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.
Highlights
Intensive diabetes treatment slows the development of retinopathy, nephropathy, and neuropathy [1]; its role in reducing cardiovascular disease (CVD) events in adult type 2 diabetes is more complex
The best fit model of risk factors associated with the time to first Cardiovascular disease (CVD) occurrence 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 basic fibroblast growth factor (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 nonsignificantly increased hazard ratios for CVD occurrence (0.82–1.78) in patients with longer diabetes duration
Summary
Intensive diabetes treatment slows the development of retinopathy, nephropathy, and neuropathy [1]; its role in reducing cardiovascular disease (CVD) events in adult type 2 diabetes is more complex. In a planned secondary analysis to the VADT (n = 399), we reported that baseline plasma bFGF was a novel www.frontiersin.org bFGF predicts CVD in diabetes significant predictor of the time to first post-baseline occurrence of coronary heart disease (CHD) [7]. The aims of the present analysis were [1] to test whether baseline plasma bFGF predicts the time to first post-baseline CVD occurrence in risk models that adjust for treatment-duration interaction, [2] to determine whether elevated bFGF at year 1 of treatment predicts the subsequent occurrence of CVD events in the VADT subjects, and [3] to investigate novel mechanisms for vascular cell growth promotion involving bFGF or long-lasting (FGF-like) autoantibodies in diabetic subsets having increased plasma bFGF
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