Cardiovascular disease and subsequent risk of psychiatric disorders: a nationwide sibling-controlled study
- Karolinska Institute, Sweden
- Sichuan University, China
- University of Iceland, Iceland
- University of North Carolina at Chapel Hill, United States
- Örebro University, Sweden
Abstract
Background: The association between cardiovascular disease (CVD) and selected psychiatric disorders has frequently been suggested while the potential role of familial factors and comorbidities in such association has rarely been investigated.
Methods: We identified 869 056 patients newly diagnosed with CVD from 1987 to 2016 in Sweden with no history of psychiatric disorders, and 910 178 full siblings of these patients as well as 10 individually age- and sex-matched unrelated population controls (N=8 690 560). Adjusting for multiple comorbid conditions, we used flexible parametric models and Cox models to estimate the association of CVD with risk of all subsequent psychiatric disorders, comparing rates of first incident psychiatric disorder among CVD patients with rates among unaffected full siblings and population controls.
Results: The median age at diagnosis was 60 years for patients with CVD and 59.2% were male. During up to thirty years of follow-up, the crude incidence rates of psychiatric disorder were 7.1, 4.6 and 4.0 per 1000 person-years for patients with CVD, their siblings and population controls. In the sibling comparison, we observed an increased risk of psychiatric disorder during the first year after CVD diagnosis (hazard ratio [HR], 2.74; 95% confidence interval [CI], 2.62-2.87) and thereafter (1.45; 95% CI, 1.42-1.48). Increased risks were observed for all types of psychiatric disorders and among all diagnoses of CVD. We observed similar associations in the population comparison. CVD patients who developed a comorbid psychiatric disorder during the first year after diagnosis were at elevated risk of subsequent CVD death compared to patients without such comorbidity (HR 1.55; 95% CI 1.44-1.67).
Conclusions: Patients diagnosed with CVD are at an elevated risk for subsequent psychiatric disorders independent of shared familial factors and comorbid conditions. Comorbid psychiatric disorders in patients with CVD are associated with higher risk of cardiovascular mortality suggesting that surveillance and treatment of psychiatric comorbidities should be considered as an integral part of clinical management of newly diagnosed CVD patients.
Funding: This work was supported by the EU Horizon 2020 Research and Innovation Action Grant (CoMorMent, grant no. 847776 to UV, PFS and FF), Grant of Excellence, Icelandic Research Fund (grant no. 163362-051 to UV), ERC Consolidator Grant (StressGene, grant no: 726413 to UV), Swedish Research Council (grant no. D0886501 to PFS) and US NIMH R01 MH123724 (to PFS).
Data availability
Data analyses were performed in STATA 17.0 (StataCorp LP). STATA script used in the primary analyses has been made available as supplementary appendix. Aggregated data used for generating figures are available in supplementary appendix. The original data used in this study are owned by the Swedish National Board of Health and Welfare and Statistics Sweden. The authors are not able to make the dataset publicly available according to the Public Access to Information and Secrecy Act in Sweden. Any researchers (including international researchers) interested in accessing the data can send request to the authorities for data application by: 1) apply for ethical approval from local ethical review board; 2) contact the Swedish National Board of Health and Welfare (https://bestalladata.socialstyrelsen.se/, email: registerservice@socialstyrelsen.se) and/or Statistics Sweden (https://www.scb.se/vara-tjanster/bestall-data-och-statistik/, email: scb@scb.se) with the ethical approval and submit a formal application for access to register data. The same contacts can be used for detailed information about how to apply for access to register data for research purposes."
Article and author information
Author details
Unnur Valdimarsdóttir
Funding
EU Horizon 2020 Research and Innovation Action Grant (CoMorMent,847776)
- Unnur Valdimarsdóttir
EU Horizon 2020 Research and Innovation Action Grant (CoMorMent,847776)
- Fang Fang
EU Horizon 2020 Research and Innovation Action Grant (CoMorMent,847776)
- Patrick Sullivan
Grant of Excellence, Icelandic Research Fund (163362-51)
- Unnur Valdimarsdóttir
ERC Consolidator Grant (StressGene,726413)
- Unnur Valdimarsdóttir
Swedish Research Council (D0886501)
- Patrick Sullivan
US NIMH R01 (MH123724)
- Patrick Sullivan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was approved by the Ethical Vetting Board in Stockholm, Sweden (DNRs 2012/1814-31/4 and 2015/1062-32). Informed consent to each participant was waived by Swedish law in nationwide registry data.
Copyright
© 2022, Shen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cardiovascular disease and subsequent risk of psychiatric disorders: a nationwide sibling-controlled study
eLife 11:e80143.
https://doi.org/10.7554/eLife.80143
Further reading
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Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD).
Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.
Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).
Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
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