C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke in patients with atrial fibrillation: a more than 10-year prospective follow-up study

Essentials We studied the C-reactive protein (CRP) gene on stroke risk in atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism genotype were followed-up for more than 10 years. Patients with the A-390/T-390 allele of the CRP gene were more likely to get ischemic stroke. The triallelic polymorphism of the CRP is related to ischemic stroke in AF patients. Summary: Background Little evidence is available regarding the impact of genetic polymorphisms on the risk of thromboembolic stroke in patients with atrial fibrillation (AF). An increasing body of evidence is demonstrating that inflammatory responses play an important role in the pathophysiology of AF. Objectives To investigate the effect of genetic polymorphisms of the C-reactive protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF. Methods A total of 725 AF patients were longitudinally followed up for > 10 years; this is the largest and longest AF follow-up cohort with genetic data. CRP promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP levels were divided into four quartiles. Results Patients with higher CRP levels were more likely to develop thromboembolic stroke than those with lower CRP levels (P<0.001, log-rank test for comparison of four quartiles). After adjustment for conventional risk factors, patients with higher CRP levels were more likely to develop thromboembolic stroke than those in the lowest CRP quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08–4.81; the lowest CRP quartile was the reference group). Patients carrying the A-390 or T-390 allele had higher CRP levels (3.35 ± 2.71 mg L⁻¹ versus 2.43 ± 2.00 mg L⁻¹), and were more likely to develop thromboembolic stroke, even after adjustment for conventional risk factors (HR 2.07, 95% CI 1.23–3.48). Conclusion The CRP triallelic polymorphism and the CRP level are associated with the risk of incident thromboembolic stroke in patients with AF.