Neutrophil Gelatinase-Associated Lipocalin Contributes to Increased Risk of Cardiovascular Death After Acute Coronary Syndrome

Figures & data

Table 1 Clinical Characteristics of the Patients with CHD After Admission

Variables	NGAL <102.5 ng/mL (n=316)	NGAL ≥102.5 ng/mL (n=317)	P Value
Age (years)	71.6 (67.4–77.8)	72.1 (68.2–79.2)	0.098
Gender (male)	174 (55.1)	161 (50.8)	0.215
BMI (kg/m^2)	25.4 (24.3–28.7)	26.2 (23.1–29.4)	0.018
Smoker	63 (19.9)	84 (26.5)	0.007
Drinker	49 (15.5)	79 (24.9)	<0.001
CVD history on admission	52 (15.5)	101 (31.9)	<0.001
Exercise regularly	124 (39.2)	101 (31.8)	0.064
Diabetes mellitus	12 (3.8)	34 (10.7)	<0.001
Heart rate (beats/min)	83±7	85±6	0.389
CV mortality during follow-up	11 (3.5)	32 (10.1)	<0.001
Systolic BP (mmHg)	129 (120–142)	133 (124–146)	0.011
Diastolic BP (mmHg)	78 (72–85)	80 (73–89)	0.012
Preserved LVEF	201 (63.6)	164 (51.7)	0.011
Hospital stay (days)	10 (5–11)	12 (7–14)	0.112
Medications
Diuretics	286 (90.5)	310 (97.8)	0.071
ACE inhibitors	218 (69.0)	253 (79.8)	0.058
Beta-blockers	132 (41.8)	89 (28.1)	0.52
Laboratory measurements
NGAL (ng/mL)	73.4±6.51	146.5±13.5	<0.001
SCr (µmol/L)	85.6±7.3	99.6±9.5	0.009
BUN (mmol/L)	5.6±3.4	7.1±3.9	0.014
FBG (mmol/L)	5.97 (4.53–7.69)	6.34 (5.12–8.83)	0.038
ALB (g/L)	41.5 (38.9–44.2)	37.6 (35.2–40.4)	<0.001
Hb (g/L)	122 (113–127)	116 (108–133)	0.019
hs-CRP (mg/L)	6.17 (1.89–21.75)	10.91 (3.24–28.55)	<0.001
BNP (pg/mL)	1432±245	1395±239	0.43
TG (mmol/L)	1.39±0.41	2.14±0.54	<0.001
LDL (mmol/L)	2.16 (1.49–2.54)	2.59 (1.53–2.81)	0.001
HDL (mmol/L)	0.79 (0.60–1.01)	0.71 (0.54–0.95)	0.104
TC (mmol/L)	3.67±0.92	4.31±1.23	0.007

Note: Data are shown as median (range), n (%) or mean ± SD.

Table 2 Logistic Regression Analysis for the Association Between Serum NGAL Levels and CVD History on Admission in Patients with CHD

Variables	Model 1	Model 2	Model 3
Serum NGAL level
Quartile 1 (low)	1.000 (ref.)	1.000 (ref.)	1.000 (ref.)
Quartile 2	1.47 (1.14–2.43)	1.45 (1.12–2.39)	1.43 (1.10–2.35)
Quartile 3	1.89 (1.31–3.52)	1.84 (1.27–3.46)	1.81 (1.25–3.44)
Quartile 4 (high)	2.46 (1.65–4.67)	2.43 (1.63–4.63)	2.41 (1.60–4.59)
P-trend	<0.001	<0.001	<0.001

Notes: Model 1: Adjusted for age, gender and BMI. Model 2: Adjusted for age, gender, BMI, smoker, drinker, exercise regularly, diabetes mellitus, BP, preserved LVEF and medications. Model 3: Adjusted for age, gender, BMI, smoker, drinker, exercise regularly, diabetes mellitus, BP, preserved LVEF and medications and laboratory measurements.

Abbreviations: NGAL, neutrophil gelatinase-associated lipocalin; CVD, cardiovascular disease; CHD, coronary heart disease; BMI, body mass index; BP, blood pressure; LVEF, left ventricular ejection fraction.

Figure 1 Kaplan–Meier analysis of CV mortality according to median levels of serum NGAL in patients with CHD.

Table 3 Cox Proportional Hazard Analysis for Associations Between Serum NGAL Levels and CV Mortality During the Follow-Up of 10 Years in Patients with CHD by Sensitivity Analysis, Using “CVD History” as a Covariate

Variables	Univariate Cox			Multivariate Cox
	HR	95% CI	P Value	HR	95% CI	P Value
Age (per 1-SD increase)	1.64	1.24–2.63	0.024	1.42	1.13–1.98	0.125
Sex	1.35	0.96–1.72	0.258
BMI (per 1-SD increase)	1.84	1.24–2.59	0.015	1.72	1.13–2.15	0.027
Smoker	1.61	1.10–1.95	0.019	1.43	1.08–1.89	0.039
Drinker	1.76	1.11–2.03	0.017	1.32	0.93–1.85	0.071
CVD history on admission	2.73	1.52–4.99	<0.001	2.30	1.39–4.56	0.009
Preserved LVEF	1.75	1.43–2.76	0.039	1.25	0.89–1.75	0.113
Diabetes mellitus	2.2	1.4–3.4	0.005	1.9	1.1–2.6	0.010
Systolic BP (per 1-SD increase)	1.50	0.87–1.71	0.110	1.21	0.73–1.56	0.215
Diastolic BP (per 1-SD increase)	1.19	0.64–1.50	0.271
Laboratory measurements
SCr (per 1-SD increase)	1.91	1.14–3.70	0.014	1.72	1.08–2.69	0.043
BUN (per 1-SD increase)	1.36	0.89–1.67	0.263
hs-CRP (per 1-SD increase)	1.51	1.09–2.40	0.042	1.22	0.95–1.72	0.102
Hb (per 1-SD increase)	1.21	0.90–1.53	0.215
ALB (per 1-SD increase)	0.74	0.24–0.93	0.031	0.82	0.41–1.35	0.076
TG (per 1-SD increase)	2.10	1.33–3.82	0.010	1.95	1.27–3.48	0.019
LDL (per 1-SD increase)	2.27	1.44–5.28	<0.001	2.09	1.36–4.53	0.011
TC (per 1-SD increase)	2.21	1.63–4.11	0.009	1.98	1.50–4.01	0.013
FBG (per 1-SD increase)	1.38	0.89–2.00	0.154
NGAL (per 1-SD increase)	2.74	1.75–5.37	<0.001	2.62	1.51–4.96	<0.001

Notes: Adjusted for age, gender, BMI, smoker, drinker, diabetes mellitus, BP, preserved LVEF and laboratory measurements (FBG, TC, TG, LDL, Hb, ALB, hs-CRP, SCr and BUN).

Abbreviations: NGAL, neutrophil gelatinase-associated lipocalin; CV, cardiovascular; CHD, coronary heart disease; CVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval; BMI, body mass index; LVEF, left ventricular ejection fraction; BP, blood pressure; SCr, serum creatinine; BUN, serum urea nitrogen; hs-CRP, high-sensitivity C-reactive protein; Hb, hemoglobin; ALB, albumin; TG, triglycerides; LDL, low-density lipoprotein cholesterol; TC, total cholesterol; FBG, fasting blood glucose.

Table 4 Association Between Serum NGAL Levels and CV Mortality During the Follow-Up of 10 Years in Patients with CHD by Stratified Analysis

Variables	Model 1	Model 2	Model 3
Angina pectoris	2.48 (1.51–5.22)	2.46 (1.44–5.01)	2.40 (1.22–4.21)
P value	<0.001	<0.001	<0.001
Myocardial infarction	2.83 (1.83–5.66)	2.78 (1.76–5.51)	2.76 (1.73–5.47)
P value	<0.001	<0.001	<0.001

Notes: Model 1: Adjusted for age, gender and BMI. Model 2: Adjusted for age, gender, BMI, smoker, drinker, exercise regularly, diabetes mellitus, BP, preserved LVEF and medications. Model 3: Adjusted for age, gender, BMI, smoker, drinker, exercise regularly, diabetes mellitus, BP, preserved LVEF, medications and laboratory measurements.

Abbreviations: NGAL, neutrophil gelatinase-associated lipocalin; CV, cardiovascular; CHD, coronary heart disease; BMI, body mass index; BP, blood pressure; LVEF, left ventricular ejection fraction.

Figure 2 Predictive value of serum NGAL in predicting CV death in patients with CHD.