Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women.
BACKGROUND
Estrogens are known to be prothrombotic, and findings from the Heart and Estrogen/progestin Replacement Study suggest that in women with clinically recognized heart disease, hormone replacement therapy (HRT) may be associated with early harm and late benefit in terms of coronary events.


OBJECTIVE
To assess whether, as hypothesized, prothrombotic mutations modify the association between HRT use and incidence of first myocardial infarction (MI).


METHODS
Population-based, case-control study conducted in a Seattle-based health maintenance organization.


METHODS
Cases were 232 postmenopausal women aged 30 to 79 years who had their first nonfatal MI between 1995 and 1998. Controls were a stratified random sample of 723 postmenopausal women without MI who were frequency-matched to cases by age, calendar year, and hypertension status.


METHODS
Risk of first nonfatal MI based on current use of HRT and the presence or absence of coagulation factor V Leiden and prothrombin 20210 G-->A variants among cases and controls, stratified by hypertension.


RESULTS
One hundred eight MI cases and 387 controls had hypertension and 124 MI cases and 336 controls did not. Among hypertensive women, the prothrombin variant was a risk factor for MI (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.52-12.1) and, in this stratum, there was also a significant interaction between use of HRT and presence of the prothrombin variant on risk of MI. Compared with nonusers of HRT with wild-type genotype, women who were current users and who had the prothrombin variant (n = 8) had a nearly 11-fold increase in risk of a nonfatal MI (OR, 10.9; 95% CI, 2.15-55.2). The interaction with the prothrombin variant was more pronounced in analyses assuming 100% compliance than in those assuming 80% compliance with HRT. The interaction was absent among nonhypertensive women and was less pronounced if hypertensive and nonhypertensive women were combined into 1 group. No interaction was found for factor V Leiden in either hypertensive or nonhypertensive women. Among hypertensive women, the estimates were affected only in trivial ways by adjustment, and the interaction with the prothrombin variant was specific to HRT.


CONCLUSIONS
Our results suggest that among postmenopausal hypertensive women, the association between HRT use and MI risk differed between those with and without the prothrombin 20210 G-->A variant. If these findings are confirmed in other studies, screening for the prothrombin variant may permit a better assessment of the risks and benefits associated with HRT in postmenopausal women.
Psaty
B M
BM
Cardiovascular Health Research Unit, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. psaty@u.washington.edu
Smith
N L
NL
Lemaitre
R N
RN
Vos
H L
HL
Heckbert
S R
SR
LaCroix
A Z
AZ
Rosendaal
F R
FR
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension; D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D017698:Postmenopause; D011516:Prothrombin / Q000235:genetics*; D012306:Risk
D004967:Estrogens; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin