Elevated Circulating Lipocalin-2 Levels Independently Predict Incident Cardiovascular Events in Men in a Population-Based Cohort

OBJECTIVE—Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of cardiovascular diseases (CVD). Lipocalin-2 (LCN2), mainly released from adipocytes, has been shown to be positively associated with CVD in cross-sectional studies. We aimed to evaluate the association of LCN2 with CVD involving a population-based cohort recruited from the Shanghai Diabetes Study. APPROACH AND RESULTS—Serum LCN2 levels were measured using ELISA. Independent predictors of CVD development were identified using Cox proportion hazards regression. The predictive performances of the various models were assessed by Kaplan–Meier analysis. At baseline, circulating LCN2 was significantly associated with a cluster of traditional cardiovascular risk factors. Baseline LCN2 levels in male subjects who developed CVD events during follow-up were significantly higher than those who did not develop CVD events (P=0.012). However, such difference was not significant in female subjects. LCN2 was a predictor of CVD in men, which remained statistically significant after adjustment for traditional cardiovascular risk factors (hazard ratio, 1.038 [95% confidence interval, 1.017–1.060]). LCN2 remained significantly associated with incident CVD even after adjustment for renal function, adiponectin, and high-sensitivity C-reactive protein levels. Kaplan–Meier analysis suggested combination of LCN2 and high-sensitivity C-reactive protein might improve the prediction of CVD events in male subjects. CONCLUSIONS—Elevated circulating LCN2 level is an independent predictor of CVD events in men in a population-based cohort and adds to the prognostic value of high-sensitivity C-reactive protein, which is currently the most extensively studied biomarker of CVD. Measurement of serum LCN2 might be useful for early detection and intervention of CVD.