Cardiovascular Risk Factors and Pregnancy Compromise

Hyperhomocysteinemia: Recent research has shown a correlation between established genetic cardiovascular risk factors and a compromised uteroplacental vascular environment. Markers of accelerated atherosclerosis, including elevated maternal plasma lipoprotein(a) and hyperhomocysteinemia (associated with the MTHFR gene polymorphism), have been implicated in recurrent early fetal loss, fetal growth restriction and preeclampsia. The homozygous state for the MTHFR gene is associated with premature athersclerosis and thrombosis, and even the moderately elevated homocysteine levels seen in heterozygotes appear to carry increased risk cardiovascular sequelae. Hyperhomocyteinemia has also been associated with unexplained recurrent early pregnancy loss, with the suggestion that correction of the maternal homocysteine levels (via folate/B6 supplementation) may favor pregnancy success. Fully 31% of women with placental abruption or placental infarct in one study were reported to be hyperhomocysteinemic. The precise mechanism of homocysteine-associated vascular injury is not clear, but most likely involves direct effects on the endothelium via generation of hydrogen peroxides, enhanced endothelial factor V activity, and impaired endothelial thrombomodulin expression. Hyperhomocysteinemia may also stimulate proliferation of vascular smooth muscle cells in vitro, contributing to the vascular dysfunction of this condition.

Thrombophilia: a state, either inherited or acquired, characterized by impaired natural anticoagulant or fibrinolytic pathways and a damaged vascular endothelium, and resulting in the abnormal formation of venous or arterial thrombosis. Status can be exacerbated by the existance of more than one predisposing factor (e.g. factor V Leiden mutation and MTHFR heterozygote).

Antithrombin III: serine protease inhibitor that acts with heparin to inhibit enzymztically active clotting factors, such as factor Xa and thrombin.

Protein C : when activated, functions as an anticoagulant, inhibiting coagulation by inactivating factor Va and factor VIIIa.

Activated protein C: plasma protein C in converted to activated protein C by the enzyme thrombin, when thrombin is bound by the receptor protein thrombomodulin on the endothelial surface.

Protein S: in its free (active) form acts as a cofactor of activated protein C.

MTHFR: 5,10 methylenetetrahydrofolate reductase (MTHFR) deficiency is a common inborn error of folate metabolism that results in hyperhomocytenemia (elevated plasma levels of homocysteine) and is considered an important genetic risk factor for systemic vascular disease. Although there are a number of identified polymorphisms, the most commonly studied (C677T) renders the enzyme thermolabile (less active) in both the heterozygous and homozygous state. Effects can be exacerbated by por diet/low folate intake. Estimated frequency in caucasians is 0.3 - 0.35, in african-americans 0.1

Factor V Leiden: a point mutation at site R506Q, present in approximately 5% of the general population, results in physiologic inhibition of factor Va, resistance to activated protein C and a predisposition to venous thrombosis.

Lipoprotein(a): lipoprotein composed of LDL cholesterol and apolipoprotein A thought to reduce vascular fibrinolytic capacity and thromboresistance, and be a marker of accelerated atherosclerosis.

Prothrombin : acts with factor Xa, along with cofactor Va, to generate thrombin (see activated protein C above). The point mutation at G20210A results in raised plasma prothrombin levels has been shown to be associated with an increased risk of myocardial infarction in young women.

Copyright © 2000-2004 EarlyPath. All rights reserved.