Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear.OBJECTIVE To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds. DESIGN, SETTING, AND PARTICIPANTS Prospective population-based cohort study of DallasHeart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020.EXPOSURES Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher. MAIN OUTCOMES AND MEASURESMajor bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis-derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds.RESULTS A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and Ն100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (Ն20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (Ն5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk.CONCLUSIONS AND RELEVANCE Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.

Key Points Question Why do individuals from Canada, the UK, and the US turn to medical crowdfunding and what factors are associated with funding success? Findings In this cross-sectional study of 3396 crowdfunding campaigns designed to raise monetary donations for medical expenses, female gender, Black race, and routine care were associated with a strong fundraising disadvantage. For campaigns primarily funding treatment, routine care was overwhelmingly represented in the US (77.9%), in contrast to Canada (21.9%) and the UK (26.6%), and crowdfunding primarily funding alternative therapies (16.0%) was more common for cancer (23.5%) vs noncancer (6.5%) diagnoses. Meaning These findings suggest that there are important differences in the reasons for medical crowdfunding across the 3 countries included in this analysis and that there are racial and gender disparities in crowdfunding success.

Background The U.S. Centers for Disease Control and Prevention (CDC) recognizes that older adults and individuals with certain medical conditions are at increased risk of severe COVID-19 infection. Understanding the proportion of the population at risk of severe infection, including among those with heart disease, could assist current vaccine strategy efforts. Methods Using data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES), we estimated the weighted prevalence of any of eight of eleven increased-risk conditions (including age ≥65) in U.S. adults aged ≥18 (N=10,581) and extrapolated these results to a population of 233.8 million U.S. adults ≥18, and subgroups from the overall population defined by race/ethnicity, education, income and history of heart disease. Results An estimated 176.1 million individuals representing 75.4% of U.S. adults had at least one increased-risk condition, 40.3% ≥2 and, 18.5% ≥3 conditions. Approximately 129 million adults aged <65 (69.2%) were also estimated to be at increased-risk. Compared to Whites, similar proportions of Blacks in the overall population (78.0 vs. 75.6%, p>0.05) and Hispanics in the younger population (70.8 vs 68.4%) were estimated to be at increased-risk. Conversely, a greater proportion of individuals with lower education and income levels were estimated to be at increased-risk both in the overall and younger population. In addition, an estimated 6.2 million individuals (14.5%) had heart disease. Among these, virtually all had at least one additional CDC risk factor (97.9%) and most had ≥2 or ≥3 risk factors (83.8% and 58.5%, respectively). Conclusions As vaccination strategies are being explored, these results demonstrate that >75% of adults in the U.S. would be considered at increased-risk for severe COVID-19 infection by CDC criteria. Risk factor prevalence alone may not adequately capture the totality of risk, particularly among Black and Hispanic racial/ethnic groups and those with heart disease.

IMPORTANCEIn 2015, the US Food and Drug Administration approved 2 new medications for treatment of heart failure with reduced ejection fraction, sacubitril/valsartan and ivabradine. However, few national data are available examining their contemporary use and associated costs. OBJECTIVE To evaluate national patterns of use of sacubitril/valsartan and ivabradine and associated therapeutic spending in Medicare Part D and Medicaid. DESIGN, SETTING, AND PARTICIPANTS In this US nationwide claims-based study, we analyzed data from the Medicare Part D Prescription Drug Event and Medicaid Utilization and Spending data sets to compare national patterns of use of sacubitril/valsartan and ivabradine between 2016 and 2017. MAIN OUTCOMES AND MEASURES Changes in total spending, per-beneficiary/claim spending, number of beneficiaries, and number of claims between 2016 and 2017 for sacubitril/ valsartan and ivabradine. RESULTS The number of Medicare beneficiaries prescribed sacubitril/valsartan increased from 35 423 to 90 606 (156% increase from 2016 to 2017). Medicare beneficiaries prescribed ivabradine increased from 15 856 to 23 213 (46% increase). In 2017, Medicare Part D spent $227 million and $7.3 million on sacubitril/valsartan and ivabradine, respectively. This represented increases of 241% and 59% compared with 2016 spending, respectively. The annual Medicare per-beneficiary spending on sacubitril/valsartan and ivabradine was $2512 and $2400. Parallel trends in use patterns and spending were observed among Medicaid beneficiaries.CONCLUSIONS AND RELEVANCE Although initial experiences suggested slow uptake after regulatory approval, these national data demonstrate an increase in use of sacubitril/ valsartan and, to a lesser degree, ivabradine in the United States. Current annual per-beneficiary expenditures remain less than spending thresholds that have been reported to be cost-effective. Ongoing efforts are needed to promote high-value care while improving affordability and access to established and emerging heart failure therapies.

IMPORTANCE Familial hypercholesterolemia variants impair clearance of cholesterol from the circulation and increase risk of coronary artery disease (CAD). The extent to which adherence to a healthy lifestyle is associated with a lower risk of CAD in carriers and noncarriers of variants warrants further study. OBJECTIVETo assess the association of the interaction between familial hypercholesterolemia variants and adherence to a healthy lifestyle with risk of CAD. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study used 2 independent data sets with gene sequencing and lifestyle data from the UK Biobank: a case-control study of 4896 cases and 5279 controls and a cohort study of 39 920 participants. Participants were recruited from 22 sites across the UK between March 21, 2006, and October 1, 2010. The case-control study included participants with CAD and controls at enrollment. The cohort study used a convenience sample of individuals with available gene sequencing data. Statistical analysis was performed from April 2, 2019, to January 20, 2022. EXPOSURES Pathogenic or likely pathogenic DNA variants classified by a clinical laboratory geneticist and adherence to a healthy lifestyle based on a 4-point scoring system (1 point for each of the following: healthy diet, regular exercise, not smoking, and absence of obesity). MAIN OUTCOMES AND MEASURES Coronary artery disease, defined as myocardial infarction inthe case-control study, and myocardial infarction, ischemic heart disease, or coronary revascularization procedure in the cohort study. RESULTSThe case-control study included 10 175 participants (6828 men [67.1%]; mean [SD] age, 58.6 [7.2] years), and the cohort study included 39 920 participants (18 802 men [47.1%]; mean [SD] age at the end of follow-up, 66.4 [8.0] years). A variant was identified in 35 of 4896 cases (0.7%) and 12 of 5279 controls (0.2%), corresponding to an odds ratio of 3.0 (95% CI, 1.6-5.9), and a variant was identified in 108 individuals (0.3%) in the cohort study, in which the hazard ratio for CAD was 3.8 (95% CI, 2.5-5.8). However, this risk appeared to vary according to lifestyle categories in both carriers and noncarriers of familial hypercholesterolemia variants, without a significant interaction between carrier status and lifestyle (odds ratio, 1.2 [95% CI, 0.6-2.5]; P = .62). Among carriers, a favorable lifestyle conferred 86% lower risk of CAD compared with an unfavorable lifestyle (hazard ratio, 0.14 [95% CI, 0.04-0.41]). The estimated risk of CAD by the age of 75 years varied according to lifestyle, ranging from 10.2% among noncarriers with a favorable lifestyle to 24.0% among noncarriers with an unfavorable lifestyle and ranging from 34.5% among carriers with a favorable lifestyle to 66.2% among carriers with an unfavorable lifestyle.