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Year : 2022  |  Volume : 8  |  Issue : 1  |  Page : 31-37

Aspirin resistance and blood biomarkers in predicting ischemic stroke recurrence: An exploratory study

1 Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Submission14-Nov-2021
Date of Decision04-Jan-2022
Date of Acceptance19-Jan-2022
Date of Web Publication21-Mar-2022

Correspondence Address:
Rameshwar Nath Chaurasia
Department of Neurology, Institute of Medical Science, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bc.bc_75_21

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BACKGROUND: Recurrent strokes cause greater complications and worse outcomes by adding to the existing neurological deficit. There is the paucity of data on serum markers of inflammation as predictors of recurrent stroke. This study was planned to analyze the clinico-etiological profile of recurrent noncardioembolic ischemic stroke, estimate aspirin resistance among regular aspirin users and evaluate blood biomarkers high-sensitivity C-reactive protein (hsCRP), Tumor necrosis factor-alpha (TNF-α), Lipoprotein-associated phospholipase A2 (Lp-PLA2) as probable predictors of stroke recurrence.
METHODS: Patients of recurrent noncardioembolic ischemic stroke fulfilling the inclusion criteria were enrolled. Detailed history, clinical examination, and investigations were obtained as per protocol. Aspirin resistance was determined by light transmission aggregometry. Serum hsCRP, TNF-α, and Lp-PLA2 levels were estimated.
RESULTS: This study included 34 males and 16 females. Majority of the patients were > 60 years (n = 30, 60%). Thirty (60%) cases had a repeat stroke after 1 year of primary event. Thirty-nine (78%) study participants had hypertension, while 15 (30%) had diabetes. Middle cerebral artery (n = 40, 80%) was the most common vascular territory. Thirty-one (62%) cases belonged to TOAST subtype 1 (large artery atherosclerosis). Seventy two percent cases were prescribed aspirin after index stroke, but only 36% were compliant. Median (range) hsCRP level was 7.5 (0.3–155) mg/L with 72% of patients having high hsCRP level (>3 mg/L). Median (range) serum PLA2 level was 11.98 (3.31–87.24) ng/ml in patients and 6.96 (0.15–61.42) ng/ml in controls (P = 0.029). Median (range) serum TNF-α level in patients was significantly higher than controls (68.22 [1.3–287] pg/ml versus 0.098 [0.002–36.31] pg/ml, P < 0.001). Aspirin resistance was found in 41.7% patients while 16.7% were semi-resistant. Mean % platelet aggregation was 34.75 ± 21.58 in patients and 64.75 ± 16.98 for controls (P < 0.001).
CONCLUSIONS: Majority of patients with recurrent stroke were elderly (>60 years), hypertensive, and non-compliant with aspirin. Aspirin resistance was an important factor in patients with antiplatelet compliance. Inflammatory biomarkers hsCRP, PLA2, and TNF-α were found to be significantly elevated in patients compared to controls.

Keywords: Aspirin resistance, high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, recurrent ischemic stroke, tumor necrosis factor alpha

How to cite this article:
Dash P, Singh VK, Gautam D, Pathak A, Kumar A, Mishra SP, Dash D, Mishra VN, Joshi D, Chaurasia RN. Aspirin resistance and blood biomarkers in predicting ischemic stroke recurrence: An exploratory study. Brain Circ 2022;8:31-7

How to cite this URL:
Dash P, Singh VK, Gautam D, Pathak A, Kumar A, Mishra SP, Dash D, Mishra VN, Joshi D, Chaurasia RN. Aspirin resistance and blood biomarkers in predicting ischemic stroke recurrence: An exploratory study. Brain Circ [serial online] 2022 [cited 2023 Jun 6];8:31-7. Available from: http://www.braincirculation.org/text.asp?2022/8/1/31/340012

  Introduction Top

Stroke is the second-leading cause of death worldwide causing 5.5 million deaths in 2016 and the second-most common cause of disability-adjusted life years (DALYs).[1] In India, the prevalence of stroke has increased by 12.2% from 1990 to 2016.[2] It was the fifth-leading cause for DALYs in 2016 and the second-leading cause of death in 2018. [3,4] The first 5-year cumulative incidence of stroke recurrence ranges from 16% to 30% in the Western world. [5,6]

Inflammation leads to atherosclerosis which in turn leads to ischemic stroke.[7],[8],[9] Various studies have evaluated pro-inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP), Tumour necrosis factor-alpha (TNF-α), Lipoprotein-associated phospholipase A2 (Lp-PLA2) in stroke.[9],[10],[11],[12],[13],[14],[15],[16] However, insufficient information is available regarding its role in the prediction of recurrent stroke.

Aspirin, the cornerstone of antiplatelet therapy, reduces the risk of vascular disease by about 25% as per the Antithrombotic Trialists' collaboration. One-third to one-half of patients who experience a recurrent stroke, are already on antiplatelet medications.[17] Poor compliance, impaired absorption and metabolism, drug interactions, nonplatelet sources of thromboxane A2 production (monocytes, macrophages), other pathways of platelet activation, increased platelet turnover, genetic polymorphisms, nonatherothromboembolic pathology, and tachyphylaxis are some of the possible reasons for recurrence while on antiplatelet therapy.[18]

There is a dearth of literature on the prevalence of aspirin resistance and markers of inflammation predicting recurrence in noncardioembolic stroke. Hence, the present study was undertaken to analyze the clinico-etiological profile of recurrent non-cardioembolic ischemic stroke, estimate aspirin resistance among regular aspirin users, and evaluate blood biomarkers (hsCRP, TNF-α, Lp-PLA2) as probable predictors of stroke recurrence.

  Methods Top

This observational, case–control hospital-based study was conducted in the Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi from January 2019 to October 2020. The study was approved by the institutional research ethics panel (No. 2019/EC/1137) and confidentiality of records was maintained.

Inclusion criteria

Patients with age ≥18 years having clinical features of recurrent stroke were included after obtaining valid informed consent. The diagnosis of patients was based on the clinical history and neuroimaging evidence (Computed Tomography and Diffusion-Weighted Imaging in magnetic resonance imaging). Age- and sex-matched healthy individuals were included as control.

Exclusion criteria

Patients with hemorrhagic stroke/venous infarct, malignancy, head trauma, severe edema, acute or chronic inflammatory disease, autoimmune disease, chronic NSAID users (>3 days/week for past 3 months), history of hemorrhagic disorder within the past 4 weeks, coagulopathy, thrombocytopenia (<90,000/μl), chronic liver or renal disease, high risk of cardio-embolism (rheumatic heart disease, coronary artery disease or cardiac arrhythmia), history of dual antiplatelets intake and not giving informed consent were excluded from the study.

Detailed history, physical and neurological examination, and investigations were done as per pre-fixed protocol. NIHSS and Modified Rankin Scale (mRS) scoring was done for quantification of stroke severity and degree of disability poststroke, respectively. [19,20] Etiological classification was done as per Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.[21] Apart from routine laboratory parameters, special biochemical tests included aspirin response test, hsCRP, TNF-α, and PLA2 levels in serum.

Method of platelet aggregation testing

Among the 50 patients, 36 were prescribed aspirin out of which only 13 patients were on regular aspirin treatment during stroke events. Platelet aggregation testing was done on those 13 cases [Figure 1]. Fresh blood was collected from antecubital veins of patients as well as controls and centrifuged at 100 x g for 20 min. Platelet-rich plasma was collected and stirred at 1200 rpm in an optical lumi-aggregometer (Chrono-log model 700-2) at 37°C for 1 min, followed by the addition of 2.5 μM adenosine diphosphate (ADP). Transmittance was then recorded. Aggregation was measured as the percentage change in the light transmission where 100% refers to transmittance through platelet-poor plasma.
Figure 1: Flowchart of aspirin response testing

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Aspirin resistance is defined as mean platelet aggregation of ≥20% with 0.5 mM arachidonic acid (AA) and ≥70% with 10 μM ADP. Fulfilling of any one parameter, either mean platelet aggregation of ≥20% with 0.5 mM AA or ≥70% with 10 μM ADP, is defined as aspirin semi-resistance. Aspirin sensitivity means platelet aggregation of ≤20% with 0.5 mM AA and ≤70% with 10 μM ADP.[22] However, this definition is widely accepted for cardiovascular diseases with no such universal definition for stroke. Since we had used lower concentration of ADP (2.5 μM) in our study owing to a fresh batch of reagent producing exaggerated aggregation at the higher standard concentration (10 μM ADP) and nonavailability of AA in our biochemistry laboratory, we had reduced the cut-off values for defining aspirin resistance. Greater than 50% aggregation was deemed as aspirin resistant, close to the values set by Sane et al.(>60%); while 25%–50% aggregation was considered semi-resistant and <25% as aspirin-sensitive in this study.[23]

Serum samples were collected within 24 hours of hospital arrival. Serum hsCRP levels were measured by the highly sensitive nephelometry method. Based on hsCRP levels, cases were classified as low risk (<1 mg/L), moderate risk (1–3 mg/L), and high risk (>3 mg/L) as per American Heart Association and Centers for Disease Control and Prevention criteria.[24]

We used GenLISA™ Human TNF-α enzyme-linked immunosorbent assay (ELISA) kit (REF: KB1145, LOT: TA0920) and Human PLA2 ELISA kit (REF: KBH4468, LOT: PLA21120) from KRISHGEN BioSystems for in vitro quantitative determination of TNF-α and PLA2 in serum respectively for patients as well as controls.

  Results Top

Fifty patients with clinical and neuroradiological evidence of recurrent noncardioembolic ischemic stroke were included during our study period. There were 34 males (68%) with a male: female ratio of 2:1. Overall, the mean age of study participants was 62.92 ± 11.8 years. Majority of the patients were >60 years (N = 30, 60%). Thirty-nine (78%) patients had a second stroke while 6 (12%) cases had a third vascular event. The median (range) time interval for stroke recurrence following index stroke was 27 (0.2-276) months. Four (8%) patients had recurrence within 1 month of index stroke while 6 (12%) patients had a re-stroke between 1 and 6 months of the first stroke. Thirty (60%) cases had a repeat stroke after 1 year of the primary event [Table 1].
Table 1: Clinico-etiological profile of recurrent ischemic stroke (noncardioembolic) cases (n=50)

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Thirty-nine (78%) study subjects had hypertension while 15 (30%) had diabetes. Two (4%) patients had coronary artery disease. Fifteen (30%) patients had multiple risk factors. Only 17/39 (43.6%) hypertensives and 8/15 (53.3%) diabetics were on regular treatment. Fourteen (28%) patients had dyslipidemia. Thirty-six (72%) patients had started aspirin treatment following the index stroke. Only 13 (36%) patients sincerely adhered to treatment while the remaining 23 (64%) cases had poor drug compliance [Table 1].

Fifteen (30%) patients had an NIHSS score of 5-15 while 10 (20%) cases had high score of 21–42. Twenty-one (42%) patients had an mRS score of 5 followed by 14 (28%) cases with a score of 4.

Middle cerebral artery was the commonest vascular territory involved in 40 (80%) cases followed by vertebrobasilar in 7 (14%) cases. Thirty-one (62%) cases belonged to TOAST subtype 1 (Large artery atherosclerosis) whereas 11 (22%) cases were subtype 3 (Small vessel occlusion). Remaining 8 (16%) cases were grouped under subtype 5 (Stroke of undetermined etiology). Forty (80%) patients survived despite stroke recurrence [Table 1].

Median (range) hsCRP level was 7.5 (0.3-155) mg/L. High hsCRP level (>3 mg/L) was present in 72% patients. hsCRP levels and NIHSS score showed moderately strong positive correlation (Pearson's coefficient 0.57) [Table 2]. Median hsCRP levels were found to be higher in patients with greater NIHSS scores as compared to those with lower NIHSS grades (P < 0.001) [Table 3]. However, hsCRP levels had a statistically insignificant correlation with the number of stroke episodes (Pearson's coefficient 0.09).
Table 2: Distribution of cases based on high-sensitivity C-reactive protein levels and platelet aggregation

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Table 3: Distribution of serum high-sensitivity C-reactive protein levels across various National Institutes of Health Stroke Scale grades

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PLA2 ELISA and TNF-α ELISA were done for 24 patients and matched controls. Median (range) serum PLA2 levels in patients was 11.98 (3.31–87.24) ng/ml which was significantly higher compared to 6.96 (0.15–61.42) ng/ml for healthy controls (P = 0.029). PLA2 levels showed a strong positive correlation with the number of stroke episodes (Pearson's coefficient 0.864). However, correlation with NIHSS score was weaker (Pearson's coefficient 0.196). Median (range) serum TNF-α levels in patients was 68.22 (1.3-287) pg/ml which was significant compared to 0.098 (0.002-36.31) pg/ml for matched controls (P < 0.001). TNF-α levels correlated strongly with the number of stroke episodes (Pearson's coefficient 0.759). However, TNF-α values correlated weakly with the NIHSS score (Pearson's coefficient 0.295).

Five (41.7%) patients had platelet aggregation of >50% with 2.5 μM ADP and were considered aspirin resistant. Two (16.7%) patients were semi-resistant while 41.7% of regular aspirin users were aspirin-sensitive [Table 2].

Overall, the mean % aggregation in patients on regular aspirin treatment was 34.75 ± 21.58 compared to 64.75 ± 16.98 for healthy controls (P < 0.001). On correlating platelet aggregation values with the number of stroke episodes; Pearson's coefficient was 0.696 which indicates a strong positive correlation, i. e., greater the platelet aggregation and aspirin resistance, more is the number of recurrent stroke episodes [Figure 2].
Figure 2: Scatter plot with a positive trendline indicating increase in number of stroke episodes with greater platelet aggregation/aspirin resistance

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  Discussion Top

Recurrent ischemic stroke (RIS) is a prevalent clinical entity despite advances in stroke prevention and treatment. Recurrent strokes have been associated with greater mortality and morbidity. [25,26] As there is the scarcity of data from the Indian terrain, this study was conducted to fathom deeper into the clinical profile of RIS.

We registered 50 patients with recurrent noncardioembolic ischemic stroke visiting our hospital for approximately 2 years. Male: female ratio was 2:1 in our study which indicates male preponderance similar to the study by Kocaman et al. wherein the majority of cases were males (55%).[27]

Sixty percent of patients were elderly people above 60 years. This was similar to the findings of Jung et al.[28] In general, age is a vital nonmodifiable risk factor for stroke and an independent predictor of recurrent stroke.[29],[30],[31]

Majority of patients (78%) had a second stroke attack. Two patients were found to have fifth stroke event which was the maximum number of episodes reported in this study. Mean time interval for recurrent stroke was 51.93 months which was similar to the study by Zhu et al. wherein the mean interval for stroke recurrence was 58.42 months.[32]

Risk factor assessment showed that hypertension was present in 78% of our study participants. Kocaman et al. reported that hypertension was the commonest risk factor seen in 85% of RIS patients similar to our study.[27] Hypertension is the most common modifiable risk factor for stroke.[33],[34],[35] The AHA/ASA 2011 guidelines and The European Stroke Organization (ESO) recommended that prevention of recurrent stroke is closely related to aggressive treatment of hypertension (Class I, Level of Evidence A).[36],[37],[38] PROGRESS study reported 28% reduction in recurrent stroke with antihypertensive drugs perindopril and indapamide.[39] Diabetes mellitus was reported in 30% of our cases, similar to RESQUE study where 24% of cases were diabetics.[33]

Only 43.6% hypertensives and 53.3% diabetics were on regular treatment while 90% of hypertensive patients in RESQUE study and 86% of hypertensives in Kocaman et al. study were on regular antihypertensive drugs. [27,33] Even though 72% of patients in our study had started aspirin treatment after index stroke, only 36% of patients had good compliance in contrast to western studies where the degree of aspirin compliance was far better. Kocaman et al. found that 67% of cases were consuming aspirin regularly while RESQUE study reported 79% of patients on antiplatelet agents. [27,33] Such poor compliance to antihypertensives, oral hypoglycaemic agents, and antiplatelets might be the responsible factor for a greater number of stroke recurrences (>2) (n = 11) in our study.

Aspirin resistance was calculated for patients on regular aspirin treatment before the current stroke episode. Aspirin resistance was present in 41.7% of patients in the present study.

The strong relationship between hs-CRP and intima-media thickness (IMT) may potentially account for the complex role of hs-CRP and IMT in the pathogenesis of cerebrovascular events.[8] LIMITS study provides evidence that hsCRP predicts risk of recurrent ischemic stroke and major vascular events among patients with recent lacunar stroke.[12] In present study also, 72% patients had high hsCRP level of >3 mg/L.

Median serum PLA2 levels in patients were higher compared to controls (P = 0.029). PLA2 levels also had a strong positive correlation with the number of stroke episodes. Tian et al. suggested that blood Lp-PLA2 levels could potentially be used as a predictor of recurrent vascular events in patients with the transient ischemic attack or first ischemic stroke. They also found elevated Lp-PLA2 levels in general population signifying its association with the risk of stroke.[40] Median serum TNF-α levels in patients was statistically significant compared to controls (P < 0.001). Furthermore, TNF-α levels had a strong positive correlation with the number of stroke episodes. Elevated TNF levels have been associated with higher risk of coronary artery disease and ischemic stroke.[41] Furthermore, Welsh et al. also reported that interleukin 6 and TNF-α were significant risk predictors of recurrent ischemic stroke.[42] However, larger studies are required to correctly assess the recurrent stroke prediction ability of PLA2 and TNF-α.

Sixty-two percent of our cases belonged to TOAST subtype 1 similar to Kocaman et al. who reported large-artery atherosclerosis as the most common subtype (34%).[27] Sixteen percent of cases were in category 5 similar to RESQUE study (15%).[33] All patients (100%) in our study underwent neuroimaging (computed tomography [CT]/magnetic resonance imaging [MRI]) similar to RESQUE study where 99.7% of patients had a CT scan.[33] Thus, meticulous efforts were taken to ensure the correct etiological classification of RIS.

Ours is the first study which analyzed the clinico-radiological profile of recurrent noncardioembolic ischemic stroke, assessed various inflammatory markers as possible predictors of RIS and assessed aspirin resistance in those patients who developed re-stroke despite on regular aspirin treatment. Biochemical tests were done with 1:1 matched patient and control blood samples. Neuroimaging (CT/MRI/magnetic resonance angiography brain) was done in all cases to ensure precise TOAST classification of RIS.

Small study cohort with a limited sample size, presence of confounding factors (age, sex, co-morbidities), and no serial measurements of inflammatory markers were major limitations of our study. The small sample size was chiefly due to coronavirus disease 2019 (COVID-19) pandemic which led to poor internal as well as external validity of the study findings. In addition, referral bias due to the inclusion of the patients from a single tertiary care center was also one of the limitations.

  Conclusions Top

Majority of recurrent noncardioembolic stroke cases were aspirin noncompliant. Among the aspirin-compliant patients, a considerable proportion was detected to have aspirin resistance. Pro-inflammatory biomarker hsCRP was significantly raised in patients with higher NIHSS scores while PLA2 and TNF-α positively correlated with the number of stroke episodes. However, long-term follow-up studies with a larger sample size are necessary to better delineate the cause of stroke recurrence and strengthen the role of biomarkers in the prediction of recurrent vascular events.


We acknowledge all our patients' relatives for giving their consent and participating in the study.

Financial support and sponsorship


Conflicts of interest

Prerana Dash and Varun Kumar Singh share first authorship together because of equal contribution. Rest there is no conflicts of interest among authors.

  References Top

GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019;18:439-58.  Back to cited text no. 1
India State-Level Disease Burden Initiative Collaborators. Nations within a nation: Variations in epidemiological transition across the states of India, 1990-2016 in the Global Burden of Disease Study. Lancet 2017;390:2437-60.  Back to cited text no. 2
Indian Council of Medical Research, Public Health Foundation of India, Institute for Health Metrics and Evaluation. India: Health of the Nation×s States – The India State-Level Disease Burden Initiative. New Delhi, India: ICMR, PHFI, and IHME; 2017.  Back to cited text no. 3
Adukia SA, Ruhatiya RS, Jain GN. Is India ready to be “stroke ready”? An appraisal of our stroke preparedness. Med J DY Patil Vidyapeeth 2020;13:431-36.  Back to cited text no. 4
  [Full text]  
Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: Incidence, recurrence, and long-term survival in ischemic stroke subtypes: A population-based study. Stroke 2001;32:2735-40.  Back to cited text no. 5
Petty GW, Brown RD Jr., Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes: A population-based study of functional outcome, survival, and recurrence. Stroke 2000;31:1062-8.  Back to cited text no. 6
Libby P. Inflammation in atherosclerosis. Nature 2002;420:868-74.  Back to cited text no. 7
Corrado E, Rizzo M, Coppola G, Fattouch K, Novo G, Marturana I, et al. An update on the role of markers of inflammation in atherosclerosis. J Atheroscler Thromb 2010;17:1-11.  Back to cited text no. 8
Di Napoli M, Elkind MS, Godoy DA, Singh P, Papa F, Popa-Wagner A. Role of C-reactive protein in cerebrovascular disease: A critical review. Expert Rev Cardiovasc Ther 2011;9:1565-84.  Back to cited text no. 9
Musunuru K, Kral BG, Blumenthal RS, Fuster V, Campbell CY, Gluckman TJ, et al. The use of high-sensitivity assays for C-reactive protein in clinical practice. Nat Clin Pract Cardiovasc Med 2008;5:621-35.  Back to cited text no. 10
Koenig W. High-sensitivity C-reactive protein and atherosclerotic disease: From improved risk prediction to risk-guided therapy. Int J Cardiol 2013;168:5126-34.  Back to cited text no. 11
Elkind MS, Luna JM, McClure LA, Zhang Y, Coffey CS, Roldan A, et al. C-reactive protein as a prognostic marker after lacunar stroke: Levels of inflammatory markers in the treatment of stroke study. Stroke 2014;45:707-16.  Back to cited text no. 12
Arenillas JF, Alvarez-Sabín J, Molina CA, Chacón 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 2003;34:2463-68.  Back to cited text no. 13
Segal HC, Burgess AI, Poole DL, Mehta Z, Silver LE, Rothwell PM. Population-based study of blood biomarkers in prediction of subacute recurrent stroke. Stroke 2014;45:2912-7.  Back to cited text no. 14
Wilensky RL, Shi Y, Mohler ER 3rd, Hamamdzic D, Burgert ME, Li J, et al. Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development. Nat Med 2008;14:1059-66.  Back to cited text no. 15
Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000;101:2149-53.  Back to cited text no. 16
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Heart disease and stroke statistics – 2014 update: A report from the American Heart Association. Circulation 2014;129:e28-292.  Back to cited text no. 17
Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet 2006;367:606-17.  Back to cited text no. 18
Adams HP Jr., Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, et al. Baseline NIH stroke scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999;53:126-31.  Back to cited text no. 19
Bonita R, Beaglehole R. Recovery of motor function after stroke. Stroke 1988;19:1497-500.  Back to cited text no. 20
Adams HP Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 1993;24:35-41.  Back to cited text no. 21
Gum PA, Kottke-Marchant K, Poggio ED, Gurm H, Welsh PA, Brooks L, et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 2001;88:230-5.  Back to cited text no. 22
Sane DC, McKee SA, Malinin AI, Serebruany VL. Frequency of aspirin resistance in patients with congestive heart failure treated with antecedent aspirin. Am J Cardiol 2002;90:893-5.  Back to cited text no. 23
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, et al. Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.  Back to cited text no. 24
Modrego PJ, Pina MA, Fraj MM, Llorens N. Type, causes, and prognosis of stroke recurrence in the province of Teruel, Spain. A 5-year analysis. Neurol Sci 2000;21:355-60.  Back to cited text no. 25
Filippi A, Bignamini AA, Sessa E, Samani F, Mazzaglia G. Secondary prevention of stroke in Italy: A cross-sectional survey in family practice. Stroke 2003;34:1010-4.  Back to cited text no. 26
Kocaman G, Dürüyen H, Koçer A, Asil T. Recurrent ischemic stroke characteristics and assessment of sufficiency of secondary stroke prevention. Noro Psikiyatr Ars 2015;52:139-44.  Back to cited text no. 27
Jung B, Yoon OY, Park KH, Lee KY, Lee YJ, Kim HT, et al. Analysis of risk factors for recurrent ischemic stroke: Based on data of outpatient clinic in a University hospital. J Korean Neurol Assoc 2004;22:598-603.  Back to cited text no. 28
The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): A major international collaboration. WHO MONICA Project Principal Investigators. J Clin Epidemiol 1988;41:105-14.  Back to cited text no. 29
Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE, et al. Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 2005;366:1773-83.  Back to cited text no. 30
Petty GW, Brown RD Jr., Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Survival and recurrence after first cerebral infarction: A population-based study in Rochester, Minnesota, 1975 through 1989. Neurology 1998;50:208-16.  Back to cited text no. 31
Zhu R, Xu K, Shi J, Yan Q. Time interval between first ever and recurrent stroke in a population hospitalized for second stroke: A retrospective study. Neurol Asia 2016;21:209-16.  Back to cited text no. 32
Leoo T, Lindgren A, Petersson J, von Arbin M. Risk factors and treatment at recurrent stroke onset: Results from the Recurrent Stroke Quality and Epidemiology (RESQUE) Study. Cerebrovasc Dis 2008;25:254-60.  Back to cited text no. 33
Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet 2008;371:1513-8.  Back to cited text no. 34
Bornstein N, Silvestrelli G, Caso V, Parnetti L. Arterial hypertension and stroke prevention: An update. Clin Exp Hypertens 2006;28:317-26.  Back to cited text no. 35
Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:227-76.  Back to cited text no. 36
European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008;25:457-507.  Back to cited text no. 37
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr., et al. The Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-72.  Back to cited text no. 38
PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001;358:1033-41.  Back to cited text no. 39
Tian Y, Jia H, Li S, Wu Y, Guo L, Tan G, et al. The associations of stroke, transient ischemic attack, and/or stroke-related recurrent vascular events with Lipoprotein-associated phospholipase A2: A systematic review and meta-analysis. Medicine (Baltimore) 2017;96:e9413.  Back to cited text no. 40
Yuan S, Carter P, Bruzelius M, Vithayathil M, Kar S, Mason AM, et al. Effects of tumour necrosis factor on cardiovascular disease and cancer: A two-sample Mendelian randomization study. EBioMedicine 2020;59:102956.  Back to cited text no. 41
Welsh P, Lowe GD, Chalmers J, Campbell DJ, Rumley A, Neal BC, et al. Associations of proinflammatory cytokines with the risk of recurrent stroke. Stroke 2008;39:2226-30.  Back to cited text no. 42


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]

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