Basic fibroblast growth factor predicts cardiovascular disease occurrence in participants from the veterans affairs diabetes trial

Abstract

Aim: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in adults with type 2 diabetes mellitus. The aim of the present study was to test whether plasma basic fibroblast growth factor (bFGF) levels predict future CVD occurrence in adults from the Veterans Affairs Diabetes Trial (VADT).

Methods: Nearly 400 veterans, 40 years of age or older having a mean baseline diabetes duration of 11.4 years were recruited from outpatient clinics at six geographically distributed sites in the VADT. Within the VADT, they were randomly assigned to intensive or standard glycemic treatment, with follow-up as much as seven and one-half years. CVD occurrence was examined at baseline in the patient population and during randomized treatment. Plasma bFGF was determined with a sensitive, specific two-site enzyme-linked immunoassay at the baseline study visit in all 399 subjects and repeated at the year 1 study visit in a randomly selected subset of 215 subjects.

Results: One hundred and five first cardiovascular events occurred in these 399 subjects. The best fit model of risk factors associated with the time to first CVD occurrence (in the study) over a seven and one-half year period had as significant predictors: prior cardiovascular event [hazard ratio (HR) 3.378; 95% confidence intervals (CI) 3.079-3.807; P < 0.0001), baseline plasma bFGF (HR 1.008; 95% CI 1.002-1.014; P = 0.01), age (HR 1.027; 95% CI 1.004-1.051; P = 0.019), baseline plasma triglycerides (HR 1.001; 95% CI 1.000-1.002; P = 0.02), and diabetes duration-treatment interaction (P = 0.03). Intensive glucose-lowering was associated with significantly decreased hazard ratios for CVD occurrence (0.38-0.63) in patients with known diabetes duration of 0-10 years, and non-significantly increased hazard ratios for CVD occurrence (0.82-1.78) in patients with longer diabetes duration.

Conclusion: High level of plasma bFGF is a predictive biomarker of future CVD occurrence in this population of adult type 2 diabetes.

Keywords: basic fibroblast growth factor; cardiovascular disease; type 2 diabetes mellitus.

Figures

Figure 1

Hazard ratio for post-baseline (A) CVD or (B) CHD occurrence in intensive treatment group by duration of diabetes known at baseline. Squares indicate point estimates and bars denote 95% confidence intervals. Point estimates are obtained from the multivariable adjusted model that includes age, prior CV event, baseline bFGF, treatment, duration, and treatment × duration and are illustrated for 5-year intervals between 0–30 years of baseline diabetes duration.

Figure 2

Endothelial cell bioactivity in the 25–75% ammonium sulfate pellet of plasma. Ammonium sulfate pellet fractions from plasma in 26 consecutively enrolled VADT subjects were tested for endothelial cell growth promotion after 4 days of incubation as described in Materials and Methods. Each point represents the mean of four–six determinations.

Figure 3

Endothelial cell stimulatory activity in protein A eluate fractions in 16 VADT plasmas was significantly correlated with increasing plasma bFGF-IR concentration. Growth activity was determined after 4 days’ incubation as described in Materials and Methods. Each point represents the mean of quadruplicate determinations.