Familial aggregation of aortic stenosis

Abstract

Purpose: Aortic stenosis is the most common valve disease in the elderly and is considered to be multifactorial and genetic components have been suggested. However, knowledge on familial occurrence on a population based level is missing. We aimed to describe the familial aggregation of aortic stenosis in the adult population. Methods: From nationwide Danish registers we included a cohort of persons born in or after 1910, with identifiable relatives. From 1977 to 2012 we identified all cases diagnosed with aortic stenosis in the cohort and relatives aged 35 years or more, who did not have a registered diagnose of cardiovascular disease before age 35 years. We also assessed for familial occurrence of aortic stenosis presenting with frequently seen cardiac co-morbidities such as ischemic heart disease and endocarditis in cohort members. We estimated incidence rate ratios (IRR) adjusted for sex, age and calendar period for aortic stenosis by family history of aortic stenosis in first degree relatives; this was done by log-linear Poisson regression analysis. Results: We followed a cohort of 4,764,969 persons free of CVD before age 35 years, for 95,871,697 persons-years and identified 59,362 persons with aortic stenosis. The median age at diagnosis of aortic stenosis in persons (n=258) with a family history of aortic stenosis in a first degree relative was 58 years, and in those (n=59,104) without such a family history the median age was 74 years (p<0.01). Given a first degree relative with aortic stenosis the IRR and 95% confidence interval (CI) for aortic stenosis was 1.61 (95% CI 1.42-1.82). In persons aged 35-55 years the IRR was 1.36 (95% CI 1.12-1.65 for aortic stenosis and in those aged 56 to 75 years the IRR was 2.13 (95% CI 1.75-2.59), and in those aged 76 years or older the IRR was 1.89 (95% CI 1.43-2.50). The risk by family history in those with certain cardiac co-morbidities was stronger. Conclusion: To our knowledge this is the first nationwide study to report and quantify the risk of aortic stenosis by family history of aortic stenosis. The risk was increased up to two-fold given a first degree relative with aortic stenosis, and the disease occurred 15-20 years earlier in life in those with a family history.