title: Prognostic Significance of Interleukin-34 (IL-34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency.
abstract: BACKGROUND
  Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long-term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin-34 (IL-34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL-34 in HF remains unclear, so that the present study aimed to determine it.
  
  
  RESULTS
  This prospective, observational study included 510 consecutive HF patients with their serum IL-34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all-cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL-34 increased, determined by log-rank tests with Kaplan-Meier curves. Serum IL-34 was also a significant prognostic predictor of the primary end point (1.301 [1.115-1.518];P=0.001), cardiovascular death (1.347 [1.096-1.655];P=0.005), HF hospitalization (1.234 [1.018-1.494];P=0.032), and all-cause mortality (1.343 [1.115-1.618];P=0.002) in HF as per SD increase in the log IL-34 level after adjusting for age, sex, traditional risk factors, and N-terminal pro-brain natriuretic peptide. Especially, IL-34 had a more-significant prognostic value in HF patients with kidney impairment than those without.
  
  
  CONCLUSIONS
  IL-34 is a significant predictor of cardiovascular death, HF hospitalization, and all-cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL-34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China cardexyanxx@hotmail.com rongtao@hotmail.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Tao
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xi
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China cardexyanxx@hotmail.com rongtao@hotmail.com.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Yan
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality*; D016022:Case-Control Studies; D002423:Cause of Death; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000276:immunology*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011379:Prognosis; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000150:complications / Q000276:immunology*
chemical_list: C529076:IL34 protein, human; D007378:Interleukins
keywords: heart failure; interleukin‐34; prognosis; renal insufficiency