POPULATION CORRELATES OF COAGULATION-FACTOR-VII - IMPORTANCE OF AGE, SEX, AND MENOPAUSAL STATUS AS DETERMINANTS OF ACTIVATED FACTOR-VII

Factor VII coagulant activity (FVIIc) has been found to be related to cardiovascular risk factors and may be an independent predictor of cor onary heart disease (CHD). Whether these associations are due to chang es in FVII activation rather than FVII concentration remain unclear. T herefore, we investigated the relationships between activated factor V II (FVIIa) and CHD risk factors in healthy subjects (336 men and 348 w omen) aged 25 to 64 years. In addition to direct quantitation of FVIIa by use of a recombinant, truncated tissue factor, FVIIc and factor VI I antigen (FVII:Ag) levels were measured by standard procedures. There were highly significant correlations between the three techniques of FVII assay (r>+.55). Plasma FVIIc and FVIIa levels increased with age in both sexes, but the rate of rise was significantly greater in women than men. At younger ages, mean values of FVIIc and FVIIa were signif icantly lower in women than men, whereas at older ages the reverse was observed. After adjustment for age, postmenopausal women had signific antly higher mean levels of FVIIc and FVIIa than did premenopausal wom en. Hormone replacement therapy significantly reversed the rise in FVI Ic in postmenopausal women, and a similar trend in FVIIa was also obse rved. Age-, sex-, and menopause-related changes in FVIIc were partly e xplained by a higher proportion of fully active FVII molecules, as ind icated by significant differences in the FVIIa-to-FVII:Ag ratio. Oral contraceptive use was associated with high FVIIc levels, and this effe ct was mainly due to an increase in FVII:Ag. Levels of FVIIa were posi tively correlated with serum cholesterol concentrations in both sexes. There were no strong associations between FVIIa levels and other CHD risk factors, including smoking habits, alcohol consumption, blood pre ssure, obesity, glucose, triglycerides, and serum lipoprotein(a) conce ntrations. Multiple regression analysis showed independent effects of age and cholesterol levels on FVIIa in men, whereas age and menopausal status were the main predictors of FVIIa in women. Our results show t hat FVII activation is associated with CHD risk factors. These finding s are consistent with a possible role for FVII in the pathogenesis of CHD. Furthermore, our data suggest that the dramatic rise in CHD incid ence in postmenopausal women as well as the cardioprotective effect of estrogen may be mediated through FVII and blood coagulation.