Clinical Studies
Association between angiotensin-converting enzyme gene polymorphisms and regression of left ventricular hypertrophy in patients treated with angiotensin-converting enzyme inhibitors

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Abstract

PURPOSE: An insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with left ventricular hypertrophy. The present study examined polymorphisms of the ACE gene in patients with essential hypertension and left ventricular hypertrophy who were participants in a long-term trial of therapy with an ACE inhibitor.

PATIENTS AND METHODS: ACE inhibitor therapy was administered for >2 years to 54 patients with hypertension who had moderate or severe left ventricular hypertrophy. Cardiac dimensions were monitored by echocardiography before the initiation of therapy and after 1 and 2 years of treatment. Serum ACE activity and plasma concentrations of brain natriuretic peptide, a marker for left ventricular hypertrophy, were also monitored.

RESULTS: Eighteen patients had the II genotype for the angiotensin-converting enzyme gene, 19 had the ID genotype, and 17 had the DD genotype. Baseline (mean ± SD) serum ACE activity was significantly greater (P <0.05) in the DD (18 ± 7 IU/L) group than in the II (7 ± 4 IU/L) or ID (12 ± 6 IU/L) groups. ACE inhibitor therapy was effective in controlling blood pressure, and it reduced posterior and septal wall thickness, left ventricular mass index, and plasma brain natriuretic peptide concentration in all three groups. Despite similar blood pressure reductions, after 2 years, mean (±SD) regression in posterior wall thickness was significantly less (P <0.05) in the DD group (−9% ± 5%) than in the ID (−21% ± 7%) and II (−21% ± 9%) groups. Similar results were seen for the reductions in brain natriuretic peptide levels. The magnitudes of regression of septal wall thickness and left ventricular mass index during therapy were less in the DD group than the II group (P <0.05).

CONCLUSION: Hypertensive patients with the DD genotype are less likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than are patients with other ACE genotypes.

Section snippets

Entry criteria and screening

Between January 1992 and June 1996, we recruited 54 patients with left ventricular hypertrophy from a group of approximately 400 hypertensive patients seen in our department. All patients underwent routine laboratory studies, chest roentgenography, and electrocardiography. We selected subjects with essential hypertension based on the results of these laboratory tests and the guidelines of the World Health Organization (25). Hypertension was defined as systolic pressure >160 mm Hg or diastolic

Patient characteristics

No differences were seen in terms of age, gender, body dimensions, and systolic and diastolic blood pressure among the three genotypes (Table 1). All patients were treated with an ACE inhibitor (enalapril or lisinopril); some also required a calcium antagonist to reduce blood pressure adequately. The decreases in blood pressure were not different in the three groups. Mean left ventricular ejection fractions in the three groups at baseline were normal and did not change significantly during the

Discussion

Long-term therapy with ACE inhibitors reduced posterior and septal wall thickness and left ventricular mass index in hypertensive patients with moderate or severe left ventricular hypertrophy. However, the magnitude of regression of posterior wall thickness was significantly less in the DD group than in the ID and II groups, and regression of septal wall thickness and left ventricular mass index was less in the DD group than the II group. These results suggest that the regression of left

Acknowledgements

The authors gratefully acknowledge the technical assistance of Atsumi Ohnishi and Yuka Inoshita (Division of Hypertension and Atherosclerosis, The First Department of Internal Medicine, Osaka City University Medical School). We also gratefully acknowledge the valuable advice of Shinichiro Ueda, MD, PhD (The Second Department of Internal Medicine, Yokohama City University Medical School).

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    Supported by a Grant-in-Aid for Scientific Research (572-690-231-646) from the Ministry of Education, Science and Culture, Japan.

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