Amelioration of the inhibition of fibrinolysis in elderly, obese subjects by moderate energy intake restriction

Abstract

A possible cause of accelerated atherothrombosis in the syndrome of insulin resistance appears to be an elevated blood concentration of plasminogen activator inhibitor type-1 (PAI-1). Insulin resistance occurs with aging, attributable partly to increased adiposity. Scarce information exists regarding the effects of weight loss in elderly, obese individuals on PAI-1 concentrations. Consequently, weight loss (9 +/- 1 kg) was induced by energy intake restriction in 19 elderly, obese individuals, and its effect on fibrinolytic system peptides was measured. Initially elevated PAI-1 concentrations decreased by 50%, with a simultaneous decrease in the concentration of tissue-type plasminogen activator (t-PA)/PAI-1 complexes but no significant change in t-PA suggested a decrease in inhibition of the fibrinolytic system. The concentration of plasmin/antiplasmin complexes (PAP complex) increased by approximately 20%, indicating augmented fibrinolytic system activity. The decline in PAI-1 correlated with that of the decrease in body weight (r = 0.5, P < 0.05) and fat mass losses (r = 0.46, P < 0.05). The increase in PAP complexes correlated with weight and fat mass losses (r = 0.4 and r = 0.46, respectively; P < 0.05 for both). No correlation was seen between fibrinolytic system variables and baseline concentrations of substrates or insulin, but the change in PAI-1 correlated with the change in plasma triacylglycerols (r = 0.58, P < 0.05). Results indicate that energy restriction sufficient to induce moderate weight loss leads to diminution of elevated plasma PAI-1 and relief of inhibition of the fibrinolytic system in elderly, obese subjects. To the extent that these changes are associated with a decrease in the progression of vasculopathy, weight loss in elderly, obese individuals may be a useful means to reduce cardiovascular morbidity and mortality.