Development and Validation of the American Heart Association's PREVENT Equations.

BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD. METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets. RESULTS: Among 6 612 004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; P=0.01). CONCLUSIONS: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables.

Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association.

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

Cardiac Arrest During Delivery Hospitalization : A Cohort Study.

BACKGROUND: Estimates of cardiac arrest occurring during delivery guide evidence-based strategies to reduce pregnancy-related death. OBJECTIVE: To investigate rate of, maternal characteristics associated with, and survival after cardiac arrest during delivery hospitalization. DESIGN: Retrospective cohort study. SETTING: U.S. acute care hospitals, 2017 to 2019. PARTICIPANTS: Delivery hospitalizations among women aged 12 to 55 years included in the National Inpatient Sample database. MEASUREMENTS: Delivery hospitalizations, cardiac arrest, underlying medical conditions, obstetric outcomes, and severe maternal complications were identified using codes from the International Classification of Diseases, 10th Revision, Clinical Modification. Survival to hospital discharge was based on discharge disposition. RESULTS: Among 10 921 784 U.S. delivery hospitalizations, the cardiac arrest rate was 13.4 per 100 000. Of the 1465 patients who had cardiac arrest, 68.6% (95% CI, 63.2% to 74.0%) survived to hospital discharge. Cardiac arrest was more common among patients who were older, were non-Hispanic Black, had Medicare or Medicaid, or had underlying medical conditions. Acute respiratory distress syndrome was the most common co-occurring diagnosis (56.0% [CI, 50.2% to 61.7%]). Among co-occurring procedures or interventions examined, mechanical ventilation was the most common (53.2% [CI, 47.5% to 59.0%]). The rate of survival to hospital discharge after cardiac arrest was lower with co-occurring disseminated intravascular coagulation (DIC) without or with transfusion (50.0% [CI, 35.8% to 64.2%] or 54.3% [CI, 39.2% to 69.5%], respectively). LIMITATIONS: Cardiac arrests occurring outside delivery hospitalizations were not included. The temporality of arrest relative to the delivery or other maternal complications is unknown. Data do not distinguish cause of cardiac arrest, such as pregnancy-related complications or other underlying causes among pregnant women. CONCLUSION: Cardiac arrest was observed in approximately 1 in 9000 delivery hospitalizations, among which nearly 7 in 10 women survived to hospital discharge. Survival was lowest during hospitalizations with co-occurring DIC. PRIMARY FUNDING SOURCE: None.

Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association.

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.

Contemporary use of cardiovascular risk reduction strategies in type 2 diabetes. Insights from the diabetes collaborative registry.

BACKGROUND: Cardiovascular disease remains the primary source of morbidity and mortality in type 2 diabetes (T2D). We characterized the change over time in the use of evidence-based therapies to reduce cardiovascular risk in US patients with T2D. METHODS: Data from a longitudinal outpatient diabetes registry were used to calculate the prescription of SGLT2i or GLP-1RA over time and among those with high-risk comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], chronic kidney disease [CKD]) and a diabetes cardiovascular composite score (DCCS; calculated as: #eligible medications prescribed/#eligible medications x 100 for SGLT2i, GLP-1RA, statin, antiplatelet/anticoagulant therapy, ACEi/ARB/ARNI). Scores ranged from 0% to 100% (higher=more optimal care). RESULTS: Among 1,001,542 outpatients from 391 US sites, 51.7% patients had ASVCD, 17.7% HF, and 23.0% CKD. The percentage of patients prescribed an SGLT2i or GLP-1RA increased over time (7.3% in 2013 to 28.8% in 2019), and 18.3% of patients with ASCVD, HF, or CKD were on at least one of these medications at last follow-up vs 25.5% of patients without any of these comorbidities. Mean DCCS was 54±36%; 54±25% in patients with ASCVD, HF, or CKD vs 52±50% in patients without any of these comorbidities (P<0.001 for both). In a hierarchical linear model, male sex, and a diagnosis of CKD were independently associated with higher DCCS whereas a diagnosis of HF or ASCVD was associated with a lower DCCS. CONCLUSIONS: In a large, contemporary cohort of patients with T2D, we found improvement in the use of SGLT2i and GLP-1RA but unexpectedly lower use in patients with ASCVD, heart failure, and CKD, highlighting a treatment-risk paradox. Further education is needed to shift the understanding of these medications as tools for glucose-lowering to cardiovascular risk reduction and to improve their implementation in clinical practice.

Coronary artery calcium and sudden cardiac death: current evidence and future directions.

PURPOSE OF REVIEW: To provide a summary of the current evidence and highlight future directions regarding coronary artery calcium (CAC) and risk of sudden cardiac death (SCD). RECENT FINDINGS: Although up to 80% of all SCD is attributed to coronary heart disease (CHD), the subclinical atherosclerosis markers that help to improve SCD risk prediction are largely unknown. Recent observational data have demonstrated that, after adjustment for traditional risk factors, there is a stepwise higher risk for SCD across increasing CAC burden such that asymptomatic patients without overt atherosclerotic cardiovascular disease (ASCVD) experience a three-fold to five-fold higher SCD risk beginning at CAC at least 100 when compared with CAC = 0. Although the mechanisms underlying increasing CAC and SCD risk have yet to be fully elucidated, risk for myocardial infarction and scar, and/or exercise-induced ischemia may be potential mediators. SUMMARY: High CAC burden is an important risk factor for SCD in asymptomatic middle-aged adults, suggesting that SCD risk stratification can begin in the early stages of CHD via measurement of calcific plaque on noncontrast computed tomography. Despite the clinical inertia for downstream functional cardiac testing after detecting high CAC, comprehensive ASCVD prevention strategies should be the primary focus for SCD risk reduction.

Demographic and regional trends of peripheral artery disease-related mortality in the United States, 2000 to 2019.

INTRODUCTION: Peripheral artery disease (PAD) is a common progressive atherosclerotic disease associated with significant morbidity and mortality in the US; however, data regarding PAD-related mortality trends are limited. This study aims to characterize contemporary trends in mortality across sociodemographic and regional groups. METHODS: The Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) was queried for data regarding PAD-related deaths from 2000 to 2019 in the overall sample and different demographic (age, sex, race/ethnicity) and regional (state, urban-rural) subgroups. Crude and age-adjusted mortality rates (CMR and AAMR, respectively) per 100,000 people were calculated. Associated annual percentage changes (APC) were computed using Joinpoint Regression Program Version 4.9.0.0 trend analysis software. RESULTS: Between 2000 and 2019, a total of 1,959,050 PAD-related deaths occurred in the study population. Overall, AAMR decreased from 72.8 per 100,000 in 2000 to 32.35 per 100,000 in 2019 with initially decreasing APCs followed by no significant decline from 2016 to 2019. Most demographic and regional subgroups showed initial declines in AAMRs during the study period, with many groups exhibiting no change in mortality in recent years. However, men, non-Hispanic (NH) Black or African American individuals, people aged ⩾ 85 years, and rural counties were associated with the highest AAMRs of their respective subgroups. Notably, there was an increase in crude mortality rate among individuals 25-39 years of age from 2009 to 2019. CONCLUSION: Despite initial improvement, PAD-related mortality has remained stagnant in recent years. Disparities have persisted across several demographic and regional groups, requiring further investigation.

With Current Safety and Efficacy Data, Should Statins Be Made Available as Nonprescription Over-the-Counter Drugs?

PURPOSE OF REVIEW: Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the liver and reduce atherosclerotic cardiovascular disease (ASCVD) risk by enhancing low-density lipoprotein (LDL) clearance from the circulation. In this review, we discuss their efficacy, safety, and real-world utilization to make a case for reclassifying statins as nonprescription over-the-counter drugs to improve access and availability with the overarching goal of increasing statin utilization in patients most likely to benefit from this class of therapy. RECENT FINDINGS: Statin efficacy for reducing risk in primary and secondary ASCVD prevention populations as well as their safety and tolerability has been thoroughly investigated in large-scale clinical trials over the past 3 decades. Despite the overwhelming scientific evidence, statins are underutilized even among those at the highest ASCVD risk. We propose a nuanced approach to use statins as nonprescription drugs that leverages a multi-disciplinary clinical model. It integrates lessons learned from experiences outside the USA with a proposed Food and Drug Administration rule change that allows nonprescription drug products with an additional condition for nonprescription use.

High-Density Lipoprotein Cholesterol in Atherosclerotic Cardiovascular Disease Risk Assessment: Exploring and Explaining the "U"-Shaped Curve.

PURPOSE OF REVIEW: Review updates for the association of HDL-cholesterol with atherosclerotic cardiovascular disease (ASCVD) and discuss the approach to incorporating HDL-cholesterol within risk assessment. RECENT FINDINGS: There is a U-shaped relationship between HDL-cholesterol and ASCVD. Both low HDL-cholesterol (< 40 mg/dL in men, < 50 mg/dL in women) and very-high HDL-cholesterol (≥ 80 mg/dL in men) are associated with a higher risk of all-cause and ASCVD mortality, independent from traditional risk factors. There has been inconsistency for the association between very-high HDL-cholesterol and mortality outcomes in women. It is uncertain whether HDL-cholesterol is a causal ASCVD risk factor, especially due to mixed results from Mendelian randomization studies and the collinearity of HDL-cholesterol with established risk factors, lifestyle behaviors, and socioeconomic status. HDL-cholesterol is a risk factor or risk enhancer in primary prevention and high-risk condition in secondary prevention when either low (men and women) or very-high (men). The contribution of HDL-cholesterol to ASCVD risk calculators should reflect its observed U-shaped association with all-cause and ASCVD mortality.

National trends and disparities in statin use for ischemic heart disease from 2006 to 2018: Insights from National Ambulatory Medical Care Survey.

BACKGROUND: Statins are a cornerstone guideline-directed medical therapy for secondary prevention of ischemic heart disease (IHD). However, recent temporal trends and disparities in statin utilization for IHD have not been well characterized. METHODS: This retrospective analysis included data from outpatient adult visits with IHD from the National Ambulatory Medical Care Survey (NAMCS) between January 2006 and December 2018. We examined the trends and predictors of statin utilization in outpatient adult visits with IHD. RESULTS: Between 2006 and 2018, we identified a total of 542,704,112 weighted adult ambulatory visits with IHD and of those 46.6% were using or prescribed statin. Middle age (50-74 years) (adjusted odds ratio [aOR] 1.65, 95% confidence interval [CI] 1.28-2.13 P < .001) and old age (≥75 years) (aOR = 1.66, CI 1.26-2.19, P < .001) compared to young age (18-49 years), and male sex (aOR = 1.35, CI 1.23-1.48, P < .001) were associated with greater likelihood of statin utilization, whereas visits with non-Hispanic (NH) Black patients (aOR = 0.75, CI 0.61-0.91, P = .005) and Hispanic patients (aOR = 0.74, CI 0.60-0.92, P = .006) were associated with decreased likelihood of statin utilization compared to NH White patient visits. Compared with private insurance, statin utilization was nominally lower in Medicare (aOR = 0.91, CI 0.80-1.02, P = .112), Medicaid (aOR = 0.78, CI 0.59-1.02, P = .072) and self-pay/no charge (aOR = 0.72, CI 0.48-1.09, P = .122) visits, however did not reach statistical significance. There was no significant uptake in statin utilization from 2006 (44.1%) to 2018 (46.2%) (P = .549). CONCLUSIONS: Substantial gaps remain in statin utilization for patients with IHD, with no significant improvement in use between 2006 and 2018. Persistent disparities in statin prescription remain, with the largest treatment gaps among younger patients, women, and racial/ethnic minorities (NH Blacks and Hispanics).

Use of primary bariatric surgery among patients with obesity and diabetes. Insights from the Diabetes Collaborative Registry.

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m2), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy.

Health equity in the implementation of genomics and precision medicine: A public health imperative.

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.

Vascular Regenerative Capacity and the Obesity Paradox in Coronary Artery Disease.

[Figure: see text].

Commitment to Hypertension Control During the COVID-19 Pandemic: Million Hearts Initiative Exemplars.

Hypertension is a major risk factor for cardiovascular diseases, but 3 of 4 US adults do not have their blood pressure adequately controlled. Million Hearts (US Department of Health and Human Services) is a national initiative that promotes a set of priorities and interventions to optimize delivery of evidence-based strategies to manage cardiovascular disease, including hypertension. The COVID-19 pandemic, however, has disrupted routine care and preventive service delivery. We identified examples of clinical and health organizations that adapted services and care processes to continue a focus on monitoring and controlling hypertension during the pandemic. Eight Hypertension Control Exemplars were identified and interviewed. They reported various adapted care strategies including telemedicine, engaging patients in self-measured blood pressure monitoring, adapting or implementing medication management services, activating partnerships to respond to patient needs or expand services, and implementing unique patient outreach approaches. Documenting these hypertension control strategies can help increase adoption of adaptive approaches during public health emergencies and routine care.

How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol.

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 (<30 mg/dL) LDL-C. Cardiovascular event reduction increases log linearly in association with lowering LDL-C, without reaching any clear plateau even when very low LDL-C levels are achieved. It is still controversial whether lower LDL-C levels are associated with significant clinical adverse effects (e.g. new-onset diabetes mellitus or possibly haemorrhagic stroke) and long-term data are needed to address safety concerns. This review presents the familial conditions characterized by very low LDL-C, analyses trials with lipid-lowering agents where patients attained very low LDL-C, and summarizes the benefits and potential adverse effects associated with achieving very low LDL-C. Given the potential for cardiovascular benefit and short-term safe profile of very low LDL-C, it may be advantageous to attain such low levels in specific high-risk populations. Further studies are needed to compare the net clinical benefit of non-LDL-C-lowering interventions with very low LDL-C approaches, in addition to comparing the efficacy and safety of very low LDL-C levels vs. current recommended targets.

Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021.

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.

Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology.

Risk assessment is a critical step in the current approach to primary prevention of atherosclerotic cardiovascular disease. Knowledge of the 10-year risk for atherosclerotic cardiovascular disease identifies patients in higher-risk groups who are likely to have greater net benefit and lower number needed to treat for both statins and antihypertensive therapy. Current US prevention guidelines for blood pressure and cholesterol management recommend use of the pooled cohort equations to start a process of shared decision-making between clinicians and patients in primary prevention. The pooled cohort equations have been widely validated and are broadly useful for the general US clinical population. But, they may systematically underestimate risk in patients from certain racial/ethnic groups, those with lower socioeconomic status or with chronic inflammatory diseases, and overestimate risk in patients with higher socioeconomic status or who have been closely engaged with preventive healthcare services. If uncertainty remains for patients at borderline or intermediate risk, or if the patient is undecided after a patient-clinician discussion with consideration of risk enhancing factors (eg, family history), additional testing with measurement of coronary artery calcium can be useful to reclassify risk estimates and improve selection of patients for use or avoidance of statin therapy. This special report summarizes the rationale and evidence base for quantitative risk assessment, reviews strengths and limitations of existing risk scores, discusses approaches for refining individual risk estimates for patients, and provides practical advice regarding implementation of risk assessment and decision-making strategies in clinical practice.