Renal Dysfunction Predicts Attenuation of Ischemic Heart Disease Mortality Risk From Elevated Glucose Among Treated Hypertensive Patients

Background Impaired fasting glucose (IFG) and renal dysfunction are recognized as independent risk factors for adverse heart outcomes. This study examines the interaction of renal dysfunction and IFG (≥110 mg/dL) upon the risk of ischemic heart disease (IHD) mortality among treated hypertensive subjects. Methods Subjects were 9918 participants in a worksite-based antihypertensive treatment program in New York City (1981 to 1999) with baseline estimated glomerular filtration rate (GFR) >30 mL/min/1.73 m2 (estimated by Cockcroft and Gault formula) observed for a mean follow-up of 9.6 ± 5.0 years (range 0.5–20.0 years). Outcome events were IHD deaths (n = 337) ascertained from the National Death Index. Cox proportional hazard models were constructed for the entire cohort to assess the interaction and then stratified by moderate renal dysfunction (MRD; GFR 60-30 mL/min/1.73 m2). Age and sex adjusted rates were calculated within MRD and NKF-defined categories. Hazard ratios for IFG were calculated within MRD strata. Results The interaction product term of MRD and IFG significantly improved (P = .001) a Cox proportional hazard model after adjusting for known cardiovascular risk factors. Among participants with GFR ≥60 mL/min/1.73 m2 the IHD mortality hazard ratio for IFG was 1.47 (95% CI = 1.09–1.99; P = .012). Conversely, among participants with MRD, the IHD mortality hazard ratio for IFG was 0.44 (95% CI = 0.21–0.94; P = .034). Conclusions These results suggest an attenuating effect modification of GFR on IHD mortality risk associated with IFG among treated hypertensive subjects. Whether the observed qualitative interaction is simply statistical or reflects a biological counter-regulatory mechanism requires additional study.