High genetic risk for depression as an independent risk factor for mortality in patients referred for coronary angiography

Front Cardiovasc Med. 2023 Jun 26:10:1125151. doi: 10.3389/fcvm.2023.1125151. eCollection 2023.

Abstract

Background: Different observations have suggested that patients with depression have a higher risk for a number of comorbidities and mortality. The underlying causes have not been fully understood yet.

Aims: The aim of our study was to investigate the association of a genetic depression risk score (GDRS) with mortality [all-cause and cardiovascular (CV)] and markers of depression (including intake of antidepressants and a history of depression) in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study involving 3,316 patients who had been referred for coronary angiography.

Methods and results: The GDRS was calculated in 3,061 LURIC participants according to a previously published method and was found to be associated with all-cause (p = 0.016) and CV mortality (p = 0.0023). In Cox regression models adjusted for age, sex, body mass index, LDL-cholesterol, HDL-cholesterol, triglycerides, hypertension, smoking, and diabetes mellitus, the GDRS remained significantly associated with all-cause [1.18 (1.04-1.34, p = 0.013)] and CV [1.31 (1.11-1.55, p = 0.001)] mortality. The GDRS was not associated with the intake of antidepressants or a history of depression. However, this cohort of CV patients had not specifically been assessed for depression, leading to marked underreporting. We were unable to identify any specific biomarkers correlated with the GDRS in LURIC participants.

Conclusion: A genetic predisposition for depression estimated by a GDRS was independently associated with all-cause and CV mortality in our cohort of patients who had been referred for coronary angiography. No biomarker correlating with the GDRS could be identified.

Keywords: all-cause mortality; cardiovascular mortality; coronary artery disease; depression; genetic risk score.

Grants and funding

This work was supported by the 7th Framework Programs Atheroremo (grant agreement number 201668) and RiskyCAD (grant agreement number 305739) of the European Union; the H2020 Programs TO_AITION (grant agreement number 848146) and TIMELY (grant agreement number 101017424) of the European Union, the German Ministry for Education and Research, project e:AtheroSysMed (systems medicine of coronary heart disease and stroke, grant number 01ZX1313A-K); and the Center for Preventive Medicine and Digital Health Baden-Württemberg CPDBW. The work of SL, AM, MK, and WM was also supported by the German Ministry for Education and Research as part of the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig (grant numbers 01EA1411A and 01EA1808A).