Correlation of Plasma Endothelial Cell Activity With Cardiovascular Events in Patients With Diabetes Mellitus Type 2

CSP 465-B, Correlation of Plasma Endothelial Cell (Basic Fibroblast Growth Factor) Activity With Cardiovascular Events in Patients with Diabetes Mellitus, Type II. Mark Zimering M.D. Objectives: Endothelial cell dysfunction plays a role in the development of the atherosclerotic vascular lesion and it is also thought to provide a mechanism for increased urinary albumin excretion in type 2 diabetes mellitus. Micro- or macroalbuminuria are associated with increased cardiovascular (CV) morbidity and mortality in type 2 diabetes mellitus. In at least one longitudinal study in older-age onset patients, micro-or macroalbuminuria robustly predicted increased CV risk independent of other diabetes-related factors.1 The pathogenetic mechanisms underlying a significant association between micro- or macroalbuminuria and CV risk in diabetes mellitus are not known but may include: growth factors, clotting factors, lipids, or hemodynamic factors. The aim of the present study is to investigate whether an angiogenic growth factor, basic fibroblast growth factor (bFGF), plays a role in increased CV risk in type 2 diabetes mellitus. Research Plan: BFGF (FGF-2) is one of the most potent known angiogenesis factors. Increased bFGF was previously associated with both endothelial cell injury and micro- or macroalbuminuria. In a prior study of 73 older-age onset veterans with type 2 diabetes mellitus (JCEM, 1996), we found plasma endothelial cell (bFGF) activity was significantly associated with glycemic levels, and (in multiple regression analysis) independently associated with both microalbuminuria and retinopathy. We will test whether plasma endothelial cell (bFGF) activity is significantly, independently associated with a pooled endpoint of cardiovascular events that includes myocardial infarction (MI), coronary revascularization, congestive heart failure (CHF), or CV mortality. We expect that increased bFGF may itself be a robust marker for increased CV risk in diabetes mellitus for t