LAUSR

Association of Depression and Cardiovascular Disease: Which Comes First? To the Editor In the August issue of JAMA Cardiology, Khambaty et al1 reported that major depressive disorder may be independently associated with incident cardiovascular disease (CVD) in those with human immunodeficiency virus (HIV) infection. This study adds to the existing literature on an association between depression and CVD in other conditions. However, caution must be exercised before assuming causality or even when considering the directionality of such a relationship. Cardiovascular disease typically has a long asymptomatic period between disease onset and symptom manifestation, and therefore, addressing whether depression is independently associated with incident CVD is challenging. With respect to the study by Khambaty et al,1 relying on International Classification of Diseases, Ninth Revision code data for prevalent CVD to identify a population without baseline CVD is inadequate and potentially misleading. The possibility that CVD, even if asymptomatic, may lead to depression is one that must also be considered in general as well as in patients with HIV infection. Cardiovascular disease, along with many other long-term illnesses, is associated with activation of inflammatory pathways,2,3 which may then lead to major depressive disorder or dysthymia.4,5 Khambaty et al1 note that reliance on International Classification of Diseases, Ninth Revision codes may have caused them to misclassify patients with unrecognized depressive disorders; however, the possibility that they may have misclassified patients with unrecognized CVD should also be considered, as should the possibility that CVD is associated with incident depression in patients with HIV infection.