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Cardiovascular Abnormalities in Patients with Major Depressive Disorder

Autonomic Mechanisms and Implications for Treatment

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Abstract

This article provides a detailed review of the association of major depression with coronary heart disease (CHD), examines the biological variables underpinning the linkage and discusses the clinical implications for treatment. When considering the co-morbidity between major depressive disorder (MDD) and CHD it is important to differentiate between (i) the prevalence and impact of MDD in those with existing CHD and (ii) MDD as a risk factor for the development of CHD. Whether the same biological mechanisms are at play in these two instances remains unknown. Depression is common in patients with CHD. Importantly, depression in these patients increases mortality. There is also consistent evidence that MDD is a risk factor for the development of CHD. The relative risk of developing CHD is proportional to the severity of depression and is independent of smoking, obesity, hypercholesterolaemia, diabetes mellitus and hypertension.

There is a clear need to identify the underlying neurochemical mechanisms responsible for MDD and their linkage to the heart and vascular system. Of particular interest are activation of stress pathways, including both the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, and inflammatory-mediated atherogenesis. Elevated sympathetic activity, reduced heart rate variability and increased plasma cortisol levels have been documented in patients with MDD. In addition to direct effects on the heart and vasculature, activation of stress pathways may also be associated with increased release of inflammatory cytokines such as interleukin-6 and tumour necrosis factor-α. Elevated levels of C-reactive protein are commonly observed in patients with MDD.

The majority of investigations examining treatment of depression following myocardial infarction have focused on safety and efficacy; there is little evidence to indicate that treating depression in these patients improves survival. Given that strategies for preventive therapy remain incompletely formulated, future research should focus on generating a better understanding of the neurobiology of MDD and heart disease as a basis for rational and effective therapy.

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Acknowledgements

Supported by grants from the National Health and Research Council of Australia and by the National Heart Foundation of Australia. The funding agencies played no role in the preparation of this manuscript and the authors report no conflicts of interest related to the submission. Dr Lambert has received honoraria from Wyeth Pharmaceuticals and Pfizer for presentations given. Dr Brown has received grants from Pfizer for previous investigator-driven research that was not related specifically to this review. Dr Barton has received honoraria for presentations given from Servier, Eli Lilly, Pfizer, Solvay Pharmaceuticals, Wyeth Pharmaceuticals, Lundbeck and AstraZeneca. He has also received research funding from Pfizer and Lundbeck and provided consultancy services to Servier, Eli Lilly and Pfizer.

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Brown, A.D.H., Barton, D.A. & Lambert, G.W. Cardiovascular Abnormalities in Patients with Major Depressive Disorder. CNS Drugs 23, 583–602 (2009). https://doi.org/10.2165/00023210-200923070-00004

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