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The initiation of statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains a debated subject, despite decades worth of clinical trial data demonstrating efficacy, effectiveness, and safety. Statin therapy, in addition to blood pressure-lowering drugs and efforts to reduce cigarette smoking, was a key component of the preventive cardiology renaissance that achieved a dramatic reduction in ASCVD-related mortality from the 1950s to 2010. However, deaths attributable to ASCVD have increased by approximately 13% in recent years, which are in part driven by incomplete treatment of risk factor burden starting in youth. Statins are a cornerstone of preventive cardiology practice, not only due to their lipid-lowering properties, but also in part due to their ability to exert pleiotropic effects that promote atherosclerotic plaque stability which reduces the likelihood of atherothrombotic clinical events. While the benefit of statin therapy undoubtedly depends on the presence and degree of atherosclerotic plaque burden, a broader statin allocation strategy on a population-based level should be considered especially in younger communities that are disproportionately affected by ASCVD risk factors. Thus, the era of precision medicine must be balanced with a pragmatic, cost-effective approach that maximizes ASCVD prevention across the life course. Herein, we examine the pros of statin pharmacotherapy in primary prevention while examining over three decades worth of basic science, translational, and clinical research in the setting of clinical practice guidelines.

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.

BACKGROUND The COVID-19 pandemic disrupted healthcare in the United States and raised concerns about certain antihypertensives, and may have impacted both prescribing practices and access to blood pressure (BP) medications. METHODS We assessed trends in BP prescription fills before and during the first year of the COVID-19 pandemic, using cross-sectional data for BP fills and tablets in the IQVIA (IMS Health) National Prescription Audit® database. Drugs filled via retail (92% coverage), mail-order (78% coverage), and long-term care (72% coverage) channels from January 2018 through December 2020 were included. Data were projected nationally and by state. RESULTS Between 2.9 and 3.4 billion BP tablets were dispensed monthly until February 2020, increasing sharply to 3.8 billion in March 2020 and declining to 3.5 billion in April, then increasing at 3-month intervals until December 2020. The number of tablets per fill increased slightly over time, with the largest increase (from 66.7 to 68.6) during February–March, 2020. Tablets were dispensed through retail channels (99.7 billion), mail-order (14.7 billion), and long-term care (5.3 billion). Rates of patients initiating new medications decreased during 2020 compared to prior years. Fills did not vary significantly by drug class. CONCLUSIONS A sharp increase in BP fills occurred with COVID-19 emergence, suggesting patients may have secured medications in preparation for potential access limitations. A decrease in new fills, indicating decreased initiation and/or modification of treatment regimens, suggests need for efforts to re-engage patients in the healthcare system and provide alternative ways to obtain medication refills and adjustments.

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.

Background: Coronary artery calcium (CAC) is commonly quantified as the product of 2 generally correlated measures: plaque area and calcium density. Objectives: The authors sought to determine whether discordance between calcium area and density has long-term prognostic importance in atherosclerotic cardiovascular disease (ASCVD) risk. Methods: The authors studied 10,373 primary prevention participants from the CAC Consortium with CAC >0. Based on their median values, calcium area and mean calcium density were divided into 4 mutually exclusive concordant/discordant groups. Cox proportional hazards regression assessed the association of calcium area/density groups with ASCVD mortality over a median of 11.7 years, adjusting for traditional risk factors and the Agatston CAC score. Results: The mean age was 56.7 years, and 24% were female. The prevalence of plaque discordance was 19% (9% low calcium area/high calcium density, 10% high calcium area/low calcium density). Female sex (odds ratio [OR]: 1.48 [95% CI: 1.27-1.74]) and body mass index (OR: 0.81 [95% CI: 0.76-0.87], per 5 kg/m 2 higher) were significantly associated with high calcium density discordance, whereas diabetes (OR: 2.23 [95% CI: 1.85-3.19]) was most strongly associated with discordantly low calcium density. Compared to those with low calcium area/low calcium density, individuals with low calcium area/high calcium density had a 71% lower risk of ASCVD death (HR: 0.29 [95% CI: 0.09-0.95]). Conclusions: For a given CAC score, high calcium density relative to plaque area confers lower long-term ASCVD risk, likely serving as an imaging marker of biological resilience for lesion vulnerability. Additional research is needed to define a robust definition of calcium area/density discordance for routine clinical risk prediction.

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.

Coronary artery calcium (CAC) is a specific marker of coronary atherosclerosis that can be used to measure calcified subclinical atherosclerotic burden. The Agatston method is the most widely used scoring algorithm for quantifying CAC and is expressed as the product of total calcium area and a quantized peak calcium density weighting factor defined by the calcification attenuation in HU on noncontrast computed tomography. Calcium density has emerged as an important area of inquiry because the Agatston score is upweighted based on the assumption that peak calcium density and atherosclerotic cardiovascular disease (ASCVD) risk are positively correlated. However, recent evidence demonstrates that calcium density is inversely associated with lesion vulnerability and ASCVD risk in population-based cohorts when accounting for age and plaque area. Here, we review calcium density by focusing on 3 main areas: 1) CAC scan acquisition parameters; 2) pathophysiology of calcified plaques; and 3) epidemiologic evidence relating calcium density to ASCVD outcomes. Through this process, we hope to provide further insight into the evolution of CAC scoring on noncontrast computed tomography.

OBJECTIVES: Sudden cardiac death (SCD) is a common initial manifestation of coronary heart disease (CHD); however, SCD risk prediction remains elusive.BACKGROUND: Coronary artery calcium (CAC) is a marker of plaque burden. Whether CAC improves risk stratification for incident SCD beyond atherosclerotic cardiovascular disease (ASCVD) risk factors is unknown.METHODS: We 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.RESULTS: The mean age was 54.4 years, 33% were women, 11% were of non-White ethnicity, and 55% had CAC >0. 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 CAC >0. 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 CAC >1,000 (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 20% (ΔC-statistic = +0.01; P = 0.54).CONCLUSIONS: 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.

BackgroundApolipoprotein A1 (ApoA1) is the principal protein component of high-density lipoprotein (HDL). Although low HDL cholesterol (HDL-C) levels are known to be associated with greater cardiovascular risk, recent studies have also shown heightened mortality risk at very high HDL-C levels.AimsTo investigate the sex-specific association between elevated ApoA1 levels and adverse outcomes, and their genetic basis.MethodsA prospective cohort study of United Kingdom Biobank participants without coronary artery disease at enrollment was performed. The primary exposure was serum ApoA1 levels. The primary and secondary outcome measures were cardiovascular and all-cause death, respectively.ResultsIn 402 783 participants followed for a median of 12.1 years, there was a U-shaped relationship between ApoA1 levels and both cardiovascular as well as all-cause mortality, after adjustment for traditional cardiovascular risk factors. Individuals in the highest decile of ApoA1 levels (1.91–2.50 g/L) demonstrated higher cardiovascular (HR 1.21, 95% CI 1.07–1.37, P < 0.0022) and all-cause mortality (HR 1.14, 95% CI 1.07–1.21, P < 0.0001) compared with those within the lowest risk eighth decile (1.67–1.75 g/L). The U-shaped relationship was present in both sexes, though more pronounced in men. Sensitivity analyses showed that cardiovascular mortality rates were higher in those with greater alcohol intake (P < 0.004). Adjustment for polygenic variation associated with higher ApoA1 levels did not attenuate the effect of very high ApoA1 levels on mortality. In the sub-group with very elevated HDL-C levels (> 80 mg/dL in men, > 100 mg/dL in women), there was no association between ApoA1 levels and mortality.ConclusionBoth very low and very elevated ApoA1 levels are associated with higher cardiovascular and all-cause mortality.

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.

Individuals with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are considered high-risk and current guidelines recommend initiating high-intensity statin therapy in this group. We sought to examine the predictive ability of zero CAC in this high-risk group.Multi-Ethnic Study of Atherosclerosis participants without clinical cardiovascular disease and baseline LDL-C ≥190 mg/dL were identified. Cardiovascular risk factors were compared between those with CAC = 0 and CAC0. Multivariable Poisson regression was used to identify predictors of CAC = 0. Association of CAC = 0 with incident cardiovascular events over a median follow-up of 13.2 years was examined using multivariable-adjusted Cox regression.246 individuals (mean age = 63 ± 9.4 years; 42% male; 31% white; 37% CAC = 0) with LDL-C ≥190 mg/dL were identified (mean LDL-C = 215 ± 27 mg/dL). Age65 years (RR = 2.17, 95%CI = 1.49-3.23), female sex (RR = 2.10, 95%CI = 1.42-3.10), and no diabetes (RR = 2.22, 95%CI = 1.18-4.17) were associated with CAC = 0. Individuals with CAC = 0 had a lower risk for future cardiovascular events (incidence rate per 1000 person-years = 4.7; 10-year risk = 3.7%; risk/year = 0.4%) than those with CAC0 (incidence rate per 1000 person-years = 26.4; 10-year risk = 20%; risk/year = 2.0%), adjusted HR 0.25 (95%CI = 0.10-0.66).Among persons with LDL-C ≥190 mg/dL, younger age, female sex, and the absence of diabetes were associated with CAC = 0. CAC = 0 was associated with a low risk of cardiovascular events, suggesting the utility of CAC assessment for stratifying risk in this high-risk group.

Aspirin use in the prevention of cardiovascular events has been a mainstay of treatment for decades. However, the use of aspirin in primary prevention of atherosclerotic cardiovascular disease has recently come under scrutiny. Several recent studies have evaluated the use of aspirin in primary prevention and the results suggest that in many patients the risks may outweigh the benefits. Closer examination of these trials suggests that the use of aspirin therapy for primary prevention may have a role but likely needs a more tailored approach and that caution is needed in prescribing aspirin for primary prevention. In conclusion, in this article we review the evolving evidence for aspirin in the primary prevention of atherosclerotic cardiovascular disease.

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