Heart-brain medicine: Update 2008

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Investigators involved in heart-brain medicine are dedicated to defining the physiology associated with interactions of the neurological and cardiovascular systems. In 2004 the Bakken Heart-Brain Institute was founded at Cleveland Clinic because we believed that furthering our understanding of this physiology could lead to a better understanding of chronic disease, define novel therapies, and improve patient outcomes.

Reprinted from Cleveland Clinic Journal of Medicine (Penn MS, Bakken EE. Heart-brain medicine: update 2007. Cleve Clin J Med 2008; 75(suppl 2):S3–S4).

Figure 1. Proposed pathways involved in psychiatrically mediated states altering cardiovascular disease and outcomes.

The 2008 Bakken Heart-Brain Summit, held last June in Cleveland, further demonstrated real progress in our understanding of the importance of heart-brain interactions in health and disease. The opening session of the 2008 Summit focused on reviewing the evidence linking psychiatric disorders—specifically depression—to increased inflammation and plaque rupture associated with worsening outcomes in patients with atherosclerotic heart disease. These pathways linking psychiatric disorders to acute coronary syndrome were proposed after the 2007 Bakken Heart-Brain Summit (Figure 1)1:
  • Depression leads to decreased vagal tone
  • Decreased vagal tone leads to increased inflammation
  • Increased inflammation leads to acute coronary syndrome.

Speakers at the 2008 Summit offered insights into the physiology, clinical measures, and molecular pathways involved in linking the heart and the brain, including:

  • Measures of heart rate variability in depression
  • The utility of heart rate variability and heart rate recovery in quantifying vagal tone and outcome in patients with and without coronary artery disease
  • Pathways of inflammation involved in acute coronary syndrome.


The 2007 and 2008 Summits highlighted the link between depression and outcomes in patients with atherosclerosis (2007)1 and the potential associated mechanisms (2008). Just as exciting are the developments since last June: numerous papers have been published demonstrating this link in clinical populations, and depression screening has been included in recommendations from the American Heart Association on the treatment of patients with coronary artery disease—recommendations that are endorsed by the American Psychiatric Association.2

The studies published since June 2008 demonstrate clear links between depression and morbidity and mortality from cardiovascular causes. A recent paper from the Nurses’ Health Study showed that individuals with depression had a higher incidence of cardiovascular death.3 Notably, subjects in the Nurses’ Health Study had no clinical evidence of atherosclerotic heart disease at enrollment. In another recent study, depression was associated with worse outcomes in patients following coronary stenting.4 Finally, and most interestingly, depression was recently associated with endothelial dysfunction in patients with atypical angina and angiographically normal coronary arteries.5 Thus, regardless of the degree of underlying atherosclerosis, depression is associated with cardiovascular morbidity or mortality.

Less clear is the relationship between depression and inflammation as measured by surrogate inflammatory markers. An analysis of the Canadian Nova Scotia Health Survey [NSHS95] Prospective Population Study suggested that increased inflammatory markers accounted for only a small portion of the risk of coronary heart disease associated with depression.6 Conversely, a recent analysis of patients with stable coronary artery disease demonstrated a strong correlation between major depressive disorders and highsensitivity C-reactive protein.7

Clearly, significant work has yet to be done to fully elucidate the molecular pathways that link depression and adverse outcomes in patients at risk for coronary artery disease. That said, it is very encouraging that professional societies are beginning to recognize the value and importance of heart-brain medicine in identifying novel strategies for improving patient outcomes.

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