Determination of plasma CRP concentrations could. C Reactive Protein in Acute Ischemic Stroke Patients in Tribhuvan University Teaching Hospital

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1 Original Article Reema Rajbhandari, MBBS, MD Bikram Gajurel, MD, DM Krishna Dhungana, MBBS, MD Krishna K Oli, MD, PHD Address for correspondence: Reema Rajbhandari, MBBS, MD reemarajbhandari@hotmail.com Received, 11 February, 2014 Accepted, 26 March, 2014 Nepal Journal of Neuroscience 11:4-9, 2014 C Reactive Protein in Acute Ischemic Stroke Patients in Tribhuvan University Teaching Hospital Introduction: At the time when tissue plasminogen activator and time factor is discussed in ischaemic stroke we have tried to study the level of in these patients. Can it be an investigative tool for screening high-risk patients like diabetes and hypertension is still to be studied. Methods: It is a descriptive prospective exploratory research study performed among 50 ischaemic stroke patients admitted in TUTH among other investigation was also done Results: is raised among ischaemic stroke patients but its relation with altered lipid profile is not so significant. Conclusions: The inclusion of as a risk factor for ischemic stroke or TIA would have important implications. Thus, the use of values may aid in identifying a potentially large number of men and women who are at risk for cerebrovascular events. This, in turn, may lead to the development of new treatment strategies for primary stroke prevention in those individuals identified as being at risk for developing cerebrovascular disease. Key Words: atheromatous plaque, c-reactive protein (), ischaemic stroke Determination of plasma concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease, increasing trend in Nepal 1 and be of prognostic value 12 There is growing evidence that C-reactive protein (), a peripheral marker of inflammation, is also a marker of generalized atherosclerosis. 15 This relationship between inflammation and atherosclerosis make a potential marker for prognosis after vascular events and a potential predictor of future vascular events like an increased risk of ischemic stroke patients. Large population-based studies show that high is a risk factor for future cardiovascular events. 11,20,21 The recent JUPITER trial shows that the use of rosuvastatin in patients with high has a significant impact both in reducing the level and in lowering future vascular events. 25 This indicates the role of inflammation in atherogenesis and suggests that can be used as marker of future events. Materials and Methods It is a descriptive prospective exploratory research study performed in the year The study conducted among patients receiving treatment from TUTH. This institute have been in the care of Ischemic stroke patients for many 4 Nepal Journal of Neuroscience, Volume 11, Number 1, 2014

2 NIHS & CT admitted in TUTH Kathmandu is taken for study. Only ischaemic stroke patients were included in this study. Sampling method/sample size/sampling frame: Universal sample of the target population. Minimum fifty confirmed cases of stroke from TUTH. Results in Stroke Figure1: Sex wise distribution 50 total Nepali patients 31 are male and 19 are female patients as demonstrated in figure years, till date and many patients have been treated from this institute. The aim of this study is to see if in ischemic stroke is raised in Nepalese subjects. The objective of this study are to study the socio demographic of the stroke, Neurological manifestation of stroke, various biological parameter in strokes, comparative & correlative study between & stroke, extent of lesion & clinical manifestation. Samples: 50 confirmed cases of stroke by ICD10, Ischemic cerebrovascular disease accounts for a substantial proportion of all strokes., one of the acute phase reactant, is an indicator of underlying systemic inflammation and a novel plasma marker of atherothrombotic disease. Among the 50 patients studied in TUTH 54% patients had left ischemic stroke, the level of in ischemic stroke patients were increased in patients mostly around the age group of years old, most of them were male (62%) patients. 28% patients were having a habit of drinking alcohol and smoking and 26% patients smoker only 40% patients were hypertensive and 22% patients with hypertension and diabetese, 30% patients did not suffer from both 4 patients were diabetic only. 20% patients had a high with borderline to high triglyceride, 18% patients with borderline to high cholesterol. Discussion Figure 2: Age wise distribution 26 patients belonged to the age group 61 to 75 years group as shown in figure 2. HDL, one of the acute-phase reactants, is an indicator of underlying systemic inflammation and a novel plasma marker of atherothrombotic disease. Our prospective data from Tribhuvan Universiy Teaching Hospital of Nepal with diagnosis of acute Ischemic stroke demonstrate a strong relationship between plasma and ischemic stroke. The Rotterdam study shows that although high is associated with the risk for future stroke, it is not useful for individual stroke prediction. 7 On the other hand the 0.95mmol/l or 1.21mmol/lbelow 37 mg/dl./ below 47 mg/dl. 1.55mmol/l60 mg/dl or above Total 50 Table 1: Comparison between HDL and Nepal Journal of Neuroscience, Volume 11, Number 1,

3 Rajbhandari et al. Figure 3: Co morbid factor wise distribution Figure 4: Risk factors wise distribution Framingham study shows that high is associated with a greater risk for ischemic stroke or TIA. 27 Studies in patients who already had a stroke shows an association between high and stroke presentation outcomes and future vascular events. 2,3,10,13,16,19,18,23 Similarly in our study the patients tend to be increased in both sexes where 27 male,14 female have more than 6mg/l. is more than 6mg/l in 52% patients with the age group of which is similar to Arjundas D et al 4 where the maximum stroke incidence was in the age-group of 50- LDL Address Optimal:2.5mmol/l or Less than 100 mg/dl Near Optimal: mmol/l or mg/dl Borderline High: m/l or mg/dl that was reported in 2002, concluded that hypertension and diabetes are the most common risk factors of strokes admitted to a tertiary hospital. 24 which was similar to our findings. In our study, total cholesterol, LDL, VLDL, TGL, showed no relation to the incidence of ischemic stroke and raised. Similar findings have been observed by Ross et al. 26 He found that altered serum cholesterol was not linked to an increased stroke incidence. However hypercholesterolemia is related to the incidence of IHD, High: mmol/l or mg/dl Table 2: Comparison between LDL and 79 years, with a mean age at incidence of 61.7±13.4 (SD) where the mean age of stroke patients was 10 years lower than that reported from studies in high-income countries. 17 Only population-based incidence studies would be able to clarify whether our results reflect the actual situation in the source population or if it is due to the fact that elderly stroke patients are less likely to be admitted to health facilities. In our study in smokers are more prone to ischemic stroke which correlates to Bonita R et al 6 studies showing smokers both current and past, have a higher risk of developing stroke. Raised are found in 56% patients with hypertension where A Malaysian study by Ong et al. which is a risk factor for stroke. His study was a large, prospective observational study of middle-aged men and he found no relationship between plasma total cholesterol concentration and incidence of fatal or nonfatal stroke. Two large meta-analyses 8,5 aggregated from very large cohorts failed to find a relationship between cholesterol and stroke. HDL - identified as the good cholesterol - helps transport lipids out of the blood, reducing the chance of these molecules becoming involved in atherosclerosis. In Jones William et al 29 cohort study performed of urban primary care patients, after correction for other common known vascular risk factors, patients with higher HDLcholesterol concentrations and those whose HDLcholesterol increased from first to second measurements 6 Nepal Journal of Neuroscience, Volume 11, Number 1, 2014

4 studies have analyzed the relationship between elevated admission levels and stroke severity or stroke etiology. Conclusions in Stroke Figure 5: CT Radiological Finding wise distribution had significantly lower risk of acute ischemic stroke, similarly in our study While comparing the lipid profile,hdl with 45 patients have HDL below 47mg/dl, more than 6mg/l are 37 cases with HDL below than 47mg/dl, 6 patients have 5-6mg/l, 2 patients have less than 5mg/l. Among 50 patients 43 patients have level more than 6mg/l,6 patients 5-6mg/l and in 3 patients is less than 5mg/l. Probably, may reflect something Triglyceride Normal Less then 150mg/dl or1.7mmol/l We conclude that in Nepali elderly men and women with ischemic stroke, was found to be raised. If the results of the present study are confirmed in other analyses of large population-based cohorts of men and women, the inclusion of as a risk factor for ischemic stroke or TIA would have important implications. Thus, the use of values may aid in identifying a potentially large number of men and women who are at risk for cerebrovascular events. This, in turn, may lead to the development of new treatment strategies for primary stroke prevention in those individuals identified as being at risk for developing cerebrovascular disease. Recommendation We believe that the role of after ischemic stroke is far more complicated than perhaps we realize it Borderline High: mg/dl mmol/l Table 3: Comparison between TG and fundamental about the patient s inflammation system. Some patients might be predisposed to intense activation of inflammation in response to a variety of stimuli such as stroke. We speculate that stroke patients in whom the inflammation system reacts most intensely may be at greater risk for subsequent events. In this way a stroke may show the abnormal reactivity of the inflammation system. levels would identify those patients whose inflammation system responds most actively to stimuli. These might be the patients at highest risk for subsequent new vascular events or death, in whom more aggressive therapy and clinical surveillance might be appropriate Moreover, the results from some studies were negative. In their pivotal review, Di Napoli et al concluded that there is insufficient evidence to justify the routine use of for either primary or secondary risk stratification for cerebrovascular disease alone 14. In addition, only few is therefore conceivable that is a non-specific biomarker of inflammation and not only acts as a marker but also is involved in the initiation and progression of atherosclerosis. At present, there is not sufficient evidence to recommend measurement of in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this. In short, there is need for more studies to clarify the exact role of in cerebrovascular disease. Nepal Journal of Neuroscience, Volume 11, Number 1,

5 Rajbhandari et al. Cholesterol Address <5.17 mmol/lless than 200 mg/dl Desirable mmol/l mg/dl Borderline high Table 4: Comparison between Cholesterol and Acknowledgement I would like to thank Professor Dr K.K.Oli, and the department of Neurology TUTH for providing me the ground to perform this study and Dr Pravesh Rajbhandari for helping me with this study. Reference 1. Anil Pandit, Amit Arjyal, Jeremy Farrar et al. Nepal: Practical Neurology,6; , Anuk T, Assayag EB, Rotstein R, et al. Prognostic implications of admission inflammatory profile in acute ischemic neurological events. Acta Neurol Scand 106: , Arenillas JF, varez-sabin J, Molina CA, Chacon P, Montaner J, Rovira A et al. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease. Stroke 34: , Arjundas D, Pandiyan U, Arjundas G, Henry B. Surveillance of stroke: WHO STEP-wise approach: A Chennai stroke unit report. Ann Indian Acad Neurol 10: , Atkins D, Psaty BM, Koepsell TD, Longstreth WT Jr, Larson EB. Cholesterol reduction and the risk for stroke in men. A meta-analysis of randomized controlled trials. Ann Intern Med 119: , Bonita R, Mendis S, Truelsen T, Bogoulovsky J, Toole J, Yatsu F. The global stroke initiative. Lancet 3: , Bos MJ, Schipper CM, Koudstaal PJ, Witteman JC, Hofman A, Breteler MM. High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study. Circulation, 114: , Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. Prospective studies collaboration. Lancet 346: , Chopp M, Zhang RL, Chen H, Li Y, Jiang N, Rusche JR. Postischemic administration of an anti-mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke.25: , Christensen H, Boysen G. C-reactive protein and white blood cell count increases in the first 24 hours after acute stroke. Cerebrovasc Dis 18: , Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P. Low grade inflammation and coronary heart disease: prospective study and updatedmetaanalyses. BMJ 321: , Di Napoli M, Schwaninger M, Cappelli R, et al. Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the Pooling Project members. PMID: PubMed - indexed for MEDLINE 13. Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke, 32: , Di Napoli M, Schwaninger M, Cappelli R, et al. Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the Pooling Project members. Stroke 36: , Elias-Smale SE, Kardys I, Oudkerk M, Hofman A, Witteman JC. C-reactive protein is related to extent and progression of coronary and extra-coronary atherosclerosis; results from the Rotterdam study. Atherosclerosis, 195: , Elkind MS, Tai W, Coates K, Paik MC, Sacco RL. High-sensitivity C-reactive protein, lipoproteinassociated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med, 166: , Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: A review of population-based studies of incidence, prevalence and case-fatality in the late 20th century. Lancet Neurol 2: 43-53, Jiang N, Moyle M, Soule HR, Rote WE, Chopp M. Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats. Ann Neurol 38: , Kocer A, Canbulat C, Gozke E, Ilhan A. C-reactive protein is an indicator for fatal outcomes in first-time stroke patients. Med Sci Monit 11: , Nepal Journal of Neuroscience, Volume 11, Number 1, 2014

6 20. Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A. C- Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to Circulation 99: , Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. Am J Epidemiol 144: , Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet;367: , Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke 30: , Ong TZ, Raymond AA: Risk factors for stroke and predictors of one-month mortality. Singapore Med J 43: , Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Jr., Kastelein JJ et al. Rosuvastatin to prevent in Stroke vascular events in men and women with elevated C-reactive protein. N Engl J Med, 359: , Ross R: The pathogenesis of atherosclerosis an update. N Engl J Med 314: , Rost NS, Wolf PA, Kase CS et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke, 32: , Rothwell NJ, Relton JK. Involvement of cytokines in acute neurodegeneration in the CNS. Neurosci Biobehav 17: , Susman Ed. Are c-reactive protein and HDL independent risk factors for stroke? Neurology Today 5: 75-83, World health Organization. The World Health Report; 2002 Reducing risks: Promoting healthy life. World Health Organization: Wolf PA, Cobb JL, Agostino RB. Epidmiology of stroke in stroke. Pathophysiology, diagnosis and management. New York p. 3-27, Wen-zhi Wang, Bin Jiang, Sheng-ping Wu, et al. Change in Stroke Incidence from a Population-Based Intervention Trial in Three Urban Communities in China: Neuroepidemiology 28: , 2007 Nepal Journal of Neuroscience, Volume 11, Number 1,

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