No Association of Plasma Prothrombin Concentration or the G20210A Mutation with Incident Cardiovascular Disease

Abstract

SummaryProthrombin is a key factor in blood clotting, a process intimately involved in thrombotic disease. We assessed prothrombin levels and G20210A genotype in a case-control study within the Cardiovascular Health Study. Cases included angina, myocardial infarction, stroke, and the presence of MRI-detectable infarcts (n ≈ 250 each). Populationbased controls free of clinical cardiovascular disease (CVD) (n ≈ 500) and a subset free of clinical and subclinical CVD (n ≈ 250) were used for comparison. The 20210 A allele, frequency 2.9%, was associated with higher mean prothrombin levels: 166.3 vs. 139.5 µg/ml (P <0.001). Significant correlates of prothrombin included gender, plasma lipids, other vitamin K-dependent proteins, and inflammatory markers, but not race, smoking, hypertension, diabetes, measures of subclinical CVD, or markers of procoagulant activity. Compared to controls, neither genotype nor prothrombin level was associated with any CVD case group. We conclude that, in the elderly, neither prothrombin level nor 20210 genotype were associated with either CVD risk factors or events. This is consistent with the lack of association of prothrombin levels with measures of underlying CVD or procoagulant markers.

Coagulation Factors II, V, IX, X, XI, and XII, Plasminogen, and α-2 Antiplasmin and Risk of Coronary Heart Disease

“…In a previous nested case-control study of the Cardiovascular Health Study, no association was found between prothrombin (factor II) levels and incident or prevalent myocardial infarction9). Small case-control studies (n=22 to 300) suggested that factors V and XI were possibly associated with CHD10–12), and factors II, X, and XII were not10,11), generally consistent with our findings.…”

Hypercoagulable states and strokes

“…Its association with arterial stroke remains controversial. This mutation has not been associated with acute ischemic stroke either in larger case-control or in prospective cohort studies [39,40].…”

Vitamin K–Dependent Protein Activity and Incident Ischemic Cardiovascular Disease

“…Periostin knockout (Pn −/− ) mice have an increased rate of ventricular rupture after myocardial infarction 36 , but increased periostin expression is also seen in ventricular hypertrophy and fibrosis 37 . In addition, prothrombin itself has been linked to CVD, associated with an increased risk of venothrombotic disease 38 but not arterial disease 39 .…”