From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.).
Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):2135-42. doi: 10.1161/ATVBAHA.114.303950. Epub 2014 Jun 26.
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.
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.
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.
中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是一种糖蛋白，储存在中性粒细胞的颗粒中，参与炎症和动脉粥样硬化过程，并可能导致斑块破裂。尽管 NGAL 在动脉粥样硬化和急性心肌梗死中具有潜在作用，但人类对血浆 NGAL 的研究仍然有限。
我们前瞻性地随访了来自社区的 5599 名随机男性和女性，这些人来自于第四届哥本哈根心脏研究。在研究开始时测量了血浆 NGAL。随访 10 年。随访期间，20%的人死亡（n=1120），15%的人（n=884）发生重大不良心血管事件。血浆 NGAL 与所有炎症标志物（高敏 C 反应蛋白、总白细胞计数、中性粒细胞计数）密切相关，与估计肾小球滤过率呈负相关（均 P<0.001）。多变量分析确定中性粒细胞计数是血浆 NGAL 的主要决定因素。在随访期间，NGAL 水平升高的患者全因死亡率和重大不良心血管事件的风险增加（均 P<0.001）。即使通过 Cox 回归分析调整混杂风险因素后，NGAL 仍然是全因死亡率和重大不良心血管事件的独立预测因素。当添加到 Framingham 风险评分中时，NGAL 提高了 c 统计量，并正确地将约 15%的患者重新分类到更合适的风险组。与高敏 C 反应蛋白相比，当这两个标志物都添加到 Framingham 风险评分中时，NGAL 使风险增加了 3 到 4 倍。
血浆 NGAL 与一般人群中的炎症密切相关。NGAL 独立与 10 年结局相关，当添加到 Framingham 风险评分中时，NGAL 不仅提高了 c 统计量，而且正确地将患者重新分类到更准确的风险类别。
