Sensitivity of Cytokine and Cytokine Mediator Detection aiding in Diagnosis of Premature Coronary Artery Disease Patients
Authors: Wafa Munir Ansari, Dilshad Ahmad Khan, Omer Jamshed Khan and Farooq Ahmad Khan
Number of views: 330
Introduction: The objective was to evaluate diagnostic accuracy
of high sensitivity C-reactive protein (hS CRP), Interleukin-18 (IL-18),
Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL- 10),
IL-18/IL- 10 ratio and their serum cut off values for identification of
Premature Coronary Artery Disease (PCAD) patients.
Method: It was a diagnostic validation case-control study carried
out at the Clinical Pathology Laboratories of the Army Medical College,
Rawalpindi, Pakistan, from May, 2013 to Jan, 2014. Two hundred
and fifty subjects aged < 45 years scheduled to undergo coronary
angiography were consecutively screened. Out of these ninetyeight
patients with > 70% stenosis, in at least one coronary vessel
on angiography, were labeled to have PCAD. An equal number of
angio-negative subjects were taken as controls from the study group.
Serum IL- 10, IL- 18 and TNF alpha were measured using Enzyme
Linked Immuno-sorbent Assay (ELISA), hS CRP on Immulite 1000
and serum cholesterol, Triglycerides and High Density Lipoprotein
(HDL) by colorimetric methods. Statistical analysis was done using
SPSS-17 and MedCalc software.
Results: Total 196 subjects consisting of 98 PCAD patients and
98 angio-negative controls participated in the study. Mean ± SD age
of PCAD patients was 40.7 ± 4.23yrs (89 males and 9 females) while
in controls it was 35.1 ± 7.55yrs (93 males and 5 females). Serum
hS CRP had highest area under curve AUC (95% confidence interval)
of 0.936 (0.89- 0.97) while AUC (95% CI) of IL-18, TNF alpha and
IL-10 were 0.853 (0.79-0.90), 0.731 (0.659-0.796) and 0.574 (0.497-
0.649) respectively. Sensitivity-specificity of hS CRP and IL-18 at cut
off value of 3.18 pg/ml and 200pg/ml were 86%-91% and 77%-81%
respectively while that of IL-18/IL-10 ratio and IL-10 at cut off values
> 138.9 and > 0.3pg/ml were 68-64% and 20-100% respectively.
Significant correlation was observed between hS CRP (p < 0.01), IL-
18 (p < 0.01) and TNF alpha (p < 0.05).
Conclusion: hS CRP and IL-18 have the best diagnostic potential
among the cytokines for detection of PCAD with high sensitivity
and specificity. IL-18/IL-10 ratio had moderate significance in the
diagnosis of PCAD although it correlated well with the disease burden.
IL-10 had 100% specificity highlighting its role in the diagnosis of the
disease but its low sensitivity is a limiting factor. Thus, hS CRP and
IL-18 are promising potential biochemical parameters aiding in the
clinical diagnosis of Premature Coronary Artery Disease.