Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial.

Abstract

OBJECTIVE:

We evaluated whether the increasing number of genetic loci for coronary artery disease (CAD) identified in the general population could be used to predict the risk of major CAD events (MCE) among participants with type 2 diabetes at high cardiovascular risk.

RESEARCH DESIGN AND METHODS:

A weighted genetic risk score (GRS) derived from 204 variants representative of all the 160 CAD loci identified in the general population as of December 2017 was calculated in 5,360 and 1,931 white participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Outcome Reduction With Initial Glargine Intervention (ORIGIN) studies, respectively. The association between GRS and MCE (combining fatal CAD events, nonfatal myocardial infarction, and unstable angina) was assessed by Cox proportional hazards regression.

RESULTS:

The GRS was associated with MCE risk in both ACCORD and ORIGIN (hazard ratio [HR] per SD 1.27, 95% CI 1.18-1.37, P = 4 × 10-10, and HR per SD 1.35, 95% CI 1.16-1.58, P = 2 × 10-4, respectively). This association was independent from interventions tested in the trials and persisted, though attenuated, after adjustment for classic cardiovascular risk predictors. Adding the GRS to clinical predictors improved incident MCE risk classification (relative integrated discrimination improvement +8%, P = 7 × 10-4). The performance of this GRS was superior to that of GRS based on the smaller number of CAD loci available in previous years.

CONCLUSIONS:

When combined into a GRS, CAD loci identified in the general population are associated with CAD also in type 2 diabetes. This GRS provides a significant improvement in the ability to correctly predict future MCE, which may increase further with the discovery of new CAD loci.

• Authors: Mario Luca Morieri, He Gao, Marie Pigeyre, Hetal S Shah, Jennifer Sjaarda, Christine Mendonca, Timothy Hastings, Patinut Buranasupkajorn, Alison A Motsinger-Reif, Daniel M Rotroff, Ronald J Sigal, Santica M Marcovina, Peter Kraft, John B Buse, Michael J Wagner, Hertzel C Gerstein, Josyf C Mychaleckyj, Guillaume Parè, Alessandro Doria
• Journal: Diabetes care (Diabetes Care) Vol. 41 Issue 11 Pg. 2404-2413 (Nov 2018) ISSN: 1935-5548 [Electronic] United States
• PMID: 30262460 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © 2018 by the American Diabetes Association.

Chemical References

• Genetic Markers
• Simvastatin
• Fenofibrate

Topics

• Aged
• Cohort Studies
• Coronary Artery Disease (diagnosis, genetics, prevention & control)
• Diabetes Mellitus, Type 2 (complications, diagnosis, drug therapy, genetics)
• Diabetic Angiopathies (diagnosis, genetics, prevention & control)
• Female
• Fenofibrate (administration & dosage)
• Genetic Association Studies
• Genetic Markers
• Genetic Predisposition to Disease
• Humans
• Male
• Middle Aged
• Molecular Diagnostic Techniques
• Polymorphism, Single Nucleotide
• Risk Assessment
• Risk Factors
• Simvastatin (administration & dosage)