Familial associations of complete atrioventricular block: a national family study in Sweden
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Complete atrioventricular block (CAVB) is a major reason for implantation of permanent pacemakers, but knowledge of CAVB inheritance is sparse. This nationwide study aimed to determine the occurrence of CAVB in first-, second-, and third-degree relatives (full siblings, half-siblings, and cousins). METHODS: The Swedish multigeneration register was linked to the Swedish nationwide patient register for the period 1997 to 2012. All Swedish full sibling, half-sibling, and cousin pairs born to Swedish parents between 1932 and 2012 were included. Competing risks and time-to-event, subdistributional hazard ratios (SHRs) according to Fine and Gray and hazard ratios using Cox proportional hazards model were estimated using robust SEs and considering the relatedness of relatives (full siblings, half-siblings, cousins). Additionally, odds ratios (ORs) for CAVB were calculated for traditional cardiovascular comorbidities. RESULTS: The study population (n=6 113 761) consisted of 5 382 928 full siblings, 1 266 391 half-siblings, and 3 750 913 cousins. In total, 6442 (0.11%) unique individuals were diagnosed with CAVB. Of these, 4200 (65.2%) were males. SHRs for CAVB were 2.91 for full siblings (95% CI, 2.43-3.49), 1.51 for half-siblings (0.56-4.10), and 3.54 for cousins (1.73-7.26) of affected individuals. Age-stratified analysis showed higher risk in young individuals born from 1947 to 1986: SHR, 5.30 (3.78-7.43) for full siblings, SHR, 3.30 (1.06-10.31) for half-siblings, and SHR, 3.15 (1.39-7.17) for cousins. Similar familial HRs according to Cox proportional hazard model and ORs were obtained without any major differences. Apart from familial relationship, CAVB was associated with hypertension (OR, 1.83), diabetes (OR, 1.41), coronary heart disease (OR, 2.08), heart failure (OR, 5.01), and structural heart disease (OR, 4.59). CONCLUSIONS: Risk of CAVB among relatives of affected individuals depends on relationship degree, being strongest in young siblings. The familial association extending to third-degree relatives indicates presence of genetic components in the cause of CAVB.
Date Issued
2023-04
Date Acceptance
2022-10-31
Citation
Circulation: Genomic and Precision Medicine, 2023, 16 (2), pp.1-9
ISSN
2574-8300
Publisher
American Heart Association
Start Page
1
End Page
9
Journal / Book Title
Circulation: Genomic and Precision Medicine
Volume
16
Issue
2
Copyright Statement
© 2023 American Heart Association, Inc.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36802810
Subjects
Editorials
Publication Status
Published
Coverage Spatial
United States
Article Number
ARTN e003654
Date Publish Online
2023-02-21