title: Depression and markers of inflammation as predictors of all-cause mortality in heart failure.
abstract: 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 8.4years, 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 6.1years 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.
  
  
  CONCLUSIONS
  Depressive symptoms and markers of inflammation and NO regulation are codominant risk factors for all-cause mortality in heart failure.
authors.affiliation: CoRPS, Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands. Electronic address: P.M.C.Mommersteeg@uvt.nl.
authors.forename: Paula M C
authors.initials: PMC
authors.lastname: Mommersteeg
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands. Electronic address: r.g.schoemaker@thorax.umcg.nl.
authors.forename: Regien G
authors.initials: RG
authors.lastname: Schoemaker
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Neurology and Alzheimer Research Centre, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands. Electronic address: p.j.w.naude@umcg.nl.
authors.forename: Petrus J W
authors.initials: PJW
authors.lastname: Naudé
authors.affiliation: Department of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Neurology and Alzheimer Research Centre, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands. Electronic address: U.L.M.Eisel@rug.nl.
authors.forename: Ulrich L M
authors.initials: ULM
authors.lastname: Eisel
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus Medical Center, The Netherlands. Electronic address: i.vandenberg-garrelds@erasmusmc.nl.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Garrelds
authors.affiliation: Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, CARIM, Maastricht University Medical Centre, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: c.schalkwijk@maastrichtuniversity.nl.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Clinical Chemistry and Hematology Laboratory, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands. Electronic address: b.westerhuis@elisabeth.nl.
authors.forename: Bert W J J M
authors.initials: BWJJM
authors.lastname: Westerhuis
authors.affiliation: CoRPS, Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands. Electronic address: W.J.Kop@uvt.nl.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Kop
authors.affiliation: CoRPS, Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands. Electronic address: J.Denollet@uvt.nl.
authors.forename: Johan
authors.initials: J
authors.lastname: Denollet
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D015897:Comorbidity; D003863:Depression / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000453:epidemiology; D000071068:Lipocalin-2 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D009569:Nitric Oxide; D002097:C-Reactive Protein
keywords: All-cause mortality; CRP; Depressive symptoms; Heart failure; Inflammation; Methylarginines; NGAL; NO regulation; Prognosis