Familial Aggregation and Heritability of Aldosteronism with Cardiovascular Events

Abstract

Context: To date, the effect of positive family history as a risk factor of primary aldosteronism (PA) is largely unknown. Studies have failed to distinguish the heritability of PA as well as the associations between positive family history of PA and clinical outcomes.

Objectives: We quantified the prevalence, the extent of familial aggregation, the heritability of PA among family members of patients with PA, and the association between positive PA family history and major cardiovascular events (MACE).

Design and settings: Using the Taiwan National Health Insurance Database, 30 245 077 National Health Insurance beneficiaries (both alive and those deceased between January 1, 1999, and December 31, 2015) were identified.

Results: We identified 7902 PA patients. Forty-four had PA (0.3%) among 10 234 individuals with affected parents, 2298 with affected offspring, 1924 with affected siblings, and 22 with affected twins. A positive family history was associated with the adjusted relative risk (RR) (95% confidence interval [CI]) of 11.60 (7.63-17.63) for PA in people with an affected first-degree relative. In subgroup analysis, the risk for PA across all relationships (parent, siblings, offspring, and spouse) showed highly significant differences to PA without family history. The accountability for phenotypic variance of PA was 51.0% for genetic factors, 24.9% for shared environmental factors, and 24.1% for nonshared environmental factors. PA patients with an affected first-degree relative were associated with an increased risk for composite major cardiovascular events (RR 1.31; 95% CI 1.24-1.40, P < .001) compared with PA patients without family history.

Conclusion: Familial clustering of PA exists among a population-based study, supporting a genetic susceptibility leading to PA. There is increased coaggregation of MACE in first-degree relatives of PA patients. Our findings suggest a strong genetic component in the susceptibility of PA, involving different kinships.

Keywords: TAIPAI; familial aggregation; heritability; primary aldosteronism.