High-sensitivity C-reactive protein modifies the prognostic value of platelet count for clinical outcomes after ischemic stroke

Background Platelets play a critical role in the formation of thrombosis and embolism, and high-sensitivity C-reactive protein (HS-CRP) is an important indicator of inflammation, which contribute to the development of ischemic stroke development. This study aimed to examine whether the relationship between baseline platelet count and adverse clinical outcomes is modulated by HS-CRP in patients with ischemic stroke. Methods A total of 3267 patients with ischemic stroke were included in the analysis. The primary outcome was a combination of death and major disability (modified Rankin Scale [mRS] score ≥3) at 1 year after ischemic stroke. Secondary outcomes included major disability, death, vascular events, composite outcome of vascular events or death, and an ordered 7-level categorical score of the mRS at 1 year. Multivariate logistic regression and Cox proportional hazards regression models were used to assess the association between the baseline platelet count and clinical outcomes stratified by HS-CRP levels when appropriate, odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI) were calculated for the highest quartiles of platelet counts compared with the lowest quartile. Results The elevated platelet count was associated with the primary outcome (OR, 3.14;95% CI, 1.77-5.58), major disability (OR, 2.07;95%CI, 1.15-3.71), death (HR, 2.75;95%CI, 1.31-5.79), composite outcome of vascular events or death (HR, 2.57;95%CI, 1.38-4.87), and the ordered 7-level categorical score of the mRS at 1 year (OR, 2.01 [95%CI, 1.33-3.04]) among patients with high HS-CRP levels (all P trend <0.05). However, platelet count was not associated with the primary outcome (OR, 1.13; 95%CI, 0.75-1.71), major disability (OR, 1.34; 95%CI, 0.87-2.08), death (HR, 0.48; 95%CI, 0.19-1.24), composite outcome of vascular events or death (HR, 0.79; 95%CI, 0.45-1.37), and the ordered 7-level categorical score of the mRS at 1 year (OR, 1.17; 95%CI, 0.91-1.49) (all P trend >0.05) in those with low HS-CRP levels. There was an interaction effect of platelet count and HS-CRP on the primary outcome, death, composite outcome of vascular events or death, and the ordered 7-level categorical score of the mRS at 1 year after ischemic stroke (all P interaction <0.05). Conclusions An elevated platelet count was associated with adverse clinical outcomes in ischemic stroke patients with high HS-CRP levels but not in those with low HS-CRP levels, the HS-CRP level had a modifying effect on the association between platelet count and clinical outcomes in patients with ischemic stroke, suggesting that strategies for anti-inflammatory and antiplatelet therapy should be developed according to the results of both platelet and HS-CRP testing. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the National Natural Science Foundation of China (grant: 82020108028). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The clinical trial was approved by the Ethics Committee at Soochow University in China and Institutional Review Board at Tulane University in the United States, as well as ethics committees at the 26 participating hospitals. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data included in this study are available upon request by contact with the corresponding author. * CATIS : China Antihypertensive Trial in Acute Ischemic Stroke HS-CRP : high-sensitivity C-reactive protein BP : blood pressure NIHSS : National Institutes of Health Stroke Scale mRS score : modified Rankin Scale (ALLHAT) : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial OR : odds ratio HR : hazard ratio CI : confidence intervals BMI : body mass index SBP : systolic blood pressure DBP : diastolic blood pressure TG : triglycerides TC : total cholesterol LDL-C : low density lipoprotein cholesterol HDL-C : high density lipoprotein cholesterol TIA : transient ischemic attack