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

Study Questions:

What is the association between neutrophil gelatinase–associated lipocalin (NGAL) levels and cardiovascular (CV) and all-cause mortality in community-dwelling older adults?

Methods:

Plasma NGAL levels were measured in 1,393 Rancho Bernardo Study participants without CV disease (CVD). Mean age at baseline was 70 years and 36% were men. Participants were followed for a mean of 11 years. The primary endpoint included CV events, CV mortality, and all-cause mortality.

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], 1.33), all-cause mortality (HR, 1.19), and a combined cardiovascular endpoint (HR, 1.26). 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 (0.835-0.842) 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).

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.

Perspective:

NGAL, also known as lipocalin-2, is a protein important in the immune response to bacterial infections. It is a marker of kidney injury, and experimental studies suggest a role as an active participant in acute coronary syndromes. The predictive value of CVD mortality was not affected by gender, body mass index, age, renal function, or coronary risk factors. However, the effect of NGAL on the C-statistic was modest. The value of NGAL as a clinically useful biomarker will require further evaluation in larger and more diverse cohorts than in the small Southern California town of Rancho Bernardo.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Dyslipidemia, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Lipid Metabolism

Keywords: Acute Coronary Syndrome, Follow-Up Studies, Bacterial Infections, Risk Factors, Creatinine, Lipocalins, Incidence, C-Reactive Protein, Body Mass Index, Biological Markers, California, Cardiovascular Diseases, Peptide Fragments, Carrier Proteins, Kidney, Natriuretic Peptide, Brain


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