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CLINICAL STUDY: RISK FACTORS

Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women

Mitsuhiro Sanada, MD, PhD^*, Yukihito Higashi, MD, PhD, Keigo Nakagawa, MD, Shota Sasaki, MD, Ichiro Kodama, MD^*, Mikio Tsuda, MD^*, Nobutaka Nagai, MD, PhD^* and Koso Ohama, MD, PhD^*

^* Department of Obstetrics and Gynecology, Faculty of Medicine, Hiroshima University, Hiroshima, Japan
First Department of Internal Medicine, Faculty of Medicine, Hiroshima University, Hiroshima, Japan

Manuscript received August 14, 2000; revised manuscript received December 28, 2000, accepted January 18, 2001.

Reprint requests and correspondence: Dr. Mitsuhiro Sanada, Department of Obstetrics and Gynecology, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
msanada64{at}hotmail.com

OBJECTIVES

We sought to evaluate the relationship between the angiotensin-converting enzyme (ACE) genotype and the change in forearm vasoreactivity in response to a three-month course of oral estrogen in postmenopausal women.

BACKGROUND

The ACE genotype is a known predictor of the response to an ACE inhibitor drug; however, it is not clear whether it can modify the effect of estrogen replacement therapy (ERT) on endothelial function in postmenopausal women.

METHODS

Fifty-five postmenopausal women received 0.625 mg of conjugated equine estrogen daily for three months. Forearm blood flow (FBF) was measured by strain-gauge plethysmography.

RESULTS

Twenty-one, 25 and 9 patients had the insertion/deletion (ID), II and DD genotypes, respectively. Plasma ACE activity was significantly higher at baseline in patients with either the DD or ID genotype than in those with the II genotype (p < 0.05). A significant decrease in plasma ACE activity with ERT was seen in the ID and II genotypes (p < 0.05), but not in the DD genotype. There were no significant differences in the FBF responses to reactive hyperemia at baseline between the three groups. Estrogen replacement therapy did not alter the FBF response to reactive hyperemia in the DD genotype (4.0 ± 1.3%), although ERT significantly increased the FBF response in the ID and II genotypes (32.6 ± 7.5% and 30.6 ± 6.5%, respectively; p < 0.05). Forearm blood flow after administration of sublingual nitroglycerin did not change over three months in any of the three groups.

CONCLUSIONS

These findings suggest that the effect of ERT in postmenopausal women on forearm endothelial function may be determined in part by the genotype of the ACE gene.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANOVA = analysis of variance   eNOS = endothelial nitric oxide synthase   ERT = estrogen replacement therapy   FBF = forearm blood flow   HDL = high density lipoprotein   ID = insertion/deletion   LDL = low density lipoprotein   NO = nitric oxide   PCR = polymerase chain reaction

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