Author + information
- Received August 2, 2000
- Revision received December 7, 2000
- Accepted January 12, 2001
- Published online May 1, 2001.
- Neville Suskin, MSc, MBChB, FRCP(C), FACC†,
- Tej Sheth, MD∗,
- Abdissa Negassa, PhD∗ and
- Salim Yusuf, MBBS, DPhil, FRCP(C), FACC∗,* ()
- ↵*Reprint requests and correspondence: Dr. Salim Yusuf, McMaster Clinic, Hamilton Health Sciences Corporation, General Site, 237 Barton Street East, Hamilton, Ontario, L8L 2X2, Canada
The aim of this study was to evaluate the impact of smoking in patients with left ventricular dysfunction.
The impact of smoking in patients with left ventricular dysfunction has not been well-studied.
We compared the incidence of death, hospitalization due to heart failure and myocardial infarction (MI) in current smokers to ex-smokers of ≤2 years and ex-smokers of >2 years duration to never-smokers among participants of the Study Of Left Ventricular Dysfunction (SOLVD) Prevention and Intervention trials. Participants all had left ventricular ejection fraction (LVEF) <35% and follow-up was over a mean of 41 months.
Complete smoking status and outcome data were available in 6,704 subjects. There were 1,562 current smokers, 1,317 ex-smokers of ≤2 years, 2,354 ex-smokers of >2 years and 1,471 never-smokers. After adjusting for baseline differences of age, LVEF, race and etiology of heart failure, current smoking was associated with a significantly increased all-cause mortality (relative risk [RR]: 1.41, 95% confidence interval [CI]: 1.25 to 1.58, p < 0.001) compared with ex-smokers and never-smokers. The incidence of death or recurrent congestive heart failure requiring hospitalization or MI was significantly greater (RR: 1.39, 95% CI: 1.26 to 1.52, p < 0.001) in current smokers compared with ex-smokers and never-smokers. There were no significant differences in the number of deaths or hospitalizations due to heart failure between ex-smokers and never-smokers. This effect was consistent across both the SOLVD Prevention and Treatment trials.
Current smoking is a powerful independent predictor of morbidity (recurrent heart failure and MI) and mortality in patients with left ventricular dysfunction. Quitting smoking appears to have a substantial and early effect (within two years) on decreasing morbidity and mortality in patients with left ventricular dysfunction, which is at least as large as proven drug treatments recommended in patients with left ventricular dysfunction.
Cigarette smoking is the major known modifiable risk factor for coronary heart disease in both men and women. Cigarette smoking substantially increases the risk of a first myocardial infarction (MI) in men and women and is responsible for a 70% excess death rate from coronary heart disease in general (1). There is considerable overlap between the effects of cigarette smoking on the cardiovascular system
and the pathophysiologic mechanisms of congestive heart failure (CHF). The pathophysiology of chronic heart failure includes structural cardiac damage that adversely affects systolic or diastolic function with compensatory hemodynamic and neurohormonal mechanisms leading to peripheral vasoconstriction, sodium retention and endothelial dysfunction (2). The constituents of inhaled tobacco damage the cardiovascular system by numerous mechanisms, including endothelial dysfunction, platelet dysfunction, increased coagulation, increased heart rate, blood pressure, increased myocardial oxygen demand and vasoconstriction (3,4). Therefore, smoking may be expected to have multiple adverse effects in patients with CHF.
Cigarette smoking increases heart rate and blood pressure, thereby increasing myocardial oxygen consumption; it increases carboxyhemoglobin, which has a negative inotropic effect, and increases left ventricular end diastolic pressure (4). Smoking is a major risk factor for the development of coronary artery disease, which is the major cause of heart failure. In addition, smoking is a strong predictor for the development of heart failure (5), of sudden death for those who have CHF (6)and of mortality in patients with idiopathic dilated cardiomyopathy (7).
Smoking cessation is universally recommended in patients with coronary artery disease and CHF. However, the effect of smoking cessation on outcome in patients with CHF is largely unknown. Compared with individuals who had never smoked, we examined the impact of current smoking, former smoking within two years (ex-smokers of ≤2 years) or more than two years (ex-smokers of >2 years) of quitting before study entry on all-cause mortality, hospitalizations due to heart failure, hospitalizations due to MI and a composite outcome of all-cause mortality or hospitalizations due to heart failure among the participants of the Studies Of Left Ventricular Dysfunction (SOLVD) Treatment (8)and Prevention (9)trials.
The SOLVD study consisted of two multicenter double-blind randomized placebo-controlled trials of patients with left ventricular ejection fraction (LVEF) <0.35. Details of the patient characteristics, design and results have been published previously (8–10). The trials evaluated the effects of the angiotensin-converting enzyme inhibitor enalapril on morbidity and mortality in patients with (9)and without (8)overt heart failure. In the SOLVD Treatment trial (9), 2,569 patients were followed for a mean of 41 months, and in the SOLVD Prevention trial (8), 4,228 patients were followed for a mean of 37 months. In the Treatment trial, enalapril significantly reduced mortality and hospitalization for heart failure (9). In the Prevention trial, enalapril significantly reduced the incidence of heart failure compared with placebo (8). The SOLVD study was approved by each center’s institutional review board, and each patient provided written informed consent.
Continuous variables were summarized using means and standard deviations. Proportions were used to summarize discrete variables. Former smokers were divided into two categories on the basis of length of duration since quitting smoking, and the cut-point was taken to be two years (i.e., ex-smokers of ≤2 years and ex-smokers of >2 years). These categories were chosen as a compromise between earlier literature that reported that, in men and women without CHF, it takes approximately three years for an ex-smoker to assume a similar risk of MI to a never-smoker (11,12); the categories were also chosen because of the desire to have roughly equal-sized groups of more than 1,000 patients to allow for appropriate power for statistical analyses.
The effect of smoking on mortality, hospitalization for CHF or MI was assessed after adjusting for a prespecified set of baseline characteristics of age, weight, gender, blood pressure at entry, heart rate at entry, previous MI, previous revascularization, history of hypertension, history of diabetes, history of heart failure, New York Heart Association class, ejection fraction, treatment allocation, etiology and cardiothoracic ratio using Cox proportional hazards model (13). A significance level of 0.05 (two-sided) was employed in assessing statistical significance. The effect of smoking and ex-smoking in the model was expressed in terms of relative risk (RR) and 95% confidence interval (CI) and adjusted for the prespecified baseline variables described earlier.
Complete smoking status data were available in 6,704 of the 6,788 subjects reported in the SOLVD trials (8,9). There were 1,562 current smokers, 1,317 ex-smokers of ≤2 years, 2,354 ex-smokers of >2 years and 1,471 never-smokers. Both current smokers and ex-smokers of ≤2 years were younger than ex-smokers of >2 years and never-smokers (Table 1). More men were current smokers as compared with women. A higher proportion of current smokers had an ischemic cause to their CHF compared with never-smokers. Likewise, a greater proportion of current smokers had a history of a previous MI compared with never-smokers. A number of important baseline differences existed between current and never-smokers. Smokers were more likely to be men, have ischemic heart disease, be nondiabetic and not have a history of hypertension.
Current smokers versus current nonsmokers
Substantially more current smokers died overall (RR: 1.41, p < 0.001), died from heart failure (RR: 1.31, p = 0.017), were admitted to the hospital for heart failure (RR: 1.21, p = 0.006) or experienced an MI (RR: 1.51, p < 0.001) compared with current nonsmokers (Tables 2 and 3, ⇓⇓Fig. 1). Current smoking was associated with an increased risk of death due to heart failure (RR: 1.41, p = 0.009) in the Treatment trial and an increased risk of MI (RR: 1.77, p < 0.001) in the Prevention trial. Current smoking was associated with a substantially increased risk of dying or being hospitalized due to heart failure or an MI (RR: 1.39, p < 0.001), and this effect was consistent across the Treatment (RR: 1.26, p < 0.001) and Prevention (RR: 1.53, p < 0.001) trials.
Current smokers versus ex-smokers of ≤2 years versus ex-smokers of >2 years versus never-smokers
Current smokers had a substantially greater all-cause mortality rate (RR: 1.40, p < 0.001) compared with never-smokers (Tables 2 and 4, Fig. 1). ⇓This effect was consistent across the Prevention (RR: 1.37, p = 0.007) and Treatment (RR: 1.38, p = 0.001) trials. There were no significant differences in the all-cause mortality rate between ex-smokers of any duration and never-smokers. Overall, there was a modest increased risk of death due to progressive heart failure in current smokers (RR: 1.28, p = 0.079) compared with never-smokers. This effect was due to the increased risk in the Treatment trial (RR: 1.34, p = 0.071). There was no significant difference in the number of heart failure deaths between never-smokers and ex-smokers ≤2 years or ex-smokers of >2 years duration. Overall, current smokers were at an increased risk of hospitalization due to heart failure (RR: 1.20, p = 0.03) compared with never-smokers. This effect was largely due to the increase in the number of hospitalizations due to heart failure in the Prevention trial (RR: 1.42, p = 0.016). Ex-smokers of any duration had similar rates of heart failure hospitalizations compared with never-smokers. Overall, more current smokers experienced an MI (RR: 1.43, p = 0.021) compared with never-smokers. This effect was largely due to the increased risk of MI among current smokers in the Prevention trial (RR: 1.57, p = 0.019). There was no significant difference in the risk of MI among never-smokers and ex-smokers of any duration in either of the trials. Current smokers were at substantially increased risk of dying or being hospitalized for heart failure or MI (RR: 1.39, p < 0.001) compared with never-smokers, while ex-smokers of any duration were at a similar risk to never-smokers of dying or being hospitalized for heart failure or MI.
The main adverse effect of current smoking (versus ex- and never-smoking) was accounted for by the increased event rate in those patients with an ischemic heart failure etiology (ischemic etiology: adjusted RR [95% CI] for mortality or MI or heart failure hospitalization in smokers vs. ex-smokers of ≤2 years vs. ex-smokers of >2 years vs. never-smokers was 1.45 [1.24 to 1.7] vs. 1.09 [0.92 to 1.29] vs. 1.00 [0.87 to 1.16] vs. 1; nonischemic etiology: 1.13 [0.89 to 1.43] vs. 1.05 [0.80 to 1.37] vs. 0.91 [0.72 to 1.15] vs. 1).
There were two main findings illustrated by this study. First, current smoking was associated with a substantially increased risk of death, hospitalization due to heart failure and MI in both Prevention and Treatment trial patients. Second, patients who stopped smoking had a lower risk of death, hospitalization due to heart failure and MI that was largely similar to that of patients who had never smoked.
Reduced risk associated with smoking cessation
Patients with reduced LVEF with or without symptoms of CHF who had never smoked or who had quit smoking had a 30% lower risk of dying over 41 months compared with patients who were current smokers after adjusting for baseline differences. There was no significant difference in mortality between patients who had never smoked compared with ex-smokers of any duration. This 30% lower mortality observed in current nonsmokers (ex- or never-smokers) compared with current smokers is of the same magnitude as that of enalapril treatment (19% mortality reduction) compared with placebo (9)and metoprolol treatment (34% mortality reduction) compared with placebo (14)and spironolactone treatment (30% mortality reduction) compared with placebo (15). Yet smoking cessation has not been emphasized as an integral part of the management of patients with heart failure.
The main adverse effect of current smoking was accounted for by the increased event rate in those patients with ischemic heart disease. The reasons for the apparent lack of association of current smoking with adverse outcome in the nonischemic patients were unclear, and this subgroup analysis should be interpreted with caution, as there were only 1,428 patients without ischemia compared with 4,080 patients with ischemia. As well, previous reports have suggested that current smoking is associated with an increased risk of mortality in patients with idiopathic dilated cardiomyopathy (7).
Time frame of reduced risk
Earlier reports have suggested that, in men and women without CHF, it takes approximately three years for an ex-smoker to assume a similar risk for MI to a never-smoker (11,12). Our study suggests that, among smokers with CHF who quit smoking, the risk of recurrent CHF or MI is substantially decreased in less than three years. This almost immediate decrease in the recurrence of CHF could, in part, be explained by the expected decrease of detrimental hemodynamic effects associated with smoking. Cigarette smoking in patients with New York Heart Association class III heart failure increases heart rate and systemic blood pressure as well as systemic and pulmonary vascular resistance, that is, increased ventricular afterload. Cigarette smoking increases oxygen demand and decreases myocardial oxygen supply, which has important negative consequences for myocardial oxygen balance (16).
The effects of smoking cessation in patients with left ventricular dysfunction on morbidity and mortality in this study were assessed by observational techniques only, which has inherent limitations. Our study was consistent with the vast majority of literature, which has utilized observational techniques to evaluate the association between smoking cessation and morbidity and mortality. We did, however, adjust our analyses for potential prognostically important differences between the groups. We did not collect any information on follow-up on smoking status after entry into the SOLVD trials. Therefore, our study may have underestimated the magnitude of the association between current smoking and adverse outcome, given that the individuals we categorized as ex-smokers may have subsequently resumed smoking.
Current smoking is a powerful independent predictor of morbidity and mortality in patients with reduced left ventricular systolic function with and without symptoms of heart failure. Quitting smoking is associated with the accomplishment of a very expeditious decrease in morbidity and mortality, which is similar in magnitude to the effect of an appropriate angiotensin-converting enzyme, beta-adrenergic blocking agent or spironolactone use in patients with reduced left ventricular systolic function and symptoms of heart failure, yet little emphasis has been placed on smoking cessation strategies in these patients. Universal introduction of smoking cessation strategies in patients with reduced left ventricular systolic function, with or without symptoms of CHF, are of critical importance and should be adopted as vigorously as proven medical therapy.
☆ Dr. Suskin was supported by a Career Scientist Award of the Ontario Ministry of Health. Dr. Yusuf was supported by a Senior Scientist Award of the Canadian Institutes of Health Research and holds a Heart and Stroke Foundation of Ontario Endowed Research Chair.
- congestive heart failure
- confidence interval
- left ventricular ejection fraction
- myocardial infarction
- relative risk
- Studies Of Left Ventricular Dysfunction
- Received August 2, 2000.
- Revision received December 7, 2000.
- Accepted January 12, 2001.
- American College of Cardiology
- ↵The health consequences of smoking: cardiovascular disease: a report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service, Office on Smoking and Health. DHHS Publication No. (PHS) 84-50204, 1983.
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