title: Plasma neutrophil gelatinase-associated lipocalin is independently associated with cardiovascular disease and mortality in community-dwelling older adults: The Rancho Bernardo Study.
abstract: OBJECTIVE
  The purpose of this study was to determine the association between neutrophil gelatinase-associated lipocalin (NGAL) levels and cardiovascular and all-cause mortality in community-dwelling older adults.
  
  
  BACKGROUND
  NGAL is a novel marker best known for its role in rapidly identifying acute kidney injury. Although expressed in atherosclerosis, its association with cardiovascular disease (CVD) in the community has not been reported.
  
  
  METHODS
  We measured plasma NGAL levels in 1,393 Rancho Bernardo Study participants without CVD, mean age 70 years. Participants were followed for a mean time period of 11 years.
  
  
  RESULTS
  During follow-up, 436 participants died (169 from CVD). In models adjusted for traditional CVD risk factors and creatinine clearance, NGAL was a significant predictor of CVD mortality (hazard ratio [HR] per SD log increase: 1.33, 95% confidence interval [CI]: 1.12 to 1.57), all-cause mortality (HR: 1.19, 95% CI: 1.07 to 1.32), and a combined cardiovascular endpoint (HR: 1.26, 95% CI: 1.10 to 1.45). After further adjusting for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), NGAL remained an independent predictor of each outcome. NGAL improved the C-statistic (0.835 to 0.842) for prediction of CVD death (p = 0.001). Net reclassification improvement (>0) with the addition of NGAL was 18% (p = 0.02); the integrated discrimination index was also significant (p = 0.01). Participants with NGAL and NT-proBNP above the median had increased risk of CVD death versus those with only NT-proBNP elevated (HR: 1.43, 95% CI: 1.12 to 1.82).
  
  
  CONCLUSIONS
  Plasma NGAL is a significant predictor of mortality and CVD in community-dwelling older adults, independent of traditional risk factors and kidney function, and adds incremental value to NT-proBNP and CRP. The potential impact of these results includes providing insight into new mechanisms of CVD and the possibility of improving screening, intervention, and prevention.
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, California 92037-7411, USA. lbdaniels@ucsd.edu
authors.forename: Lori B
authors.initials: LB
authors.lastname: Daniels
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.forename: Paul
authors.initials: P
authors.lastname: Clopton
authors.forename: Gail A
authors.initials: GA
authors.lastname: Laughlin
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Alan S
authors.initials: AS
authors.lastname: Maisel
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002140:California / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D057187:Independent Living; D053208:Kaplan-Meier Estimate; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D015999:Multivariate Analysis; D009204:Myocardial Revascularization; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain