Abstract 15100: Nonfasting Glucose and Ischemic Heart Disease a Mendelian Randomization Approach
Background Elevated plasma glucose levels associate with increased risk of ischemic heart disease (IHD), but whether this is a causal relationship is unknown. We tested whether elevated nonfasting glucose levels cause IHD.
Methods Using a Mendelian randomization approach, we studied 80,522 white persons from Copenhagen, Denmark of which 14,058 developed IHD: the Copenhagen City Heart Study, a prospective general population study with 35 years follow-up (1976-2011); the Copenhagen General Population Study, a cross-sectional/prospective general population study (2003-2011); and the Copenhagen Ischemic Heart Disease Study, a case-control study (1991-2011). Individuals were genotyped for variants in GCK (rs4607517), G6PC2 (rs560887), ADCY5 (rs11708067), DGKB (rs2191349), and ADRA2A (rs10885122), all associated with elevated fasting glucose levels in genome-wide association studies.
Results Risk of IHD increased stepwise with increasing nonfasting glucose levels. The hazard ratio for IHD in individuals with nonfasting glucose levels ≥11 mmol/L (≥198mg/dL) versus <5 mmol/L (<90mg/dL) was 7.3 (95%CI: 4.5-12.1) adjusted for age and gender and 2.6 (1.4-4.8) adjusted multifactorially. Increasing number of glucose increasing alleles associated with increasing nonfasting glucose levels, and with increased risk of IHD. The estimated causal odds ratio for IHD by instrumental variable analysis for a 1 mmol/L (18mg/dL) increase in nonfasting glucose levels due to genotypes combined was 1.25 (1.03-1.52), while the corresponding observed hazard ratio for IHD by Cox regression was 1.18 (1.15-1.22).
Conclusion Like common nonfasting glucose elevation, plasma glucose increasing polymorphisms associate with increased risk of ischemic heart disease. These data are compatible with a causal association.
- © 2011 by American Heart Association, Inc.