Cigarette smoking has been associated with lower mortality after an acute coronary event. We hypothesized that the improved survival in smokers is related to demographic differences and sought to further evaluate the gender disparities in smokers after an acute coronary event. A prospective cohort of 3,588 patients hospitalized at a single center from 1999 to 2006 was identified. Smoking status, in-hospital and 6-month follow-up death, and cardiovascular events (i.e., myocardial infarction, stroke, cardiac-related rehospitalization, and unscheduled revascularization) were assessed. The prevalence of smoking in men increased over time. The smokers were younger at presentation with fewer co-morbidities than nonsmokers. Male smokers had lower mortality (3.2% vs 5.4%, p = 0.04) and fewer cardiovascular events (33.1% vs 42.4%, p = 0.003) at 6 months than nonsmokers. However, after adjusting for age and co-morbidities, smoking was not an independent predictor of events (odds ratio 0.88, 95% confidence interval 0.67 to 1.17). Female smokers had mortality (5.6% vs 8.4%, p = 0.15) and cardiovascular events (54.5% vs 49.7%, p = 0.28) at 6 months similar to that of nonsmokers, with a nonsignificant trend toward increased risk after adjustment (odds ratio 1.31, 95% confidence interval 0.90 to 1.93). Among smokers, female gender remained a significant risk factor for cardiovascular events at 6 months (odds ratio 2.35, 95% confidence interval 1.58 to 3.50), even after adjustment for age and co-morbidities. In conclusion, smokers experienced acute coronary event events earlier than did nonsmokers. Younger age and fewer co-morbidities likely account for most observed survival benefit in smokers, although female smokers are more likely to experience cardiovascular complications by 6 months than male smokers.
The University of Michigan Health System’s acute coronary event (ACS) registry provides a real-life cohort of patients with ACS on whom extensive data on cardiac risk factors, smoking history, and ACS management and outcomes have been collected. Using these data, we examined whether smoking status was associated with adverse outcomes during the index hospitalization and 6 months after ACS events among men versus women who smoked cigarettes at their admission.
Methods
All patients admitted to the University of Michigan Health System from January 1, 1999 to December 31, 2006 with a diagnosis of ACS were eligible for study inclusion. The patients <18 years old and those with noncardiovascular causes for the ACS event, such as trauma, surgery, or aortic aneurysm, were excluded from the present study. The full details of the ACS registry have been previously published.
Data regarding the ACS type and in-hospital events were collected by chart review by trained study personnel. ACS was defined as unstable angina, ST-segment elevation myocardial infarction, or non–ST-segment elevation myocardial infarction. A standard diagnosis of ACS was used. The discharge medications, including aspirin, β blockers, angiotensin-converting enzyme inhibitors or angiotensin receptors, and statins, were assessed.
The independent variables included demographics and medical history, as documented in the patients’ medical records, and a family history of coronary artery disease. Hypertension was defined as a medical history of systemic hypertension, either treated or untreated, and hyperlipidemia was defined as a previous diagnosis of hyperlipidemia or the use of lipid-lowering medications before admission. Smoking status was categorized into current, former, and never and collapsed into a binary variable (current or former/never). The primary outcomes included in-hospital cardiovascular disease (CVD) events, a composite end point of recurrent myocardial infarction (MI), stroke, and death, and the 6-month cardiovascular events, which included the documented occurrence of MI, stroke, cardiac-related rehospitalization, unscheduled revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or death. The secondary end points consisted of individual events, including recurrent MI, stroke, and death during the index hospitalization and recurrent MI, stroke, cardiac-related rehospitalization, unscheduled revascularization, and death at 6 months.
The research coordinators were trained to abstract the data from medical charts. The 6-month follow-up data were obtained by telephone interviews or a review of the medical records. The institutional review board at the University of Michigan approved all aspects of the present study.
The patients with ACS were categorized as smokers or nonsmokers (former or never smokers); within each group, the differences in characteristics were determined by gender. The differences in characteristics between women (smokers and nonsmokers) and men (smokers and nonsmokers) were also compared. A p value of ≤0.05 was considered statistically significant. For testing the differences between the groups, either the t test or the Wilcoxon rank-sum test for continuous variables was used, as indicated by the data. For the categorical data, the chi-square statistic was used, with Yates’ correction factor, as indicated by the data. Fisher’s exact test was used if the expected number of observations in any cell was <5. Multivariate logistic regression analyses were performed for in-hospital and 6-month outcomes, adjusting for age and cardiovascular risk factors.
Results
A total of 3,588 patients admitted to the University of Michigan Medical Center from January 1, 1999 to December 31, 2006 with a diagnosis of ACS were included in the present study. Of these, 137 died in-hospital before discharge, 3,451 patients were discharged, and 356 (10.3%) were lost to follow-up at 6 months.
The patients actively smoking at their admission constituted 24% of the study population (n = 863). The incidence of male patients with ACS who reported currently smoking increased from 20.3% in 1999 to 31.1% in 2005 to 26.5% in 2006 (p = 0.003 for trend). No such trend was observed among the female patients with ACS.
Male smokers were more than 9 years younger than the nonsmoking men at their ACS admission ( Table 1 ), and the female smokers were more than 13 years younger than the nonsmoking women. A history of cardiovascular disease, including MI and revascularization, was observed more often among nonsmoking men than male smokers and nonsmoking women than female smokers.
| Characteristic | Men | Women | ||||
|---|---|---|---|---|---|---|
| Nonsmokers (n = 1,725) | Smokers (n = 596) | p Value | Nonsmokers (n = 1,000) | Smokers (n = 267) | p Value | |
| Age (years) | 64.4 ± 12.9 | 55.2 ± 11.2 | <0.001 | 69.9 ± 13.4 | 56.6 ± 12.8 | <0.001 |
| White | 1,160 (67.2%) | 347 (58.2%) | <0.001 | 626 (62.6%) | 168 (62.9%) | 0.92 |
| Body mass index (kg/m 2 ) | ||||||
| 25–29.9 | 365 (24.7%) | 127 (25.0%) | 0.91 | 144 (17.7%) | 50 (21.7%) | 0.17 |
| ≥30 | 200 (13.6%) | 56 (11.0%) | 0.14 | 161 (19.8%) | 38 (16.5%) | 0.26 |
| Family history of coronary artery disease | 350 (44.8%) | 163 (54.0%) | 0.01 | 206 (42.6%) | 58 (52.7%) | 0.05 |
| Medical history | ||||||
| Myocardial infarction | 751 (43.5%) | 215 (36.1%) | 0.001 | 438 (43.8%) | 89 (33.3%) | 0.002 |
| Stroke | 165 (9.6%) | 45 (7.6%) | 0.14 | 154 (15.4%) | 26 (9.8%) | 0.02 |
| Hyperlipidemia ⁎ | 1,153 (67.0%) | 330 (55.5%) | <0.001 | 624 (62.7%) | 152 (56.9%) | 0.09 |
| Diabetes mellitus | 555 (32.2%) | 114 (19.2%) | <0.001 | 367 (36.7%) | 69 (25.8%) | 0.001 |
| Hypertension † | 1,172 (68.3%) | 330 (55.6%) | <0.001 | 816 (81.7%) | 175 (66.0%) | <0.001 |
| Acute coronary syndrome type | ||||||
| ST-segment elevation myocardial infarction | 309 (17.9%) | 195 (32.7%) | <0.001 | 162 (16.2%) | 63 (23.6%) | <0.01 |
| Non–ST-segment elevation myocardial infarction | 995 (57.7%) | 292 (49.0%) | <0.001 | 601 (60.1%) | 135 (50.6%) | <0.01 |
| Unstable angina pectoris | 421 (24.4%) | 109 (18.3%) | <0.002 | 237 (23.9%) | 69 (25.8%) | 0.47 |
⁎ Previous diagnosis of dyslipidemia or lipid-lowering medications on admission.
† Previous diagnosis of elevated blood pressure or hypertension.
Differences in ACS type ( Table 1 ) and management ( Table 2 ) were observed by smoking status for both genders. Both male and female smokers were more likely to present with STEMI and to receive percutaneous coronary intervention than were nonsmokers. The receipt of cardiac medications on discharge was similar among smokers and nonsmokers for both men and women, although women were overall less likely to receive medical therapy at discharge, including aspirin (p <0.001), β blockers (p = 0.008), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p <0.001), and statins (p <0.001).
| Management | Men | Women | ||||
|---|---|---|---|---|---|---|
| Nonsmokers (n = 1,725) | Smokers (n = 596) | p Value | Nonsmokers (n = 1,000) | Smokers (n = 267) | p Value | |
| Thrombolytics | 98 (5.7%) | 69 (11.6%) | <0.001 | 31 (3.1%) | 16 (6.0%) | 0.03 |
| Percutaneous coronary intervention | 803 (46.6%) | 320 (53.7%) | <0.01 | 356 (35.6%) | 123 (46.1%) | <0.01 |
| Coronary artery bypass grafting | 151 (8.8%) | 74 (12.4%) | <0.01 | 79 (7.9%) | 27 (10.1%) | 0.25 |
| Discharge medications | ||||||
| Aspirin | 1,573 (91.2%) | 552 (92.6%) | 0.28 | 858 (85.8%) | 231 (86.5%) | 0.77 |
| β Blockers | 1,457 (84.5%) | 499 (83.7%) | 0.67 | 814 (81.4%) | 211 (79.0%) | 0.38 |
| Statins | 1,295 (75.1%) | 452 (75.8%) | 0.71 | 698 (69.8%) | 187 (70.0%) | 0.94 |
| Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers | 1,120 (64.9%) | 413 (69.3%) | 0.05 | 619 (61.9%) | 166 (62.2%) | 0.94 |
Overall, the rates of in-hospital events were similar for both male and female smokers compared to nonsmokers ( Table 3 ). No significant differences were observed among men (nonsmokers vs smokers) for the combined end point of in-hospital cardiovascular events, and a similar pattern was observed for women by smoking status.
| Outcomes | Men | Women | ||||
|---|---|---|---|---|---|---|
| Nonsmokers | Smokers | p Value | Nonsmokers | Smokers | p Value | |
| In-hospital | ||||||
| Patients | 1,725 | 596 | 1,000 | 267 | ||
| Death | 60 (3.5%) | 17 (2.9%) | 0.47 | 49 (5.0%) | 11 (4.1%) | 0.56 |
| Recurrent myocardial infarction | 90 (5.2%) | 26 (4.4%) | 0.40 | 45 (4.5%) | 16 (6.0%) | 0.31 |
| Stroke | 11 (0.6%) | 8 (1.3%) | 0.10 | 5 (0.5%) | 3 (1.1%) | 0.26 |
| Combined cardiovascular disease events | 148 (8.7%) | 45 (7.7%) | 0.43 | 91 (9.3%) | 30 (11.2%) | 0.34 |
| At 6 months | ||||||
| Patients | 1,488 | 508 | 866 | 233 | ||
| Death | 81 (5.4%) | 16 (3.2%) | 0.04 | 73 (8.4%) | 13 (5.6%) | 0.15 |
| Recurrent myocardial infarction | 83 (7.6%) | 14 (4.2%) | 0.03 | 44 (7.0%) | 13 (8.7%) | 0.48 |
| Stroke | 16 (1.2%) | 3 (0.7%) | 0.59 | 9 (1.2%) | 2 (1.1%) | 0.99 |
| Cardiac-related rehospitalization | 384 (28.7%) | 88 (21.0%) | 0.002 | 254 (32.9%) | 69 (36.7%) | 0.32 |
| Unscheduled revascularization | 91 (7.4%) | 17 (4.4%) | 0.04 | 49 (6.9%) | 23 (13.5%) | 0.005 |
| Combined cardiovascular disease events | 469 (42.4%) | 108 (33.1%) | 0.003 | 320 (49.7%) | 84 (54.5%) | 0.28 |
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