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Depression as a non-causal variable risk marker in coronary heart disease

Anna Meijer, Marij Zuidersma and Peter de Jonge*

Author Affiliations

Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands

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BMC Medicine 2013, 11:130  doi:10.1186/1741-7015-11-130

Published: 15 May 2013



After decades of investigations, explanations for the prospective association between depression and coronary heart disease (CHD) are still incomplete.


Depression is often suggested to be causally related to CHD. Based on the available literature, we would rather argue that depression can best be regarded as a variable risk marker, that is, a variable that fluctuates together with mechanisms leading to poor cardiovascular fitness. Despite numerous efforts, no evidence is found that manipulation of depression alters cardiovascular outcomes - a key premise for determining causality. To explain the concept of a variable risk marker, we discuss several studies on the heterogeneity of depression suggesting that depression is particularly harmful for the course of cardiovascular disease when it appears to be a physiological consequence of the cardiovascular disease itself.


We conclude that instead of depression being a causal risk factor for CHD, the association between depression and CHD is likely confounded, at least by the cardiac disease itself.

Cardiovascular disease; Depression; Causality; Risk marker; Risk factor