Evaluation of Serum Levels of Inflammation, Fibrinolysis and Oxidative Stress Markers in Coronary Artery Disease Prediction: A Cross-Sectional Study

Abolhasani, Sakhavat; Shahbazloo, Shahnam Valizadeh; Saadati, Hossein Mozafar; Mahmoodi, Neda; Khanbabaei, Nafiseh

doi:10.5935/abc.20190159

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Original Article • Arq. Bras. Cardiol. 113 (4) • Oct 2019 • https://doi.org/10.5935/abc.20190159 copy

Evaluation of Serum Levels of Inflammation, Fibrinolysis and Oxidative Stress Markers in Coronary Artery Disease Prediction: A Cross-Sectional Study

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background:

Coronary Artery Disease (CAD) has long been recognized as a global health issue. Inflammation, Fibrinolysis and Oxidative Stress play an important role in the disruption of plaques leading to CAD. Markers that reflect this pathophysiologic mechanism may have prognostic value.

Objective:

To estimate the serum concentrations of high-sensitivity C-reactive protein (hs-CRP), sialic acid (SA), vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), oxidized low density lipoprotein (OX-LDL) and malondialdehyde (MDA) with significant prognostic value in patients with CAD.

Methods:

The markers included, hs-CRP, SA, VN, PAI-1, OX-LDL and MDA, were compared between 160 angiographically diagnosed CAD patients and 20 age- and sex-matched healthy individuals. The subjects were divided into 4 groups according to angiography results, and association between all risk factors of CAD was studied. Serum levels of SA, VN, PAI-1, and OX-LDL were measured by enzyme-linked immunosorbent assay (ELISA); MDA was measured based on reaction with thiobarbituric acid (TBA); and hs-CRP level was estimated by immunoturbidimetry using a commercial kit. The diagnostic value of these variables was further assessed by ROC curve analysis. Multiple logistic regression was used to evaluate the diagnostic power of the combination. Furthermore, p < 0.05 was considered as significant.

Results:

Serum levels of hs-CRP, SA, VN, PAI-1, and OX-LDL were significantly higher in patient groups compared to control group (p < 0.001). Using both normal and CAD patients as subjects, ROC analysis was performed. The cutoff for OX-LDL, MDA, PAI-1, VN, hs-CRP and SA was 2.67 (ug/mL), 5.49 (mmol/mL), 67 (ng/mL), 254 (ng/mL), 3.4 (mg/dL), 7/89 (mg/dL), respectively. Eventually, the complete diagnostic efficacy was classified as: SA, hs-CRP, PAI-1, OX-LDL, MDA and VN.

Conclusion:

Serum levels SA, hs-CRP, VN, PAI-1, OX-LDL and MDA may be predictive of adverse cardiovascular outcomes. Interestingly, these analyses can help as diagnostic and monitoring markers in CAD patients.

Keywords
Coronary Artery Disease; Biomarkers; Inflammation Fibrinolysis; Oxidative Stress; Sialic Acids; Vitronectin

Characteristic	Control	No Stenosis	1VD	2VD	3VD	p value
Sample size	20	40	40	40	40	-
Age(mean(SD))	57.5(3.2)	58.80(7.5)	58.9(7.9)	61.0(11.8)	60.5(10.5)	0.37^* * One-way analysis of variance;
Sex(male/female)	17/3	21/19	31/9	30/10	25/15	0.30^ Chi square test.
Smoking (N (%))	0(0%)	13(32.5)	19(47.5)	16(40)	24(60)	0.004^ Chi square test.
Hypertension (N (%))	0(0%)	25(62.5)	26(65)	12(30)	19(47.5)	0.01^ Chi square test.
Diabetes (N (%))	0(0%)	7(17.5%)	11(27.5%)	12(30%)	15(37.5%)	0.02^ Chi square test.

p Value	3VD	2VD	1VD	No Stenosis	Control	Variable
0.001^* * Performed by ANOVA test.	3.13 ± 0.42	2.76 ± 0.38	2.62 ± 0.27	2.28 ± 0.32	1.41 ± 0.22	OX-LDL (ug/mL)¹ 1 Mean ± standard deviation;
0.001^* * Performed by ANOVA test.	7.12 ± 1.21	6.39 ± 0.66	5.25 ± 0.98	5.20 ± 0.44	4.32 ± 0.86	MDA (mmol/mL)¹ 1 Mean ± standard deviation;
0.001^* * Performed by ANOVA test.	86.8 ± 6.8	76.9 ± 4.7	75 ± 14.2	51.5 ± 10.8	41.7 ± 11.9	PAI-1 (ng/mL)¹ 1 Mean ± standard deviation;
0.001^ Performed by Kruskal-Wallis test.	361 (95.75)	264 (100.75)	304 (184.25)	208 (61.75)	200 (26)	VT (ng/mL)² 2 Median (inter quartile range).
0.001^ Performed by Kruskal-Wallis test.	5.23 (1.05)	7.53 (0.86)	5.21 (0.39)	1.52 (1.03)	2.54 (0.78)	hs-CRP (mg/dL)² 2 Median (inter quartile range).
0.001^* * Performed by ANOVA test.	169.9 ± 15.3	138.3 ± 12.3	108.6 ± 9.2	60 ± 11.6	51.0 ± 5.0	SA (mg/dL)¹ 1 Mean ± standard deviation;

Test Variable	Area	SD^a	p value^b	Asymptotic 95% Confidence Interval
Test Variable	Area	SD^a	p value^b	Lower bound	Upper bound
OX-LDL	0.870	0.032	.000	0.806	0.934
MDA	0.804	0.034	.000	0.738	0.869
PAI-1	0.951	0.010	.000	0.921	0.992
VT	0.799	0.036	.000	0.729	0.869
SA	0.962	0.021	.000	0.921	0.998
hs-CRP	0.971	0.032	.000	0.953	0.995

index	Positive criteria	Sensitivity/%	Specificity/%	False negative /%	False positive/%
SA	≥ 89.7 (mg/dL)	94	96	6	4
hs-CRP	≥ 3.4 (mg/dL)	94	93	6	7
PAI-1	≥ 67 (ng/mL)	92	90	8	10
VT	≥ 254 (ng/mL)	70	83	30	17
OX-LDL	≥ 2.67 (ug/mL)	70	75	30	25
MDA	≥ 5.49 (mmol/mL)	74	77	26	23

Index	Sensitivity/%	Specificity/%
OX-LDL, MDA, PAI-1, SA, hs-CRP	97	95
OX-LDL, MDA, SA, hs-CRP, VN	98	97
OX-LDL, VT, PAI-1, SA, hs-CRP	98	97
VT, MDA, PAI-1, SA, hs-CRP	97	97
OX-LDL, MDA, PAI-1, VT, SA, hs-CRP	99	99

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[1] Mailing Address: Sakhavat Abolhasani, Department of Clinical Biochemistry, School of Medicine - Shahid Beheshti University of Medical Sciences, Yemen Street, Chamran Highway, Tehran - Iran, E-mail: bio.sakhi@gmail.com.