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Connor Iapoce is an associate editor for HCPLive and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at email@example.com.
A favorable lifestyle is associated with a lower risk of coronary artery disease in carriers and noncarriers of FH variants.
New findings suggest carriers of familial hypercholesterolemia variants have at least a 3-fold increased risk of coronary artery disease (CAD),
However, risk varied significantly according to healthy lifestyle characteristics and a favorable lifestyle was associated with lower risk of CAD in both carriers and noncarriers of FH variants.
“We found that, despite a minimal association between adherence to a healthy lifestyle and LDL cholesterol concentrations, adherence to a healthy lifestyle may mitigate the risk of CAD,” wrote study author Amit V. Khera, MD, MSc, Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital.
Khera and colleagues analyzed gene sequencing and lifestyle data in a case-control study of 10,175 individuals and cohort study of 39,920 individuals to evaluate the extent a healthy lifestyle lessens the risk of CAD.
Study populations were recruited from 22 sites in the United Kingdom between March 2006 - October 2010. The case-control study consisted of those with CAD diagnosis and controls at enrollment, while the cohort study used a sample of individuals with available gene sequencing data.
Investigators defined CAD based on self-report of myocardial infarction, hospitalization records confirming a diagnosis of myocardial infarction or ischemic heart disease, coronary revascularization procedures. Both study populations measured LDL-cholesterol concentrations in biospecimens at study enrollment.
Additionally, in both studies, carriers of a pathogenic or likely pathogenic FH variant were identified using gene sequencing data and classified by a clinical laboratory geneticist. They adapted a 4-point scoring system for the evaluation of a healthy lifestyle, with 1 point each for:
Data show the case-control study included 10,175 participants and the cohort study included 39,920 participants. Investigators identified any of 24 pathogenic or likely pathogenic FH variants in 35 of 4896 CAD cases (0.7%) and in 12 of 5279 controls (0.2%).
They observed LDL-C concentrations were signficantly higher in carriers of a FH variant compared to noncarriers (untreated concentrations, 201 versus 148 mg/dL; adjusted difference, 53 mg/dL [95% CI, 48 - 58 mg/dL; P <.001).
On average, individuals who carried a FH variant had a 3-fold increased odds of CAG compared with noncarriers (adjusted odds ratio [OR], 3.0 (95% CI, 1.6 - 5.9). In the cohort study, a FH variant was identified in 108 individuals (0.3%), with a hazard ratio (HR) for CAD at 3.8 (95% CI, 2.5 - 5.8; P <.001).
Investigators observed the risk appeared to vary according to healthy lifestyle characteristics in both carriers and noncarriers of FH variants. A significant interaction was not seen between carrier status and lifestyle (OR, 1.2; 95% CI, 0.6 - 2.5; P = .62).
Then, among carriers of a FH variant, a favorable lifestyle conferred 86% lower risk of CAD compared to an unfavorable lifestyle (adjusted HR, 0.14 [95% CI, 0.04 - 0.41).
Using a Cox proportional hazards regression model, investigators noted the estimated risk of CAD by the age of 75 years varied according to lifestyle characteristics.
It ranged from 10.2% among noncarriers with a favorable lifestyle to 24.0% among noncarriers with an unfavorable lifestyle and ranged from 34.5% among carriers with a favorable lifestyle to 66.2% among carriers with an unfavorable lifestyle.
The study, “Association of the Interaction Between Familial Hypercholesterolemia Variants and Adherence to a Healthy Lifestyle With Risk of Coronary Artery Disease,” was published in JAMA Network Open.