High-Sensitive C-Reactive Protein Predicts Recurrent Stroke and Poor Functional Outcome

Acute minor ischemic stroke and transient ischemic attack (TIA) are common, and patients with recent stroke or TIA are at high risk for subsequent stroke. It is estimated that 10% to 20% of these patients have a stroke within 3 months after the index event, most of which even occur within the first 2 days. Though several clinical risk factors have been reported to be associated with recurrent stroke, these characteristics do not fully explain the risk of recurrence of stroke. Inflammation is increasingly recognized as playing a central role in atherosclerosis and cardiovascular disease. High-sensitive C-reactive protein (hsCRP), one of the most investigated inflammatory makers in cardiovascular research, has been independently associated with increased risk of recurrent cardiovascular events. However, the association between hsCRP and recurrent stroke is less established. On the contrary, disability from stroke has brought huge personal and societal burden. Though the predictive value of hsCRP in mortality has been proved, its association with functional disability in the patients with stroke is still undefined. The CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial showed that the combination of clopidogrel and aspirin was superior to aspirin alone in reducing recurrent stroke in patients with acute minor stroke or high-risk TIA during 90-day and 1-year Background and Purpose—Minor stroke and transient ischemic attack are common disorders with high rate of subsequent disabling stroke. We aim to investigate the role of high-sensitive C-reactive protein (hsCRP) in predicting recurrent stroke and poor functional outcome. Methods—In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, 3044 (59%) consecutive patients from 73 (64%) prespecified centers had hsCRP levels measured. The primary outcome was any stroke within 90 days. The secondary outcome included combined vascular events and dependence or death defined as modified Rankin Scale score of 2 to 6 at 90 days and a new vascular event during 1-year follow-up. The associations of hsCRP with recurrent stroke and functional outcome were analyzed by using Cox proportional hazards and logistic regression models. Results—Elevated hsCRP (>3.0 mg/L) was observed in 32% of the study population. Patients with hsCRP >3 mg/L had an increased risk of recurrent stroke (adjusted hazard ratio, 1.46; 95% confidence interval, 1.08–1.98; P=0.039), ischemic stroke and combined vascular events, and poor functional outcome (adjusted odds ratio, 1.68; 95% confidence interval, 1.22–2.32; P=0.002) compared with those with hsCRP <1 mg/L within 90-day follow-up period. High hsCRP levels also independently predicted recurrent stroke during 1-year follow-up. There was no interaction of hsCRP levels with randomized antiplatelet therapy. Conclusions—High hsCRP levels predict recurrent stroke and poor functional outcome in acute patients with minor stroke or transient ischemic attack. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. (Stroke. 2016;47:2025-2030. DOI: 10.1161/STROKEAHA.116.012901.)