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 ≥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 ≥11.1 mmol/l. Of these 164 subjects, 55 (33.5%) had 2hPG ≥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 ≥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.