Angiotensin-Converting Enzyme Gene Polymorphism Influences Degree of Left Ventricular Hypertrophy and Its Regression in Patients Undergoing Operation for Aortic Stenosis Go ¨ran Dellgren, MD, Maria J. Eriksson, MD, Irina Blange, PhD, Lars-Åke Brodin, MD, PhD, Kjell Rådegran, MD, PhD, and Christer Sylve ´n MD, PhD Insertion (I)/deletion (D) polymorphism of the angioten- sin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in pa- tients 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 polymor- phism 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 ge- notype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aor- tic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197  47 g/m 2 ) preoperatively than those with ID (175  41 g/m 2 ) or II (155  43 g/m 2 ) 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 signif- icant 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 geno- type appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload. 1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;84:909 –913) A ngiotensin-converting enzyme (ACE) gene poly- morphism at locus 17q23 of a noncoding region (intron 16) has been suggested to influence cardiovas- cular morbidity. 1–6 Although data from different in- vestigations conflict to some extent, the DD genotype appears to be related to adverse effects in regard to ischemic or idiopathic dilated cardiomyopathy, 7 hy- pertrophic cardiomyopathy, 8,9 and cardiac hypertro- phy and remodeling. 10,11 In patients with idiopathic chronic heart failure, the DD genotype was found not only to be related to increased left ventricular mass, but also to be an independent risk factor for mortality. 12 Preoperative studies of patients with symptomatic aortic stenosis (AS) have demonstrated a poor corre- lation between the degree of AS and the degree of left ventricular hypertrophy (LVH). 13,14 The absence of a clear relation between the stenosis-dependent pressure load on the left ventricle and the degree of ventricular hypertrophy suggests that the left ventricular pheno- type is dependent on a polygenic background. ACE gene polymorphism could be one important factor in this respect. Therefore, the aim of the present study was to evaluate whether ACE gene polymorphism is correlated with LVH in patients with AS before and after aortic valve replacement. METHODS Patient selection: Eighty-two patients with AS (40 women and 42 men, mean age 75  8 years) under- went aortic valve replacement between 1990 and 1995 with either a stentless bioprosthesis or an aortic allo- graft. Indication for aortic valve replacement was in all cases symptomatic AS verified by echocardiogra- phy (aortic valve area 1 cm 2 and/or a mean trans- valvular gradient of 30 mm Hg). A Biocor (Belo Horizonte, Brazil) stentless xenograft (n = 49), a Baxter (Baxter Inc., Irvine, California) stentless xeno- graft (n = 4), or an aortic allograft (n = 29) was used. We only included patients with stentless bioprostheses or allografts because these valves are considered being less obstructive than other valve alternatives, thereby minimizing the pressure overload of the left ventricle. All surviving patients receiving any of these valve prostheses were investigated in a prospective study using Doppler echocardiography before aortic valve replacement and approximately 1 year (mean 15, range 6 to 21 months) after operation. Hemodynamic From the Departments of Cardiothoracic Surgery and Cardiology, Karolinska Institute, Huddinge University Hospital, Huddinge; and the Departments of Thoracic Surgery and Clinical Physiology, Karolinska Hospital, Stockholm, Sweden. This study was supported by the Swed- ish Medical Research Council (9515), the Swedish Heart and Lung Foundation, Stiftelsen Serafimerlasarettet, and by the Swedish Institute, Stockholm, Sweden. Manuscript received January 25, 1999; revised manuscript received May 20, 1999, and accepted May 24. Address for reprints: Go ¨ran Dellgren, MD, Department of Cardio- thoracic Surgery, Huddinge University Hospital, S-141 86 Huddinge, Sweden. E-mail: gorandellgren@hotmail.com. 909 ©1999 by Excerpta Medica, Inc. All rights reserved. 0002-9149/99/$–see front matter The American Journal of Cardiology Vol. 84 October 15, 1999 PII S0002-9149(99)00464-6