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
Lespérance F, Frasure-Smith N, Théroux P and Irwin M;
Commented by , 23 Feb 2004
Background
Depression is an independent risk factor for cardiac events in previously healthy subjects, and also in patients with established coronary artery disease (CAD). Among several proposed mechanisms to explain the links between CAD and depression, the role of inflammation is gaining interest.
Atherosclerotic plaque development is associated with cytokine release, such as interleukin-6 (IL-6); acute phase reactants, such as C-reactive protein (CRP); and endothelial shedding of soluble intercellular adhesion molecules (sICAMS). Preliminary evidence suggests depressed patients show similar patterns of immune activation.
Purpose
Examine the relationship between depression and inflammatory markers in patients recovering from acute coronary syndromes.
Methods
Plasma levels of sICAM-1 and IL-6, and serum levels of CRP were measured in participants following hospitalization for acute coronary syndromes. The Structured Clinical Interview for DSM-IV was used to establish the diagnosis of major depression. Differences between depressed and nondepressed patients on background variables and inflammatory markers were evaluated by ANOVA and chi-square tests. Multiple linear regression assessed relationships between inflammatory markers and background variables.
Results
481 subjects were evaluated 23-120 days post-discharge (mean=59.7 days). Mean age was 60, 18.9% were female. 81.7% had an acute MI at index hospitalization. 49.1% had a metabolic syndrome, comprising the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, high blood pressure and fasting glucose. 7.3% had a current major depressive episode (MDE), first MDE in 4.4%; overall lifetime prevalence of depression was 21.2%.
Depressed patients had significantly higher sICAM-1 levels (p=0.002), even after adjusting for potential confounders (gender, smoking, metabolic syndrome) (p=0.04). This finding was most marked in patients with a first MDE. When antidepressant treatment was added to the model, the relationship waqs slightly attenuated (p=0.06).
Although no significant association between depression and IL-6 was observed, there was an association between depression and CRP when accounting for statin therapy. Depressed patients not taking statins had significantly higher CRP levels (p=0.009); in patients taking statins, there was no relationship between CRP and depression (p=0.41).
Discussion
These results suggest higher levels of the endothelial activation marker sICAM-1 in depressed patients with recent acute ischemic events, a group with increased morbidity and mortality. The etiologic basis of higher sICAM-1 levels in depressed CAD cannot be elucidated from the study’s cross-sectional design.
The authors, however, provide intriguing hypotheses. Depressed patients have higher sympathetic activity, also shown to induce the expression of cellular adhesion molecules. Preliminary evidence has also demonstrated depression itself, in the absence of traditional cardiac risk factors, to be associated with endothelial dysfunction.
The vascular depression hypothesis (ref. 1) of late-life depression is another intriguing model, whereby atherosclerosis of cerebral arteries may be induced by chronic inflammation triggered by sICAM release.
Higher levels of ICAM have, in fact, been found in the dorsolateral prefrontal cortex of post-mortem late-life depressed subjects (ref. 2). Lending support to this model, the link between sICAM-1 and depression in this study were most marked in patients with their first MDE.
Depressed patients not taking statins were twice as likely to have high CRP levels, while no association between depression and CRP was observed in patients taking statins. Also noteworthy, the relationship between sICAM-1 and depression was weakened with antidepressant treatment. Thus, raising questions about a potentially mutative role of statins and antidepressants in the relationship between depression and cardiac events.
Limitations in addition to the cross-sectional design, include a refusal rate of 48.5% limiting the generalizability of the findings.
References
1. Alexopoulos GS, Meyers BS, Young RC, et al. “Vascula depression” hypothesis. Archives of General Psychiatry 1997;54:915-922
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2. Thomas AJ, Ferrier IN, Kalaria RN,et al. American Journal of Psychiatry 2000;157:1682-1684
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