High-Sensitivity C-Reactive Protein and Soluble CD40 Ligand as Indices of Inflammation and Platelet Activation in 880 Patients With Nonvalvular Atrial Fibrillation

Abstract

BACKGROUND AND PURPOSE: There is now considerable evidence that atrial fibrillation is associated with an inflammatory state. We tested the hypothesis that plasma levels of C-reactive protein (CRP; an index of inflammation) and soluble CD40 ligand (an index of platelet activation, with links to inflammation) could be related to 3 established stroke risk stratification schema (SPAF, CHADS(2), and NICE), recognized stroke risk factors or other cardiovascular disease, and prognosis. METHODS: We studied 880 subjects with atrial fibrillation recruited from subjects receiving aspirin 325 mg/d (alone or combined with fixed inefficacious doses of warfarin) from the Stroke Prevention in Atrial Fibrillation (SPAF) III clinical trial. CRP and soluble CD40 ligand were measured by enzyme-linked immunosorbent assay. RESULTS: With respect to the SPAF III stroke risk stratification criteria, those with moderate to high risk had the highest levels of CRP (Kruskal Wallis test, P<0.001), but those with the highest risk had the lowest levels of soluble CD40 ligand (P=0.01). Similarly, CRP levels increased in a positive fashion with increasing stroke risk with respect to the CHADS(2) and NICE risk stratification criteria, whereas soluble CD40 ligand levels were negatively associated with stroke risk. CRP levels were higher among those patients with raised body mass index, diabetes, hypertension, ischemic heart disease, peripheral vascular disease, and recent heart failure, but not those with thromboembolism. Patients were followed-up for a mean time of 453 (standard deviation, 229) days, and all-cause mortality (log rank test, P=0.001), and vascular events (P=0.05), but not stroke, were more common in patients with high CRP levels. Soluble CD40 ligand levels were not related to stroke, vascular events, or all-cause mortality. CONCLUSIONS: Among atrial fibrillation patients, CRP was positively correlated to stroke risk and related to stroke risk factors and prognosis (mortality, vascular events). Soluble CD40 ligand levels were lowest in those at moderate to high risk of stroke and not related to prognosis. The use of CRP in risk stratification for atrial fibrillation merits further study.