Stress related disorders and risk of cardiovascular disease: population based, sibling controlled cohort studyBMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l1255 (Published 10 April 2019) Cite this as: BMJ 2019;365:l1255
- Huan Song, postdoctoral fellow1 2,
- Fang Fang, associate professor2,
- Filip K Arnberg, associate professor3 4,
- David Mataix-Cols, professor5 6,
- Lorena Fernández de la Cruz, assistant professor5 6,
- Catarina Almqvist, professor2 7,
- Katja Fall, associate professor2 8,
- Paul Lichtenstein, professor2,
- Gudmundur Thorgeirsson, professor1,
- Unnur A Valdimarsdóttir, professor1 2 9
- 1Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland
- 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- 3National Centre for Disaster Psychiatry, Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
- 4Stress Research Institute, Stockholm University, Stockholm, Sweden
- 5Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- 6Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
- 7Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
- 8Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
- 9Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA
- Correspondence to: H Song or
- Accepted 12 March 2019
Objective To assess the association between stress related disorders and subsequent risk of cardiovascular disease.
Design Population based, sibling controlled cohort study.
Setting Population of Sweden.
Participants 136 637 patients in the Swedish National Patient Register with stress related disorders, including post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366 370 matched unexposed people from the general population.
Main outcome measures Primary diagnosis of incident cardiovascular disease—any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhythmia/conduction disorder, and fatal cardiovascular disease)—and 16 individual diagnoses of cardiovascular disease. Hazard ratios for cardiovascular disease were derived from Cox models, after controlling for multiple confounders.
Results During up to 27 years of follow-up, the crude incidence rate of any cardiovascular disease was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling based comparisons, the hazard ratio for any cardiovascular disease was 1.64 (95% confidence interval 1.45 to 1.84), with the highest subtype specific hazard ratio observed for heart failure (6.95, 1.88 to 25.68), during the first year after the diagnosis of any stress related disorder. Beyond one year, the hazard ratios became lower (overall 1.29, 1.24 to 1.34), ranging from 1.12 (1.04 to 1.21) for arrhythmia to 2.02 (1.45 to 2.82) for artery thrombosis/embolus. Stress related disorders were more strongly associated with early onset cardiovascular diseases (hazard ratio 1.40 (1.32 to 1.49) for attained age <50) than later onset ones (1.24 (1.18 to 1.30) for attained age ≥50; P for difference=0.002). Except for fatal cardiovascular diseases, these associations were not modified by the presence of psychiatric comorbidity. Analyses within the population matched cohort yielded similar results (hazard ratio 1.71 (1.59 to 1.83) for any cardiovascular disease during the first year of follow-up and 1.36 (1.33 to 1.39) thereafter).
Conclusion Stress related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, history of somatic/psychiatric diseases, and psychiatric comorbidity.
Contributors: UAV, FF, and HS were responsible for the study concept and design. HS, UV, and FF did the data analysis. UAV, HS, FF, GT, FKA, PL, CA, DMC, LFC, and KF interpreted the data. HS, UAV, FF, FKA, PL, CA, DMC, LFC, KF, and GT drafted the manuscript. HS and UAV had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. HS and UAV are the guarantors.
Funding: The study was supported by Grant of Excellence, Icelandic Research Fund (grant No 163362-051 to UAV), and ERC Consolidator Grant (StressGene, grant No 726413 to UAV); by the Karolinska Institutet (Senior Researcher Award and Strategic Research Area in Epidemiology to FF); and by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework (grant No 340-2013-5867 to CA).
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work other than that detailed above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The study was approved by the Regional Ethics Review Board in Stockholm, Sweden (Dnr 2013/862-31/5).
Data sharing: No additional data available.
Transparency: The study guarantors affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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