04. Psychiatric Disorders and Subsequent Risk of Cardiovascular Disease

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In a prior episode of Quick Takes, we talked about patient Eliza, a 60-year-old woman with new onset of depressive symptoms 6 months after suffering a myocardial infarction. We wondered how to accurately diagnose depression in Eliza given her medical comorbidities, and we also talked about the safety and efficacy of using an SSRI in someone with a cardiac history like hers. We learned that among medical conditions, the effect size for SSRIs is actually highest in patients with myocardial infarctions and that SSRIs are safe and well-tolerated in this population. This month, we examine the other side of the coin. What about the cardiac risk for patients newly diagnosed with a psychiatric illness? Are they at higher risk for cardiovascular disease as a result of their psychiatric diagnosis? In other words, is the relationship between heart disease and psychiatric illness bidirectional? A new study using databases from 3 countries including a cohort of over 900,000 subjects with psychiatric diagnoses confirms that psychiatric illness does increase the risk for cardiac disease and importantly suggests that the risk is independent of familial factors.

I’m Scott Beach for the Psychopharmacology Institute, and this is Quick Takes.

The subjects of this study, diagnosed with psychiatric illnesses between 1987 and 2016, were compared to over 1 million unaffected siblings and age- and sex-matched populations in a 10:1 ratio. The study revealed that patients with psychiatric disorders had higher rates of cardiovascular disease compared with siblings and matched controls. This heightened risk was most pronounced in the first year following psychiatric diagnosis and persisted for up to 30 years, affecting both men and women across all age groups. Direct associations were identified between psychiatric disorders and risks for hypertension, ischemic heart disease, venous thromboembolism, angina, and stroke. Notably, patients with anorexia exhibited the highest cardiovascular disease risk, whereas those with autism spectrum disorder showed no increased risk, likely due to their average diagnosis age of 12 years.

Previous research has consistently linked psychiatric disorders with a higher risk for cardiovascular disease, encompassing conditions from major depression to generalized anxiety and panic disorder, and outcomes ranging from hypertension to myocardial infarction. The association between depression and acute coronary syndrome is well-established, whereas other links, like anxiety and heart failure, have yielded mixed results. It is widely accepted that psychiatric illness elevates the risk for adverse cardiac outcomes.

The underlying reasons for this link have been extensively theorized. One hypothesis suggests a direct causal relationship, where psychological distress could lead to autonomic dysfunction, inflammation, endothelial changes, and platelet aggregation, all potentially causing adverse cardiac outcomes. A notable example is Takotsubo cardiomyopathy, or broken heart syndrome, where acute psychological stress leads to significant, sometimes reversible, cardiac changes. This condition exemplifies the profound impact of psychological distress on cardiac health.

Another theory proposes that mediating illnesses or behaviors contribute to the increased cardiac risk. For instance, patients with generalized anxiety disorder often have higher rates of tobacco use, diabetes, and high cholesterol, potentially driving their elevated cardiac risk. Similarly, depressed patients’ poor health habits, like lack of exercise and nonadherence to medical recommendations, might be the actual risk factors rather than the psychiatric illness itself.

A third theory considers genetic or familial factors as potential contributors to both psychiatric and cardiac diseases. However, this study’s inclusion of unaffected siblings, who displayed similar cardiac disease rates as the general population, argues against this genetic or familial link.

This study also highlights the higher morbidity and mortality rates in patients with psychiatric illnesses due to cardiac disease. Depressive symptoms following acute coronary syndrome significantly increase morbidity and mortality rates over 5 years. The American Heart Association even recognizes depression as a risk factor for adverse events post–myocardial infarction. Research suggests that each point increase on the PHQ-9 scale raises the cardiac readmission risk by 9% over 6 months for patients with major depressive disorder hospitalized for cardiac illness.

Given the heightened risk of new cardiovascular illness in the year following a mental illness diagnosis, it is crucial to closely monitor patients, especially those with new psychiatric diagnoses. This includes encouraging follow-up with medical providers, discussing health behaviors, and advocating for better screening and treatment among medical colleagues.

Abstract

Psychiatric Disorders and Subsequent Risk of Cardiovascular Disease: A Longitudinal Matched Cohort Study Across Three Countries

Qing Shen, Dorte Helenius Mikkelsen, Laura Birgit Luitva, Huan Song, Silva Kasela, Thor Aspelund, Jacob Bergstedt, Yi Lu, Patrick F Sullivan, Weimin Ye, Katja Fall, Per Tornvall, Yudi Pawitan, Ole A Andreassen, Alfonso Buil, Lili Milani, Fang Fang, Unnur Valdimarsdóttir

Background: Several psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown.

Methods: In this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N = 875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N = 30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively.

Findings: During up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79-1.98) and thereafter (1.37; 95% CI, 1.34-1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort.

Interpretation: Independent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders.

Reference

Shen, Q., Mikkelsen, D. H., Luitva, L. B., Song, H., Kasela, S., Aspelund, T., Bergstedt, J., Lu, Y., Sullivan, P. F., Ye, W., Fall, K., Tornvall, P., Pawitan, Y., Andreassen, O. A., Buil, A., Milani, L., Fang, F., & Valdimarsdóttir, U. (2023). Psychiatric disorders and subsequent risk of cardiovascular disease: A longitudinal matched cohort study across three countries. EClinicalMedicine, 61, 102063.