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 2,980 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 (National Institutes of Health Stroke Scale [NIHSS]; primary endpoint), infarct core volume, and collateral status (secondary endpoints). RESULTS: Out of 320 patients, 19.7% (n = 63) were current smokers and 18.8% (n = 60) were former smokers. Admission NIHSS, reperfusion success, and modified Rankin Scale (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% confidence interval [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). 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.

Association of prestroke metformin use, stroke severity, and thrombolysis outcome.

OBJECTIVE: To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis. METHODS: Data from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET. RESULTS: Of 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET-). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0-4.0] vs 3 [IQR 1.0-4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups. CONCLUSIONS: Patients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.