Abstract
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.
Highlights
Cardiovascular disease (CVD) remains to be a leading cause of death and major public health burden with high prevalence [1]
Neutrophil to lymphocyte ratio (NLR) is another marker for inflammation that has been reported to be associated with coronary heart disease (CHD) incidence in asymptomatic subjects [7], and poor prognosis in patients with acute coronary syndromes [8]
NLR has been associated with poor short-term outcome among ischemic stroke patients [9], and ischemic stroke among patients with non-valvular atrial fibrillation (AF) [10], there has been no study on the association of NLR with future ischemic stroke incidence among generally healthy subjects
Summary
Cardiovascular disease (CVD) remains to be a leading cause of death and major public health burden with high prevalence [1]. Implementation of novel nontraditional risk factors which add predictive value for CVD is needed to improve prevention and management of CVD. Elevated C-reactive protein (CRP), a well-studied marker for chronic inflammation, has been shown to be an independent risk factor for both coronary heart disease (CHD)[4] and ischemic stroke events [5], and has been suggested to be implemented in risk prediction models [6]. Neutrophil to lymphocyte ratio (NLR) is another marker for inflammation that has been reported to be associated with CHD incidence in asymptomatic subjects [7], and poor prognosis in patients with acute coronary syndromes [8]. We have investigated elevated NLR as a risk factor for ischemic stroke incidence in a generally healthy population
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