Abstract
Background: Although the renin-angiotensin system and insulin resistance (IR) have been identified as major regulators of plasminogen activator inhibitor type-1 (PAI-1), their roles in hypertensive subjects is not clearly defined. Methods: We examined the effect of dietary salt restriction on PAI-1 levels in 239 hypertensive subjects from three centers. Subjects were placed on a 200 and 10 mmol/day sodium diets for 1-week periods. Plasma renin activity (PRA) and PAI-1 levels were measured on the last day of both diets and fasting insulin, glucose, and aldosterone (ALDO) levels, only on the low salt diet. Results: Sodium restriction increased PAI-1 levels from 32.1 ± 2.5 ng/mL to 39.8 ± 3.2 ng/mL (P = .009). There was a strong positive correlation between PAI-1 levels and PRA (r = 0.228, P = .0004), IR (r = 0.222, P = .001), triglycerides (r = 0.275, P < .001), and ALDO (P = .018 for linear trend). The patients were divided into low renin (low IR and ALDO levels), nonmodulators (normal PRA, high IR, and low ALDO levels), and modulators (normal PRA, intermediate IR, and normal ALDO levels) groups to assess the relative contribution of each factor to PAI-1 levels. Modulators had significantly (P = .019) higher PAI-1 levels compared to the low renin and nonmodulators who had similar PAI-1 levels. Conclusions: Plasma renin activity, IR, and ALDO all correlate with PAI-1 levels in the hypertensive subjects. However, the data suggest that ALDO may be an important factor contributing to the variability of PAI-1 levels in individual hypertensive subjects.