Abstract 54: Procalcitonin, Copeptin and Midregional Pro-atrial Natriuretic Peptide as Markers of Ischemic Stroke Risk: The Northern Manhattan Study

Abstract

Background: Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke. We hypothesized that selected blood biomarkers of infection (procalcitonin, or PCT), hypothalamic-pituitary-axis function (copeptin), and hemodynamic stress (midregional pro-atrial natriuretic peptide, or MRproANP) would be associated with incident ischemic stroke risk in the multi-ethnic, urban Northern Manhattan Study (NOMAS) cohort. Methods: A case-cohort study was performed among initially stroke-free participants from the prospective population-based NOMAS study. The mean follow up was 11 years. Cases were defined as first ischemic stroke (including fatal) with available baseline blood (n=172). We randomly selected controls among those who did not develop an event (n=344). Biomarkers were measured in a blinded batch analysis (Laboratory of the Medical University Clinic, Aarau, Switzerland, using B.R.A.H.M.S assays by Thermo Fisher Scientific). We calculated hazard ratios and 95% confidence intervals (HR, 95% CI) using Cox proportional hazards models, with inverse probability weighting to correct for the case-cohort study design, to estimate the association with risk of stroke after adjusting for demographic, behavioral, and medical risk factors. Results: Mean age of cases was 72 (IQR 65-78); 59% were female. After full adjustment, those with PCT in the top quartile, compared to the lowest quartile, were at increased risk of ischemic stroke (adjusted HR 1.98, 95% CI 1.02-3.83). Those with MRproANP levels in the top quartile, compared to the lowest quartile, were also at increased risk of stroke (adjusted HR 3.45, 95% CI 1.58-7.52), but not those with higher copeptin levels. The distribution of MRproANP differed by stroke etiology. Levels of MRproANP were greater for cardioembolic strokes (CE), and MRproANP levels were predictive of CE (adjusted HR 3.29 per SD, 95% CI 1.89-5.72). Conclusion: Higher levels of procalcitonin, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with ischemic stroke risk in this multiethnic, urban cohort. MRproANP was specifically associated with cardioembolic stroke risk. Further study is needed to confirm these results.