Is acquired activated protein C resistance a cardiovascular risk?

Cardiovascular Risk? To the Editor: We have read the article by Kiechl et al1 demonstrating that acquired activated protein C resistance (APC) may be a risk factor for atherosclerosis and arterial thrombosis in whites. We2 previously demonstrated that acquired APC resistance is associated not only with venous thrombosis (deep vein thrombosis and pulmonary thromboembolism) but also with arterial thrombotic disease (cerebral infarction and coronary artery disease) in the Japanese population. It is well known that no Japanese has factor V Leiden mutation because of the founder effect of this mutation.3 Thus, it is likely that in Japanese, some environmental factors might contribute to APC resistance. In addition, we demonstrated a positive association of APC sensitivity ratio with plasma levels of the activated form of factor VII (FVIIa, an activation marker of the early phase of the tissue factor pathway of coagulation4 in healthy subjects; correlation coefficient 20.38, P,0.05, n533).2 This association was also found in subjects with a predisposing condition of thrombosis, namely, protein C deficiency (correlation coefficient 20.40, P,0.005, n553). More recently, pregnancy-related APC resistance has also been reported5 to be associated with thrombin-antithrombin complex (an indicator of in vivo thrombin generation) (correlation coefficient with APC sensitivity ratio 20.274, P50.01, n5128). Thus, the APC resistance may reflect the global insensitivity of APC and may provide a good method to assess the hypercoagulable state in vivo. The hypercoagulable state induced by acquired APC resistance should be given greater emphasis in clinical practice in the future.