Date of Award

January 2018

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)



First Advisor

Walter N. Kernan


People who smoke cigarettes are 2-4 times more likely to have a stroke and 2-5 times more likely to have a myocardial infarction compared with people who do not smoke. On a population level, it is estimated that smoking accounts for 33% of all cardiovascular deaths. Fortunately, quitting smoking can rapidly normalize risk. After an MI, smoking cessation reduces the risk of recurrent coronary events to the level of a never-smoker's after 3 years. While the benefits of smoking cessation in patients with cardiovascular disease are well-known, the benefits of smoking cessation after stroke have never been adequately examined and remain unquantified. In this research, we tested the hypothesis that smoking cessation after an ischemic stroke or transient ischemic attack (TIA) improves outcome, compared to continued smoking. We conducted a prospective observational cohort study of 1072 men and women who were current cigarette smokers at the time they were enrolled in the Insulin Resistance Intervention after Stroke (IRIS) trial. The IRIS trial was conducted during 2005-2015 to test the effectiveness of pioglitazone, compared with placebo, for prevention of stroke or MI among non-diabetic patients with a recent qualifying stroke or TIA; the main finding was that pioglitazone significantly reduced the risk of subsequent stroke or MI.5 A tobacco use history was obtained at baseline and updated during annual interviews. Cox regression models were used to estimate the differences in rates of stroke, MI, or death between quitters and continuing smokers after 4.8 years of IRIS participation. Pre-specified adjustment variables were age, sex, stroke [vs. TIA] as index event, prior history of stroke, history of hypertension, history of coronary artery disease, systolic blood pressure, diastolic blood pressure, and pioglitazone treatment. By the time of randomization, 450 (42%) patients had quit smoking. Among quitters, the 5-year risk of stroke, MI, or death was 15.7%, compared to 22.6% for patients who continued to smoke (adjusted hazard ratio, 0.66; 95% confidence interval, 0.48-0.90). Cessation of cigarette smoking after an ischemic stroke or TIA was associated with significant health benefits over 4.8 years in the IRIS trial cohort.


This is an Open Access Thesis.

Open Access

This Article is Open Access