Plasma Neutrophil Gelatinase–Associated Lipocalin Is Independently Associated With Cardiovascular Disease and Mortality in Community-Dwelling Older Adults: The Rancho Bernardo Study

Objectives rpose 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. ound s 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. s sured 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. s 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). sions 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.