Metabolic approach to the diagnosis and treatment of atherosclerotic peripheral vascular disease.
Metabolic and clinical peculiarities of patients with peripheral vascular disease (PVD) were evaluated in two studies. In the first study lipid and lipoprotein composition of 20 patients with PVD were examined. Twelve of these patients were normolipidemic, the other 8 hypertriglyceridemic. Ten normolipidemic and ten hyperlipidemic age-matched subjects served as controls. High density lipoprotein cholesterol (HDL-C) levels were markedly reduced in the hypertriglyceridemic, both with (35.1 +/- 5.0 mg/dl) and without (36.2 +/- 11.7 mg/dl) PVD as compared to the normolipidemic patients (47.0 +/- 6.3 mg/dl) and controls (48.1 +/- 10 mg/dl). All the PVD patients showed an increased apolipoprotein B content in the very low density lipoproteins (VLDL) as compared to controls (p less than 0.001). A significant correlation between VLDL-cholesterol and apo B levels was detected in both groups; however, two distinct populations could be clearly separated (slopes of the regression lines: PVD patients = 0.350; controls = 0.215, p less than 0.0001). These data suggest a possible discriminatory power of VLDL-apo B levels in PVD patients independent of other metabolic parameters. In the second study, the clinical activity of metformin (N, N-dimethylbiguanide) a widely used antidiabetic agent, on arterial blood flow was evaluated in 15 patients with PVD. Flow was determined by quantitative strain-gauge plethysmography during a cross-over trial, comparing 6 months of drug and placebo administration. Metformin (850 mg tid) significantly increased arterial flow after a standardized ischemia in both sequences. In spite of the minimal changes of plasma lipid levels during metformin, a highly significant increase of HDL-C levels (+8.3% during the whole treatment) was demonstrated. Plasma levels of isoprotein AI-1 were also raised during the metformin period. Although the mechanism/s of the beneficial effects of metformin on flow cannot, at present be defined, the reported results underline the significant therapeutic potential of this metabolic drug treatment in PVD.