Intra-Individual Reproducibility of Early and Late C-Reactive Protein and Interleukin-6 in Patients with Non-Severe Ischaemic Stroke and Carotid Atherosclerosis.

Introduction: Acute and late inflammatory markers including high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) are associated with future vascular events after stroke. However, few longitudinal studies exist examining the intra-individual reproducibility of inflammatory biomarker measures at different timepoints after atherosclerotic stroke. We sought to examine the reproducibility of hsCRP and IL-6 in a cohort of patients with minor stroke or transient ischaemic attack (TIA) caused by ipsilateral carotid atherosclerosis.

Methods: Two observational cohort studies (DUCASS and BIOVASC) were pooled. Included patients had non-severe ischaemic stroke and ipsilateral internal carotid artery stenosis (≥50%). Patients had bloods drawn within 2 weeks of their index stroke/TIA event which was stored for later analysis. All patients included were followed up at 5 years, and repeat phlebotomy was performed. Bloods were analysed for hsCRP and IL-6 using high-throughput immunochemiluminescence. Difference between baseline and follow-up blood levels and intraclass correlation (ICC) was calculated.

Results: Ninety-five participants were included, median age 69 (IQR: 63-77), and 51 (53.7%) had TIA as their presenting event. When biomarkers were dichotomised (for hsCRP <2 mg/L or ≥2 mg/L, and for IL-6 <7.5 pg/mL [median] or ≥7.5 pg/mL), 68.4% (IL-6) and 65.2% (hsCRP) of participants remained in the same risk category (high or low) over time. However, when analysed as a continuous variable, ICC coefficients were low: ICC for IL-6 0.14 (95% CI: -0.06 to 0.33), ICC for hsCRP 0.05 (95% CI: -0.14 to 0.25). ICC increased after removing outliers. Clinical characteristics and treatment were not associated with observed variability.

Conclusion: Our results suggest that concordance between early- and late-phase inflammatory marker risk categories is modest, and absolute levels are not highly correlated at early and late timepoints, despite associations at both times with future vascular risk. Investigators should standardise timing of phlebotomy and analysis protocols in future studies of inflammatory biomarkers.