Aim: The study objectives were to investigate the association between selected CYP2C9 and VKORC1 single nucleotide polymorphisms with serious bleeding or thrombotic risk, and to estimate mean daily maintenance dose of warfarin and international normalized ratio measurements among Blacks receiving warfarin anticoagulation. Methods: We conducted a retrospective cohort study among 230 Black adults receiving warfarin for a minimum of three consecutive months with a confirmed date of first dosage. Results: A lower mean daily maintenance dosage of warfarin was required to maintain an international normalized ratio measurement within the therapeutic range among Blacks with the VKORC1-1639G>A variant alleles ([G/A vs G/G, p = 0.02], [A/A vs G/A, p = 0.008] and [A/A vs G/G, p = 0.001]). Conclusion: Data indicated that VKORC1-1639A variant allele influenced warfarin daily maintenance dosage among our small, likely admixed Black patient population.

IMPORTANCE Atherosclerotic cardiovascular disease (ASCVD) kills approximately 1 in every 3 US women. Current cholesterol, hypertension, and aspirin guidelines recommend calculating 10-year risk of ASCVD using the 2013 Pooled Cohort Equations (PCE). However, numerous studies have reported apparent overestimation of risk with the PCE, and reasons for overestimation are unclear. OBJECTIVE We evaluated the predictive accuracy of the PCE in the Women's Health Initiative (WHI), a multiethnic cohort of contemporary US postmenopausal women. We evaluated the effects of time-varying treatments such as aspirin and statins, and ascertainment of additional ASCVD events by linkage with the Centers for Medicare and Medicaid Services (CMS) claims. DESIGN, SETTING, AND PARTICIPANTS The WHI recruited the largest number of US women (n = 161 808) with the racial/ethnic, geographic, and age diversity of the general population (1993-1998). For this study, we included women aged 50 to 79 (n = 19 995) participating in the WHI with data on the risk equation variables at baseline and who met the guideline inclusion and exclusion criteria. Median follow-up was 10 years. MAIN OUTCOMES AND MEASURES For this study, ASCVD was defined as myocardial infarction, stroke, or cardiovascular death. RESULTS Among the 19 995 women (mean [SD] age, 64 [7.3] years; 8305 [41.5%] white, 7688 [38.5%] black, 3491 [17.5%] Hispanic, 103 [0.5%] American Indian, 321 [1.6%] Asian/Pacific Islander, and 87 [0.4%] other/unknown), a total of 1236 ASCVD events occurred in 10 years and were adjudicated through medical record review by WHI investigators. The WHI-adjudicated observed risks were lower than predicted. The observed (predicted) risks for baseline 10-year risk categories less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, and 10% or more were 1.7 (2.8), 4.4 (6.2), 5.3 (8.7), and 12.4 (18.2), respectively. Small changes were noted after adjusting for time-dependent changes in statin and aspirin use. Among women 65 years or older enrolled in Medicare, WHI-adjudicated risks were also lower than predicted, but observed (predicted) risks became aligned after including events ascertained by linkage with CMS for additional surveillance for events: 3.8 (4.3), 7.1 (6.4), 8.3 (8.7), and 18.9 (18.7), respectively. Similar results were seen across ethnic/racial groups. Overall, the equations discriminated risk well (C statistic, 0.726; 95% CI, 0.714-0.738). CONCLUSIONS AND RELEVANCE Without including surveillance for ASCVD events using CMS, observed risks in the WHI were lower than predicted by PCE as noted in several other US cohorts, but risks were better aligned after including CMS events.

Background-Cardiovascular events occur among statin-treated patients, albeit at lower rates. Risk factors for this "residual risk" have not been studied comprehensively. We aimed to identify determinants of this risk above and beyond lipid-related risk factors. Methods and Results-A total of 9251 coronary patients with low-density lipoprotein cholesterol <130 mg/dL randomized to double-blind atorvastatin 10 or 80 mg/d in the Treating to New Targets (TNT) study had complete on-treatment 1-year lipid data. Median follow-up was 4.9 years. The primary end point was major cardiovascular events (n=729): coronary death, nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. Multivariable determinants of increased risk were older age (adjusted hazard ratio [aHR], 1.13 per 1 SD [8.8 years]; 95% confidence interval [CI], 1.04-1.23), increased body mass index (aHR, 1.09; 95% CI, 1.02-1.17 per 4.5 kg/m), male sex (aHR, 1.33; 95% CI, 1.07-1.65), hypertension (aHR, 1.38; 95% CI, 1.17-1.63), diabetes mellitus (aHR, 1.33; 95% CI, 1.11-1.60), baseline apolipoprotein B (aHR, 1.19; 95% CI, 1.11-1.28 per 19 mg/dL), and blood urea nitrogen (aHR, 1.10; 95% CI, 1.03-1.17 per 4.9 mg/dL), in addition to current smoking, prior cardiovascular disease, and calcium channel blocker use. Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70-0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL). On-treatment 1-year lipids or apolipoproteins were not additionally associated with risk in multivariable models. Known baseline variables performed moderately well in discriminating future cases from noncases (Harrell c index=0.679). Conclusions-Determinants of residual risk in statin-treated secondary prevention patients included lipid-related and nonlipid factors such as baseline apolipoproteins, increased body mass index, smoking, hypertension, and diabetes mellitus. A multifaceted prevention approach should be underscored to address this risk.

In patients with heart failure (HF), mortality is lower in women versus men. However, it is unknown whether the survival advantage in women compared with men is present in both whites and African Americans with HF. The inception cohort consisted of adults ≥65 years with incident HF after enrollment in the CHS, a prospective population-based study of cardiovascular disease. Of 5,888 CHS subjects, 1,264 developed new HF and were followed up for 3 years. Subjects were categorized into 4 race-gender groups, and Cox proportional hazard regression models were used to examine whether 3-year total and cardiovascular mortality differed among the 4 groups after adjusting for sociodemographic factors, co-morbidities, and treatment. A gender-race interaction was also tested for each outcome. In subjects with incident HF, African Americans had more hypertension and diabetes than whites, and white men had more coronary heart disease than other gender-race groups. Receipt of cardiovascular treatments among the 4 groups was similar. Mortality rates after HF were lower in women compared with men (for white women, African-American women, African-American men, and white men, total mortality was 35.5, 33.6, 44.4, and 40.5/100 person-years, and cardiovascular mortality was 18.4, 19.5, 20.2, and 22.7/100 person-years, respectively). After adjusting for covariates, women had a 15% to 20% lower risk of total and cardiovascular mortality compared with men, but there was no significant difference in outcome by race. The gender-race interaction for either outcome was not significant. In conclusion, in older adults with HF, women had significantly better survival than men irrespective of race, suggesting that gender-based survival differences may be more important than race-based differences.

Background Supervised exercise therapy (SET) is recommended in patients with symptomatic peripheral arterial disease (PAD) as first‐line therapy, although patient adoption remains low. Home‐based exercise therapy (HBET) delivered through smartphones may expand access. The feasibility of such programs, especially in low‐resource settings, remains unknown. Methods Smart Step is a pilot randomized trial of smartphone‐enabled HBET vs walking advice in patients with symptomatic PAD in an inner‐city hospital. Participants receive a smartphone app with daily exercise reminders and educational content. A trained coach performs weekly phone‐based coaching sessions. All participants receive a Fitbit Charge HR 2 to measure physical activity. The primary outcome changes in 6‐minute walking test (6MWT) distance at 12 weeks over baseline. Secondary outcomes are the degree of engagement with the smartphone app and changes in health behaviors and quality of life scores after 12 weeks and 1 year. Results A total of 15 patients are randomized as of December 15, 2019 with a mean (SD) age of 66.1 (5.8) years. The majority are female (60%) and black (87%). At baseline, the mean (SD) ABI and 6MWT were 0.86 (0.29) and 363.5 m, respectively. Enrollment is expected to continue until December 2020 to achieve a target size of 50 participants. Conclusions The potential significance of this trial will be to provide preliminary evidence of a home‐based, “mobile‐first” approach for delivering a structured exercise rehabilitation program. Smartphone‐enabled HBET can be potentially more accessible than center‐based programs, and if proven effective, may have a potential widespread public health benefit.

Despite the growing awareness of adverse events with acute coronary syndrome and vigilance to refine pharmacological and interventional therapies, the understanding of how these events present in and affect women and the elderly remains limited. Pathophysiological differences in these subgroups and under-representation in large trials create a medical gap in sex-and age-related outcomes and in our knowledge of how best to detect, diagnose, and treat acute coronary syndrome. This review provides a general overview of recent advances in non-ST elevation myocardial infarction management in women and the elderly and elucidates areas where further exploration is needed.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in women. Historically, medical research has focused on male patients, and subsequently, there has been decreased awareness of the burden of ASCVD in females until recent years. The biological differences between sexes and differences in societal expectations defined by gender roles contribute to gender differences in ASCVD risk factors. With these differing risk profiles, risk assessment, risk stratification, and primary preventive measures of ASCVD are different in women and men. In this review article, clinicians will understand the risk factors unique to women, such as preeclampsia, gestational diabetes, and those that disproportionately affect them such as autoimmune disorders. With these conditions in mind, the approach to ASCVD risk assessment and stratification in women will be discussed. Furthermore, the literature behind the effects of primary preventive measures in women, including lifestyle modifications, aspirin, statins, and anticoagulation, will be reviewed. The aim of this review article was to ultimately improve ASCVD primary prevention by reducing gender disparities through education of physicians.

Little is known about electrocardiographic (ECG) characteristics of menopausal women with or at increased risk of coronary heart disease (CHD). Data from 10,101 participants in the Raloxifene Use for The Heart (RUTH) trial were used to correlate baseline ECG abnormalities with clinical characteristics. Baseline characteristics that were statistically significantly associated (p ≤ 0.05) with ECG findings in univariate analyses were used to derive multivariate model selection. Of 59% normal electrocardiograms, 50% were from women with CHD and 69% from women at increased risk of CHD. In the women with CHD, 59% reported a previous myocardial infarction (MI); 43% had a normal electrocardiogram, and 49% had a definite ECG Q-wave MI. Women in the increased-risk group had not reported a previous MI, yet 11% had a definite ECG Q-wave MI. Of women reporting hypertension, 35% had ECG evidence of left ventricular hypertrophy, but 58% did not have an abnormal electrocardiogram. Significantly more women with diabetes in the increased-risk and documented CHD cohorts had abnormal electrocardiograms (p < 0.01 for the 2 cohorts). Percent abnormal electrocardiograms increased with increasing age (55 to 64, 65 to 74, and ≥75 years, p < 0.01) in all cohorts. Angina and coronary artery bypass graft surgery, but not percutaneous coronary intervention, predicted an abnormal electrocardiogram. In conclusion, there were high percentages of normal electrocardiograms in the increased-risk and documented CHD groups of RUTH participants, with substantial discrepancy between MI history and ECG MI documentation, and increasing age was the predominant correlate with an abnormal electrocardiogram in all 3 cohorts.