Depression and 24-Hour Urinary Cortisol in Medical Outpatients with Coronary Heart Disease: The Heart and Soul Study
Otte C, Marmar CR Pipkin SS, et al. ;
Commented by , 23 Sep 2004
Background
Depression is common in coronary heart disease (CHD), and carries increased morbidity and mortality. Elevated cortisol has been associated with both depression and CHD independently. Thus, cortisol may serve as a mediator between depression, cardiovascular disease and cardiac morbidity.
Purpose
Examine the association between current depression and 24-hour urinary cortisol levels in CHD.
Methods
Cross-sectional design involving 693 outpatients with documented CHD enrolled in the Heart and Soul Study (ref. 1). Current and lifetime depression were evaluated using the Computerized Diagnostic Interview Schedule (CDIS-IV). 24-hour urine was collected and analyzed for urinary cortisol.
Potential confounding variables by history included age, gender, smoking, checklist of 45 medical illnesses, medications, alcohol consumption and body mass index. Blood pressure, fasting glucose, glycosylated hemoglobin and lipid profile were also obtained. Cardiac disease severity was determined by echocardiogram (ejection fraction) and exercise stress test.
Parametric and non-parametric statistical tests were used.
Results
138 (20%) of the sample had depression. Depressed patients were younger, more likely to be female, smoke, use psychotropic medications and less likely to use statins. Adjusting for covariates, depressed patients had higher cortisol levels than nondepressed (adjusted mean ± SD: 41 ± 21 μg/day vs. 36 ± 21 μg/day; p = .01).
The incidence of depression increased by quartile of cortisol (p<.01). Adjusting for covariates, patients in the highest quartile of cortisol had twice the odds of being depressed compared with the lowest quartile (OR 2.4, 95% CI 1.3-4.4, p < .01).
The presence of comorbid generalized anxiety or posttraumatic stress disorder (measured by CDIS-IV) in 14% (N=97) of the sample did not influence the assocaition between depression and cortisol. There was no association between cortisol and markers of cardiac disease severity.
Discussion
While activation of the hypothalamic-pituitary-adrenal (HPA) axis has long been proposed as an important link between CHD and depression, this is the first study to demonstrate a direct association by increased cortisol levels in depressed CHD patients.
The study’s strengths include its large sample size, where many such studies evaluating mechansims between depression and CHD have been small. Reliable measures of depression and cardiac severity were used, and important confounds were considered.
Main limitations include the cross-sectional design, whereby direction of causality cannot be determined. Only 17% of the sample being women also limits its generalizability.
The association between low perceived social support (LPSS) and cortisol would have been valuable, as LPSS has been consistently implicated in the development and maintenance of depression in CHD patients. Those with a weaker support network may be more vulnerable to stress and activation of their HPA axis.
As for the role of stress, all depressed patients were informed of this diagnosis and asked to follow-up with their primary care providers, just prior to the 24-hour urine collection. It is possible that this information may have contributed to stress and a transient rise in cortisol.
The significantly lower use of statins in the depressed group is an interesting finding, and raises further questions about the potential mutative role of statins in the association between depression and cardiac disease (ref. 2).
There was no association between cardiac disease severity and cortisol, which weakens the theory of cortisol being a mediator between depression and cardiac mortality. The potential, however, for cortisol to trigger future coronary events in depressed patients was argued. In fact, the researchers plan to adress this question by following the sample prospectively.
References
1. B. Ruo, J.S. Rumsfeld, M.A. Hlatky, H. Liu, W.S. Browner and M.A. Whooley, Depressive symptoms and health-related quality of life The Heart and Soul Study, JAMA 290(2003), pp. 215–221.
2. Lespérance F, Frasure-Smith N, Théroux P, Irwin M. The Association Between Major Depression and Levels of Soluble Intercellular Adhesion Molecule 1, Interleukin-6, and C-Reactive Protein in Patients With Recent Acute Coronary Syndromes Am J Psychiatry 2004 161: 271-277.