Plasma neutrophil gelatinase-associated lipocalinin in the general population: association with inflammation and prognosis.

Abstract

OBJECTIVE:

Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein stored in granules of neutrophil leukocytes participating in inflammatory and atherosclerotic processes and possibly plaque rupture. Despite the putative role of NGAL in atherosclerosis and acute myocardial infarction, human studies of plasma NGAL are still limited.

APPROACH AND RESULTS:

We prospectively followed 5599 randomly selected men and women from the community in the fourth Copenhagen Heart Study. Plasma NGAL was measured at study entry. Participants were followed for 10 years. During follow-up, 20% died (n=1120) and 15% (n=884) developed a major adverse cardiovascular event. Plasma NGAL associated strongly with all inflammatory markers (high-sensitivity C-reactive protein, total leukocyte count, neutrophil count) and inversely with estimated glomerular filtration rate (all, P<0.001). Multivariate analysis identified neutrophil leukocyte count as the main determinant of plasma NGAL. During follow-up, participants with increasing NGAL had increased risk of all-cause mortality and major adverse cardiovascular event (both, P<0.001). Even after adjustment for confounding risk factors by Cox regression analysis, NGAL remained an independent predictor of both all-cause mortality and major adverse cardiovascular event. When added to the Framingham risk score, NGAL improved c-statistics and correctly reclassified ≈15% into more appropriate risk groups. In comparison with high-sensitivity C-reactive protein, when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk.

CONCLUSIONS:

Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c-statistics and correctly reclassifies participants into more accurate risk categories.

• Authors: Søren Lindberg, Jan S Jensen, Rasmus Mogelvang, Sune H Pedersen, Søren Galatius, Allan Flyvbjerg, Nils E Magnusson
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 34 Issue 9 Pg. 2135-42 (Sep 2014) ISSN: 1524-4636 [Electronic] United States
• PMID: 24969771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Acute-Phase Proteins
• Biomarkers
• Inflammation Mediators
• LCN2 protein, human
• Lipocalin-2
• Lipocalins
• Proto-Oncogene Proteins
• C-Reactive Protein

Topics

• Acute-Phase Proteins
• Adult
• Aged
• Biomarkers
• C-Reactive Protein (analysis)
• Cardiovascular Diseases (epidemiology)
• Comorbidity
• Female
• Glomerular Filtration Rate
• Humans
• Inflammation (blood)
• Inflammation Mediators (blood)
• Kaplan-Meier Estimate
• Leukocyte Count
• Lipocalin-2
• Lipocalins (blood)
• Male
• Middle Aged
• Mortality
• Neutrophils
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Proto-Oncogene Proteins (blood)
• Risk Assessment
• Risk Factors
• Sampling Studies