Ilana Spokoyny, MD

Blood biomarkers are an active research interest, with the potential for predicting ischemic stroke via identification of novel risk pathways. The authors of this paper tested the associations between ischemic stroke and three blood markers: procalcitonin (PCT), copeptin, and midregional-pro-atrial natriuretic peptide (MRproANP). These biomarkers were chosen because they represent three different pathophysiological processes. Procalcitonin is associated with bacterial infections and was chosen with the hope of finding a link between infection and ischemic (especially non-cardioembolic) stroke. Copeptin is a hypothalamic stress hormone, which was chosen because chronic activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may promote vascular risk factors. MRproANP was hypothesized to be a marker of hemodynamic dysfunction and thereby a potential marker of (especially cardioembolic) stroke.

A nested case-control study was performed among initially stroke-free patients enrolled in the Northern Manhattan Study (NOMAS). 172 cases of first ischemic stroke were compared to 344 randomly selected controls. Primary endpoint (occurrence of first ischemic stroke) was detected using phone calls and prospective monitoring of hospital admissions and discharges. Patients with intracerebral hemorrhage were excluded.

PCT levels in the blood may reflect ongoing subclinical inflammatory processes triggered by bacterial endotoxins. It is unclear why there was an association of PCT with specifically small vessel stroke subtype. MRproANP was associated with cardioembolic stroke subtype, which may represent cardiac pathology (which has also been linked to ANP) causing cardioembolic strokes. Interventions based on these associations must be validated in prospective clinical trials, but this is a strong first step in developing better risk models and blood-based diagnostic tools for ischemic stroke. If these are validated and incorporated into clinical practice, one could imagine using MRproANP to help distinguish cardioembolic from non-cardioembolic sources of cryptogenic stroke, or using procalcitonin as one of the factors helping to distinguish mild strokes or TIAs from mimics. 
The adjusted hazard ratios for new ischemic stroke comparing the highest to lowest quartiles of PCT and MRproANP were 1.9 (1.0-3.8) and 3.5 (1.6-7.5), respectively. Stroke etiology was determined using based on the TOAST criteria. High PCT levels (top quartile) were associated with small vessel stroke (HR 5.1, 1.4-18.7) and high MRproANP levels (top quartile) were associated with cardioembolic stroke (HR 16.3, 3.7-70.9).