Familial Aggregation and Heritability of Primary Aldosteronism with Cardiovascular Events: A Population-Based Family Cohort Study
36 Pages Posted: 17 Dec 2018More...
Background: The effect of positive family history as a risk factor of primary aldosteronism (PA) is so far 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. 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) .
Methods: Using the Taiwan National Health Insurance Database, 30,245,077 NHI beneficiaries (both alive and those deceased between January 1, 1999 and December 31, 2015) were identified. A 1:4 matched cohort of PA cases without affected first degree kinship was constructed.
Findings: We identified 7902 PA in 10,234 individuals with affected parents, 2,298 with affected offspring, 1,924 with affected siblings, and 22 with affected twins. A positive family history was associated with the adjusted relative risk (RR) (95% CI) of 11.60 (7.63-17.63) for people with an affected first-degree relative. RR (95% CI) was 46.00 (25.30-83.62) for individuals with affected siblings, 5.63 (3.04-10.43) for affected parents, 7.27 (4.04-13.09) for affected offsprings, and 5.33 (2.67-10.62) for affected spouses. The accountability for phenotypic variance of PA was 51.0% for genetic factors, 24.9% for shared environmental factors, and 24.1% for non-shared environmental factors. PA patients with an affected first-degree relative were associated with an increased risk for composite major cardiovascular events (RR, 11.62; 95% CI, 7.64-17.67, p < 0.001) compared with PA patients without family history.
Interpretation: Familial clustering of PA exists among a population-based study, supporting a genetic susceptibility leading to PA. There are increased co-aggregation of MACEs in first-degree relatives of PA patients. Screening for first-degree relatives of PA patients could lead to early diagnosis and targeted treatment of un-diagnosed PA.
Funding Statement: The authors state: "None."
Declaration of Interests: No competing interest was declared. No financial conflict of interest exists.
Ethics Approval Statement: This study has been approved both by the Institutional Review Board of the Chang Gung Memorial Hospital and the data holder of the NHI database. The NHI database was fully encrypted to allow confidentiality protection and all data can only be accessed in the specific computer center operated by the Administration of National Health Insurance. Patient consents were exempted.
Keywords: Primary aldosteronism, familial aggregation, heritability, TAIPAI
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