleep medicine as a specialty, patients can get the help they need in finding that perfect nightly slumber, and just maybe a healthier cardiovascular system.

Han, H., Wang, Y. Zong, G., et al. Sleep duration and risks of incident cardiovascular disease and mortality amoung people with type 2 diabetes. Front. Cardiovasc. Med., 31 October 2022 

https://doi.org/10.3389/fcvm.2022.1034785

US Preventive Services Task Force. Screening for Obstructive Sleep Apnea in Adults: US Preventive Services Task Force Recommendation Statement. 

 2022;328(19):1945–1950. doi:10.1001/jama.2022.20304

Articles

Gregory Weiss, MD, provides insight into his perspective on the evolving recognition of the role of sleep health in cardiovascular disease prevention. 

Putting the Debate to Rest: Recognizing the Role of Sleep in Cardiovascular Health, with Gregory Weiss, MD

Managing cardiovascular disease often requires the ability to identify the many pieces contributing to the disease and its outcomes much like a jigsaw puzzle that only reveals a picture when the pieces are properly placed together. 

Like any good detective, cardiologists continually study the patterns of presentation and admissions to hospitals for cardiovascular events in an attempt to decipher a code that could lead to preventing those admissions. A recent article published in the Journal of the American Heart Association sought to describe what men and women are presenting to the emergency department with, when they come for cardiovascular care.

As might be expected, the authors found striking differences in how and for what reasons men and women present to the hospital with cardiovascular complaints. For instance, women more commonly present with essential hypertension (16% of admissions), followed by hypertensive heart or kidney disease (14.1%), and finally atrial fibrillation/flutter (10.2%).1 Men most often presented with hypertensive heart or kidney disease (14.7%), followed by essential hypertension (10.8%), and then myocardial infarction (10.7%).

 We see in these data that men are at higher risk of presenting with conditions that affect the heart while women were more likely to have conditions that affect the blood vessels of the brain.

Looking at risk allows us to target areas for intervention prior to presenting with cardiovascular events. It appears that women are at lower risk overall for admission with a cardiovascular event but also had an elevated risk for dying from the specific diseases they present with, most notably stroke.1 Mamas Mamas, BMBCh, DPhil, the lead author of this study points out that sex differences and cardiovascular risk have long been known, however, this large sample of patients provides a more a more detailed understanding of sex disparities in hospitalization and the cumulative risk for death.

While sex disparities are important, we are seeing an increasing number of new factors that have unknown contributions to the burden of disease our patients realize. For instance, we know that the earth is in a warming phase and more and more extreme weather events are occurring and with greater frequency than previously reported. Kidney disease and cardiovascular disease have long been associated with each other. Now, in light of changing weather patterns, researchers have become interested in the impact of increasing temperatures on emergency department visits.

Yanji Qu, MD, PhD, and Wangjian Zhang, MD, PhD, recently published an article in the American Journal of Kidney Diseases examining the link between emergency visits and extreme ambient heat in New York. Extreme heat was defined as a daily temperature exceeding the 90th percentile for that month.

 They found that extreme heat exposure was significantly associated with increased risk for emergency visits for acute kidney injury, kidney stones, and urinary infections.

 While not specifically looking at cardiovascular disease this is one of the first investigations looking at environmental heat and hospital visits.

It is convenient to simply think of heat stroke or dehydration as consequences of rising summer temperatures, especially in urban settings. However, heat is associated with many health problems from respiratory distress to increased coronary oxygen demand. More study must be done beyond the renal literature to identify those at risk for poor outcomes related to climate change. Increasing awareness is an important first step. At risk patients can be targeted for community outreach and efforts to provide cooler home environments. Telemedicine has become a regular part of practice since COVID-19 and could be employed to prevent exposure to the elements in the future.

In the 2 studies reviewed here, we see several patient characteristics that appear unrelated. The truth is that sex, environment, cardiovascular disease, and kidney health, are likely related on many levels. It is our job as clinicians and researchers to put the puzzle pieces together so that the picture becomes clear enough to make a difference in our patients lives.

Mamas, M. A., Raisi-Estabragh, Z., Kobo, O. et al. Differential patterns and outcomes of 20.6 million cardiovascular emergency department encounters for men and women in the united states. J Am Heart Assoc. 2022;11:e026432. DOI: 10.1161/JAHA.122.026432

Qu, Y. Zang, W. Boutelle, A. M. et al. Associations between ambient extreme heat exposure and emergency department visits related to kidney disease. Am J Kidney Dis. 2022 Sep 30;S0272-6386(22)00918-0. doi: 10.1053/j.ajkd.2022.09.005.

In his latest column, Gregory Weiss, MD, examines a pair of studies examining different causes of cardiometabolic events from contemporary data and provides perspective on the implications of their findings. 

What Brings Cardiovascular Patients to the Hospital? With Gregory Weiss, MD

Hypertension disorders of pregnancy (HDP) are serious conditions that affect nearly one-quarter of all pregnancies and are currently the leading cause of perinatal maternal death around the world.

 It was previously known that HDP were associated with increased risk for cardiovascular disease (CVD) as far out as 20 or more years after the pregnancy, however, short term risk had yet to be defined.

Gestational hypertension or preeclampsia is defined as persistent elevated blood pressures during pregnancy and may put the lives of the mother and baby at risk in the short term. A great deal of focus has been put on the acute treatment of HDP due to the potential for loss of life prior to or even after delivery of the infant. The period over the next ten years following delivery has not been studied extensively.

Lisa Levine, MD, and colleagues sought to describe the prevalence of cardiovascular disease among women with HDP as compared to those without over the ten-year period following their pregnancy.

 The authors compared 84 patients with a history of HDP with 51 who did not.

 Of special note, 85% of participants were of African American race.

The results of the study revealed that women who experienced a HDP were 2.4 times more likely to experience new hypertension over the next 10 years compared to women who did not.

 Interestingly, while HDP predisposed women to hypertension, there was no increased risk for other CVD risk factors such as diabetes and no differences in key cardiovascular tests such as echocardiography and endothelial function tests.

What these results mean is that simply suffering from a hypertensive disorder of pregnancy puts a woman at risk for chronic hypertension within the next ten years.

 In addition to making this discovery, the authors noted that many of the women enrolled, including those who developed HDP and those who did not, may have had undiagnosed stage 1 or 2 hypertension prior to becoming pregnant.

This realization underscores the need for better screening and diagnosis regardless of pregnancy.

“[This study] along with studies with similar findings, further highlights the importance of routine screening for hypertension in this population,” Levine added. “Future studies should evaluate the optimal time period to screen for postpartum hypertension and a monitoring plan for these at-risk women.”

One important difference between this study and prior investigations was the inclusion of a diverse racial cohort. A lack of racial diversity in prior studies made extrapolation to a greater population difficult at best. Too many studies lack such diversity, a fact that ignores the plain truth that many diseases, hypertension in particular, disproportionally affect people of color.

Although these results may seem intuitive the post-partum period may see many women slip under the radar especially if they have a relatively uneventful delivery. Because obstetrics is a specialty unto itself, continuity of care and referrals to general practitioners and in the case of new hypertension internists and cardiologists may be lacking. The first inclination of a new mother is to go home and take care of her baby. Nevertheless, this study uncovers an important opportunity that should not be missed by obstetricians. Knowing that hypertension during pregnancy places the parturient at twice the risk for short term hypertension thereafter necessitates referral and close follow up.

It is important for all patients including young mothers who are often taken for granted as being healthy to be screened and treated appropriately. We know that hypertension puts these women at risk for the same cardiovascular outcomes as the general population. Postpartum cardiovascular care should include a referral plan that includes the regular monitoring of blood pressures and treatment as needed ongoing.

Levine, L. D., Ky, B., Lewey, J., et al. Prospective evaluation of cardiovascular risk 10 years after a hypertensive disorder of pregnancy. J Am Coll Cardiol. 2022 Jun, 79 (24) 2401–2411

Dr. Gregory Weiss provides perspective on a recent study suggesting women with gestational hypertension were at an increased risk of chronic hypertension later in life. 

HDPs Linked to Worsened Risk of Chronic Hypertension Later in Life

Vaccines for COVID-19 have become a routine part of life all over the world since the end of the first year of the global pandemic. The rapid production and authorization of several vaccines with activity against COVID-19 lead to widespread vaccination across the globe and are largely responsible for dramatic reductions in hospitalization and death as a result of the novel coronavirus. 

Even before the rollout of the first batches of mRNA vaccines and then the more conventional vaccine types, reactions from the general public ranged from enthusiastic hope to frank skepticism and fear.

Despite significant trepidation about the speed with which the COVID-19 vaccines were produced, the first 2 were approved and distributed for use in December of 2020. While phase 3 clinical trials did not reveal any significant adverse events, anecdotal reports began to emerge from European centers that patients were suffering more thromboembolic events following COVID-19 vaccination.

 Jacob Dag Berild, MD, and fellow researchers in Norway, Finland, and Denmark sought to determine the association if any between 3 COVID-19 vaccines and post-vaccination clotting problems.

The 3 vaccines examined in this project included the 2 mRNA vaccines, BnT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), as well as the ChAd0x1nCoV-19 (AZD1222 AstraZeneca) vaccine.

 The authors used national patient registers to identify hospital visits and admissions secondary to thromboembolic and thrombocytopenic complications.

Primary outcomes included relative rates of coronary artery disease, coagulation disorders, and cerebrovascular disease while secondary outcomes included coagulation disorders and cerebrovascular disease (intracranial hemorrhage, cerebral thromboembolic events, and cerebral vein thrombosis).

By vaccine type the following results were obtained:

In the month following vaccination 305 events of coronary artery disease, 226 events of coagulation disorders and 231 events of cerebrovascular disease were observed.

 Significant relative risk scores were seen for coagulation disorders including venous thrombosis, thrombocytopenia, and cerebral venous thrombosis.

In the month following vaccination 3359 cases of coronary artery disease, 1674 cases of coagulation disorders, and 3228 cases of cerebrovascular diseases were observed.

 The relative risk for coagulation disorders was 1.12, and for cerebrovascular diseases was 1.09.

 No rate increases were observed for coronary artery disease and only small rate increases were seen for cerebrovascular thrombosis and coagulation disorders; however, these increases were only seen in the oldest birth cohorts.

In the month following vaccination 399 cases of coronary artery disease, 177 cases of coagulation disorders, and 358 cases of cerebrovascular disease were observed.

 Relative risk scores over 1 were observed for all the main outcomes and rate increases were observed for most secondary outcomes with the exception of thrombocytopenia or purpura.

As with the Pfizer vaccine, the vast majority of outcomes occurred in the oldest cohort.

The authors performed post hoc absolute risk analyses and found that while the relative risk for adverse outcomes was significantly increased the absolute risk only amounts to 4.9 events per 100,000 doses of vaccine.1 This is a very important result. While any adverse events should be taken seriously these data mean that the vast majority of individuals receiving COVID-19 vaccination will be protected from hospitalization and death and not experience an adverse event.

In summary, the results Berild and colleagues obtained show that vaccination with AZD1222 (AstraZeneca) was associated with increased rates of hospital contacts for thromboembolic coagulation disorders, especially thrombocytopenia.1 In addition, an increased risk for cerebrovascular thrombosis was seen after vaccination with AZD1222 and was consistent and robust across all 3 countries studied.1 The authors also observed statistically significant increases in the risk of hospital contacts for thrombocytopenic and thromboembolic events after BNT162b2 and the mRNA-1273 vaccination.

 However, the risk was small compared with those after AZD1222 vaccination. Finally, with the mRNA vaccines, the national estimates varied, with increased risk observed only in the oldest cohorts, with sensitivity analysis checking underlying assumptions of the analyses being inconsistent at best.

A pair of main takeaways can be garnered from these data. The AstraZeneca AZD122 COVID-19 vaccine increases the risk for thromboembolic events while the 2 mRNA vaccines studied only do so to a much smaller extent and with less consistency. With continued doubt from the general public these results should show skeptics that the benefits sharply outweigh the risk. More research is needed to define the risk with mRNA vaccines. This study serves as a good foundation for further investigation while reassuring clinicians that we should continue to recommend full COVID-19 vaccination, especially for high-risk individuals.

Berild, J. D., Larsen, V. B., Hviid, A. et al. Analysis of Thromboembolic and Thrombocytopenic Events After the AZD1222, BNT162b2, and MRNA-1273 COVID-19 Vaccines in 3 Nordic Countries. 

. 2022;5(6):e2217375. doi:10.1001/jamanetworkopen.2022.17375

Dr. Gregory Weiss provides perspective on a recent study detailing the risks of thrombosis observed with different COVID-19 vaccines among patients from a group of countries in Europe. 

Studies Detail Thrombosis Risks Associated with Different COVID-19 Vaccines

It has long been known that thyroid hormone levels are linked to cardiovascular (CV) regulation and that hyper- and hypo-thyroid states are detrimental to CV health. What is less clearly understood is how the intensity of thyroid hormone therapy affects CV risk and mortality. 

The authors of this study sought to evaluate the association between thyroid replacement intensity and cardiovascular mortality by examining a large pool of data from the Veterans Health Administration database.

Josh Evron, MD, and colleagues looked at 705,307 adults who received thyroid replacement therapy.

 They found that 10.8% of those patients died of cardiovascular causes.

 Thyrotropin and Free T4 levels were gathered for all patients in the study to determine if therapy led to exogenous hypo-, euthyroid, or hyper-thyroid conditions. The authors used regression modeling to produce survival analyses with cardiovascular mortality from myocardial infarction, heart failure, or stroke representing the primary outcomes studied.

The results clearly showed that patients with exogenous hyperthyroidism (thyrotropin levels <0.1 mIU/L) and those with exogenous hypothyroidism (thyrotropin levels >-20mIU/L) had increased risk of cardiovascular mortality when compared to patients who remained euthyroid.

 The association between exogenous hypo- and hyper-thyroid states and mortality increase with higher or lower thyrotropin levels in the hypo- and hyper-thyroid ranges.

This study provides a unique perspective looking at cardiovascular risk based on a very common treatment, thyroid replacement therapy. When prescribing a replacement therapy, the goal of treatment is to achieve a normal level in vivo of whatever hormone you are replacing. This is not as easy as it seems.

Arriving at the appropriate dose takes time and requires frequent measurements of thyrotropin and free thyroxine levels. Even during stable therapy patient factors may change the response, absorption, and metabolism of thyroid hormone. Thus, the intensity of treatment the authors are talking about is a constantly moving target.

The results of this study highlight the importance of regular testing and a willingness among clinicians to put in the work. The authors found that allowing thyroid replacement therapy to fall short or overshoot has real consequences in the form of increased cardiovascular mortality.

This means lives are at stake. This is the essence of a modifiable risk factor. Only, in this case, the modification is not a behavior the patient exhibits but one the clinician is responsible for. The authors state that variability in free T4 levels and thyroid hormone dosage adjustment are inevitable and thus agree with my assertion that regular monitoring and small targeted adjustments are essential parts of not only good thyroid care but also cardiovascular risk mitigation.

These results and conclusions are underscored by the fact that cardiovascular disease is the leading cause of death in the United States. Even though this was an observational study, the results are robust.

An important feature of these results was the linear relationship up and down between the extent of hypo- or hyperthyroid intensity and CV risk. This gives clinicians some room to work while at the same time placing guard rails and warning signs on the limits of acceptability where over and undertreating are concerned.

More work is needed. While the authors have identified an area where we as clinicians can improve, they have also brought up a few new questions. It needs to be determined if there are sex differences in this effect. Further, the degree to which comorbidities were managed was not examined in this study. It is clear however, that tighter observation, monitoring, and intervention are in order with regards to thyroid replacement therapy.

Centers for Disease Control and Prevention. Heart disease. Accessed July 29, 2021. 

https://www.cdc.gov/nchs/fastats/heart-disease.html

Benjamin EJ, Muntner P, Alonso A, et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56-e528. doi:10.1161/CIR.0000000000000659

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2792219

Dr. Gregory Weiss breaks down a recent JAMA study that provides estimates of the impact over- and under-treatment with thyroid hormone treatment on cardiovascular disease risk in a cohort of US Veterans.

Too Much or Too Little of a Good Thing: Thyroid Treatment and Cardiovascular Risk

ACC Guidance on Cardiovascular Consequences of COVID-19

The impact of the novel coronavirus (COVID-19) pandemic on the world has been unprecedented in modern times. While respiratory involvement is the characteristic presentation of infection with COVID-19, it has become increasingly apparent that cardiovascular complications are common as well. A diverse list of cardiovascular testing anomalies and complications have been reported and range from biomarker elevations and echocardiographic abnormalities to myocardial injury, thrombosis, and arrhythmias.

It also appears that long COVID-19 cardiovascular symptoms and laboratory findings may persist following acute illness and may include chest pain, shortness of breath, fatigue, palpitations and diagnostic results indicating myocardial injury in both symptomatic and asymptomatic COVID-19 patients.

 In light of these facts the American College of Cardiology (ACC) thought it prudent to issue guidance with regards to three specific areas of post COVID-19 cardiovascular care: Myocarditis and other Myocardial Involvement, Post-acute Sequelae of SARS-CoV-2 Infection, and Return to Play (exercise) for athletes after COVID-19.

Myocarditis is a term used to describe nonspecific inflammation of the heart muscle. It is often accompanied by symptoms such as chest pain, shortness of breath, and the feeling of palpitations. Clinically, patients with myocarditis may have variable presentations so the ACC workgroup chose to separate myocarditis into three diagnostic categories:

Possible myocarditis: Patients who are symptomatic with elevated troponin values and abnormal electrocardiographic and or echocardiographic findings but without positive cardiac biopsy.

Probable myocarditis: Features of possible myocarditis with follow-up biopsy within six months consistent with previous myocarditis.

Definite myocarditis: Features of possible myocarditis but with positive biopsy or cardiac resonance imagery.

Data suggests that men are at higher risk for COVID-19 related myocarditis. The workgroup recommends that patients with mild to moderate or deteriorating symptoms be hospitalized for close monitoring, follow-up testing, and treatment. Those with severe disease should be hospitalized at facilities with advanced heart failure programs and mechanical circulatory support availability.

While recognized, the development of myocarditis after a second mRNA COVID vaccine is rare. The ACC recommends that, unless contraindicated, anyone eligible for a COVID-19 mRNA vaccine should get one.

The mainstays of treatment for clinically significant myocarditis remain supportive. Beta-blocking drugs and angiotensin inhibiting medications may be used in less severe disease without significantly diminished heart function. Corticosteroids may be employed when confirmed inflammation is present. Patients in cardiogenic shock may benefit from extracorporeal membrane oxygenation (ECMO) support until the inflammation recedes. Cardiac MRI should be performed to evaluate long term damage after improvement.

Long COVID is defined by a constellation of new, returning, or persistent health problems lasting four or more weeks after COVID-19 infection.

 This condition appears to affect as many as 10-30% of infected individuals and is characterized by fatigue, tachycardia, and exercise intolerance. The ACC workgroup suggest that these patients should undergo evaluation from a cardiovascular standpoint with additional evaluation if a specific condition such as myocarditis is suspected. Management should be targeted to specific symptoms. A “downward spiral” has been recognized whereby patients who suffer from fatigue exercise less and spend more time in bed leading to a worsening of symptoms. The workgroup suggests that low level exercise be encouraged with non-upright or recumbent exercise being used to avoid worsening fatigue. Beta blocking medications may be employed for tachycardia and nonsteroidal anti-inflammatory drugs sparingly for chest pain without evidence of ischemia.

The workgroup has issued guidelines for the return to competitive sports and intense exercise training. The group recommends that athletes recovering from COVID-19 with ongoing cardiopulmonary symptoms or those requiring hospitalization undergo further evaluation with electrocardiogram, troponin assays, and echocardiogram. These athletes should abstain from exercise for three to six months if diagnosed with myocarditis. Cardiac testing is not recommended for asymptomatic athletes. These athletes should abstain from training for three days to ensure that symptoms do not develop. For those with symptoms, they may return to training once symptoms resolve. Repeat cardiac testing and cardiac MRI are not recommended once symptoms have resolved.

In conclusion, the ACC continues to set the benchmarks in cardiovascular care. In this recent consensus statement on the cardiovascular implications following COVID-19 infection, the college addresses post infections myocarditis, long COVID syndrome, and returning to play for athletes infected with COVID-19. While these guidelines will undoubtedly aid clinicians in caring for patients the workgroup co-chair, Ty Gluckman, MD, MHA, warns that the best means to diagnose and treat myocarditis and long COVID continues to evolve.

Gluckman, T. J., Bhave, N. M., Allen, L.A., et al. 2022 ACC Expert consensus decision pathway on cardiovascular sequelae of COVID-19 in adults: myocarditis and other myocardial involvement, post-acute Sequelae of SARS-CoV-2 infection, and return to play: A report of the american college of cardiology solution set oversight committee. J Am Coll Cardiol. Mar 16, 2022. Epublished DOI: 10.1016/j.jacc.2022.02.003

Dr. Gregory Weiss, a cardiovascular anesthesiologist, provides perspective into the American College of Cardiology's recently released guidance related to the long-term consequences of COVID-19, which includes information on myocarditis, return to athletics, and more.