Correlation Analysis and Diagnostic Value of Serum Homocysteine, Cystatin C and Uric Acid Levels with the Severity of Coronary Artery Stenosis in Patients with Coronary Heart Disease

Figures & data

Table 1 Comparison of the Clinical Data of Patients in Two Groups

Variables	Research Group (n=765)	Control Group (n=647)	χ²/t	p
Age, yr	60.17±10.13	63.70±10.22	−1.775	0.184
Male, n(%)	402 (52.55)	361 (55.80)	0.817	0.366
BMI, kg/m^2	24.07±1.87	23.64±1.42	1.450	0.149
Smoking, n(%)	392 (51.24)	301 (46.52)	3.124	0.077
Hypertension, n(%)	450 (58.82)	407 (62.91)	2.449	0.118
Type II diabetes, n(%)	181 (23.66)	151 (23.34)	0.020	0.887
LVEF, %	42.35±7.14	45.32±8.58	−2.172	0.034
NT-ProBNP, pg/mL	3938.31±2225.03	2052.49±1153.55	7.76	0.000
Atrial fibrillation, n(%)	199 (26.06)	138 (21.32)	4.232	0.040
Hyperlipidemia, n(%)	348 (45.49)	280 (43.28)	0.696	0.404
TC, mmol/L	4.97±0.25	4.90±0.28	1.730	0.085
TG, mmol/L	1.70±0.44	1.59±0.42	1.519	0.130
LDL-C, mmol/L	3.52±0.400	3.50±0.39	1.113	0.267
HDL-C, mmol/L	1.01±0.20	1.07±0.20	−1.903	0.058
Fasting plasma glucose, mmol/L	7.04±1.26	5.93±0.98	5.593	0.000
Scr, μmol/L	99.52±13.36	96.43±13.71	1.393	0.165
eGFR, mL/min/1.73m^2	65.24±14.02	65.96±13.48	−0.314	0.754

Notes: There were no statistically significant differences on baseline data of the patients in the 2 groups except LVEF, NT-ProBNP, atrial fibrillation, fasting plasma glucose (p < 0.05).

Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; NT-ProBNP, N-terminal pro-brain natriuretic peptide; Scr, serum creatinine; TC, total cholesterol; triglyceride; TG, triglyceride.

Table 2 The Serum Levels and Clinical Diagnostic Value of Cys C, Hcy and UA

Biomarkers	Research Group (n=765)	Control Group (n=647)	t^a	p^a	AUC	Z	p	95% CI		Cut Off value	Sensitivity (%)	Specificity (%)	Youden Index
								Lower	Upper
Hcy (μmol/L)	16.89±6.26	12.75±2.74	3.022	0.000	0.761	6.782	0.0001	0.697	0.816	>12.62	84.85	53.19	0.3804
Cys C(mg/L)	1.10±0.34	0.96±0.15	2.436	0.016	0.612	2.634	0.0084	0.543	0.678	>1.17	28.48	95.74	0.2423
UA (μmol/L)	347.88±71.68	310.87±61.34	2.137	0.034	0.639	3.145	0.0017	0.570	0.704	>315	65.45	57.45	0.2290

Notes: ^aStands for the Student’s t-test between the research group and control group.

Abbreviations: AUC, Area Under The Curve; CI, confidence interval; Cys C, cystatin C; Hcy, homocysteine; UA, uric acid.

Table 3 The Relationship Between Gensini Score and Variables

Variables	Spearman Correlation Analysis		Multivariate Linear Regression Analysis
	r	p	β	p
Age	0.227	0.003	0.178	0.029
Gender	−0.009	0.910	–	–
BMI	0.231	0.003	0.138	0.046
Smoking	0.095	0.225	–	–
Hypertension	0.148	0.045	0.039	0.580
LVEF	0.127	0.104	0.116	0.089
NT-ProBNP	0.294	0.000	0.180	0.011
Atrial fibrillation	0.153	0.049	0.025	0.716
Type II diabetes	0.248	0.001	0.154	0.034
Hyperlipidemia	0.087	0.267	–	–
TC	0.001	0.994	–	–
TG	0.031	0.694	–	–
LDL-C	0.100	0.202	–	–
HDL-C	−0.101	0.196	−0.025	0.715
Fasting plasma glucose	0.252	0.001	0.134	0.047
Scr	0.411	0.000	–	–
eGFR	−0.318	0.000	−0.182	0.024
Hcy	0.314	0.000	0.278	0.017
Cys C	0.295	0.000	0.417	0.006
UA	0.307	0.000	0.149	0.044

Notes: For the patients with CHD, Spearman correlation analysis showed that Gensini score was positively correlated with age, BMI, hypertension, NT-ProBNP, atrial fibrillation, type II diabetes, fasting plasma glucose, serum creatinine, eGFR, serum Hcy, Cys C and UA levels (r > 0, p < 0.05). While multivariate linear regression analysis displayed that there was a significantly positive correlation between Gensini score and some variables including age, BMI, NT-ProBNP, Type II diabetes, fasting plasma glucose, Hcy, Cys C and UA (β > 0, p < 0.05), and a significantly negative correlation between Gensini score and eGFR (β = −0.182, p = 0.024).

Abbreviations: BMI, body mass index; CHD, coronary heart disease; Cys C, cystatin C; eGFR, estimated glomerular filtration rate; Hcy, homocysteine; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; NT-ProBNP, N-terminal pro-brain natriuretic peptide; Scr, serum creatinine; TC, total cholesterol; triglyceride; TG, triglyceride; UA, uric acid.

Figure 1 The ROC curve of Hcy, Cys C and UA for diagnostic value of CHD. The ROC curve analysis of Hcy, Cys C and UA showed that the AUC were 0.761 (95% CI, 0.697–0.816), 0.612 (95% CI, 0.543–0.678) and 0.639 (95% CI, 0.570–0.704) for CHD, respectively. For Hcy, Cys C and UA, respectively, the optimal cut-off value, the sensitivity and specificity in diagnosing CHD were shown in (a-c). In addition, the AUC of Hcy was the highest (0.761) among the three, and there was notably significant difference when compared with the other two (p = 0.0003 and 0.0193), shown in (d). While the Youden index showing the authenticity of the test was 0.3804, 0.2423 and 0.2290, respectively.

Abbreviations: AUC, area under the curve; CHD, coronary heart disease; CI, confidence interval; Cys C, cystatin C; Hcy, homocysteine; ROC, receiver-operating characteristic; UA, uric acid.

Table 4 The Clinical Diagnostic Value of Combined Detection of Hcy, Cys C and UA

Biomarkers	AUC	p	95% CI		Sensitivity%	Specificity%	Youden Index
			Lower	Upper
Hcy+Cys C	0.762	<0.0001	0.698	0.817	85.45	53.19	0.3865
Hcy+UA	0.769	<0.0001	0.706	0.824	84.24	55.32	0.3956
Cys C+UA	0.657	0.0001	0.588	0.720	42.42	85.11	0.2753
Hcy+Cys C+UA	0.768	<0.0001	0.706	0.823	67.88	72.34	0.4022

Notes: The ROC curve analysis of combined Hcy with Cys C, combined Hcy with UA, combined Cys C with UA and combined Hcy and Cys C with UA showed that AUC were 0.762 (95% CI, 0.698–0.817), 0.769 (95% CI, 0.706–0.824), 0.657 (95% CI, 0.588–0.720) and 0.768 (95% CI, 0.706–0.823) for CHD, as well as the sensitivity and specificity in diagnosing CHD. The AUC of combined Hcy with Cys C, combined Hcy with UA and combined Hcy and Cys C with UA having no statistically significant difference (p > 0.05), was higher as compared with combined Cys C with UA, and the difference was statistically significant (p = 0.014, 0.0024 and 0.0027). The Youden index presented that the authenticity of combined Cys C with UA was 0.2753.

Abbreviations: AUC, Area Under The Curve; CI, confidence interval; Cys C, cystatin C; Hcy, homocysteine; ROC curve, receiver operator characteristic curve; UA, uric acid.

Figure 2 The ROC curve of combined detection of Hcy, Cys C and UA for diagnosing CHD. The ROC curve analysis of combined Hcy with Cys C, combined Hcy with UA, combined Cys C with UA and combined Hcy and Cys C with UA were drawn in (a-d), showing that AUC were 0.762 (95% CI, 0.698–0.817), 0.769 (95% CI, 0.706–0.824), 0.657 (95% CI, 0.588–0.720) and 0.768 (95% CI, 0.706–0.823) for CHD. The AUC of combined Hcy with Cys C, combined Hcy with UA and combined Hcy and Cys C with UA having no statistically significant difference (p > 0.05), was higher as compared with combined Cys C with UA, and the difference was statistically significant (p = 0.014, 0.0024 and 0.0027). The Youden index presented that the authenticity of combined Cys C with UA was 0.2753. While the combined Hcy and Cys C with UA had the lowest sensitivity (p<0.001) but the highest specificity (p < 0.05).

Abbreviations: AUC, area under the curve; CHD, coronary heart disease; CI, confidence interval; Cys C, cystatin C; Hcy, homocysteine; ROC, receiver-operating characteristic; UA, uric acid.

Table 5 The Comparison of the AUC Among the Hcy, Combined Hcy with Cys C, Combined Hcy with UA and Combined Hcy and Cys C with UA

Biomarkers	AUC	p	95% CI		Sensitivity%	Specificity%	Youden Index
			Lower	Upper
Hcy	0.761	<0.0001	0.697	0.816	84.85	53.19	0.3804
Hcy+Cys C	0.762	<0.0001	0.698	0.817	85.45	53.19	0.3865
Hcy+UA	0.769	<0.0001	0.706	0.824	84.24	55.32	0.3956
Hcy+Cys C+UA	0.768	<0.0001	0.706	0.823	67.88	72.34	0.4022

Notes: The AUC of Hcy, combined Hcy with Cys C, combined Hcy with UA and combined Hcy and Cys C with UA was the same amount 0.761–0.769, and the difference among them was not statistically significant (p > 0.05). The sensitivity and specificity of the biomarkers above displayed that the combined Hcy and Cys C with UA had the lowest sensitivity (p < 0.001) but the highest specificity (p < 0.05), whose Youden index was 0.4022, showing a high authenticity of the test.

Abbreviations: AUC, Area Under The Curve; CI, confidence interval; Cys C, cystatin C; Hcy, homocysteine; UA, uric acid.