Estrogen replacement therapy, thrombophilia, and atherothrombosis.
In a consecutive case series, cross-sectional study of 401 women referred for hyperlipidemia therapy, (110 [27%] on estrogen replacement therapy [ERT]), we assessed whether ERT-mediated thrombophilia and heritable thrombophilia (20210 G-->A prothrombin gene [PTG], Factor V Leiden gene mutation [FV]) interacted as risk factors for atherothrombotic cardiovascular disease (ATCVD). Thirty-eight percent of women (152/401) had > or = 1 ATCVD event, 57 (14%) had > or = 2 ATCVD events. Fifteen women (3.7%) were PTG heterozygotes, 24 (6.0%) were FV heterozygotes, (there was 1 double heterozygote [0.25%]); 363 (91%) were wild-type normal for both genes. Of the 152 women with > or = 1 ATCVD event, 21 (14%) had > or = 1 thrombophilic gene mutation, versus 17/249 (7%) without events (X(2) = 5.4, P =.02). In women on ERT and with both genes wild-type normal, 23 of 96 (24%) had > or = 1 ATCVD event versus 8 of 14 (57%) on ERT and with > or = 1 thrombophilic mutation, X(2) = 6.6, P =.01. By stepwise logistic regression, in 401 women (152 with > or = 1 ATCVD event, 249 no events), positive explanatory variables for ATCVD included FV and/or PTG (risk odds ratio, 2.59, 95% confidence interval [CI] 1.26 to 5.36, P =.01) and a PTG*ERT interaction term (risk odds ratio, 2.27, 95% CI 1.36 to 3.79, P =.0017). After deleting 23 FV heterozygotes and 14 PTG heterozygotes and 1 double heterozygote from the 401 women, ERT was protective against ATCVD events, with a risk odds ratio of 0.50 and 95% CI of 0.29 to 0.87 P =.014. PTG and FV may increase risk for ATCVD, particularly in the presence of ERT, whereas ERT may be protective against ATCVD when PTG and FV are absent.
Glueck
Charles J
CJ
Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA.
Wang
Ping
P
Fontaine
Robert N
RN
Sieve-Smith
Luann
L
Lang
James E
JE
D002318:Cardiovascular Diseases / Q000453:epidemiology*; D015331:Cohort Studies; D015897:Comorbidity; D003430:Cross-Sectional Studies; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005165:Factor V / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology*; D016015:Logistic Models; D009154:Mutation; D016017:Odds Ratio; D011516:Prothrombin / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D019851:Thrombophilia / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D013927:Thrombosis / Q000453:epidemiology*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin