The smoker's paradox: Insights from the angiographic substudies of the TIMI trials

Background: Despite increased risk for coronary artery disease and acute myocardial infarction (AMI), smokers have a paradoxically lower mortality after thrombolysis for AMI than non-smokers. We determined the clinical risk profiles and coronary flow characteristics of patients in the TIMI trials according to smoking status, focusing on microvascular flow. Methods: Among 2,573 patients in the TIMI 4, 10A, 10B and TIMI 14 trials, epicardial flow post-thrombolysis was measured using angiographic TIMI flow grades and the corrected TIMI frame count (CTFC). Microvascular flow was measured by TIMI Myocardial Perfusion Grade (TMPG) and, in TIMI 14, the percentage of ST segment resolution. Results: Clinically, the mean age (54 vs. 62 years), the prevalence of diabetes mellitus (11% vs. 16%) and hypertension (26% vs. 40%), and the 30-day mortality (2.6% vs. 6.2%) were lower among smokers than nonsmokers (all p less than or equal to 0.001). Angiographically, single-vessel disease (48% vs. 40%) and non-left anterior descending infarct arteries (65.4% vs. 60.8%) were more common among smokers (both p less than or equal to 0.01). Epicardial TIMI grade 3 flow was achieved more often in smokers than nonsmokers (61% vs. 56%) and the CTFC was faster (34 vs. 37 frames/sec, both p less than or equal to 0.01), especially in LAD lesions. However, the frequency of normal microvascular flow (TMPG 3) was similar among smokers and non-smokers (24% vs. 29%, p = 0.16), as was the frequency of complete ST segment resolution (50% vs. 46%, p = 0.29). Conclusions: Smokers have lower mortality after AMI than non-smokers, due in large part to lower clinical risk profiles and faster epicardial flow. Differences in tissue-level perfusion do not appear to contribute to lower mortality in smokers.