April 2010
Reviewer: Jeff C. Huffman, MD
Association between clinical depression and endothelial function measured by forearm hyperemic reactivity
Psychosom Med 2010; 72(1):20-26
Background: Clinical depression (and depressive symptoms) have been independently associated with the development of coronary heart disease and cardiac mortality. The mechanisms of this connection are not yet well-known, but are likely a result of both behavioral and physiologic effects of depression leading to poor cardiac outcomes. Among the physiologic mechanisms that may be important in this link, endothelial dysfunction appears is of increasing interest. Impaired function of the endothelium is a risk factor for cardiac events, and several prior studies have found that major depression is associated with endothelial dysfunction. However, the authors report that no study had previously examined a link between formally-diagnosed depressive disorders and endothelial function among patients with known cardiac disease.
Methods: The authors selected a subset of patients from a larger study of cardiac exercise stress tests at the Montreal Heart Institute (May 2005–December 2006). This subset of patients (only a subset was selected because of limited endothelial function testing capacity) underwent diagnostic assessment for major and minor depression using the PRIME-MD, baseline data (including CHD status) was collected, and endothelial function was measured using a novel method called forearm hyperemic reactivity (FHR) to assess for relative uptake ratio (RUR) between a hyperemic and control arm—lower RUR correlates with worse endothelial function. The authors report the FHR technique to be similar to the more well-established technique of flow-mediated dilation of the brachial artery. FHR was compared among patients with no depression, minor depression, and MDD.
Results: A total of 323 patients were enrolled; 132 had established CHD and 191 were considered "at risk" for CHD. In total 7% (n=23) had minor depression and 7% (n=23) met MDD criteria. On analyses that accounted for baseline variables (including CHD status, BMI, smoking, hypertension, biomarkers, and medications), both MDD and minor depression patients had significantly lower RUR (i.e., worse endothelial function) than patients without depression; there was no difference in RUR between patients with major or minor depression. When analyses were repeated using just the CHD patients, the findings were essentially the same.
Discussion: These results suggest that patients with major or minor depression who have CHD—or are "at risk" for CHD based on the symptoms/profile leading to a stress test—appear to have endothelial dysfunction. It was interesting to note that the patients with minor depression appear to have a risk of endothelial dysfunction that is just as great as those with MDD; this to some degree mirrors the literature on depression and cardiac outcomes that has found that depressive symptoms—and not just full clinical depression/MDD—are associated with adverse cardiac effects. Given that endothelial dysfunction appears to be an early marker of atherosclerosis and a risk factor for recurrent cardiac events, this relationship is a potentially vital one in determining how depression may lead to poor cardiac outcomes. Interestingly, there is some suggestion that the SSRIs may improve endothelial function, though this literature is both small and somewhat mixed.
This well-done study did have several limitations. The method of measuring endothelial function was a novel one, and although it may be as good or better than more well-established methods, there is less known about it and other endothelial function studies have used flow-mediated dilation. There was a relatively small number of patients with MDD (the more important depressed population, since there are no established treatments for minor depression), and thus some caution should be used in making major statements based on 23 patients with MDD. CHD severity was not assessed, and the population was primarily male. Finally, the authors may have not been aware of a study by Pizzi and colleagues (Eur Heart J 2008) that found depressive symptoms to be linked with endothelial dysfunction among a larger cohort of patients at risk for (but without) CHD. However, those results do not adversely impact the results of this study, which is consistent with these findings and unlike the prior study uses formally diagnosed depression and a cohort with known CHD.
Overall, this is a well-done study that links depression and endothelial dysfunction in a cardiac population. Future studies should confirm these findings and further assess the impact of depression treatment on endothelial function.