Activated protein C resistance and the FV : R(506)Q mutation in a random population sample - Associations with cardiovascular risk factors and coagulation variables

Activated protein C (APC) resistance, defined as a low APC ratio, is associ ated with the factor V mutation R(506)Q (factor V Leiden). APC ratio map al so be influenced by other clinical and coagulation variables, which we stud ied in 460 men and 495 women aged 25-74 years, from a random population sam ple (Glasgow MONICA Survey). APC ratio correlated positively with APTT; and inversely with factor VIIIc, factor IXc, antithrombin activity, prothrombi n F1+2 fragment, and thrombin-antithrombin complexes; but not with other co agulation variables. APC ratio decreased with age, but APTT did not. APC ra tio and APTT were significantly lower in women versus men? and were signifi cantly lower in users of oral contraceptives or hormone replacement therapy . The EV:R(506)Q mutation (prevalence 2.5%) was associated with lower APC r atio and protein C and S activities and with higher factor VIIIc levels; bu t not with increases in F1+2 fragment or thrombin-antithrombin complexes. A PC ratio correlated inversely with total cholesterol and di astolic blood p ressure; and in women with triglycerides, systolic blood pressure, and body mass index. Obesity was associated with a significantly lower APC ratio. I n contrast, smoking markers correlated positively with APC ratio in men. Th ese associations of APC ratio may be relevant to the increased risks of ven ous thrombosis with age, female sex, oestrogen use,obesity and high factor VIIIc levels. The association of APC resistance with elevated plasma levels of coagulation markers suggests that this phenotype represents an in vivo hypercoagulable state.