Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study

OBJECTIVE: To test the hypothesis that fasting hyperglycemia (FHG) and 2-h postchallenge glycemia (2hPG) independently increase the risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: During 1991-1995, we examined 3,370 subjects from the Framingham Offspring Study who were free from clinical CVD (coronary heart disease, stroke, or intermittent claudication) or medication-treated diabetes, and we followed them for 4 years for incident CVD events. We used proportional-hazards regression to assess the risk associated with FHG (fasting plasma glucose > or =7.0 mmol/l) and 2hPG, independent of the risk predicted by standard CVD risk factors. RESULTS: Mean subject age was 54 years, 54% were women, and previously undiagnosed diabetes was present in 3.2% by FHG and 4.9% (164) by FHG or a 2hPG > or =11.1 mmol/l. Of these 164 subjects, 55 (33.5%) had 2hPG > or =11.1 without FHG, but these 55 subjects represented only 1.7% of the 3,261 subjects without FHG. During 12,242 person-years of follow-up, there were 118 CVD events. In separate sex- and CVD risk-adjusted models, relative risk (RR) for CVD with fasting plasma glucose > or =7.0 mmol/l was 2.8 (95% CI 1.6-5.0); RR for CVD per 2.1 mmol/l increase in 2hPG was 1.2 (1.1-1.3). When modeled together, the RR for FHG decreased to 1.5 (0.7-3.6), whereas the RR for 2hPG remained significant (1.1, 1.02-1.3). The c-statistic for a model including CVD risk factors alone was 0.744; with addition of FHG, it was 0.746, and with FHG and 2hPG, it was 0.752. CONCLUSIONS: Postchallenge hyperglycemia is an independent risk factor for CVD, but the marginal predictive value of 2hPG beyond knowledge of standard CVD risk factors is small.