Association of the Interaction Between Familial Hypercholesterolemia Variants and Adherence to a Healthy Lifestyle With Risk of Coronary Artery Disease - PubMed

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. 2022 Mar 1;5(3):e222687.
doi: 10.1001/jamanetworkopen.2022.2687.
Association of the Interaction Between Familial Hypercholesterolemia Variants and Adherence to a Healthy Lifestyle With Risk of Coronary Artery Disease
1 Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston.
2 Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston.
3 Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
4 Department of Medicine, Harvard Medical School, Boston, Massachusetts.
5 Department of Medicine, UT Southwestern Medical Center, Dallas, Houston, Texas.
6 Center for Computational Health, IBM Research, Cambridge, Massachusetts.
7 Verve Therapeutics, Cambridge, Massachusetts.
PMID: 35294538
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Association of the Interaction Between Familial Hypercholesterolemia Variants and Adherence to a Healthy Lifestyle With Risk of Coronary Artery Disease
Akl C Fahed et al. JAMA Netw Open.
2022
doi: 10.1001/jamanetworkopen.2022.2687.
Authors
1 Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston.
2 Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston.
3 Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
4 Department of Medicine, Harvard Medical School, Boston, Massachusetts.
5 Department of Medicine, UT Southwestern Medical Center, Dallas, Houston, Texas.
6 Center for Computational Health, IBM Research, Cambridge, Massachusetts.
7 Verve Therapeutics, Cambridge, Massachusetts.
PMID: 35294538
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Abstract
Importance: Familial hypercholesterolemia variants impair clearance of cholesterol from the circulation and increase risk of coronary artery disease (CAD). The extent to which adherence to a healthy lifestyle is associated with a lower risk of CAD in carriers and noncarriers of variants warrants further study.
Objective: To assess the association of the interaction between familial hypercholesterolemia variants and adherence to a healthy lifestyle with risk of CAD.
Design, setting, and participants: This cross-sectional study used 2 independent data sets with gene sequencing and lifestyle data from the UK Biobank: a case-control study of 4896 cases and 5279 controls and a cohort study of 39 920 participants. Participants were recruited from 22 sites across the UK between March 21, 2006, and October 1, 2010. The case-control study included participants with CAD and controls at enrollment. The cohort study used a convenience sample of individuals with available gene sequencing data. Statistical analysis was performed from April 2, 2019, to January 20, 2022.
Exposures: Pathogenic or likely pathogenic DNA variants classified by a clinical laboratory geneticist and adherence to a healthy lifestyle based on a 4-point scoring system (1 point for each of the following: healthy diet, regular exercise, not smoking, and absence of obesity).
Main outcomes and measures: Coronary artery disease, defined as myocardial infarction in the case-control study, and myocardial infarction, ischemic heart disease, or coronary revascularization procedure in the cohort study.
Results: The case-control study included 10 175 participants (6828 men [67.1%]; mean [SD] age, 58.6 [7.2] years), and the cohort study included 39 920 participants (18 802 men [47.1%]; mean [SD] age at the end of follow-up, 66.4 [8.0] years). A variant was identified in 35 of 4896 cases (0.7%) and 12 of 5279 controls (0.2%), corresponding to an odds ratio of 3.0 (95% CI, 1.6-5.9), and a variant was identified in 108 individuals (0.3%) in the cohort study, in which the hazard ratio for CAD was 3.8 (95% CI, 2.5-5.8). However, this risk appeared to vary according to lifestyle categories in both carriers and noncarriers of familial hypercholesterolemia variants, without a significant interaction between carrier status and lifestyle (odds ratio, 1.2 [95% CI, 0.6-2.5]; P = .62). Among carriers, a favorable lifestyle conferred 86% lower risk of CAD compared with an unfavorable lifestyle (hazard ratio, 0.14 [95% CI, 0.04-0.41]). The estimated risk of CAD by the age of 75 years varied according to lifestyle, ranging from 10.2% among noncarriers with a favorable lifestyle to 24.0% among noncarriers with an unfavorable lifestyle and ranging from 34.5% among carriers with a favorable lifestyle to 66.2% among carriers with an unfavorable lifestyle.
Conclusions and relevance: This study suggests that, among carriers and noncarriers of a familial hypercholesterolemia variant, significant gradients in risk of CAD are noted according to adherence to a healthy lifestyle pattern. Similar to the general population, individuals who carry familial hypercholesterolemia variants are likely to benefit from lifestyle interventions to reduce their risk of CAD.
Conflict of interest statement
Conflict of Interest Disclosures:
Dr Fahed reported serving as a consultant for and holding equity in Goodpath. Dr Ellinor reported receiving sponsored research support from Bayer AG and IBM Research; personal fees from MyoKardia; and serving on advisory boards or serving as a consultant for Bayer AG, Quest Diagnostics, and Novartis. Dr Ng is an employee of IBM Research. Dr Khera reported receiving grants from IBM Research and the National Human Genome Research Institute during the conduct of the study; being an employee of and holding equity in Verve Therapeutics; serving as a scientific advisor to and receiving personal fees from Amgen, Maze Therapeutics, Navitor Pharmaceuticals, Sarepta Therapeutics, Novartis, Silence Therapeutics, Korro Bio, Veritas International, Color Health, Third Rock Ventures, Illumina, Foresite Labs, and Columbia University (National Institutes of Health); receiving speaking fees from Illumina, MedGenome, Amgen, and the Novartis Institute for Biomedical Research; and being listed as a co-inventor on a patent application for use of imaging data in assessing body fat distribution and associated cardiometabolic risk. No other disclosures were reported.
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