Plasma Neutrophil Gelatinase-Associated Lipocalinin in the General Population

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.

The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease

“…The colocalization of NGAL with matrix metallo protein 9 (MMP-9) in plaques and infarcted hearts suggests a role for NGAL in the MMP-9 mediated remodeling (Hemdahl et al, 2006). In a 10-year follow up study performed in a healthy population, higher baseline NGAL levels were associated with adverse cardiac events and all-cause mortality (Lindberg et al, 2014). The association of higher NGAL levels with cardiovascular risk was previously reported in a population of community dwelling elderly (Daniels et al, 2012).…”

“…In a study of NGAL in a healthy population, NGAL was associated with other markers of inflammation, including Creactive protein and neutrophil count (Lindberg et al, 2014). NGAL levels are upregulated in different autoimmune disorders (Shashidharamurthy et al, 2013;Rubinstein et al, 2008).…”

Atherosclerosis

“…A human prospectively investigation found that this glycoprotein was positively associated with cardiovascular events including atherosclerotic disease. 75 These two recent human studies provide clinical evidence that neutrophils may play an important role in the development of atherosclerosis. 76 …”

Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction

“…By contrast, eGFR was mainly associated with plasma NGAL when eGFR was reduced [15]. Accordingly, we speculate that in healthy humans, plasma NGAL mainly reflects inflammation, whereas the kidney only contributes to plasma NGAL in the setting of chronic kidney disease or AKI.…”

“…By contrast, when eGFR is in the normal range (>60 ml/min) eGFR contributes little to plasma NGAL [15]. …”