Valvular Heart Diseases
Angiotensin-converting enzyme gene polymorphism influences degree of left ventricular hypertrophy and its regression in patients undergoing operation for aortic stenosis☆

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Abstract

Insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in patients with cardiomyopathy and congestive heart failure. Patients with aortic stenosis (AS) have varying degrees of LVH at a given valve area. The aim of this study was to examine the relation between ACE gene polymorphism and the degree of LVH in patients undergoing operation for AS. Eighty-two patients who underwent operation for AS with a stentless valve were followed prospectively with echocardiographic assessments of left ventricular mass index (LVMI). ACE gene polymorphism was determined by polymerase chain reaction. The genotype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aortic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197 ± 47 g/m2) preoperatively than those with ID (175 ± 41 g/m2) or II (155 ± 43 g/m2) genotypes (p = 0.01). LVMI decreased significantly in DD (p <0.001) and ID (p <0.001) genotypes but not in the II genotype during follow-up (mean 15 months). There was a significant difference in regression of LVMI over time between genotypes (p = 0.0056), with no significant difference between genotypes at follow-up. The DD genotype of the ACE gene is associated with increased preoperative LVH in patients treated surgically for AS. The DD genotype appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload.

Section snippets

Patient selection

Eighty-two patients with AS (40 women and 42 men, mean age 75 ± 8 years) underwent aortic valve replacement between 1990 and 1995 with either a stentless bioprosthesis or an aortic allograft. Indication for aortic valve replacement was in all cases symptomatic AS verified by echocardiography (aortic valve area <1 cm2 and/or a mean transvalvular gradient of >30 mm Hg). A Biocor (Belo Horizonte, Brazil) stentless xenograft (n = 49), a Baxter (Baxter Inc., Irvine, California) stentless xenograft

Results

The genotype frequency of the ACE gene was 32% (26 of 82) for the DD, 50% (41 of 82) for the ID, and 18% (15 of 82) for the II genotype. The frequencies of the I and D alleles in our study, including only Caucasians, were 43% and 57%, respectively. There was no significant difference in age, gender, body surface area, or preoperative hypertension between patients with different genotypes. Maximum and mean pressure differences across the aortic valve and left ventricular measurements, as

Discussion

This study demonstrates that the genotype frequency of the ACE gene in patients undergoing operation for AS does not deviate from that reported for the normal Caucasian population (DD 29%, ID 50%, II 22%).6 Also, the frequencies of the I and D alleles in patients undergoing surgery for AS were similar to our previously published data from control subjects—44% and 56%, respectively.12

The preoperative evaluation of patients with AS often shows that some have developed severe LVH, while others

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    ☆

    This study was supported by the Swedish Medical Research Council (9515), the Swedish Heart and Lung Foundation, Stiftelsen Serafimerlasarettet, and by the Swedish Institute, Stockholm, Sweden.

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