Association Between Plasma Neutrophil Gelatinase‐Associated Lipocalin and Cardiac Disease Hospitalizations and Deaths in Older Women

BACKGROUND: Neutrophil gelatinase‐associated lipocalin (NGAL) or lipocalin 2 may promote atherosclerosis and plaque instability leading to increased risk of cardiac events. We investigated the relationships between plasma NGAL, cardiovascular disease biomarkers, and long‐term cardiac events. METHODS AND RESULTS: The study population consisted of 1131 ambulant older white women (mean age 75 years) without clinical coronary heart disease (CHD) and measures of plasma NGAL in the Perth Longitudinal Study of Ageing Women with 14.5‐year CHD and heart failure hospitalizations or death (events) captured using linked records. Over 14.5 years, 256 women had CHD events, while 118 had heart failure events. Per SD increase in log‐transformed NGAL there was a 35% to 37% increase in relative hazards for CHD and heart failure events in unadjusted analyses, which remained significant after adjustment for conventional risk factors for CHD events (hazard ratio 1.29, 95% CI 1.13–1.48, P<0.001) but not heart failure (P>0.05). Women in the highest 2 quartiles of NGAL had higher relative hazards for CHD events compared with women in the lowest quartile hazard ratio 1.61, 95% CI 1.08–2.39, P=0.019 and hazard ratio 1.97, 95% CI 1.33–3.93, P=0.001, respectively. These associations were independent of high‐sensitivity cardiac troponin I, homocysteine, and estimated renal function. NGAL correctly reclassified 1 in 4 women who sustained a CHD event up in risk and 1 in 10 women without CHD events down in risk. CONCLUSIONS: NGAL was associated with increased risk of long‐term CHD events, independent of conventional risk factors and biomarkers. These findings provide mechanistic insight into the role of NGAL with cardiac events.