Inheritance conjointly contributing to fibrinolysis and hyperlipidemia

Area of Science:

• Cardiovascular Genetics
• Hemostasis and Thrombosis
• Lipid Metabolism

Background:

• Hyperlipidemia is a significant risk factor for cardiovascular disease.
• Lipoprotein (a) [Lp(a)] levels are associated with increased thrombotic risk.
• Fibrinolytic system activity plays a crucial role in regulating blood clot breakdown.

Purpose of the Study:

• To investigate the within-family relationships of basal fibrinolytic activity and its determinants in hyperlipidemic subjects with varying Lp(a) levels.
• To assess the heritability of key fibrinolytic factors, including plasminogen activator inhibitor activity (PAI-Fx) and tissue plasminogen activator activity (tPA-Fx).

Main Methods:

• Study included hyperlipidemic probands with high Lp(a) (> 35 mg/dL) and their first-degree relatives, and probands with Lp(a) < 35 mg/dL and their relatives.
• Assessed plasma levels of PAI-Fx, tPA-Fx, Lp(a), apolipoproteins (apo B, apo A-1), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), plasminogen, and alpha 2-antiplasmin.
• Statistical analyses included correlation coefficients and stepwise regression to identify determinants and heritability.

Main Results:

• Significant within-family correlations were observed for PAI-Fx and tPA-Fx, suggesting heritability.
• High-Lp(a) probands' tPA-Fx correlated with relatives' tPA-Fx, while probands' PAI-Fx correlated with relatives' PAI-Fx.
• Triglycerides (TG) and Quetelet index were independent determinants of fibrinolytic factors, while Lp(a) influenced fibrinogen levels.

Conclusions:

• The study demonstrates significant within-family heritability of key fibrinolytic regulators, PAI-Fx and tPA-Fx, in hyperlipidemic kindreds.
• Genetic factors likely play a substantial role in determining basal fibrinolytic activity.
• Understanding these heritable components can inform strategies for managing thrombotic risk in hyperlipidemic populations.