Genetic Risk, Coronary Heart Disease Events, and the Clinical Benefit of Statin Therapy

By Jessica L. Mega, N. Stitziel, J. G. Smith, Daniel Chasman, M. Caulfield, James J. Devlin, F. Nordio, Craig L. Hyde, C. Cannon, F. M. Sacks and 7 more. The Lancet, 2015

642 citations recorded by the source corpus.

Background Genetic variants have been associated with the risk of coronary heart disease (CHD). We tested whether a composite of these variants could identify the risk of both incident as well as recurrent CHD events and distinguish individuals who derived greater clinical benefit from statin therapy. Methods A community-based cohort and four randomized controlled trials of both primary (JUPITER and ASCOT) and secondary (CARE and PROVE IT-TIMI 22) prevention with statin therapy totaling 48,421 individuals and 3,477 events were included in these analyses. We examined the association of a genetic risk score based on 27 genetic variants with incident or recurrent CHD, adjusting for established clinical predictors. We then investigated the relative and absolute risk reductions in CHD events with statin therapy stratified by genetic risk. Data from studies were combined using meta-analysis. Findings When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient of risk for incident or recurrent CHD was demonstrated with the multivariable-adjusted HRs (95% CI) for CHD for the intermediate and high genetic risk categories vs. low genetic risk category being 1.32 (1.20-1.46, P<0.0001) and 1.71 (1.54-1.91, P<0.0001), respectively. In terms of the benefit of statin therapy in the four randomized trials, there was a significant gradient of increasing relative risk reduction across the low, intermediate, and high genetic risk categories (13%, 29%, and 48%, P=0.0277). Similarly, greater absolute risk reductions were seen in those individuals in higher genetic risk categories (P=0.0101), resulting in an approximate three-fold gradient in the number needed to treat (NNT) in the primary prevention trials. Specifically, in the primary prevention trials, the NNT to prevent one MACE over 10 years for the low, intermediate, and high GRS individuals was 66, 42, and 25 in JUPITER and 57, 47, and 20 in ASCOT. Interpretation A genetic risk score identified individuals at increased risk for both incident and recurrent CHD events. Individuals with the highest burden of genetic risk derived the largest relative and absolute clinical benefit with statin therapy.

Subfields: Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/2080d9b9823cb4fb84c5da1d9a245b100b31539e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Surgery

Citations in the corpus

Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel (2017, methodology): “LDL-C than did persons with the lowest tertile of the genetic risk score.(53) The genetic score used in this study may have included vari-”
2016 European Guidelines on cardiovascular disease prevention in clinical practice (2016, background): “Recently, a genetic risk score based on 27 genetic variants enabled the identification of subjects at increased risk of CAD, who would benefit the most from statin therapy, even after adjustment for family history.(84) Still, it is likely that some reported associations might be due to chance,(85) a”
Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming (2018, background): “For atherosclerosis development, increased circulating levels of LDL cholesterol have been linked mechanistically and genetically to clinical event risks (Mega et al., 2015).”
Integrative omics for health and disease (2018, background): “…associated with an outcome can be actionable, particularly in the form of lifestyle change recommendations, including diet, monitoring and preventive treatments; indeed, individuals with high genetic risk of coronary heart disease experience greater benefits from statin treatment 103,104 .”
2016 European Guidelines on cardiovascular disease prevention in clinical practice. (2016, background): “Recently, a genetic risk score based on 27 genetic variants enabled the identification of subjects at increased risk of CAD, who would benefit the most from statin therapy, even after adjustment for family history.(84) Still, it is likely that some reported associations might be due to chance,(85) a”
Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting (2017, methodology): “JUPITER and ASCOT-LLA data are from Mega et al.(5)”
2016 European Guidelines on cardiovascular disease prevention in clinical practice (2017, positive): “Recently, a genetic risk score based on 27 genetic variants enabled the identification of subjects at increased risk of CAD, who would benefit the most from statin therapy, even after adjustment for family history [84].”
Genomic Risk Prediction of Coronary Artery Disease in 480,000 Adults Implications for Primary Prevention (2019, background): “As our data have suggested that higher genetic risk can at least partly be attenuated by lipidlowering and/or antihypertensive therapies, it implies that individuals at high genetic risk may gain the most from early initiation of these therapies and, therefore, constitute a subpopulation for which p”
Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease (2016, neutral): “0 or 1 healthy lifestyle factor 2193 (28) 3,321 (16) 4,945 (22) 1098 (26)”