Precision medicine as a predictive factor for risk of hospitalization of recurrent ischemic stroke patients treated with low dose aspirin. A pilot study

ABSTRACT

Recurrent ischemic stroke risk after transient ischemic attack was underestimated by most of epidemiological studies due to the widespread use of very different and sometimes restrictive definitions for recurrent stroke instead of a standard definition, making it difficult to assess the benefit of early prevention of recurrence. Knowing that early intervention by treatment with aspirin reduced fatal recurrent stroke and proved to be cost effective by reducing hospital admission, it was worthwhile studying the pharmacogenetics association as well as biological risk factors of aspirin intolerance for patients with recurrent ischemic stroke. Accordingly, our primary outcome was to investigate the association of CYP2C9*3 (Rs1057910) polymorphism as well as other factors such as diabetes, hypertension and smoking with aspirin intolerance for these patients. The secondary outcome was to study the correlation between TNF-alpha as an inflammatory mediator and the prognosis of ischemic stroke for these patients. Our results showed that although smoking and heterozygous A/C of Rs1057910 still have a higher prevalence however statistically insignificant risk for ischemic stroke recurrence compared with other risk factors; OR1.69 and 1.9, 95%CI (0.471–1.695) and (0.321–11.257) respectively. Also, our results suggest that there is a borderline statistically significant correlation between recurrent stroke prognosis and TNF alpha (p = 0.043). Conclusion: This study failed to detect association of Rs1057910 variant of CYP2C9 gene with preventive aspirin for patients with ischemic stroke. However, a somehow significant association was detected between ischemic stroke prognosis and TNF- α as an inflammatory marker. Further research investigations on larger sample size population are encouraged.

KEYWORDS:

• Recurrence
• ischemic stroke
• Rs1057910
• aspirin
• TNF-alpha
• CYP2C9

List of abbreviations

TIATransient ischemic attacksSNPSingle Nucleotide PolymorphismCTComputed TomographyMRIMagnetic Resonance ImagingAHAAmerican Heart Association GuidelinesTNF–alphatumor necrosis factor-alphaLAALarge atherosclerotic arterySAASmall atherosclerotic arteryTOASTTrial of Org 10,172 in Acute Stroke TreatmentRT-PCRReal Time polymerase chain reaction systemSPSSStatistical Package for the Social SciencesNIHSSNational Institutes of Health Stroke scalingROCReceiver operating characteristic curve analysisHDLHigh-density lipoproteinCHCholesterolTGTriglyceridesLDLLow-density lipoproteinHTNHypertensionDMdiabetes mellitus.

Acknowledgments

We are thankful to those who provided their informed consent to participate in the study by permitting access to their private record and withdrawal of blood sample in the purpose of sequencing and genotyping analysis.

Disclosure statement

The writers say they have no conflicting agendas.

Availability of data

Participants in the study were given the assurance that raw data would be kept private and wouldn’t be disclosed because the information gathered in this study was sensitive.

Data not accessible; sensitive information was used.

Ethics statement

The Director General of Health Services of Kasr AL Aini hospital approved the procedure for collecting samples from ischemic stroke patients, processing the samples, transporting the samples, and extracting the RNA from the samples.

Informed consent

Prior to collecting samples, each participant gave their written consent. The local Ethics Committee of the Clinical and Chemical Pathology Department of Cairo University authorised the project. (number: I-350316/May 2016).

Role of the funding source

This research is funded by the three authors of this manuscript. For detailed information about sponsor role, please refer to section of author contributions.

Author contributions

Hanan Mostafa, an anaesthesiologist subspecialized in surgical critical care and part of intensive care team in Kasr AL Ainy, helped in patient selection and data collection. Mevidette Adel ELMadani conceived and designed the study, performed statistical analysis, interpreted results and drafted the manuscript. Eman ALHussain A.Gawad curated the data and performed DNA extraction and genotyping analysis. Radwa Marwan Abdel Halim recruited patients, performed sample collection and reviewed the drafted manuscript.