Familial Aggregation and Heritability of Aldosteronism with Cardiovascular Events
Open Access
- 20 March 2020
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 105 (6), e2176-e2184
- https://doi.org/10.1210/clinem/dgz257
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
Funding Information
- Center for Big Data Analytics and Statistics (CORPG3G072, CMRPG3G1401, CORPG3G0231, CMRPG3F0833)
- Chang Gung Memorial Hospital
- Applied Health Research Data Integration Service
- National Health Insurance Administration
- Taiwan National Science Council (106-2314-B-002 -166 -MY3, 107-2314-B-002 -026 -MY3, 104-2314-B-002-125-MY3)
- National Taiwan University Hospital (106-FTN20, 106-P02, UN106-014, 106-S3582, 105-P05, VN105-04, 105-S3061, VN104-07, 108-S4231)
- Ministry of Science and Technology
- Republic of China (MOST 106-2321-B-182-002)
This publication has 47 references indexed in Scilit:
- Prevalence of Cardiovascular Disease and Its Risk Factors in Primary AldosteronismHypertension, 2018
- GENETICS IN ENDOCRINOLOGY: The expanding genetic horizon of primary aldosteronismActa Endocrinologica, 2018
- Risk of new-onset diabetes mellitus in primary aldosteronismJournal of Hypertension, 2017
- Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care PracticeJournal of the American College of Cardiology, 2017
- The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomesScientific Reports, 2017
- Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronismNature Genetics, 2013
- The Prevalence of Familial Hyperaldosteronism in Apparently Sporadic Primary Aldosteronism in Germany: a Single Center ExperienceHormone and Metabolic Research, 2012
- Prevalence and Characteristics of Familial HyperaldosteronismHypertension, 2011
- Familial or Genetic Primary Aldosteronism and Gordon SyndromeEndocrinology and Metabolism Clinics of North America, 2011
- Primary aldosteronismJournal of Hypertension, 2000