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Heartache and heartbreak—the link between depression and cardiovascular disease

Abstract

The close, bidirectional relationship between depression and cardiovascular disease is well established. Major depression is associated with an increased risk of coronary artery disease and acute cardiovascular sequelae, such as myocardial infarction, congestive heart failure, and isolated systolic hypertension. Morbidity and mortality in patients with cardiovascular disease and depression are significantly higher than in patients with cardiovascular disease who are not depressed. Various pathophysiological mechanisms might underlie the risk of cardiovascular disease in patients with depression: increased inflammation; increased susceptibility to blood clotting (owing to alterations in multiple steps of the clotting cascade, including platelet activation and aggregation); oxidative stress; subclinical hypothyroidism; hyperactivity of the sympatho-adrenomedullary system and the hypothalamic–pituitary–adrenal axis; reductions in numbers of circulating endothelial progenitor cells and associated arterial repair processes; decreased heart rate variability; and the presence of genetic factors. Early identification of patients with depression who are at risk of cardiovascular disease, as well as prevention and appropriate treatment of cardiovascular disease in these patients, is an important and attainable goal. However, adequately powered studies are required to determine the optimal treatment regimen for patients with both depression and cardiovascular disorders.

Key Points

  • Depression is associated with increased risk of coronary artery disease, and increased morbidity and mortality after myocardial infarction, CABG surgery, congestive heart failure, or mitral valve replacement

  • Depression-associated biological alterations include increased inflammation, a clotting diathesis, decreased variability in heart rate, increased activity of the sympathoadrenal and pituitary–adrenal axes, and a reduction in circulating endothelial progenitor cells

  • Depression-associated biological alterations might mediate the link between depression and cardiovascular disease

  • Results are inconclusive from studies designed to determine whether successful treatment of depression in patients with cardiovascular disease is associated with a reduction in subsequent major cardiac events

  • Further research is required to determine whether normalization of these depression-associated biological alterations, resulting from effective treatment, contribute to a reduced risk of cardiovascular disease

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Figure 1: Biological factors that might mediate the relationship between major depression and cardiovascular disease.
Figure 2: Alterations in platelet activation in response to arterial damage in patients with depression.
Figure 3: The effect of depression on arterial repair.

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Acknowledgements

P. J. Goldschmidt-Clermont's research is supported by grants from the National Cancer Institute and NIH (R01CA136387). C B. Nemeroff's research is supported by grants from the NIH (NIMH MH-078775, MH-094759, and NIDA DA-031201).

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Both authors contributed to researching the data for the article, writing the manuscript, discussions of its content, and review and editing of the manuscript before submission.

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C B. Nemeroff has acted as a consultant for Roche, Shire, SK Pharma, Takeda, Lilly, and Xhale and is a stockholder of CeNeRx BioPharma, NovaDel Pharma, PharmaNeuroBoost, Revaax, and Xhale. He is also a member of the scientific advisory boards for the American Foundation for Suicide Prevention, Anxiety and Depression Association of America, BioPharma, CeNeRx, National Alliance for Research on Schizophrenia and Depression, PharmaNeuroBoost, Skyland Trail, and Xhale. He is currently, or has served in the past 2 years, on the board of directors of the American Foundation for Suicide Prevention, Gratitude America, the Anxiety and Depression Association of America, NovaDel Pharma, and Skyland Trail. P. J. Goldschmidt-Clermont is a shareholder and board member of Health Management Associates, Mednax and OPKO Health, Inc, and a stockholder and scientific advisory board member for Synecor.

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Nemeroff, C., Goldschmidt-Clermont, P. Heartache and heartbreak—the link between depression and cardiovascular disease. Nat Rev Cardiol 9, 526–539 (2012). https://doi.org/10.1038/nrcardio.2012.91

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