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Abstract: Even before its role in platelet inhibition was fully characterized in the 1980s, aspirin had been incorporated into the cardiovascular disease care algorithm. Early trials examining its use in unstable angina and acute myocardial infarction revealed evidence of its protective role in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Large trials assessing use in the primary prevention setting and optimal dosing regimens were studied in the late 1990s and early 2000s. As a cornerstone of cardiovascular care, aspirin was incorporated into primary and secondary ASCVD prevention guidelines in the United States and mechanical heart valve guidelines. However, in recent years, with significant advances in medical and interventional ASCVD therapies, scrutiny has been placed on the bleeding profile of aspirin, and guidelines have adapted to new evidence. Updates in primary prevention guidelines reserve aspirin only for patients at higher ASCVD risk and low bleeding risk – though questions remain in ASCVD risk assessment as risk-enhancing factors have proven difficult to incorporate on a population level. New thoughts regarding aspirin use in secondary prevention – especially with the concomitant use of anticoagulants - have altered recommendations as additional data accrued. Finally, a recommendation for aspirin and vitamin K antagonists with mechanical heart valves has been modified. Despite aspirin losing a foothold in cardiovascular care, new evidence has strengthened claims for its use in women at high risk for preeclampsia.

Review of the US and European literature indicates that most patients at high risk for atherosclerotic cardiovascular disease (ASCVD are not treated with high-intensity statins, despite strong clinical-trial evidence of maximal statin benefit. High-intensity statins are recommended for 2 categories of patients: those with ASCVD (secondary prevention) and high-risk patients without clinical ASCVD. Most patients with ASCVD are candidates for high-intensity statins, with a goal for low-density lipoprotein cholesterol reduction of 50% or greater. A subgroup of patients with ASCVD are at very high risk and can benefit by the addition of nonstatin drugs (ezetimibe with or without bile acid sequestrant or bempedoic acid and/or a proprotein convertase subtilisin/kexin type 9 inhibitor). High-risk primary prevention patients are those with severe hypercholesterolemia, diabetes with associated risk factors, and patients aged 40 to 75 years with a 10-year risk for ASCVD of 20% or greater. In patients with a 10-year risk of 7.5% to less than 20%, coronary artery calcium scoring is an option; if the coronary artery calcium score is 300 or more Agatston units, the patient can be up-classified to high risk. If high-intensity statin treatment is not tolerated in high-risk patients, a reasonable approach is to combine a moderate-intensity statin with ezetimibe. In very high-risk patients, proprotein convertase subtilisin/kexin type 9 inhibitors lower low-density lipoprotein cholesterol levels substantially and hence reduce risk as well.

Background: The impact of the COVID-19 pandemic on participation in and availability of cardiac rehabilitation (CR) is unknown. Methods: Among eligible Medicare fee-for-service beneficiaries, we evaluated, by month, the number of CR sessions attended per 100 000 beneficiaries, individuals eligible to initiate CR, and centers offering in-person CR between January 2019 and December 2021. We compared these outcomes between 2 periods: December 1, 2019 through February 28, 2020 (period 1, before declaration of the pandemic-related national emergency) and October 1, 2021 through December 31, 2021 (period 2, the latest period for which data are currently available). Results: In period 1, Medicare beneficiaries participated in (mean±SD) 895±84 CR sessions per 100 000 beneficiaries each month. After the national emergency was declared, CR participation sharply declined to 56 CR sessions per 100 000 beneficiaries in April 2020. CR participation recovered gradually through December 2021 but remained lower than prepandemic levels (period 2: 698±29 CR sessions per month per 100 000 beneficiaries, P =0.02). Declines in CR participation were most marked among dual Medicare and Medicaid enrollees and patients residing in rural areas or socially vulnerable communities. There was no statistically significant change in CR eligibility between the 2 periods. Compared with 2618±5 CR centers in period 1, there were 2464±7 in period 2 ( P Conclusions: The COVID-19 pandemic was associated with a persistent decline in CR participation and the closure of CR centers, which disproportionately affected rural and low-income patients and the most socially vulnerable communities. Innovation in CR financing and delivery is urgently needed to equitably enhance CR participation among Medicare beneficiaries.

Purpose This review describes the considerations for the design and implementation of a hybrid cardiac rehabilitation (HYCR) program, a patient-individualized combination of facility-based cardiac rehabilitation (FBCR) with virtual cardiac rehabilitation (CR) and/or remote CR. Review methods To help meet the goal of the Millions Hearts Initiative to increase CR participation to 70% by 2022, a targeted review of the literature was conducted to identify studies pertinent to the practical design and implementation of an HYCR program. Areas focused upon included the current use of HYCR, exercise programming considerations (eligibility and safety, exercise prescription, and patient monitoring), program assessments and outcomes, patient education, step-by-step instructions for billing and insurance reimbursement, patient and provider engagement strategies, and special considerations. Summary A FBCR is the first choice for patient participation in CR, as it is supported by an extensive evidence base demonstrating effectiveness in decreasing cardiac and overall mortality, as well as improving functional capacity and quality of life. However, to attain the CR participation rate goal of 70% set by the Million Hearts Initiative, CR programming will need to be expanded beyond the confines of FBCR. In particular, HYCR programs will be necessary to supplement FBCR and will be particularly useful for the many patients with geographic or work-related barriers to participation in an FBCR program. Research is ongoing and needed to develop optimal programming for HYCR.

Low-density lipoprotein cholesterol (LDL-C) is a proven causative factor for developing atherosclerotic cardiovascular disease. Individuals with genetic conditions associated with lifelong very low LDL-C levels can be healthy. We now possess the pharmacological armamentarium (statins, ezetimibe, PCSK9 inhibitors) to reduce LDL-C to an unprecedented extent. Increasing numbers of patients are expected to achieve very low (

This study updates cardiac rehabilitation (CR) utilization data in a cohort of Medicare beneficiaries hospitalized for CR-eligible events in 2017, including stratification by select patient demographics and state of residence.We identified Medicare fee-for-service beneficiaries who experienced a CR-eligible event and assessed their CR participation (≥1 CR sessions in 365 d), engagement, and completion (≥36 sessions) rates through September 7, 2019. Measures were assessed overall, by beneficiary characteristics and state of residence, and by primary (myocardial infarction; coronary artery bypass surgery; heart valve repair/replacement; percutaneous coronary intervention; or heart/heart-lung transplant) and secondary (angina; heart failure) qualifying event type.In 2017, 412 080 Medicare beneficiaries had a primary CR-eligible event and 28.6% completed ≥1 session of CR within 365 d after discharge from a qualifying event. Among beneficiaries who completed ≥1 CR session, the mean total number of sessions was 25 ± 12 and 27.6% completed ≥36 sessions. Nebraska had the highest enrollment rate (56.1%), with four other states also achieving an enrollment rate50% and 23 states falling below the overall rate for the United States.The absolute enrollment, engagement, and program completion rates remain low among Medicare beneficiaries, indicating that many patients did not benefit or fully benefit from a class I guideline-recommended therapy. Additional research and continued widespread adoption of successful enrollment and engagement initiatives are needed, especially among identified populations.

IMPORTANCE: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. OBJECTIVE: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. EXPOSURES: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). MAIN OUTCOMES AND MEASURES: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. RESULTS: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). CONCLUSIONS AND RELEVANCE: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

Cardiovascular disease remains the leading cause of death in patients with diabetes. Cardiovascular disease in diabetes is multifactorial, and control of the cardiovascular risk factors leads to substantial reductions in cardiovascular events. The 2015 American Heart Association and American Diabetes Association scientific statement, “Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence,” highlighted the importance of modifying various risk factors responsible for cardiovascular disease in diabetes. At the time, there was limited evidence to suggest that glucose-lowering medications reduce the risk of cardiovascular events. At present, several large randomized controlled trials with newer antihyperglycemic agents have been completed, demonstrating cardiovascular safety and reduction in cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and heart failure. This AHA scientific statement update focuses on (1) the evidence and clinical utility of newer antihyperglycemic agents in improving glycemic control and reducing cardiovascular events in diabetes; (2) the impact of blood pressure control on cardiovascular events in diabetes; and (3) the role of newer lipid-lowering therapies in comprehensive cardiovascular risk management in adults with diabetes. This scientific statement addresses the continued importance of lifestyle interventions, pharmacological therapy, and surgical interventions to curb the epidemic of obesity and metabolic syndrome, important precursors of prediabetes, diabetes, and comorbid cardiovascular disease. Last, this scientific statement explores the critical importance of the social determinants of health and health equity in the continuum of care in diabetes and cardiovascular disease.

Ty J. Gluckman, MD, FACC, Chair Niti R. Aggarwal, MD, FACC Nicole M. Bhave, MD, FACC Gregory J. Dehmer, MD, MACC Olivia N. Gilbert, MD, MSc, FACC Chayakrit Krittanawong, MD Dharam J. Kumbhani, MD, SM, FACC Andrea L. Price, CPHQ, RCIS, AACC Javier A. Sala-Mercado, MD, PhD David E.

Million Hearts and partners have been committed to raising national cardiac rehabilitation participation rates to a goal of 70%. Quality improvement tools, resources, and surveillance models have been developed in support. Efforts to enhance research programs and collaborative initiatives have created momentum to accelerate implementation of new care models.

Dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet, have been shown to improve cardiac health. Intermittent fasting is another type of popular dietary pattern that is based on timed periods of fasting. Two different regimens are alternative day fasting and time-restricted eating. Although there are no large, randomized control trials examining the relationship between intermittent fasting and cardiovascular outcomes, current human studies that suggest this diet could reduce the risk for cardiovascular disease with improvement in weight control, hypertension, dyslipidemia, and diabetes. Intermittent fasting may exert its effects through multiple pathways, including reducing oxidative stress, optimization of circadian rhythms, and ketogenesis. This review evaluates current literature regarding the potential cardiovascular benefits of intermittent fasting and proposes directions for future research.

Although significant progress has been made to reduce the global burden of cardiovascular disease, efforts have focused primarily on treatment of manifest disease rather than on prevention of events. An enormous opportunity exists to transition focus from intervention to providing equal attention to prevention of cardiovascular disease. The nascent specialty of "preventive cardiology" is emerging from the background of long-established services such as lipid, diabetes, hypertension, and general cardiology clinics. It is incumbent on the cardiology community to invest in cardiovascular prevention because past gains are threatened with the rising tide of obesity and diabetes. Now is the time to establish a dedicated preventive cardiology subspecialty to train the clinicians of the future. This American College of Cardiology Council Perspective aims to define the need for preventive cardiology as a unique subspecialty, broaches controversies, provides a structure for future training and education, and identifies possible paths forward to professional certification.

The decline in cardiovascular (CV) mortality over the last 50 years can be largely attributed to advances in preventive care [(1)][1]. Despite these improvements, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide [(1)][1]. Recent advances in

Recent reviews have emphasized the need for a health equity agenda in genomics research. To ensure that genomic discoveries can lead to improved health outcomes for all segments of the population, a health equity agenda needs to go beyond research studies. Advances in genomics and precision medicine have led to an increasing number of evidence-based applications that can reduce morbidity and mortality for millions of people (tier 1). Studies have shown lower implementation rates for selected diseases with tier 1 applications (familial hypercholesterolemia, Lynch syndrome, hereditary breast and ovarian cancer) among racial and ethnic minority groups, rural communities, uninsured or underinsured people, and those with lower education and income. We make the case that a public health agenda is needed to address disparities in implementation of genomics and precision medicine. Public health actions can be centered on population-specific needs and outcomes assessment, policy and evidence development, and assurance of delivery of effective and ethical interventions. Crucial public health activities also include engaging communities, building coalitions, improving genetic health literacy, and building a diverse workforce. Without concerted public health action, further advances in genomics with potentially broad applications could lead to further widening of health disparities in the next decade.

Hypertension treatment and control prevent more cardiovascular events than management of other modifiable risk factors. Although the age-adjusted proportion of US adults with controlled blood pressure (BP) defined as

Coronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident sudden cardiac death (SCD) beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown.SCD is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive.The authors studied 66,636 primary prevention patients from the CAC Consortium. Multivariable competing risks regression and C-statistics were used to assess the association between CAC and SCD, adjusting for demographics and traditional risk factors.The mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC0. A total of 211 SCD events (0.3%) were observed during a median follow-up of 10.6 years, 91% occurring among those with baseline CAC0. Compared with CAC = 0, there was a stepwise higher risk (P trend 0.001) in SCD for CAC 100 to 399 (subdistribution hazard ratio [SHR]: 2.8; 95% CI: 1.6-5.0), CAC 400 to 999 (SHR: 4.0; 95% CI: 2.2-7.3), and CAC1,000 (SHR: 4.9; 95% CI: 2.6-9.9). CAC provided incremental improvements in the C-statistic for the prediction of SCD among individuals with a 10-year risk 7.5% (ΔC-statistic = +0.046; P = 0.02) and 7.5% to 20% (ΔC-statistic = +0.069; P = 0.003), which were larger when compared with persons with a 10-year risk20% (ΔC-statistic = +0.01; P = 0.54).Higher CAC burden strongly associates with incident SCD beyond traditional risk factors, particularly among primary prevention patients with low-intermediate risk. SCD risk stratification can be useful in the early stages of CHD through the measurement of CAC, identifying patients most likely to benefit from further downstream testing.

This article describes the October 2020 proceedings of the Million Hearts Cardiac Rehabilitation Think Tank: Accelerating New Care Models, convened with representatives from professional organizations, cardiac rehabilitation (CR) programs, academic institutions, federal agencies, payers, and patient representative groups. As CR delivery evolves, terminology is evolving to reflect not where activities occur (eg, center, home) but how CR is delivered: in-person synchronous, synchronous with real-time audiovisual communication (virtual), or asynchronous (remote). Patients and CR staff may interact through ≥1 delivery modes. Though new models may change how CR is delivered and who can access CR, new models should not change what is delivered—a multidisciplinary program addressing CR core components. During the coronavirus disease 2019 (COVID-19) public health emergency, Medicare issued waivers to allow virtual CR; it is unclear whether these waivers will become permanent policy post-public health emergency. Given CR underuse and disparities in delivery, new models must equitably address patient and health system contributors to disparities. Strategies for implementing new CR care models address safety, exercise prescription, monitoring, and education. The available evidence supports the efficacy and safety of new CR care models. Still, additional research should study diverse populations, impact on patient-centered outcomes, effect on long-term outcomes and health care utilization, and implementation in diverse settings. CR is evolving to include in-person synchronous, virtual, and remote modes of delivery; there is significant enthusiasm for implementing new care models and learning how new care models can broaden access to CR, improve patient outcomes, and address health inequities.

Supplemental Digital Content is available in the text., Objective: The underlying pathobiology of the paradoxical relationship between obesity and adverse outcomes in coronary artery disease (CAD) is unclear. Our objective was to determine the association between obesity and circulating progenitor cell (CPC) counts—a measure of intrinsic regenerative capacity—in asymptomatic individuals and patients with CAD and its impact on the obesity paradox. Approach and Results: CPCs were enumerated by flow cytometry as CD45med+ cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 years of age; 28% obese) and 1277 patients with CAD (66 years of age; 39% obese). The association between obesity and CPCs was analyzed using linear regression models. The association of obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-year follow-up in patients with CAD was studied using Cox models. Obesity was independently associated with 16% to 34% higher CPC counts (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated by systemic inflammation, insulin resistance, or secretion but partly attenuated by cardiorespiratory fitness and body composition. In patients with CAD, obesity was associated with 8% to 12% higher CPC counts and 30% lower risk of adverse outcomes. Compared with nonobese patients, only obese patients with high CPC counts (CD34+ cells ≥median, 1806 cells/mL) were at a lower risk (hazard ratio, 0.52 [95% CI, 0.31–0.88]), whereas those with low counts (

Background: Absence of coronary artery calcium (CAC) identifies asymptomatic individuals at low cardiovascular disease risk. Carotid artery plaque is a marker of increased risk, but its association with cardiovascular risk and incident CAC in people without CAC is unclear. Methods: Multi-Ethnic Study of Atherosclerosis participants with CAC score of 0 at enrollment who also underwent carotid plaque measurement using B-mode ultrasonography were prospectively followed for incident coronary heart disease, stroke, and cardiovascular disease events, and CAC (score >0 on up to 3 serial computed tomography scans). The association of carotid plaque presence and plaque score (Ln[score+1]) at baseline with cardiovascular events and incident CAC was evaluated with Cox proportional hazards regression models adjusted for demographics, risk factors, and statin use. Results: Among these 2673 participants (58 years, 64% women, 34% White, 30% Black, 24% Hispanic, and 12% Chinese), carotid plaque at baseline was observed in 973 (36%) and the median plaque score (range, 1–12) among those with plaque was 1. A total of 79 coronary heart disease, 80 stroke, and 151 cardiovascular disease events were observed during 16.1 years of follow-up. Carotid plaque presence and plaque score were independently associated with coronary heart disease risk (HRs, 1.66 [95% CI, 1.04–2.66]; and 1.48 [95% CI, 1.01–2.17], respectively) but not with stroke and cardiovascular disease risk. A total of 973 (36.4%) participants developed CAC over the evaluation period (median 9.3 years). Carotid plaque presence and plaque score were independently associated with incident CAC (HRs, 1.34 [95% CI, 1.18–1.54]; and 1.37 [95% CI, 1.21–1.54]), respectively. Conclusions: The presence and extent of carotid plaque are associated with long-term coronary heart disease risk and incident CAC among middle-aged asymptomatic individuals with an initial CAC score of 0.

The measurement of high-density lipoprotein cholesterol is highly utilized by clinicians to help predict cardiovascular risk, but this measure is not causally associated with atherosclerotic cardiovascular disease events. The use of Mendelian randomization studies has led to a change in investigative attention from the high-density lipoprotein cholesterol concentration to its physiological functions. High-density lipoprotein plays key roles in important pathways related to the development of atherosclerotic disease including reverse cholesterol transport, oxidation and inflammation, and endothelial function as well as in other physiological systems including immune system modulation, cellular apoptosis, and endothelial progenitor cell homeostasis. The identification of dysfunctional high-density lipoprotein may better predict future cardiovascular events compared to numerical high-density lipoprotein cholesterol and aid in enhanced clinical risk stratification. The emergence of discrete physiological measurements of high-density lipoprotein, such as cholesterol efflux capacity and the high-density lipoprotein inflammatory index, may provide an opportunity for clinical application in the future. However, the validity of these measurements and their commercial availability remain barriers to a realistic transition to clinical medicine.

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are both manifestations of end-organ damage of the metabolic syndrome. Through multiple pathophysiological mechanisms, CVD and NAFLD are associated with each other. Systemic inflammation, endothelial dysfunction, hepatic insulin resistance, oxidative stress, and altered lipid metabolism are some of the mechanisms by which NAFLD increases the risk of CVD. Patients with NAFLD develop increased atherosclerosis, cardiomyopathy, and arrhythmia, which clinically result in cardiovascular morbidity and mortality. Defining the mechanisms linking these 2 diseases offers the opportunity to further develop targeted therapies. The aim of this comprehensive review is to examine the association between CVD and NAFLD and discuss the overlapping management approaches.

Despite historical evidence suggesting an inverse association between HDL cholesterol (HDL-C) and adverse cardiovascular events, pharmacological efforts to increase HDL-C and improve outcomes have not been successful. Recently, a U-shaped association between HDL-C and adverse events has been demonstrated in several population cohorts, further complicating our understanding of the clinical significance of HDL. Potential explanations for this finding include genetic mutations linked to very high HDL-C, impaired HDL function at high HDL-C levels, and residual confounding. However, our understanding of this association remains premature and needs further investigation.

James L. Januzzi, Jr, MD, FACC, Chair Tariq Ahmad, MD, MPH, FACC Brendan Everett, MD, FACC William Hucker, MD, PHD Dharam J. Kumbhani, MD, SM, FACC Joseph E. Marine, MD, FACC Pamela B. Morris, MD, FACC Robert N. Piana, MD, FACC Sunil V. Rao, MD, FACC Marielle Scherrer-Crosbie, MD, PhD

Atherosclerotic cardiovascular disease (ASCVD) and its associated economic burden are increasing globally. Although cardiac rehabilitation is a vital component of secondary prevention with proven benefits, it is underutilized due to numerous barriers, especially in resource-limited settings. New care models for delivery of comprehensive prevention programs such as community-based, home-based, and "hybrid" models implementing m-health, e-health, and telemedicine need to be adopted. Such new care models should be offered to all patients with established ASCVD (coronary, cerebral, and peripheral) and additionally to those at high risk of developing ASCVD with multiple risk factors for panvascular prevention.