Blood Glucose and Coronary Artery Disease in Nondiabetic Patients

Abstract

OBJECTIVE -Nondiabetic patients were studied to determine whether modest elevations in blood glucose may be associated with a greater incidence of coronary artery disease (CAD).RESEARCH DESIGN AND METHODS -Baseline morning blood glucose determinations were evaluated with respect to subsequent coronary disease using records from 24,160 nondiabetic patients. CAD was identified from myocardial infarction, new diagnoses of angina, or new prescriptions for nitroglycerin that occurred more than a year after baseline glucose determinations.RESULTS -Of 24,160 patients studied, 3,282 patients developed CAD over a total analysis time at risk of 77,048 years. Higher baseline morning glucose (100 -126 vs. Ͻ100 mg/dl) was associated with a 53.9% greater myocardial infarction incidence rate, an 18.6% greater acute coronary syndrome incidence rate, and a 26.4% greater number of new prescriptions for nitrates (all P Ͻ 0.05). A Cox proportional hazards model with adjustment for age, BMI, sex, creatinine, lipids, smoking, and medications showed that elevated fasting glucose was associated with an increased hazard for new CAD (hazard ratio 1.13 [95% CI 1.05-1.21], glucose Ͼ100 vs. Ͻ100 mg/dl). Kaplan-Meier analysis showed that elevated baseline glucose was associated with a progressive increase risk of CAD with time.CONCLUSIONS -Patients with higher baseline blood glucose levels in the absence of diabetes and after adjustment for covariants have a significantly greater risk for development of CAD. Diabetes Care 29:998 -1001, 2006N ondiabetic patients were studied to determine whether elevations in blood glucose may be associated with increased risk for coronary artery disease (CAD). Although diabetes is a known risk factor for CAD (1-3), the risk of higher blood glucose in the absence of diabetes is unclear (4,5). Pathologic consequences from modest elevations of glucose are plausible since impaired glucose tolerance and impaired fasting glucose have been associated with macrovascular disease (6) and greater mortality (7). Patients presenting with acute coronary syndrome frequently have glucose intolerance (8), and it has been reported that glucose intolerance but not impaired fasting glucose may be associated with CAD (5,9). In contrast, meta-analysis indicates that glucose above a threshold of 100 mg/dl may also be a significant risk (10). Since impaired fasting glucose is increasingly common, affecting Ͼ35 million adults in the U.S. (11), and CAD affects a majority of older adults, associations between these common, morbid, and potentially fatal conditions are of clinical importance.Adverse consequences from hyperglycemia may reflect effects of glucose as well as hyperinsulinemia. Glycemic effects include elevations in reactive oxygen species and formation of advanced glycation products (12). Hyperinsulinemia has been associated with mitogenic effects on vascular smooth muscle cells (13,14). Because elevated blood glucose is a common and potentially treatable condition, characterization of whether higher blood glucose may contr...

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