Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is associated with an increased prevalence of pre-mature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific dif-ferences 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 con-firmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial dis-tribution 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 < 55 years in men and < 65 years in women). Women with premature ASCVD had higher mean treated total cholesterol (216 vs. 179 mg/dl, p = < 0.001) 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. (c) 2022 National Lipid Association. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study retrospectively examined the burden and risk factors of premature ASCVD in men and women with FH. The results showed a high prevalence of premature ASCVD in both genders, and significant differences were observed in predictive factors and lipid treatment outcomes for women with premature ASCVD.