Increased plasma basic fibroblast growth factor is associated with coronary heart disease in adult type 2 diabetes mellitus

Abstract

Basic fibroblast growth factor (bFGF) is a potent endothelial and smooth muscle cell mitogen that does not normally circulate. Plasma bFGF-like bioactivity was increased in association with persistent microalbuminuria (a risk marker for cardiovascular disease) in adult type 2 diabetes mellitus. In the present study, we tested whether baseline plasma bFGF immunoreactivity (IR) predicts the occurrence of a subset of cardiovascular disease outcomes in adults with advanced type 2 diabetes mellitus from the Veterans Affairs Diabetes Trial (mean: age, 59 years; diabetes duration, 11 years; baseline hemoglobin A1c, 9.5%). Plasma bFGF-IR was determined with a sensitive and specific 2-site enzyme-linked immunoassay in 399 patients at the baseline visit. These results were then evaluated as possible predictors of the occurrence of prespecified cardiovascular or coronary heart disease end points. There was a borderline-significant association (P = .07) between plasma bFGF-IR and the main study cardiovascular disease outcome (myocardial infarction, congestive heart failure, cerebrovascular accident, amputation, cardiovascular death, coronary, cerebrovascular or peripheral revascularization, and inoperable coronary artery disease). Plasma bFGF-IR was significantly associated with the occurrence of coronary heart disease (P = .01). After adjusting for clinical risk factors, bFGF (hazard ratio [HR], 1.013; 95% confidence interval [CI], 1.007-1.019; P < .0001), prior macrovascular event (HR, 3.55; 95% CI, 2.154-5.839; P < .0001), and duration of diabetes (HR, 1.041; 95% CI, 1.012-1.071; P = .0055) were all significantly associated with time to first postrandomization coronary heart disease occurrence. These results suggest that increased plasma bFGF-IR may be a novel risk marker for coronary heart disease occurrence in adult men with advanced type 2 diabetes mellitus.