What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 diabetes mellitus (n=579). Intervention: Neutrophil gelatinase-associated lipocalin (NGAL) and small dense low-density lipoprotein cholesterol (sdLDL-C). Primary outcome: Major adverse cardiovascular and cerebrovascular events (MACCE) (HR 1.008 (NGAL), HR 1.059 (sdLDL-C), 95% CI 1.006-1.009 (NGAL), 1.046-1.072 (sdLDL-C), p=<0.001).

September 13, 2022Open Access

Clinical significance of neutrophil gelatinase-associated lipocalin and sdLDL-C for coronary artery disease in patients with type 2 diabetes mellitus aged ≥ 65 years

Q: What are the key findings of this study?

Elevated baseline levels of NGAL (HR 1.008) and sdLDL-C (HR 1.059) were independently associated with an increased risk of major adverse cardiovascular and cerebrovascular events in T2DM patients aged ≥65 years.

Key Result

Elevated baseline levels of NGAL (HR 1.008) and sdLDL-C (HR 1.059) were independently associated with an increased risk of major adverse cardiovascular and cerebrovascular events in T2DM patients aged ≥65 years.

Study Design

Type

Cohort (n=579)

Multicenter

Structured PICO

Do elevated levels of NGAL and sdLDL-C predict the occurrence of MACCE in T2DM patients aged ≥ 65 years?

Population

579 patients with type 2 diabetes mellitus (T2DM) aged ≥ 65 years (mean age 72.5, 63.7% male) without severe liver/kidney disease, infectious disease, malignant tumor, or thyroid disease.

Intervention

Measurement of serum neutrophil gelatinase-associated lipocalin (NGAL) and small dense low-density lipoprotein cholesterol (sdLDL-C) levels

Outcome

Major adverse cardiovascular and cerebrovascular events (MACCE: cardiovascular or cerebrovascular death, acute coronary syndrome, coronary stent implantation, and stroke)composite

Elevated serum NGAL and sdLDL-C levels are independent predictors of major adverse cardiovascular and cerebrovascular events in elderly patients with type 2 diabetes mellitus.

Main Result

Effect estimate: HR 1.008 (NGAL), HR 1.059 (sdLDL-C) (95% CI 1.006-1.009 (NGAL), 1.046-1.072 (sdLDL-C))

p-value: p=<0.001

Limitations

Relatively small sample size
Lack of anthropometric measures such as waist circumference or waist-to-hip ratio
Unclear association with ischemic heart failure
Efficacy of concurrent medications not documented
Lack of data on oxidative stress
Single ethnicity (Chinese) limits generalizability

Abstract

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 in T2DM to CAD. Methods 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 sdLDL-C and other characteristics. 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 4-year follow-up (interquartile range (IQR) = 2.7 years), the levels of NGAL, sdLDL-C, hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (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) closely. 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 = 1.008, 95% confidence interval ( CI ): 1.006–1.009, P < 0.001) and sdLDL‐C (HR = 1.059, 95% CI : 1.046–1.072, P < 0.001) were independently associated with occurrence of MACCE. ROC curve analysis showed that NGAL and sdlDL‐C could strongly predict the occurrence of MACCE (area under ROC (AUC) = 0.79, 95% CI : 0.75–0.84, P < 0.001) (AUC = 0.76, 95% CI : 0.72–0.80, P < 0.001). Combined NGAL with sdlDL‐C could predict the occurrence of MACCE well (AUC = 0.87, 95% CI : 0.84–0.90, P < 0.001). Conclusions The higher NGAL and sdLDL-C in T2DM patients aged ≥ 65 years were significantly and independently associated with the risk of MACCE. Serum NGAL and sdLDL‐C showed higher clinical values than other lipid biomarkers or other chronic inflammation which were expected to be the most effective predictors of MACCE assessment.

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