Article

Depression and heart rate variability in patients with coronary heart disease

Author and Disclosure Information

 

References

RELATIONSHIP AMONG HRV AND OTHER POSSIBLE BIOLOGICAL PATHWAYS

As discussed earlier, other biological pathways that may link depression to increased mortality have been reported. The two that have received the most support are proinflammatory and procoagulant processes. 18,19 Studies of medically healthy depressed psychiatric patients and of depressed CHD patients have found depression to be associated with higher levels of the inflammatory risk markers interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor–alpha (TNF-α) and with inflammatory-procoagulant markers such as fibrinogen,56–60 as well as with platelet activation. Low HRV and elevations in proinflammatory or procoagulant markers generally have been described as though they are independent pathways. However, both inflammatory and coagulant responses can be modulated by ANS activity,61,62 and a cholinergic anti-inflammatory pathway was recently proposed in which there is vagal efferent inhibition of proinflammatory cytokine release, thereby reducing systemic inflammation.62,63 Low HRV, reflecting reduced vagal activity, should therefore be associated with higher levels of both proinflammatory and procoagulant markers. Recent studies have found a relationship between HRV activity and increased markers of inflammation in other high-risk patients, including those with heart failure64,65 and with acute coronary syndrome.66

In a recent study of 44 patients with major depression, moderate negative correlations were found between fibrinogen and four measures of HRV.67 IL-6 was also negatively correlated with one measure of HRV (total power) and was marginally related to two others (VLF and LF power). On the other hand, neither CRP nor TNF-α was significantly related to any measure of HRV. The finding that fibrinogen and IL-6 are moderately related to HRV suggests a link between these factors in depressed CHD patients. Thus, these risk markers, which are commonly found in patients with depression, may be related and contribute to the increased mortality associated with depression. This possibility should be investigated in larger mechanistic studies of depression and cardiac morbidity and mortality.

SUMMARY AND FUTURE DIRECTIONS

Low HRV and other markers of cardiac ANS dysfunction in depressed patients are likely to contribute to the elevated risk associated with depression in patients with CHD. More work is needed to clarify the physiologic and behavioral mechanisms underlying depression’s role as a risk factor for mortality in patients with CHD. Work is also needed to identify treatments that improve both depression and HRV, and to determine whether such treatments might also improve survival in these patients.68

Next Article: