Sex differences in effects of valsartan administration on cardiovascular outcomes in hypertensive patients: findings from the Jikei Heart Study.
OBJECTIVE
The randomized Jikei Heart Study has demonstrated that the addition of valsartan to conventional treatments prevents more cardiovascular events in Japanese patients with hypertension. This substudy analyses the sex difference in cardiovascular disease risk reduction in the Jikei Heart Study.


METHODS
Treatment effects were evaluated by sex (1038 women and 2043 men) as hazard ratios with 95% confidence intervals (CIs) using Cox regression models adjusted for age, BMI, smoking, dyslipidemia, diabetes, antihypertensives, and statin use at baseline.


RESULTS
Women were older, had higher SBP, total and low-density lipoprotein cholesterol but were less frequently smokers or diabetics, and had a lower DBP and incidence of coronary artery disease. A greater incidence of primary endpoint, a composite of cardiovascular events, occurred in men versus women [hazard ratio 1.37 (95% CI 1.02-1.85)]. Men in the valsartan group had a significant reduction in the primary endpoint [hazard ratio 0.6 (95% CI 0.44-0.82), P = 0.001], whereas a nonsignificant effect was found in women [hazard ratio 0.64 (95% CI 0.39-1.06), P = 0.075]. However, statistical heterogeneity of this valsartan effect was not found between sexes, and women of at least 55 years of age, mostly after menopause, in the valsartan group showed a significant risk reduction for the primary endpoint [hazard ratio 0.60 (95% CI 0.36-0.99)].


CONCLUSIONS
The valsartan effect was significant in men and in elderly women but consistent in both sexes. A potential cardiovascular protection by valsartan therapy might be attributed to the cardiovascular risk level but not to the sex difference.
Yoshida
Hiroshi
H
Department of Laboratory Medicine, Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan. hyoshida@jikei.ac.jp
Shimizu
Mitsuyuki
M
Ikewaki
Katsunori
K
Taniguchi
Ikuo
I
Tada
Norio
N
Yoshimura
Michihiro
M
Rosano
Giuseppe
G
Dahlöf
Björn
B
Mochizuki
Seibu
S
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D040242:Risk Reduction Behavior; D012737:Sex Factors; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine