Inheritance conjointly contributing to fibrinolysis and hyperlipidemia.

ABSTRACT

Our specific aim was to assess within-family relationships of basal fibrinolytic activity and its determinants in hyperlipidemic probands (n = 34) with high lipoprotein (a) [Lp(a)] levels (> 35 mg/dL) and their first-degree relatives (n = 74) and in hyperlipidemic probands (n = 19) with Lp(a) < 35 and their first-degree relatives (n = 23). Probands' plasminogen activator inhibitor activity (PAI-Fx), the major fibrinolysis inhibitor, correlated with first-degree relatives' PAI-Fx in high-Lp(a) kindreds (r = .30, P = .06) and in Lp(a) < 35 kindreds (r = .43, P < or = .05). Probands' tissue plasminogen activator activity (tPA-Fx), the major fibrinolysis activator, was inversely associated with first-degree relatives' PAI-Fx in high-Lp(a) kindreds (r = -.30, P = .06) and in Lp(a) < 35 kindreds (r = -.49, P < or = .025). These correlations [irrespective of probands' Lp(a)] pointed to within-family heritability of the major fibrinolysis inhibitor, PAI-Fx, and the fibrinolysis stimulator, tPA-Fx. There were many other within-family correlations. High-Lp(a) probands' tPA-Fx, the stimulator of fibrinolysis, correlated with first-degree relatives' tPA-Fx (r = .32, P < or = .05). High-Lp(a) probands' plasminogen was inversely correlated with first-degree relatives' alpha 2-antiplasmin, a major fibrinolytic inhibitor (r = -.41, P < or = .01), and with their Lp(a) [r = -.24, P < or = .05]. High-Lp(a) probands' tPA-Fx correlated inversely with first-degree relatives' apolipoprotein (apo) B (r = -.28) and triglyceride ([TG] r = -.41), and positively with their high-density lipoprotein cholesterol ([HDLC] r = .40) and apo A-1 (r = .33; all P < or = .025). High-Lp(a) probands' PAI-Fx correlated positively with first-degree relatives' apo B (r = .34) and TG (r = .47), and inversely with HDLC (r = -.34) and apo A-1 (r = -.30; all P < or = .01). By stepwise regression, the Quetelet index (a measure of relative ponderosity) was independently inversely associated with tPA-Fx (P < or = .05) and positively associated with tPA-Ag and PAI-Fx (P < or = .05). TG was a positive independent determinant of PAI-Fx (P < or = .05), alpha 2-antiplasmin (P < or = .05), and plasminogen (P < or = .05). Lp(a) was a positive, independent determinant of fibrinogen (P < or = .05).(ABSTRACT TRUNCATED AT 400 WORDS)