Available online 22 November 2022

Familial hypercholesterolemia confers an elevated risk of premature ASCVD.

The present study demonstrates sex-related disparities in risk factors for ASCVD.

Premature ASCVD in individuals with FH are driven by risk factors beyond LDL-C.

Comprehensive management of all risk is key to reducing ASCVD burden.

: 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.

: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH.

: 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.

: 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).

: 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.

Familial Hypercholesterolemia

Atherosclerotic Cardiovascular Disease

Low-density lipoprotein- cholesterol

Hypertension

Diabetes mellitus

Smoking

Sex disparities

© 2022 Published by Elsevier Inc. on behalf of National Lipid Association.