Association between apolipoprotein E alleles and calcific valvular heart disease

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.