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 |
Externí odkaz: |