Supplementary Material for: Resolving the Smoking Paradox: No Evidence for Smoking-Induced Preconditioning in Large Vessel Occlusion Stroke

Introduction: Smoking is an established risk factor for stroke. However, several studies have reported a better outcome after stroke for patients who smoke. According to this “smoking paradox” hypothesis, smoking might promote less severe strokes, higher collateral scores and smaller infarct cores. Methods: In this retrospective study, we screened data of 2980 acute ischemic stroke patients with MCA-M1 occlusion treated with mechanical thrombectomy. Patients were categorized according to smoking status (current, former or never). We assessed univariate associations between clinical characteristics and smoking status. Subsequently, we used adjusted regression analysis to evaluate associations of smoking with stroke severity on admission (NIHSS, primary endpoint), infarct core volume and collateral status (secondary endpoints). Results: Out of 320 patients, 19.7% (n = 63) were current and 18.8% (n = 60) former smokers. Admission NIHSS, reperfusion success and mRS after 3-6 months were similar in all groups. Current smokers were younger, more often male and less likely to have atrial fibrillation compared to former and never smokers. In regression analyses, smoking status was neither associated with admission NIHSS (estimate 0.54, 95% CI -1.27 – 2.35, p = 0.557) nor with collateral status (estimate 0.79, 95% CI 0.44 – 1.44, p = 0.447) or infarct core volume (estimate -0.69, 95% CI -15.15 – 13.77, p = 0.925 for current vs. never smokers). Discussion/Conclusion: We could not confirm the smoking paradox. Our results support the fact that smoking causes stroke at a younger age, highlighting the role of smoking as a modifiable vascular risk factor.