The Impact of Smoking on Acute Ischemic Stroke

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Smoking The Impact of Smoking on Acute Ischemic Stroke Wei-Chieh Weng, M.D.

cerebrovascular disease, and total atherosclerotic cardiovascular disease Pathogenesis of atherosclerosis Smoking and atherosclerosis Adverse effect on serum lipids ( LDL / TG and HDL) Damage the

JAMA, 1998 10,914 subjects, progression of intimal-medial thickness of the carotid artery as assessed by ultrasound N: nonsmoker P: past smoker C: current smoker -E: without exposure to enviornmental

1 Smoking The Impact of Smoking on Acute Ischemic Stroke Wei-Chieh Weng, M.D. Department of Neurology, Chang-Gung Memorial Hospital, Kee-Lung, Taiwan Smoking related mortality Atherosclerotic vascular disease Lung cancer COPD Independent major risk factor for CAD, cerebrovascular disease, and total atherosclerotic cardiovascular disease Pathogenesis of atherosclerosis Smoking and atherosclerosis Adverse effect on serum lipids ( LDL / TG and HDL) Damage the vascular wall Contribute to the inflammatory response ( CRP and Fibrinogen) Elevation in serum homocysteine Free radical-mediated oxidative stress The Atherosclerosis Risk in Communities (ARIC) Study. JAMA, ,914 subjects, progression of intimal-medial thickness of the carotid artery as assessed by ultrasound N: nonsmoker P: past smoker C: current smoker -E: without exposure to enviornmental smoke +E: with exposure to environmental smoke Cerebrovascular disease Cigarette smoking as a risk factor for stroke: the Frammingham study, JAMA, 1988;259: Cigarette smoking and risk of stroke in the Chinese adult population, stroke, 2008;39: Positive and dose-responsive relationship between smoking and risk of stroke Risk of recurrent stroke? RR of incidence RR of mortality Male Female

Prediction of recurrent stroke and vascular death in patients with transient ischemic attack or nondisabling stroke, stroke, 2010;41:487-493.

2 Prediction of recurrent stroke and vascular death in patients with transient ischemic attack or nondisabling stroke, stroke, 2010;41: Prognostic effect The smoking thrombolysis paradox and acute ischemic stroke, Neurology 2005;65: After adjusting for covariates, recent smokers who received thrombolysis had a significantly greater drop in 24-hour median stroke severity scores from baseline than nonsmokers who received thrombolysis and lower mortality over 1 year. Smoker nonsmoker p value ΔNIHSS at 24 hours Survival rate at 1 year 82.0% 73.2% Improved outcome after atherosclerotic stroke in male smoker, Journal of the Neurological Sciences 260 (2007) Effect of Smoking Status on Outcome after Acute Ischemic Stroke, Cerebrovascular Disease 2006;21: Limitations Baseline variables? Functional status before acute stroke? First-ever or recurrent stroke? Duration of follow-up Smoking status after acute stroke? Questions What is the immediate impact of smoking on acute ischemic stroke? Is there any difference of prognostic effect between first-ever and recurrent stroke?

3 Patients Stroke Registry in Chang Gung Healthcare System (SRICHS) Total number of patients in 2009: 4274 Lacking on either admission or discharge Length of hospital stay within 30 days Total number of patients in study: 2901 Demographics, vascular risk factors, lab findings, NIHSS, medical complications, and length of acute ward stay Definition: Methods Smokers: any history of smoking before admission Recurrent stroke: information from patients or medical records ΔNIHSS= NIHSS score on admission discharge Severe neurological deficit: NIHSS 6 Favorable recovery: ΔNIHSS > 0 Statistics: SPSS 12.0 for Windows χ2 test for categorical variables Independent sample t test for continuous variables Multivariate logistic regression analysis Significance: p<0.05 Baseline data Nonsmokers (n=2009) Smokers (n=892) p value Results Age 69.3± ±12.7 <0.001 Male 959 (47.7%) 856(96.0%) <0.001 Risk factors Hypertension 1398(69.6%) 552(61.9%) <0.001 DM 699(34.8%) 248(27.8%) Hyperlipidemia 426(21.3%) 188(21.2%) Previous stroke 565(28.1%) 247(27.7%) Previous TIA 78(3.9%) 34(3.8%) Ischemic heart disease 164(8.2%) 81(9.1%) VHD 19(0.9%) 6(0.7%) Af 147(7.3%) 53(5.9%) CHF 34(1.7%) 20(2.2%) Baseline data Nonsmokers (n=2009) Smokers (n=892) p value Lab Fever 83(4.1%) 30(3.4%) SBP 145.7± ± DBP 81.7± ± Anemia 589(29.3%) 191(21.4%) <0.001 Old lesion on brain CT 933(46.6%) 400(44.8%) Stroke mechanism Small vessel 893(44.4%) 412(46.2%) Large vessel 237(11.8%) 128(14.3%) Cardioembolism 320(15.9%) 114(12.8%) Other determined etiology 20(1.0%) 17(1.9%) Undetermined etiology 539(26.8%) 221(24.8%) Severity on admission NIHSS 5.8± ±5.0 <0.001 Course and Outcome Nonsmokers (n=2009) Smokers (n=892) p value Status upon discharge NIHSS 5.1± ±5.4 <0.001 BI 71.8± ±29.2 <0.001 mrs 2.7± ±1.9 <0.001 Neurological change ΔNIHSS 0.7± ± Functional change ΔBI 8.0± ± ΔmRS 0.4± ± Pneumonia 111(5.5%) 33(3.7%) Acute ward stay (days) 9.4± ±

4 Severe neurological deficit on admission NIHSS 6 on admission OR (95% CI) p value Age ( ) <0.001 Male ( ) Af ( ) Previous stroke ( ) <0.001 Previous TIA 0.493( ) Dyslipidemia ( ) <0.001 Old lesion on brain CT ( ) <0.001 Smoking ( ) Change of neurological deficit ΔNIHSS> 0 OR (95% CI) p value First ever stroke Pneumonia ( ) <0.001 NIHSS on admission ( ) <0.001 Smoking ( ) Recurrent stroke Pneumonia 0.295( ) <0.001 Dyslipidemia ( ) <0.001 NIHSS on admission ( ) <0.001 TOAST classification ( ) Smoking ( ) Favorable baseline characteristics Characteristics of smoker with acute stroke Discussion Young age, male, high DBP, less hypertension, less anemia, lower initial NIHSS score Similar favorable baseline data as previous studies Favorable baseline characteristics in smokers may play an important role in prognosis. Minor risk factor True prognostic effect of smoking may appear after adjusting baseline difference. The occurrence of stroke is 5 years earlier in smoker than that in nonsmokers. Prognostic influence Smokers have less severe neurological deficit on admission than did nonsmokers in acute stroke. Smoking is not independently associated with initial severity and interval change of neurological deficit in this study. Short-term outcome may reveal the true appearance of prognosis. Increased confounders in study of long-term prognosis Effect of cessation of smoking Effect of change in other risk profiles Effect of other co-morbidity First-ever and recurrent stroke We hypothesized that smoker with recurrent stroke will show poor outcome due to smoking. There was no significant difference in either first-ever or recurrent stroke. Maybe too minor to show the effect if patients have multiple major risk factors

Limitations Patient data lack of admission or discharge record were excluded in the analysis. Sugar is not considered as a variable Onset timing is not well defined.

Smoking is not significantly associated with initial severity and interval change of neurological deficit.

5 Limitations Patient data lack of admission or discharge record were excluded in the analysis. Sugar is not considered as a variable Onset timing is not well defined. Ex-smoker and pack-year are not differentiated. Conclusions The occurrence of stroke is 5 years earlier in smoker than that in nonsmokers despite relatively good risk profiles. Smoking is not significantly associated with initial severity and interval change of neurological deficit. Prognostic effect of smoking in stroke is relatively minor when comparing with the contribution to occurrence. True prognostic influence of smoking may appear after adjusting confounders adequately. Prospective study is needed to clarify the uneven results in the further. Thanks for your attention!! Coronary artery disease (CAD) MI is increased sixfold in women and threefold in men who smoke at least 20 cigarettes per day Cigarette smoking increases all-cause and cardiovascular mortality. Patients who continue to smoke in the presence of CAD have an increased risk of reinfarction and an increased risk of death, including sudden cardiac death. Smoker's Paradox Despite the role of smoking in atherosclerosis, several studies have reported that smokers who receive a fibrinolytic agent for an acute MI have a better outcome than nonsmokers.

Prognostic influence Smoking predicts long-term mortality in stroke Preventive Medicine 42 (2006) 128 131 Smoker's Paradox Despite the role of smoking in atherosclerosis, several studies have

6 Prognostic influence Smoking predicts long-term mortality in stroke Preventive Medicine 42 (2006) Smoker's Paradox Despite the role of smoking in atherosclerosis, several studies have reported that smokers who receive a fibrinolytic agent for an acute MI have a better outcome than nonsmokers. How about cerebral infarction? Recurrent stroke Improved outcome after atherosclerotic stroke in male smoker, Journal of the Neurological Sciences 260 (2007) Nonsmokers (n=565) Smokers (n=247) p value Status upon discharge NIHSS 7.1± ±6.1 <0.001 BI 61.5± ± mrs 3.3± ± Neurological change ΔNIHSS 0.4± ± Functional change ΔBI 8.5± ± ΔmRS 0.4± ± Pneumonia 48(8.5%) 13(5.3%) Acute ward stay (days) 10.3± ± The smoking thrombolysis paradox and acute ischemic stroke, Neurology 2005;65:

Clinical Features and Subtypes of Ischemic Stroke Associated with Peripheral Arterial Disease

Cronicon OPEN ACCESS EC NEUROLOGY Research Article Clinical Features and Subtypes of Ischemic Stroke Associated with Peripheral Arterial Disease Jin Ok Kim, Hyung-IL Kim, Jae Guk Kim, Hanna Choi, Sung-Yeon