Bempedoic acid for heterozygous familial hypercholesterolemia: From bench to bedside

Bempedoic acid is a first-in-class, oral, inhibitor of cholesterol biosynthesis that is approved for use in patients with atherosclerotic cardiovascular disease (ASCVD) and for primary prevention in individuals with heterozygous familial hypercholesterolemia (HeFH) by the United States Food and Drug Administration. Pooled data from the phase III clinical trials, CLEAR Harmony and CLEAR Wisdom, have demonstrated the safety and efficacy of bempedoic acid with regard to lowering of low-density lipoprotein cholesterol (LDL-C) in patients with HeFH as an adjunct or alternative to currently existing lipid-lowering therapies. CLEAR Outcomes is a cardiovascular outcomes trial that is currently underway that will provide additional insight as to where bempedoic acid will fit into treatment regimens among the non-statin lipid-lowering therapy options. Patients who might particularly benefit from bempedoic acid are those with HeFH and those unable to take adequate doses of statins or take any statin therapy altogether who need additional LDL-C lowering. In this review, we will discuss the profile of bempedoic acid from its design, development, and its place in therapy for the management of LDL-C for the purposes of ASCVD prevention

Secondary Prevention of Cardiovascular Disease in Women: Closing the Gap

Cardiovascular disease (CVD) remains the leading cause of death in women globally. Younger women (<55 years of age) who experience MI are less likely to receive guideline-directed medical therapy (GDMT), have a greater likelihood of readmission and have higher rates of mortality than similarly aged men. Women have been under-represented in CVD clinical trials, which limits the generalisability of results into practice. Available evidence indicates that women derive a similar benefit as men from secondary prevention pharmacological therapies, such as statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, icosapent ethyl, antiplatelet therapy, sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. Women are less likely to be enrolled in cardiac rehabilitation programs than men. Mitigating risk and improving outcomes is dependent on proper identification of CVD in women, using appropriate GDMT and continuing to promote lifestyle modifications. Future research directed at advancing our understanding of CVD in women will allow us to further develop and tailor CVD guidelines appropriate by sex and to close the gap between diagnoses, treatment and mortality

Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors. OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH. METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and sex-stratified analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension, and current smoking. RESULTS: Among the cohort, 98/280 men (35%) and 89/502 women (18%) had premature ASCVD (defined as \u3c55 years in men and \u3c65 years in women). Women with premature ASCVD had higher mean treated total cholesterol (216 vs. 179 mg/dl, p=\u3c0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005). CONCLUSION: These data confirm that high percentages of women and men with FH develop premature ASCVD, and suggest that FH may narrow the observed sex difference in premature ASCVD onset. These data support more aggressive prevention and treatment strategies in FH, including in women, to reduce non-lipid risk factors and residual hypercholesterolemia

Racial/Ethnic Disparities and Determinants of Sufficient Physical Activity Levels

Introduction. It is important to identify racial/ethnic groups that may be less likely to achieve sufficient physical activity levels, and to address barriers to meeting physical activity requirements. Methods. Cross-sectional data from the 2006-2015 National Health Interview Survey (NHIS) was used to compare self-reported sufficient physical activity among different racial/ethnic groups: non-Hispanic (NH) Whites, NH Blacks, NH Asians, and Hispanics. Sufficient physical activity was defined as ≥150 minutes per week of moderate-intensity physical activity, ≥75 minutes per week of vigorous-intensity physical activity, or ≥150 minutes per week of moderate and vigorous physical activity. Results. The study sample consisted of 296,802 individuals, mean age ± standard error age 46.4 ± 0.10 years, 52% women, 70% NH White, 12% NH Black, 5% NH Asian, 14% Hispanic. The prevalence of sufficient physical activity in the overall population was 46%, while it was 48% among NH Whites, 39% among NH Blacks, 45% among NH Asians, and 40% among Hispanics. In multivariable-adjusted models (odds ratio; 95% confidence interval), NH Blacks (0.79; 0.64,0.97), NH Asians (0.72; 0.62,0.85) and Hispanics (0.71; 0.61,0.82) were significantly less likely to engage in sufficient physical activity compared with NH Whites. Older age, women, and low income were inversely associated with sufficient physical activity, while a college education or higher was directly associated with it. Conclusions. NH Black, NH Asian, and Hispanic adults are less likely to engage in sufficient physical activity levels compared with NH Whites. It is important to address barriers to meeting physical activity thresholds to help achieve optimal cardiovascular health

Racial disparities in modifiable risk factors and statin usage in Black patients with familial hypercholesterolemia

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively

Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study

Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort

The role of ezetimibe in the treatment of cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Despite the success of treatment of CVD with statin therapy, a number of patients remain at high risk for CVD. Ezetimibe is a non-statin agent that inhibits intestinal cholesterol absorption, leading to reductions in low-density lipoprotein cholesterol (LDL-C). A number of clinical studies evaluating the use of ezetimibe therapy have resulted in discordant data regarding its safety and efficacy. In this review, we discuss the findings from these studies as well as potential indications for the use of ezetimibe for LDL-C lowering and cardiovascular event reduction