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on October 6, 2003

Circulation. 2003
Published online before print October 6, 2003, doi: 10.1161/01.CIR.0000097560.96431.3E
A more recent version of this article appeared on October 14, 2003
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© American Heart Association, Inc.

Clinical Investigation and Reports

Association Between Apolipoprotein E Alleles and Calcific Valvular Heart Disease

Gian M. Novaro, MD; Ravish Sachar, MD; Gregory L. Pearce, MS; Dennis L. Sprecher, MD Brian P. Griffin, MD

From the Department of Cardiology, Cleveland Clinic Florida, Weston, Fla (G.M.N.), and the Departments of Cardiovascular (R.S., B.P.G.) and Preventive Medicine (G.L.P., D.L.S.), The Cleveland Clinic Foundation, Cleveland, Ohio.

Correspondence to Gian M. Novaro, MD, Department of Cardiology, Desk A-23, The Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd, Weston, FL 33331. E-mail novarog{at}ccf.org

Received June 10, 2002; de novo received July 18, 2003; revision received August 14, 2003; accepted August 18, 2003.

Background— Studies on apolipoprotein E (apoE) alleles have reported an increased risk of coronary heart disease in patients with the apoE4 allele. Given the risk factor and histological similarities between coronary and calcific valvular heart disease (aortic stenosis [AS] and mitral annular calcification [MAC]), we postulated that apoE alleles might be associated with the development of these valvular lesions.

Methods and Results— We evaluated the association between apoE alleles and calcific valvular lesions in 802 patients undergoing transthoracic echocardiography using logistic regression analyses. No difference was noted in genotype distribution (P=0.59) or prevalence of apoE4 between those with or without MAC (30% versus 27%, respectively; P=0.57). Compared with patients without AS, the genotype distribution of patients with AS differed significantly (P=0.03), with increasing prevalences of the apoE 4 allele (27% in those without versus 40% in those with AS; P=0.01). In multivariate analyses adjusting for age, gender, low-density lipoprotein cholesterol levels, and coronary artery disease, increasing age and the apoE4 allele were significant independent predictors of AS (odds ratio, 1.94; 95% confidence interval, 1.01 to 3.71; P=0.046), whereas the apoE4 allele was not predictive of MAC.

Conclusions— These findings support extension of the importance of the apoE4 allele beyond atherosclerosis and Alzheimer’s disease to calcific AS.


Key Words: stenosis • apolipoproteins • calcification • genomics




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