Depression, Inflammation, and Incident Cardiovascular Disease in Women With Suspected Coronary Ischemia
Key result
Depression is linked to ~2.6-fold higher cardiovascular risk in women with suspected ischemia.
- HR 2.58
- P=0.0009
- n=559
Why the study?
It was unclear whether inflammation serves as a mechanism linking depression to cardiovascular disease.
Does inflammation (measured by C-reactive protein and interleukin-6) explain the relationship between depression and incident cardiovascular disease events in women with suspected coronary ischemia?
Key Points
- To examine prospectively whether inflammatory biomarkers explain the association between depression and incident cardiovascular disease in women with suspected coronary ischemia.
- Prospective cohort study of N=559 women with suspected coronary ischemia followed over a median of 5.9 years.
- Classified participants into depression, possible depression, or no depression using baseline Beck Depression Inventory scores (threshold ≥10) and clinical treatment history.
- Measured baseline plasma C-reactive protein (CRP) and interleukin (IL)-6 to assess their role in predicting cardiovascular events (nonfatal myocardial infarction, stroke, heart failure, and cardiovascular mortality).
- Depression significantly predicted incident cardiovascular disease events (HR 2.58, p=0.0009), whereas possible depression did not (HR 1.12, p=0.68).
- Compared to women without depression, those with depression had 70% higher CRP (p=0.0008) and 25% higher IL-6 (p=0.04).
- Adding CRP and IL-6 to multivariable models reduced the depression risk estimate by only 13% and 4%, respectively, leaving depression as an independent predictor.
Study Design
Type
Cohort (n=559)
Structured PICO
Does inflammation (measured by C-reactive protein and interleukin-6) explain the relationship between depression and incident cardiovascular disease events in women with suspected coronary ischemia?
P
Population
559 women with suspected coronary ischemia who completed the Beck Depression Inventory at baseline, followed for 5.9 years.
E
Exposure
Exposure to depression, classified into 2 groups: 1) depression (both elevated depressive symptoms with BDI >=10 and a previous diagnosis of depression requiring treatment); 2) possible depression (having either indicator of depression, but not both)
C
Comparator
Women with no depression (having neither elevated depressive symptoms [BDI >=10] nor a previous diagnosis of depression requiring treatment)
O
Outcome
Composite incidence of cardiovascular disease (CVD) events (hospital stays for nonfatal myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) over 5.9 years of follow-upcomposite
Main Result
Hazard Ratio: 2.58
p-value: p=0.0009
In women with suspected coronary ischemia, both depression and inflammatory biomarkers (CRP and IL-6) are independent predictors of incident cardiovascular events, with inflammation explaining only a small fraction of the depression-related cardiovascular risk.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“What is clear is that inflammation does not play a substantial role. We need to look at other things. Perhaps there is a change in the ability of platelets to aggregate.”
“We know from other studies that there is a relationship between depression and elevation of certain inflammatory molecules, but no one knows for sure what the mechanism is.”
Implication
Depression independently predicts CVD events beyond CRP/IL-6; extends prior associations but leaves mechanisms and interventions open.
Abstract
Objectives The purpose of this study was to examine prospectively whether inflammation explains the relationship between depression and cardiovascular disease (CVD). Background It is unclear whether inflammation is a mechanism linking depression to CVD. Methods We measured C-reactive protein (CRP) and interleukin (IL)-6 in 559 women with suspected coronary ischemia who completed the Beck Depression Inventory (BDI) at baseline and were followed over 5.9 years. We considered indicators of past and current depression to classify women into 3 groups: 1) depression, having both elevated depressive symptoms (BDI > or =10) and a previous diagnosis of depression requiring treatment; 2) possible depression, having either indicator but not both; and 3) no depression, having neither indicator of depression. The main outcome was incidence of CVD events (hospital stays for nonfatal myocardial infarction, stroke, congestive heart failure, and CVD-related mortality). Results Compared with women without depression, women with depression had a 70% higher CRP (p = 0.0008) and a 25% higher IL-6 (p = 0.04), whereas women with possible depression had 30% higher CRP (p = 0.02) and 28% higher IL-6 (p = 0.01). Depression was a significant predictor of CVD (hazard ratio 2.58, p = 0.0009), but possible depression was not (hazard ratio 1.12, p = 0.68). Adjustment for other patient factors did not substantially affect the results. Addition of CRP decreased the estimate for depression by 13% and addition of IL-6 decreased it by 4%. Both depression and inflammatory biomarkers remained independent predictors of outcome. Conclusions Despite their robust association with depression, inflammatory biomarkers explain only a small portion of the association between depression and CVD incidence.
Discussion
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Cite This Study
Vaccarino et al. (2007) conducted a cohort in Suspected coronary ischemia (n=559). Depression (elevated depressive symptoms BDI ≥10 and previous diagnosis of depression requiring treatment) vs. No depression was evaluated on Incidence of cardiovascular disease events (hospital stays for nonfatal myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) (HR 2.58, p=0.0009). Depression predicted incident cardiovascular disease in women with suspected ischemia (HR 2.58, p=0.0009), an effect only partially explained by CRP and IL-6.