Background: In patients with heart failure (HF) depressive symptoms have been associated with mortality, as well as biological risk factors, including inflammation, nitric oxide (NO) regulation, and oxidative stress. We investigated the joint predictive value of depressive symptoms, inflammation and NO regulation on all-cause mortality in patients with HF, adjusted for covariates. Methods: Serum levels of inflammation (TNFα, sTNFr1, sTNFr2, IL-6, hsCRP, NGAL), NO regulation (l-arginine, ADMA, and SDMA), and oxidative stress (isoprostane 8-Epi Prostaglandin F2 Alpha) were measured in 104 patients with HF (mean age 65.7. ±. SD 8.4. years, 28% women). Depressive symptoms (Beck Depression Inventory, BDI) were measured as continuous total, cognitive, and somatic symptoms, as well as categorized presence of mild/moderate depression (cut-off BDI ≥10). In Cox proportional hazard models we adjusted for age, sex, poor exercise tolerance and comorbidity. Results: After on average 6.1. years follow-up (SD = 2.9, range 0.4-9.2), 49 patients died. Total and somatic depressive symptoms, mild/moderate depression, higher NGAL, sTNFr2, IL-6, hsCRP and SDMA serum levels were significantly associated with a higher all-cause mortality rate, adjusted for covariates. The findings were most consistent for CRP level and somatic depressive symptoms. When combined, both depressive symptoms and markers of inflammation and NO regulation remained significantly associated with all-cause mortality. These associations were not confounded by age, sex, poor exercise tolerance and comorbidity. Conclusion: Depressive symptoms and markers of inflammation and NO regulation are codominant risk factors for all-cause mortality in heart failure.

All-cause mortality, CRP, Depressive symptoms, Heart failure, Inflammation, Methylarginines, NGAL, NO regulation, Prognosis,
Brain, Behavior, and Immunity
Department of Internal Medicine

Mommersteeg, P.M.C, Schoemaker, R.G, Naudé, P.J.W, Eisel, U.L.M, Garrelds, I.M, Schalkwijk, C.G, … Denollet, J. (2016). Depression and markers of inflammation as predictors of all-cause mortality in heart failure. Brain, Behavior, and Immunity, 57, 144–150. doi:10.1016/j.bbi.2016.03.012