Research articles

By Dr. Amithnandan D Dwivedi , Dr. Suchi Tripathi , Dr. Sunny Garg , Dr. Asif Iqbal , Prof. Kamlakar Tripathi
Corresponding Author Dr. Amithnandan D Dwivedi
Institute of Medical Sciences, - India 221005
Submitting Author Dr. Amit Nandan Dhar Dwivedi
Other Authors Dr. Suchi Tripathi
Institute Of Medical Sciences. Department Of Medicine, - India

Dr. Sunny Garg
Institute Of Medical Sciences. Department Of Medicine, - India

Dr. Asif Iqbal
Institute Of Medical Sciences. Department Of Medicine, - India

Prof. Kamlakar Tripathi
Institute Of Medical Sciences. Department Of Medicine, - India


Stroke; High sensitive c reactive protein (hsCRP), CT Angiography (CTA); Type II Diabetes.

Dwivedi AD, Tripathi S, Garg S, Iqbal A, Tripathi K. CT Angiography and hsCRP evaluated in Type II Diabetes Complicated with Stroke. Anatomical and Biochemical Correlation. WebmedCentral NEUROLOGY 2013;4(2):WMC004038
doi: 10.9754/journal.wmc.2013.004038

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Submitted on: 18 Feb 2013 06:31:03 AM GMT
Published on: 18 Feb 2013 12:31:50 PM GMT


Aims and objectives: Endothelial dysfunction is considered as root cause of vascular diseases like stroke, myocardial infarction (MI) and venous thromboembolism. Soluble endothelial dysfunction markers are emerging as surrogate markers of disease risk. We aim to correlate the findings of Computed Tomography Angiography (CTA) with hsCRP in patients of Type II Diabetes presenting with stroke.

Material and method: 40 patients of Type II Diabetes diagnosed to have ischemic stroke or Transient Ischemic Attack (TIA) based on clinical history, examinations and imaging were included. We assessed high sensitive C - reactive protein (hsCRP), levels in all patients within 24 hours and CT-Angiography of bilateral neck vessels within 48 hours of hospital admission.

Results: Increase in hsCRP, was significant in cases as compared to controls. This biochemical marker correlated significantly with CT Angiographic findings.

Conclusion: This study demonstrates that hsCRP, is good surrogate biochemical marker for assessing disease risk and burden in patient of Type II Diabetes presenting with stroke. It showed a linear correlation and statistical significance with CT angiography score. Our study gives a good opportunity to combine anatomical details with disease pathophysiology at biochemical level.


Endothelial dysfunction has a central role in the pathogenesis of many vascular diseases related to atherosclerosis [1]. It is associated with a number of conventional risk factors including hypercholesterolemia, smoking, hypertension, diabetes mellitus, insulin resistance and obesity [2]. It is useful to measure biological markers of vascular endothelial function in vivo because such markers might provide insight into the evolution and prognosis of complication like stroke in patients of Type II diabetes. CT Angiography of neck vessels gives anatomical details of the vessels and the disease burden at a macroscopic level. Among several markers of inflammation, hsCRP is found to be significant in people with diabetes. Several studies demonstrate that hsCRP remained a significant predictor of diabetes risk even after adjusting with body mass index, family history of diabetes mellitus, smoking and other factors [3]. CTA has been rarely used to measure disease burden and define the pathology of native vessels.


This research work was a hospital based cross sectional study conducted in Department of Medicine and Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India, in accordance with the declaration of Helsinki guidelines on good clinical practice. The Institutional ethical committee approved the study and written informed consent was obtained from each patient.

Patients of Type II Diabetes diagnosed to have ischemic stroke or Transient Ischemic Attack (TIA) based on clinical history, examinations and imaging were taken up. A Non Contrast Computerized Tomography (NCCT) of head was performed in every patient. Patients with cerebrovascular hemorrhage and cardio-embolic ischemia were excluded from the study. Computed Tomography Angiography (CTA), using 64-slice CT scanner (GE Light speed) was performed in every patient within 48 hours. Patients with age <40yrs, renal failure, hemorrhagic stroke, infection, patients on anticoagulants, antiplatelet agents, Angiotensin Converting  Enzyme (ACE) inhibitors and statins were excluded from the study. A total of 40 patients and 40 controls were studied. A detailed clinical history and physical examination were conducted. Physical examinations included anthropometric measurements such as height, weight, body mass index and waist circumference. Venous blood samples were drawn from the cases within 24 hours and serum was separated from the blood and preserved in -80 degree Celsius temparature till the estimation. The serum hsCRP level was measured by sandwich enzyme-linked immune-sorbent assay (ELISA) kit (Diagnostic Biochem Canada) as per manufacturer’s protocol.

We graded CTA findings by a scoring system:

0 – No changes
1 – Eccentric or focal changes without calcification without narrowing
2 – Eccentric changes or focal changes with calcification without significant stenosis
3 – Circumferential changes without calcification without stenosis
4 – Circumferential changes with calcification without significant stenosis
5 – Significant stenosis.

In case of multiple lesions, scores were summated. Each side was scored in this fashion and finally the scores of both sides were added

Statistical analysis

Sigma stat version 3.5 was used to calculate all statistical data. If the data were normally distributed than the measure of central tendency and dispersion used was mean ± standard deviation. If the data were not normally distributed than the measure of central tendency and dispersion used was median ± Inter Quartile range. Means of two groups were compared by using student t-test. Medians of two groups were compared by using Mann Whitney rank sum test. Correlations between two quantitative variables were achieved through Pearson’s correlation. Comparison between two proportions was done by Chi-square test, but if 20% variables were below 5; Fisher exact tests was used.


In our study, patients with recent stroke or TIA (cases) were compared with controls. Both the groups were comparable in baseline characteristics like age, sex ratio and BMI. (Table 1).

Level of hsCRP was significantly higher in cases (8.75±3.45) as compared to controls (1.15±1.0). Multidetector CT Angiographic findings were more prevalent in cases. The CTA score was higher in cases (4±4) as compared to controls, but was not statistically significant (Table 2). Levels of hsCRP correlated significantly with the CTA scores and the disease burden (Fig 1).


The participants of this study have basic physical characteristics viz. age, height, weight, BMI and sex-ratio similar to other studies on biochemical markers of ischemic stroke and TIA performed in the past [4]. In our study, we found that the markers of endothelial dysfunction like hsCRP were significantly higher in cases than in controls. This signifies that patients of Type II diabetes with ischemic stroke had more oxidative stress than in healthy controls.

 Raised hsCRP account for this increased risk and is an independent risk factor for ischemic stroke [5-7]. Extensive work by Cao et al and Curb et al also provided similar evidence that elevated hsCRP is predictive of stroke independent of carotid intima-media thickening (IMT) and development of risk factors like diabetes and hypertension [8,9]. Our study also correlated levels of hsCRP with CTA scores. Even after extensive search of literature, we could not find a study on analysis of correlation between biochemical markers of endothelial dysfunction and CTA findings.

CTA scores, which signify anatomical extent and severity of atherosclerosis, correlated significantly and linearly with levels of hsCRP. Rothwell PM et al and Takaya N et al showed that some parameters of carotid artery atherosclerosis such as carotid artery stenosis, type of plaque, and presence of complications are identified factors for the future stroke risk [10,11].

Cases with stroke had a higher oxidative stress in the form a significantly higher hsCRP .This suggests that hsCRP not only have a prognostic value in patients but may also play an etiological role in atherosclerosis and stroke. This finding corroborates with the fact that CRP is not only a marker of atherosclerosis but is actually involved in pathogenesis of early atherosclerosis as shown in the work by Torzewski M et al [12].


This study demonstrates that hsCRP, is a good surrogate biochemical marker for assessing disease risk and burden in patients of Type II diabetes suffering from ischemic stroke. It showed a linear correlation and statistical significance with CT angiography score. A combination of CTA score and levels of hsCRP gives a good opportunity to combine anatomical details with disease pathophysiology at biochemical level.




1. D. Versari, E. Daghini, A. Virdis, L. Ghiadoni and S. Taddei, “Endothelial dysfunction as a target for prevention of cardiovascular disease,” Diabetes Care, vol. 32, no. Suppl 2, pp. S314-321, 2009.
2. W. Bakker, E.C. Eringa, P. Sipkema and V.W. van Hinsbergh, “Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity,” Cell Tissue Res, vol. 335, no. 1, pp. 165-189, 2009.
3. Francisco G, Hernández C, Chacón P, Mesa J, Simó R. Factors influencing CRP levels in the diabetic population. Med Clin (Barc). 2005 Mar 12;124(9):336-7
4. M. Mishra, H. Kumar, S. Bajpai, R.K. Singh and K. Tripathi, “Level of serum IL-12 and its correlation with endothelial dysfunction, insulin resistance, proinflammatory cytokines and lipid profile in newly diagnosed T2DM,” Diabetes Res Clin Pract, 2011 (DOI: 10.1016/j.diabres.2011.07.037).
5. A. Ghasemi, S. Zahedi Asl, Y. Mehrabi, N. Saadat and F. Azizi, “Serum nitric oxide metabolite levels in a general healthy population: relation to sex and age” Life Sci, vol. 83, no. 9-10, pp. 326-331, 2008.
6. A.Ozkul, A. Akyol, C. Yenisey, E. Arpaci, N. Kiylioglu and C. Tataroglu, “Oxidative stress in acute ischemic stroke,” Journal of Clinical Neurosciences, vol. 14, no. 11, pp. 1062-1066, 2007.
7. S.K. Vijay, M. Mishra, H. Kumar and K. Tripathi, “Effect of pioglitazone and rosiglitazone on mediators of endothelial dysfunction, markers of angiogenesis and inflammatory cytokines in Type-2 Diabetes,” Acta Diabetol, vol. 46, no. 1, pp. 27-33, 2009.
8. J.J. Cao, C. Thach, T.A. Manolio et al, “C-reactive protein, carotid intimamedia thickness, and incidence of ischemic stroke in the elderly: the cardiovascular health study,” Circulation, vol. 108, no. 2, pp. 166-170, 2003.
9. J.D. Curb, R.D. Abbott, B.L. Rodriguez et al, “C-reactive protein and the future risk of thromboembolic stroke in healthy men,” Circulation, vol. 107, no. 15, pp. 2016-2020, 2003.
10. P.M. Rothwell, R. Gibson and C.P. Warlow, “Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis,” Stroke, vol. 31, no. 3, pp. 615-621, 2000.
11. N. Takaya, C. Yuan, B. Chu et al, “Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study,” Circulation, vol. 111, no. 21, pp. 2768-2775, 2005.
12. M. Torzewski, C. Rist, R.F. Mortensen et al, “C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis,” Arterioscler Thromb Vasc Biol, vol. 20, no. 9, pp. 2094-2099, 2000.

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