Abstract 9843: Sex-Related Differences in Premature Cardiovascular Disease in Individuals with Familial Hypercholesterolemia

Abstract

Background: Familial hypercholesterolemia (FH) is associated with elevated risk for premature atherosclerotic cardiovascular disease (ASCVD) (<55 years in men and <65 years in women). Little is known about sex-specific differences in risk factors and treatment outcomes in individuals with FH and premature ASCVD. Objective: To characterize sex-specific risk factor burdens and treatment outcomes in individuals with FH and premature ASCVD. Methods: The prevalence of premature ASCVD in 782 adults with FH (diagnosed by clinical scores and/or genetic testing) from 7 US-based lipid clinic practices was assessed retrospectively. A multivariate logistic mixed effects model with random study site effect and sex-specific analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension (HTN), and current smoking. Results: 98/280 men and 89/502 women had premature ASCVD. Women with premature ASCVD were older by an average of 3 years (mean age 58 vs. 55 years, p= 0.04) and had higher on treatment total cholesterol (216 vs. 178 mg/dl, p<0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005) (Table 1). In men, the strongest predictors of premature ASCVD were HTN (OR 5.39, 95% CI 2.85, 10.93, p<0.001) and DM (OR 2.25 95% CI 1.17, 4.37, p=0.016). In women, the strongest predictors of premature ASCVD were HTN (OR 5.48, 95% CI 3.22, 9.71, p<0.001) and smoking (OR 2.85, 95% CI 1.35, 5.94, p=0.005). Treated LDL-C was not a significant predictor of ASCVD in either men or women. Conclusion: The normal delay in age of onset of ASCVD in women vs. men may be shortened in individuals with FH. Both women and men with FH have an increased risk of premature ASCVD in the setting of HTN, but risks from smoking and DM differ by sex. Women with FH and premature ASCVD had higher on-treatment LDL-C. Aggressive treatment strategies are needed to reduce risk factor burdens and residual hyperlipidemia in these patients.