Inheritance conjointly contributing to fibrinolysis and hyperlipidemia.
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)
Glueck
C J
CJ
Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229.
Glueck
H I
HI
Tracy
T
T
Speirs
J
J
Stroop
D
D
D000328:Adult; D002318:Cardiovascular Diseases / Q000150:complications; D005215:Fasting / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis / Q000235:genetics*; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010958:Plasminogen / Q000032:analysis; D015849:Plasminogen Inactivators / Q000032:analysis; D011446:Prospective Studies; D012044:Regression Analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis; D000979:alpha-2-Antiplasmin / Q000032:analysis
D008055:Lipids; D008074:Lipoproteins; D015849:Plasminogen Inactivators; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D010958:Plasminogen; D010959:Tissue Plasminogen Activator