Genetic tools for coronary risk assessment in type 2 diabetes: A cohort study from the ACCORD clinical trial

Autor: Marie Pigeyre, Michael J. Wagner, Hertzel C. Gerstein, Josyf C. Mychaleckyj, Daniel M. Rotroff, Alessandro Doria, Mario Luca Morieri, Santica M. Marcovina, Timothy Hastings, Peter Kraft, Hetal Shah, Patinut Buranasupkajorn, Guillaume Paré, Christine Mendonca, He Gao, Ronald J. Sigal, Alison A. Motsinger-Reif, John B. Buse, Jennifer Sjaarda
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Simvastatin
Endocrinology
Diabetes and Metabolism

Type 2 diabetes
Coronary Artery Disease
030204 cardiovascular system & hematology
Coronary artery disease
Cohort Studies
0302 clinical medicine
Fenofibrate
Risk Factors
Myocardial infarction
education.field_of_study
Hazard ratio
Aged
Diabetes Mellitus
Type 2

Diabetic Angiopathies
Female
Genetic Predisposition to Disease
Humans
Middle Aged
Molecular Diagnostic Techniques
Polymorphism
Single Nucleotide

Risk Assessment
Genetic Association Studies
Genetic Markers
Single Nucleotide
Type 2
Cohort study
medicine.medical_specialty
Cardiovascular and Metabolic Risk
Population
03 medical and health sciences
Diabetes mellitus
Internal medicine
Internal Medicine
medicine
Diabetes Mellitus
Polymorphism
education
Advanced and Specialized Nursing
Unstable angina
business.industry
fungi
medicine.disease
030104 developmental biology
business
Zdroj: Diabetes Care
Popis: 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.
Databáze: OpenAIRE