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. 2023 Jan-Feb;17(1):150-156.
doi: 10.1016/j.jacl.2022.11.009. Epub 2022 Nov 22.

Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia

Anandita Agarwala  1 , Elena Deych  2 , Laney K Jones  3 , Amy C Sturm  4 , Karen Aspry  5 , Zahid Ahmad  6 , Christie M Ballantyne  7 , Anne C Goldberg  8
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Free article

Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia

Anandita Agarwala et al. J Clin Lipidol. 2023 Jan-Feb.
Free article

Abstract

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 <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.

Keywords: Atherosclerotic cardiovascular disease; Diabetes mellitus; Familial hypercholesterolemia; Hypertension; Low-density lipoprotein- cholesterol; Sex disparities; Smoking.

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Conflict of interest statement

Disclosures/Conflicts of Interest Dr Aspry has contracted research paid to institution from Amgen, Akcea, Esperion, and Novartis. She received speaker honoraria in 2020–2021 from MedScape/WebMD, and the National Lipid Association. Dr Ahmad serves on the advisory board for Esperion. Dr Ballantyne receives significant grant/research support that is paid to the institution from Abbott Diagnostic, Akcea, Amgen, Esperion, Novartis, Regeneron, Roche Diagnostic, National Institutes of Health, American Heart Association, and American Diabetes Association. He is a consultant for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, Astra Zeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma Inc, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi‐Synthelabo. Dr Goldberg receives modest honoraria from Esperion and Merck, and significant honoraria from the National Lipid Association. She receives modest research grants from Amarin, Amgen, and Pfizer and significant research grants from Novartis, Regeneron, Sanofi, and Ionis/Akcea. The remaining authors have no disclosures to report.

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