Elevated neutrophil to lymphocyte ratio and ischemic stroke risk in generally healthy adults

Elevated neutrophil to lymphocyte ratio (NLR) has been reported as a marker for chronic inflammation, associated with poor prognosis in ischemic stroke patients, but there has been no study that investigated its association with ischemic stroke risk. This study was conducted to investigate elevated NLR as an independent risk factor for ischemic stroke incidence. Our retrospective cohort study included 24,708 generally healthy subjects aged 30-75 who received self-referred health screening at Seoul National University Hospital. Data on ischemic stroke incidence was retrieved from national medical claims registry. Median follow-up time was 5.9 years (interquartile range 4.2 years). Adjusted for major cardiovascular risk factors, compared to subjects with NLR<1.5, subjects with 2.5≤NLR<3.0, 3.0≤NLR<3.5, and NLR≥3.5 had elevated risk for ischemic stroke incidence with aHR (95% CI) of 1.76 (1.09-2.84), 2.21 (1.21-4.04), and 2.96 (1.57-5.58), respectively. NLR showed significant improvement in discrimination for ischemic stroke incidence compared to traditional cardiovascular risk factors (C-index 0.748 vs. 0.739, P = 0.025). There was significant net improvement in reclassification in Framingham risk for ischemic stroke incidence after addition of NLR, with IDI 0.0035 (P<0.0001), and NRI 6.02% (P = 0.0015). This reclassification for ischemic stroke incidence by NLR was markedly pronounced among subjects with atrial fibrillation with CHA2DS2-VASc<2 (NRI 42.41%, P = 0.056). Our study suggests elevated NLR to be an independent risk factor for ischemic stroke incidence in generally healthy adults. Future studies are needed to validate our results and further assess how subjects with elevated NLR should be managed within current guidelines.