Risk of ischemic heart disease death from impaired fasting glucose and impaired renal function attenuated by their interaction among male hypertensive subjects

Purpose Our study assessed the joint association of impaired fasting glucose (IFG: serum glucose ≥ 110 mg/dL) and impaired renal function (IRF: creatinine clearance ≤60 mL/min) with the risk for ischemic heart disease (IHD) death in treated male hypertensive subjects. Methods We examined data for 6831 participants in the Worksite Hypertension Control Program with baseline creatinine clearance and serum glucose values. Patients with preexisting renal disease were excluded, as were those with follow-up less than 180 days. Mean follow-up time was 10.5 years (range 0.5–22.5). Mean age at entry was 52 years. IHD death outcomes (n = 373) were defined as those with International Classification of Diseases, 9th revision (ICD-9), codes 410 through 414 ascertained from the National Death Index. Serum glucose was dichotomized as impaired fasting glucose (IFG) and normal. Creatinine clearance, estimated by the Cockcroft–Gault formula, was dichotomized as IRF and normal. Cox proportional hazards models were constructed with IFG, IRF, age, ethnicity, systolic blood pressure, cholesterol, blood urea nitrogen, body mass index, smoking, and a previous history of cardiovascular disease, diabetes, left ventricular hypertrophy, or prior antihypertensive treatment. Results IFG and IRF each showed a significant positive association with IHD. An interaction product term of IRF and IFG significantly (P = 0.004) improved the model. The product term was negatively associated with IHD (hazard ratio HR = 0.46; 95% confidence interval CI = 0.26, 0.80; P = 0.006). Stratifying by IRF found IFG a highly significant predictor of IHD (HR = 1.49; 95% CI = 1.13, 1.95; P = 0.004) in the normal renal stratum; in the IR stratum, IFG was not a significant predictor of IHD (HR = 0.62; 95% CI = 0.36, 1.08; P = 0.09). Conclusion These results suggest an attenuating qualitative interaction between creatinine clearance less than 60 mL/min and IFG among treated male hypertensive subjects. Whether the observed qualitative interaction is simply statistical or reflects a biological counter-regulatory mechanism that mitigates the atherosclerotic effects of IFG and IRF needs further study.