Dataset Information

Plasma neutrophil gelatinase-associated lipocalin is independently associated with cardiovascular disease and mortality in community-dwelling older adults: The Rancho Bernardo Study.

ABSTRACT: 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.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.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.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 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).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.

SUBMITTER: Daniels LB

PROVIDER: S-EPMC3312791 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Plasma neutrophil gelatinase-associated lipocalin is independently associated with cardiovascular disease and mortality in community-dwelling older adults: The Rancho Bernardo Study.

Daniels Lori B LB Barrett-Connor Elizabeth E Clopton Paul P Laughlin Gail A GA Ix Joachim H JH Maisel Alan S AS

Journal of the American College of Cardiology 20120301 12

<h4>Objectives</h4>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.<h4>Background</h4>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.<h4>Methods</h4>We measured plasma NGAL l ...[more]

PMID: 22421304

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Project description:BackgroundCardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are known as predictors of CVD in these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. Recently, elevated NGAL levels have been reported in patients with CVD. This study aimed to evaluate the association between plasma NGAL levels and LVH/LVDD in patients with CKD.MethodsThis study included 332 patients with pre-dialysis CKD (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2). Two-dimensional echocardiography was performed to measure the left ventricular mass index (LVMI). Tissue Doppler imaging was used to measure early mitral inflow velocity (E) and the peak early mitral annular velocity (E'). Diastolic function was estimated using E' and the ratio of E to E' (E/E'). The associations of echocardiographic index with clinical and laboratory variables (age, sex, diabetes, hypertension, eGFR, albumin, uric acid, calcium, phosphate, total cholesterol, hemoglobin, C-reactive protein, intact parathyroid hormone (PTH), the inferior vena cava collapse index (IVCCI) < 50%, and plasma NGAL) were investigated using univariate and multivariate analyses.ResultsIn multivariate logistic regression analysis, plasma NGAL was an independent predictor of LVH (OR: 1.02, 95% CI: 1.01-1.02), P < 0.001). In addition, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVH. Plasma NGAL (OR: 1.02, 95% CI: 1.01-1.02, P < 0.001) was also an independent factor of LVDD. Furthermore, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVDD. Receiver operating characteristic curve analysis (area under the curve: 0.835, 95% CI: 0.792-0.879) showed the best cutoff value of plasma NGAL for identifying LVDD was ≥ 258 ng/ml with an associated sensitivity of 77.6% and a specificity of 87.6%.ConclusionPlasma NGAL levels were independent predictors of LVH and LVDD in patients with pre-dialysis CKD, suggesting that plasma NGAL could be a biomarker for LVH and LVDD in these patients.

Project description:ObjectiveThis study aimed to compare the levels of plasma neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-9, high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL)-1β across different clinical presentations of coronary artery disease and to evaluate the relationship between those biomarkers and the severity of coronary artery lesions in patients without kidney disease.MethodsWe examined 365 eligible patients who underwent coronary angiography. A total of 124 ST-segment elevation myocardial infarction (STEMI) patients, 117 stable angina pectoris (SAP) patients and 124 patients without atherosclerotic plaques were enrolled in the study. Plasma NGAL, MMP-9, hs-CRP, and IL-1β were measured in all patients using the enzyme-linked immunosorbent assay (ELISA) method. According to the SYNTAX score, the STEMI patients and SAP patients were divided into another set of 2 groups: a high score group (≥ 33, n = 29) and a low score group (<33, n = 212). The relationship between those biomarkers and the severity of coronary stenosis was examined by Spearman correlation analysis; the ability for NGAL to discriminate severe coronary stenosis was examined by receiver operating characteristic (ROC) curve; the influencing factors for the SYNTAX score were determined by logistic regression analysis.ResultsPlasma NGAL, MMP-9, and hs-CRP levels in STEMI patients were higher than in the SAP patients and control subjects (P<0.05, respectively), and plasma NGAL and hs-CRP levels were significantly higher in the SAP patients than in control subjects (P<0.05, respectively), while plasma IL-1β was similar among the 3 groups (P>0.05, respectively). The SYNTAX score was positively related to NGAL (r = 0.363, P<0.001), MMP-9 (r = 0.377, P<0.001), and hs-CRP (r = 0.163, P<0.011); the SYNTAX score was not related to IL-1β (r = -0.043, P = 0.510). Plasma NGAL was positively related to MMP-9 (r = 0.601, P<0.001) and IL-1β (r = 0.159, P = 0.014). The area under the ROC curve for NGAL discriminating severe coronary stenosis was 0.838 (95% CI: 0.752-0.923, P<0.001), which was greater than that for MMP-9 [0.818, (95% CI: 0.724-0.912, P<0.001)], IL-1β [0.485, (95% CI: 0.369-0.601, P = 0.791)], and hs-CRP [0.607, (95% CI: 0.492-0.722, P = 0.061)]. Multivariate regression analysis showed that plasma NGAL levels were independently related to high SYNTAX scores [OR = 1.109, (95% CI: 1.104-1.114), P<0.001].ConclusionPlasma NGAL, MMP-9, and hs-CRP levels in STEMI patients were higher than those in the SAP patients and control subjects. NGAL had a better ability to discriminate severe coronary stenosis than MMP-9, IL-1β, and hs-CRP. NGAL may be a novel biomarker to aid in risk stratification in coronary heart disease patients.

Dataset Information

Plasma neutrophil gelatinase-associated lipocalin is independently associated with cardiovascular disease and mortality in community-dwelling older adults: The Rancho Bernardo Study.

Publications

Plasma neutrophil gelatinase-associated lipocalin is independently associated with cardiovascular disease and mortality in community-dwelling older adults: The Rancho Bernardo Study.

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