Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 59, Issue 12, Pages 1101-1109Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2011.11.046
Keywords
biomarkers; cardiovascular disease; elderly; natriuretic peptides; risk factors
Categories
Funding
- National Institute on Aging [AG07181, AG028507]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK31801]
- American Heart Association
- Sandra Daugherty Foundation
- Abbott Diagnostics
- Roche Diagnostics
- Alere Inc.
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Objectives 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 proB-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. (J Am Coll Cardiol 2012;59:1101-9) (C) 2012 by the American College of Cardiology Foundation
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