Impaired fibrinolysis and insulin resistance in patients with hypertension

Plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) antigens and activities were measured in 28 patients with hypertension and 12 normal controls. Steady state plasma glucose (SSPG) concentrations were also determined after an infusion of somatostatin, insulin and glucose. Patients with hypertension were further subdivided into two groups: insulin resistance (SSPG > 190 mg/dL, n = 14) and no insulin resistance (SSPG < 190 mg/dL, n = 14). As compared to normal controls, hypertensive patients, either with or without insulin resistance, had significant (P < .005) increases in PAI-1 activity (18.6 +/- 1.3 v 8.1 +/- 0.8 IU/mL), PAI-1 antigen (31.1 +/- 2.0 v 12.7 +/- 0.9 ng/mL) and tPA antigen (15.5 +/- 0.9 v 8.8 +/- 0.9 ng/mL), and significant decrease in tPA activity (0.43 +/- 0.05 v 1.02 +/- 0.16 IU/mL) than normotensive controls. Furthermore, hypertensive patients with insulin resistance had significantly higher PAI-1 activity (22.0 +/- 2.2 v 15.3 +/- 0.8 IU/mL, P = .006) and tPA antigen (17.4 +/- 1.2 v 13.6 +/- 1.3 ng/mL, P = .02) than did hypertensive patients without insulin resistance. However, PAI-1 antigen was insignificantly higher (34.1 +/- 2.9 v 28.1 +/- 2.4 ng/mL, P = .06) and tPA activity insignificantly lower (0.42 +/- 0.08 v 0.43 +/- 0.08 IU/mL, P = .47) in hypertensive patients with insulin resistance than in those without insulin resistance. In addition, PAI-1 activity and tPA antigen were significantly correlated with blood pressure, SSPG, triglyceride, HDL-cholesterol and integrated glucose response to an oral load of 75 g glucose. Thus, patients with hypertension have impaired fibrinolytic activity due to increased PAI-1 when compared to normotensive controls, and the magnitude of this fibrinolytic defect is greater in hypertensive patients who have insulin resistance. Insulin resistance with associated metabolic abnormalities may be one of the causes for impaired fibrinolysis in hypertension.