A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women's Health Initiative

Background While there is increasing recognition of the risks associated with hypoglycemia in patients with diabetes, few studies have investigated incident cause-specific cardiovascular outcomes with regard to low fasting glucose in the general population. Objective We hypothesized that low fasting glucose would be associated with cardiovascular disease risk and all-cause mortality in postmenopausal women. Methods To test our hypothesis, we used both continuous incidence rates and Cox proportional hazards models in 17,287 participants from the Women's Health Initiative with fasting glucose measured at baseline. Participants were separated into groups based on fasting glucose level: low (< 80 mg/dL), normal/reference (80–99 mg/dL), impaired (100–125 mg/dL), and diabetic (≥ 126 mg/dL). Results Participants were free of cardiovascular disease at enrollment, had mean age of 62 years, and were 52% Caucasian, 24% African American, 8% Asian, and 12% Hispanic. Median follow-up was 15 years. Graphs of continuous incidence rates compared to fasting glucose distribution exhibited evidence of a weak J-shaped association with heart failure and mortality that was predominantly due to participants with treated diabetes. Impaired and diabetic fasting glucose were positively associated with all outcomes. Associations for low fasting glucose differed, with coronary heart disease (HR = 0.64 (0.42, 0.98)) significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and not significant. Conclusions Fasting glucose at the upper range, but not the lower range, was significantly associated with incident cardiovascular disease and all-cause mortality.