Clinical significance of neutrophil gelatinase-associated lipocalin and sdLDL-C for coronary artery disease in patients with type 2 diabetes mellitus aged ≥ 65 years
Authors: Chen Yanhong , Fu Yu , Wang Shixin , Chen Pengsheng , Pei Yunfeng , Zhang Jiao , Zhang Rui , Niu Guoping , Gu Feng , Li Xiaoli 
Published: November 2022

Abstract
Background and aims
Although type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) share many common pathological and physiological characteristics, there are few studies assessing the predictive capacity of novel biomarkers in occurrence and development of CAD in T2DM patients aged ≥ 65 years. In addition, T2DM patients aged ≥ 65 years are prone to CAD. Therefore, it is of great significance to find novel biomarkers for the development CAD in T2DM.

Methods
In this retrospective cohort study, 579 T2DM patients aged ≥ 65 years were consecutively enrolled in this work, and 177 of whom had major adverse cardiovascular and cerebrovascular events (MACCE: cardiovascular or cerebrovascular death, acute coronary syndrome, coronary stent implantation, and stroke) during the follow up. Univariate and multivariate factors were employed to analyze the correlation between each variable and the occurrence of MACCE, and the Spearman’s rank correlation analysis was performed to assess the relationships between Neutrophil gelatinase-associated lipocalin (NGAL) and small dense low-density lipoprotein-cholesterol (LDL-C) (sdLDL-C). The receiver operating characteristic (ROC) curve was adopted to determine the predictive value of NGAL and sdLDL-C elevation for MACCE in T2DM patients aged ≥ 65 years.

Results
After a median 48 months follow-up [19, (10 ~ 32) ], the levels of NGAL, sdLDL-C, hemoglobin A1c (HbA1c), LDL-C, and apolipoprotein B (ApoB) were significantly higher while those of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A I (ApoA–I) were lower in MACCE positive group. NGAL correlated to body mass index (BMI) (r = 0.391, P = 0.001) and triglyceride (TG) (r = 0.228, P = 0.032), and high-sensitivity CRP (hsCRP) (r = 0.251, P = 0.007), and neutrophils (r = 0.454, P = 0.001), sdlDL–C level was found to be positively correlated with LDL-C (r = 0.413, P = 0.001), TG (r = 0.432, P = 0.001), and ApoB (r = 0.232, P = 0.002); and it was negatively correlated with HDL-C (r = -0.362, P = 0.031) and ApoA–I (r = -0.402, P = 0.001). Age-adjusted Cox regression analysis showed that NGAL (HR = 1.006, 95% confidence interval (CI): 1.005–1.008, P < 0.001) and sdLDL–C (HR = 1.052, 95% CI: 1.037–1.066, P < 0.001) were independently associated with occurrence of MACCE. ROC curve analysis showed that NGAL (area under ROC (AUC) = 0.79, 95% CI: 0.75–0.84, P < 0.001) and sdlDL–C (AUC = 0.76, 95% CI: 0.72–0.80, P < 0.001) could predict the occurrence of MACCE (area under ROC. NGAL combined with sdlDL–C could predict the occurrence of MACCE well (AUC = 0.87, 95% CI: 0.84–0.90, P < 0.001).

Conclusion
The higher NGAL and sdLDL-C in T2DM patients aged ≥ 65 years were significantly and independently associated with the risk of MACCE, and showed higher clinical values than other lipid biomarkers or other chronic inflammation, so they were expected to be the most effective predictors of MACCE assessment.