| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1996;94:614-621.)
© 1996 American Heart Association, Inc.
Articles |
Effects of Cigarette Smoking on the Angiographic Evolution of Coronary Atherosclerosis
A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy
the Division of Cardiology, Hartford Hospital, Hartford, Conn.
Correspondence to David Waters, MD, Division of Cardiology, Hartford Hospital, 80 Seymour St, Hartford, CT 06102-5037.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background Although smoking increases both the risk of developing coronary disease and the risk of coronary events in patients with known coronary atherosclerosis, the effect of smoking on the evolution of coronary atherosclerosis as assessed by serial angiography is poorly defined.
Methods and Results Ninety smokers with coronary atherosclerosis shown on a recent angiogram and with fasting cholesterol levels between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial of cholesterol-lowering therapy, along with 241 nonsmokers and ex-smokers. Lovastatin at a mean dose of 36 mg/d lowered total and LDL cholesterol by 21±11% and 29±11%, respectively, but these levels changed by <2% in placebo-treated patients. Coronary arteriography was repeated after 2 years in 72 smokers and their 557 lesions were measured blindly with an automated quantitative system, along with 1752 lesions in 227 nonsmokers. Coronary change score, the per-patient mean of the minimal lumen diameter changes for all qualifying lesions, worsened by 0.16±0.16 mm in smokers and by 0.07±0.15 mm in nonsmokers in the placebo group (P<.001). Lovastatin-treated smokers had less worsening (0.07±0.15 mm) than placebo-treated smokers (P=.024). One or more coronary lesions progressed in 16 of 34 lovastatin-treated smokers and in 28 of 38 placebo-treated smokers (47% versus 74%, P<.001). In the placebo group, new coronary lesions developed in 21 of 38 smokers and in 28 of 115 nonsmokers (55% versus 24%, P<.001); fewer lovastatin-treated smokers developed new lesions (15% versus 55%, P<.001).
Conclusions Smoking accelerates coronary progression and new lesion formation as assessed by serial quantitative coronary arteriography. Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in smokers.
Key Words: atherosclerosis • smoking • coronary disease
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Since 1940, when researchers at the Mayo Clinic reported an association between cigarette smoking and coronary heart disease,1 numerous studies have documented that smoking substantially increases the risk of myocardial infarction, sudden cardiac death, stroke, peripheral vascular disease, and aortic aneurysm.2 3 Smoking not only increases the risk of the development of coronary heart disease but also increases morbidity and mortality in patients with known coronary atherosclerosis.4 5 6 7 8
The adverse effects of cigarette smoke are mediated by several mechanisms. Active smoking and environmental exposure to tobacco smoke cause endothelial dysfunction and increase platelet aggregability.9 10 Smokers have increased thromboxane production,11 increased plasma viscosity, and increased fibrinogen levels.12 Smoking impairs coronary vasoreactivity13 14 and facilitates coronary spasm.15 The angina threshold is reduced because carboxyhemoglobin decreases oxygen delivery and because the rate-pressure product increases at rest and during exercise.16 Smokers have higher total and IDL cholesterol levels and lower HDL cholesterol levels than control subjects.17 18
These data suggest that coronary atherosclerosis should progress more rapidly in smokers than in nonsmokers. However, in 8 of 9 studies in which serial coronary arteriography was performed mainly for clinical indications, smoking was not associated with an increased rate of coronary progression.19 20 21 22 23 24 25 26 The other study included only 32 patients, and cigarette pack-years smoked among the 12 current smokers correlated with a coronary progression score.27 The results of coronary angiographic trials provide more reliable data because coronary arteriography was repeated prospectively, irrespective of symptoms, and because coronary lesions were usually measured quantitatively. But no smokers, or only a very few, were enrolled in 5 of these trials,28 29 30 31 32 and in 6 others the results for smokers were not reported separately.33 34 35 36 37 38 Smoking was not one of the variables that correlated with angiographic outcome by multivariate analysis in the Familial Atherosclerosis Treatment Study (FATS)39 and the St Thomas Atherosclerosis Regression Study (STARS).40 The International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT)41 was larger, with 230 evaluable patients, and included more current smokers (n=67) than FATS or STARS. Current smokers in INTACT developed more new lesions than did nonsmokers or ex-smokers, with no differences among the groups for progression of established lesions. In summary, studies with serial coronary arteriography have yielded contradictory results with respect to the effect of smoking on the evolution of coronary atherosclerosis.
In the Canadian Coronary Atherosclerosis Intervention Trial (CCAIT),42 90 of the 331 patients who enrolled and 72 of the 299 who underwent follow-up angiography were current smokers. Smoking status was ascertained at each follow-up visit and entered on the case report forms. Overall, lovastatin significantly slowed coronary progression and prevented the appearance of new coronary lesions compared with placebo. The purpose of this report is to describe the coronary angiographic changes of smokers compared with nonsmokers in CCAIT and to assess the response of smokers to treatment.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Selection
The design features of this trial, including the criteria for patient selection, were described in detail in a previous report.43 Women without childbearing potential or men were recruited if their fasting total serum cholesterol was
220 and 
300 mg/dL. Coronary arteriography must have been performed within 12 weeks of study entry. Patients aged 21 to 50 years with an extent score 4, 51 to 60 years with a score 5, or 61 to 65 years with a score 6 met the angiographic eligibility criteria. Extent score was calculated by counting the number of segments containing coronary lesions between 5% and 75% by visual assessment. The age limit was increased from 65 to 70 years after enrollment had begun. The main exclusion criteria were (1) coronary angioplasty in the 6 months preceding the qualifying coronary arteriogram or previous coronary bypass surgery, (2) coronary angioplasty or bypass surgery planned within the 24-month study period, (3) ejection fraction <40%, (4) left main coronary artery stenosis >50%, (5) triple-vessel disease with preseptal left anterior descending stenosis >70%, (6) any coexisting severe illness that would make repeat arteriography ethically unjustifiable, (7) myocardial infarction or unstable angina within 6 weeks before study entry or after the entry coronary arteriogram, (8) a technically suboptimal coronary arteriogram, (9) plasma triglycerides >500 mg/dL, (10) concurrent use of lipid-lowering drugs, cyclosporine, anticoagulants, corticosteroids, or cimetidine, (11) elevated hepatic enzymes or impaired renal function, and (12) patients living too far away from the clinic or any potential condition or problem that might hinder follow-up or compliance or present an unacceptable risk to the patient. Written informed consent was obtained from each patient. The trial was approved by the ethics committees of each of the participating institutions.
Enrollment Procedures
All patients undergoing coronary arteriography in each of the clinical centers were tracked by the study nurses until they were either enrolled in the trial or declared ineligible. The most common reasons for exclusion were failure to meet the age-extent score criteria, fasting total serum cholesterol outside of the required range, previous coronary bypass surgery, ejection fraction <40%, and planned coronary revascularization. Between October 1988 and June 1990, 21 395 consecutive arteriograms were screened to identify 488 patients who met the study entry criteria; 331 of them (68%) were enrolled. Patients were randomized and began treatment a mean of 31±16 days (range, 0 to 79) after their baseline coronary arteriogram. Patients, study personnel, and other clinic staff were blinded to treatment allocation and lipid levels throughout the trial.
Drug Treatment
Patients began double-blind treatment with either placebo or lovastatin 20 mg taken immediately after the evening meal. In each center, a physician otherwise uninvolved in the trial monitored serum lipid levels and recommended dose changes on the basis of a predetermined algorithm. Drug doses were increased over the first 16 weeks of the trial in a stepwise manner to a maximum of 40 mg twice per day in an attempt to attain a target LDL cholesterol level 130 mg/dL. To preserve blinding, placebo-treated patients had their doses modified in a similar pattern to patients receiving lovastatin. All patients received counseling from a dietitian at study entry with the goal of adhering to the American Heart Association phase I diet. With the exception of those who had contraindications or developed side effects, all patients were treated with enteric-coated aspirin 325 mg on alternate days to reduce the risk of thrombotic coronary events.
Follow-up Procedures During the Study
After the randomization visit when treatment was initiated, 20 visits were planned over the ensuing 24 months of the study. At each visit, patients were questioned about their smoking habits and current smokers were encouraged to quit. Smoking status was recorded on the case report forms. The use of concomitant medication to control angina was left to the discretion of the referring physician. All cardiovascular intercurrent events were categorized according to predetermined standard definitions43 by one investigator who was blinded to treatment assignment. Repeat coronary arteriography was scheduled for 24 months after study entry but was performed earlier in 21 patients. The reason for early arteriography was myocardial infarction in 5 patients, documented or suspected unstable angina in 10 patients, and a persistent, unacceptable level of stable angina in 6 patients. At the visit 1 week before coronary arteriography, antianginal medication was adjusted to be identical to that taken at the time of the first arteriogram, especially for coronary vasodilators. The angiographic procedures followed in the trial have been described previously.43
The pair of arteriograms for each patient were interpreted together in the core quantitative angiographic laboratory by a radiologist and technicians blinded to treatment allocation, the order of the films, and the identity of the patient. For each lesion and segment, an end-diastolic frame from each arteriogram with identical angulation that best showed the stenosis at its most severe was chosen. The Cardiovascular Measurement System developed by Reiber et al44 was used in this trial to measure coronary segments and lesions, as previously described in detail.42 43 45 A change in minimal lumen diameter 0.4 mm was taken to represent a true change, either progression or regression. This cut point was selected because it was twice the standard deviation of repeat measurements of lesions filmed at 1- to 6-month intervals.45
End Points of the Trial
The angiographic definitions and end points of this trial were established before the study was unblinded and any of the arteriograms were interpreted and are described in detail elsewhere.43 The primary end point of the trial is a comparison between the lovastatin and placebo groups for coronary change score, defined as the per-patient mean of the minimal lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those <25% on both films. Lesions below this threshold were excluded because the measurement system does not distinguish them from normal variations in segment diameter. The treatment groups were compared for 5 secondary end points: (1) proportion of patients classified as progressors, (2) proportion of patients classified as regressors, (3) proportion of patients with one or more new lesions, (4) proportion of patients with one or more new total occlusions, and (5) coronary change score, including only lesions 50% in diameter stenosis at baseline. A progressor and a regressor were defined, respectively, as patients with one or more lesions narrowing or widening by 0.4 mm. A new lesion was defined as a stenosis that was not apparent on the first film or was <25% in diameter stenosis but that narrowed by 0.4 mm in minimal lumen diameter at the second angiogram.
Statistical Analyses
The statistical procedures used in the trial are defined in detail elsewhere.42 43 For the purpose of this report, ex-smokers at baseline are grouped with participants who never smoked. Smoking status almost never changed during the trial (a few smokers stopped for variable periods, but most were not able to quit entirely); thus, smoking status at study entry was used for classification. Baseline characteristics between groups were compared with the use of the 
2 test, Fisher's exact test, or a two-sample t test as appropriate. All randomized patients with interpretable follow-up arteriograms are included in the end point analyses regardless of their compliance status or the timing of the follow-up arteriogram. Coronary change score was compared between treatment groups with the use of both ANOVA and ANCOVA models. The categorical secondary end points were analyzed with the use of the Mantel-Haenszel test with treatment and smoking as blocking factors. Coronary change score was compared between treatments for smokers and nonsmokers. A multivariable regression analysis that included clinical and angiographic descriptors, concomitant medication, and baseline lipid values was performed to determine which factors correlated with coronary change score. A probability value of .05 was considered significant, and tests were two sided.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Baseline Features of the Study Population
At study entry, 90 patients were current smokers and 241 were either ex-smokers or had never smoked. The clinical and angiographic characteristics of the smokers and nonsmokers are compared in Table 1
. Smokers were on average 4.4 years younger (P<.001). None of the other differences between the groups attained statistical significance.
|
Effect of Treatment on Plasma Cholesterol Levels
The plasma lipid levels for smokers and nonsmokers in the two treatment groups at baseline and during the trial are listed in Table 2. None of the baseline differences in lipid levels between lovastatin- and placebo-treated smokers or between lovastatin- and placebo-treated nonsmokers were statistically significant. The mean prescribed dose of lovastatin per day was 35 mg for smokers and 32 mg for nonsmokers (P=NS). Lovastatin lowered total and LDL cholesterol levels in both smokers and nonsmokers (P<.001). The decreases in smokers (19% for total cholesterol and 26% for LDL cholesterol) were slightly less than the corresponding decreases in nonsmokers (21% [P=NS] and 29% [P=NS]). These values have been averaged over the 24 months of the study and include results for the 9 lovastatin-treated patients who stopped taking the study drug. Plasma lipid levels in placebo-treated patients remained relatively stable during the trial, as listed in Table 2.
|
Coronary Change Score
Of the 90 smokers enrolled in the study, 72 (80%) underwent follow-up angiography; 256 qualifying lesions from 34 lovastatin-treated smokers and 301 lesions from 38 placebo-treated smokers are included in the end point analysis, as shown in Table 3. The mean minimal lumen diameter at baseline was similar in smokers as in nonsmokers (1.54 versus 1.51 mm [P=NS]); however, the mean diameter stenosis was 37.7% in smokers and 40.7% in nonsmokers (P=.013).
|
Coronary change score, defined as the per-patient mean of the minimal lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those <25% on both films, was -0.07±0.15 mm in nonsmokers and -0.16±0.16 mm in smokers in the placebo group (P<.001). The score of lovastatin-treated smokers was similar to placebo-treated nonsmokers and was much better than placebo-treated smokers (-0.07±0.15 versus -0.16±0.16 mm [P=.024]). Lovastatin-treated nonsmokers had a better score than placebo-treated nonsmokers (-0.04±0.13 mm compared with -0.07±0.15 mm), but this difference was not statistically significant.
Categorical Analyses
The angiographic results on a per-patient basis for smokers and nonsmokers are shown in Table 4. One or more coronary lesions progressed in 16 of 34 lovastatin-treated smokers and 28 of 38 placebo-treated smokers (47% versus 74%, P=.029). One or more new lesions developed during the trial in 5 of the 34 lovastatin-treated smokers compared with 21 of the 38 placebo-treated smokers (15% versus 55%, P<.001). Among nonsmokers, the lovastatin group contained fewer progressors and fewer patients with new lesions, but the differences were statistically significant only for the category of progression alone, excluding patients with mixed changes. Regression, new occlusions, and recanalizations were less common findings and were not significantly influenced by treatment in either smokers or nonsmokers.
|
Progression alone occurred in 41 of 72 smokers and 83 of 227 nonsmokers (57% versus 37%, P=.002). Similarly, new lesions developed much more commonly in smokers: 36% versus 20% (P=.007). New occlusions were slightly but not statistically significantly more common in smokers (14% versus 11%). Regression only (excluding patients with mixed changes) was seen somewhat more often in smokers (13% versus 7%, P=.105), being particularly frequent in lovastatin-treated smokers (7 of 34, 21%).
Clinical Events
Coronary events during the trial were classified according to standard, predefined criteria43 by an investigator blinded to treatment allocation and are listed in Table 5. The mortality rate was 3.3% in smokers (3 of 90) and 0.4% in nonsmokers (1 of 241). The myocardial infarction rate was 5.6% in smokers and 2.5% in nonsmokers; however, unstable angina occurred in 7.1% of nonsmokers and 4.4% of smokers. Overall, one or more of these events occurred in 11.1% of smokers and 9.5% of nonsmokers. Significant differences in event rates between subgroups of patients are not expected because the sample size is too small and the duration of follow-up too short.
|
Multivariable Analyses
A multiple regression analysis including all of the study patients was performed on coronary change score with the use of the following factors: sex; treatment group; history of hypertension, diabetes, or angina; treatment with ß-blockers, calcium channel blockers, or ACE inhibitors; history of smoking; current smoking; number of coronary lesions; baseline minimal lumen diameter; and baseline lipid values. Current smoking was associated with a worsening coronary change score (P=.006). Better scores were associated with higher baseline HDL cholesterol levels (P=.001), wider baseline minimal lumen diameters (P=.002), the lovastatin treatment group (P=.002), a history of hypertension (P=.02), and more lesions 25% at baseline (P=.028). None of the other factors were significant at the P<.1 level.
The same variables were included in multiple regression analyses to determine which were related to the development of new coronary lesions. In the lovastatin group, only HDL cholesterol level at baseline correlated with new lesions (P<.001), being on average 33.6 mg/dL in patients with new lesions and 42.8 mg/dL in those without. In placebo patients, the strongest independent predictor of new lesions was current smoking (P<.001).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This study demonstrates that coronary atherosclerosis progresses much more rapidly in smokers than in nonsmokers. The rate of progression, a mean narrowing of minimal lumen diameter of all coronary lesions by 0.16 mm in 2 years in placebo-treated smokers, was more than double the rate of 0.07 mm in placebo-treated nonsmokers. Furthermore, new lesions developed in more than half of placebo-treated smokers compared with less than one quarter of placebo-treated nonsmokers. Cholesterol lowering slowed the progression of coronary atherosclerosis and prevented the development of new lesions in smokers; in fact, the benefit of cholesterol lowering appeared greater in smokers than in nonsmokers because smokers in the control group fared so poorly. This outcome was attained with the use of lovastatin, which at a mean dose of 34 mg per day lowered total cholesterol by an average of 24% and LDL cholesterol by 32% overall.
Previous Studies
As noted in the introduction, previous studies in which coronary arteriography was repeated usually for clinical indications have not shown a relationship between smoking and accelerated coronary progression,19 20 21 22 23 24 25 26 with one exception.27 Smoking has not been reported to be associated with coronary progression in the 13 other coronary angiographic trials of cholesterol lowering28 29 30 31 32 33 34 35 36 37 38 39 40 ; the exclusion or near absence of smokers in some trials and a failure to report data separately for smokers in others accounts for this circumstance. In INTACT, 163 nonsmokers or ex-smokers and 67 current smokers completed the trial.41 Progression and regression of established lesions occurred at similar rates in these two groups, but new lesions developed in 51% of smokers and 42% of nonsmokers. The patients who smoked throughout the entire 3 years of follow-up had significantly more new lesions than the other groups. The difference between the proportion of placebo-treated smokers and nonsmokers in our trial who developed new lesions, 55% and 24%, respectively, is wider than the difference in INTACT. Our trial also showed that smokers had more progression of established lesions. Differences in patient characteristics, length of follow-up, and methods of coronary lesion measurement may account for such differences between trials.
In a series of 313 patients who had two coronary arteriograms mainly for clinical indications, current smoking was independently associated (P<.05) with more new coronary occlusions46 but not with other types of progression.22 These data were gathered between 1970 and 1982, when coronary patients were rarely treated with aspirin. In our trial, new occlusions were slightly but not significantly more common in smokers than nonsmokers; however, all patients took low-dose aspirin as part of the study protocol, and this factor would be expected to reduce the incidence of new occlusions. Smoking causes endothelial dysfunction,9 10 increased platelet aggregability,9 10 and increases the risk of myocardial infarction.2 Our trial is underpowered to detect differences in the incidences of new occlusions or myocardial infarctions, yet a trend toward a higher mortality and more infarctions was observed in smokers.
Clinical Relevance of Angiographic End Points
Progression of coronary atherosclerosis, usually by the mechanism of plaque rupture and overlying thrombosis, causes unstable angina and myocardial infarction47 48 49 ; yet most progression occurs without associated symptoms. However, three studies have demonstrated that progression is a strong predictor of subsequent coronary events.50 51 52 In our experience,50 among patients followed for nearly 4 years after another angiographic trial, those who had had progression between the angiograms had a relative risk for subsequent cardiac death of 7.3 (95% CI, 2.2 to 24.7; P<.0001) and by multivariate analysis, progression was as strong a predictor of future coronary events as ejection fraction or number of diseased vessels. Smokers would therefore be expected to have a worse outcome after completion of the trial on the basis of their high rate of progression during the trial. That they do have a worse outcome is already known from epidemiological data and other studies.2 3 4 5 6 A major effect of smoking in our trial was greatly enhanced new lesion formation; in fact, by multiple regression analysis, smoking was the strongest independent predictor of new lesions in the placebo group. Although new lesions are rarely severe enough to cause myocardial ischemia, they are clinically relevant because the risk of a coronary event increases with the number of coronary lesions seen at angiography,53 and the lesion responsible for a coronary event is usually mild until it undergoes plaque rupture.54 55 Lesions at highest risk for plaque rupture are not large but have a high lipid content and a thin fibrous cap.56 The propensity for smokers to develop new lesions is probably one factor that contributes to their higher myocardial infarction rates by providing them with more sites to develop plaque rupture.
Enhanced new lesion formation may also partly explain why smokers develop coronary disease more often and at an earlier age compared with nonsmokers. In clinically healthy smokers, endothelial dysfunction and an exaggerated vasoconstrictive response to endothelin-1 have been described.57 These functional changes could be part of the pathway by which smoking stimulates the development of new lesions. Other risk factors for coronary atherosclerosis--diabetes,58 hypercholesterolemia,59 and postmenopausal status60 --are also associated with endothelial dysfunction.
Limitations of the Study
This trial was too small to detect differences in clinical outcomes between smokers and nonsmokers or to compare angiographic outcomes in smaller subgroups, for example, ex-smokers versus never-smokers or heavy versus light smokers. When study subjects are not randomly assigned to the categories being compared, unappreciated biases may confound the results. Yet multiple regression analyses identified smoking as an independent predictor of both progression and new lesion formation. Coronary arteriography defines only the dimensions of the lumen of the coronary artery; it provides no information about atherosclerosis within the vessel wall, where the disease is localized until its later stages. Finally, the adverse cardiovascular consequences of smoking have been amply documented such that the findings of this study are no surprise.
Clinical Implications: Effect of Cholesterol Lowering in Smokers
Smoking cessation should be the primary goal of risk factor modification in smokers with coronary atherosclerosis. However, many patients do not quit, and their physicians may focus on smoking to the exclusion of other modifiable risk factors. This study clearly demonstrates that cholesterol-lowering therapy provides angiographic benefit to smokers, reducing their rate of progression by more than half (from a mean of 0.16 to 0.07 mm) and greatly reducing the proportion of those who develop new lesions (from 55% to 15%). Furthermore, a subgroup analysis from the Scandinavian Simvastatin Survival Study shows that cholesterol lowering reduces coronary events in smokers: the relative risk for treated to untreated smokers was 0.69 (95% CI, 0.55 to 0.86).61 Therefore, smokers with coronary disease should be treated aggressively with cholesterol-lowering therapy; the degree of benefit that they obtain will be greater than for nonsmokers. For subjects without documented atherosclerosis, the National Cholesterol Education Program Adult Treatment Guidelines recommend lower target LDL cholesterol levels when two or more risk factors are present.62 For smokers, our data provide indirect support for this recommendation because new lesion formation is greatly accelerated in smokers, and cholesterol lowering slows this process. Finally, in middle-aged Scottish men with hypercholesterolemia, cholesterol lowering significantly reduced the risk of coronary death or myocardial infarction by 31% both in smokers and nonsmokers.63
|
Footnotes |
|---|
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.
Received January 16, 1996; revision received April 16, 1996; accepted May 6, 1996.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. English JP, Willius FA, Berkson J. Tobacco and coronary disease. JAMA. 1940;115:1327-1329.
2. Reducing the Health Consequences of Smoking: 25 Years of Progress: A Report of the Surgeon General: Executive Summary. Rockville, Md: US Department of Health and Human Services; 1989 (DHHS Publication No. [CDC] 89-8411).
3.
Bartecchi CE, MacKenzie TD, Schrier RW. The human cost of tobacco use. N Engl J Med. 1994;330:907-912, 975-980.
4. Sparrow D, Dawber TR, Colton T. The influence of cigarette smoking on prognosis after a first myocardial infarction. J Chron Dis. 1978;31:425-432.[Medline] [Order article via Infotrieve]
5.
Vlietstra RE, Kronmal RA, Oberman A, Frye RL, Killip T. Effect of cigarette smoking on survival of patients with angiographically documented coronary artery disease. JAMA. 1986;255:1023-1027.
6. Hallstrom AP, Cobb LA, Ray R. Smoking as a risk factor for recurrence of sudden cardiac arrest. N Engl J Med. 1986;314:271-275.[Abstract]
7.
Barry J, Mead K, Nabel EG, Rocco MB, Campbell S, Fenton T, Mudge GH Jr, Selwyn AP. Effect of smoking on the activity of ischemic heart disease. JAMA. 1989;261:398-402.
8. Cavender JB, Rogers WJ, Fisher LD, Gersh BJ, Coggin CJ, Myers WO, for the CASS Investigators. Effects of smoking on survival and morbidity in patients randomized to medical or surgical therapy in the Coronary Artery Surgery Study (CASS): 10-year follow-up. J Am Coll Cardiol. 1992;2:287-294.
9. Davis J, Shelton L, Eigenberg D, Hignite C, Watanabe I. Effects of tobacco and non-tobacco cigarette smoking on endothelium and platelets. Clin Pharmacol Ther. 1985;37:529-533.[Medline] [Order article via Infotrieve]
10.
Davis J, Shelton L, Watanabe I, Arnold P. Passive smoking affects endothelium and platelets. Arch Intern Med. 1989;149:386-389.
11.
Nowak J, Murray JJ, Oates JA, FitzGerald GA. Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes. Circulation. 1987;76:6-14.
12. McBride PE. The health consequences of smoking: cardiovascular diseases. Med Clin North Am. 1992;76:333-353.[Medline] [Order article via Infotrieve]
13. Klein LW, Ambrose J, Pichard A, Holt J, Gorlin R, Teichholz LE. Acute coronary hemodynamic response to cigarette smoking in patients with coronary artery disease. J Am Coll Cardiol. 1984;3:879-886.[Abstract]
14. Nicod P, Rehr R, Winniford MD, Campbell WB, Firth BG, Hillis LD. Acute systemic and coronary hemodynamic and serologic responses to cigarette smoking in long-term smokers with atherosclerotic coronary artery disease. J Am Coll Cardiol. 1984;4:964-971.[Abstract]
15. Scholl JM, Benacerraf A, Ducimetiere P, Chabas D, Brau J, Chapelle J, Thery JL. Comparison of risk factors in vasospastic angina without significant fixed coronary narrowing to significant fixed coronary narrowing and no vasospastic angina. Am J Cardiol. 1986;57:199-202.[Medline] [Order article via Infotrieve]
16. Aronow W. Effect of passive smoking on angina pectoris. N Engl J Med. 1978;299:21-24.[Abstract]
17. Muscat JE, Harris RE, Haley NJ, Wynder EL. Cigarette smoking and plasma cholesterol. Am Heart J. 1991;121:141-147.[Medline] [Order article via Infotrieve]
18.
Steiner G, Schwartz L, Shumak S, Poapst M. The association of increased levels of intermediate-density lipoproteins with smoking and with coronary artery disease. Circulation. 1987;75:124-130.
19.
Bemis CE, Gorlin R, Kemp HG, Herman MV. Progression of coronary artery disease: a clinical arteriographic study. Circulation. 1973;47:455-464.
20.
Kramer JR, Matsuda Y, Mulligan JC, Aronow M, Proudfit WL. Progression of coronary atherosclerosis. Circulation. 1981;63:519-526.
21.
Vanhaecke J, Piessens J, Van de Werf F, Willems JL, De Geest H. Angiographic evolution of coronary atherosclerosis in non-operated patients. Eur Heart J. 1983;4:547-556.
22. Moise A, Theroux P, Taeymans Y, Waters DD, Lesperance J, Fines P, Descoings B, Robert P. Clinical and angiographic factors associated with progression of coronary artery disease. J Am Coll Cardiol. 1984;3:659-667.[Abstract]
23. Shea S, Sciacca RR, Esser P, Han J, Nichols AB. Progression of coronary atherosclerotic disease assessed by cinevideodensitometry: relation to clinical risk factors. J Am Coll Cardiol. 1986;8:1325-1331.[Abstract]
24. Benchimol D, Benchimol H, Bonnet J, Dartigues JF, Couffinhal T, Bricaud H. Risk factors for progression of atherosclerosis six months after balloon angioplasty of coronary stenosis. Am J Cardiol. 1990;65:980-985.[Medline] [Order article via Infotrieve]
25. Nobuyoshi M, Tanaka M, Nosaka H, Kimura T, Yokoi H, Hamasaki N, Kim K, Shindo T, Kimura K. Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol. 1991;18:904-910.[Abstract]
26. Alderman EL, Corley SD, Fisher LD, Chaitman BR, Faxon DP, Foster ED, Killip T, Sosa JA, Bourassa MG, and the CASS participating investigators and staff. Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). J Am Coll Cardiol. 1993;22:1141-1154.[Abstract]
27. Raichlen JS, Healy B, Achuff SC, Pearson TA. Importance of risk factors in the angiographic progression of coronary artery disease. Am J Cardiol. 1986;57:66-70.[Medline] [Order article via Infotrieve]
28.
Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987;257:3233-3240.
29. Ornish D, Brown S, Scherwitz LW, Billings JH, Armstrong WT, Ports TA, McLanahan SM, Kirkeeide RL, Brand RJ, Gould KL. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet. 1990;336:129-133.[Medline] [Order article via Infotrieve]
30.
Kane JP, Malloy MJ, Ports TA, Phillips NR, Diehl JC, Havel RJ. Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA. 1990;264:3007-3012.
31.
Schuler G, Hambrecht R, Schlierf G, Niebauer J, Hauer K, Neumann J, Hoberg E, Drinkmann A, Bacher F, Grunze M, Kubler W. Regular physical exercise and low fat diet: effect on progression of coronary artery disease. Circulation. 1992;86:1-11.
32. Sacks FM, Pasternak RC, Gibson CM, Rosner B, Stone PH. Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Lancet. 1994;344:1182-1186.[Medline] [Order article via Infotrieve]
33.
Levy RI, Brensike JF, Epstein SE, Kelsey SF, Passamani ER, Richardson JM, Loh IK, Stone NJ, Aldrich RF, Battaglini JW, Moriarity DJ, Fisher ML, Friedman L, Friedewald W, Detre KM. The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of the NHLBI Type II Coronary Intervention Study. Circulation. 1984;69:325-337.
34. Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, Pearce MB, Yellin AE, Edmiston A, Smink RD, Sawin HS, Campos CT, Hansen BJ, Tuna N, Karnegis JN, Sanmarco ME, Amplatz K, Castenada-Zuniga WR, Hunter DW, Bissett JK, Weber FJ, Stevenson JW, Leon AS, Chalmers TC, and the POSCH Group. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. N Engl J Med. 1990;323:946-955.[Abstract]
35.
Blankenhorn DH, Azen SP, Kramsch DM, Mack WJ, Cashin-Hemphill L, Hodis HN, DeBoor LWV, Mahrer PR, Masteller MJ, Vailas LI, Alaupovic P, Hirsch LJ, and the MARS Research Group. Coronary angiographic changes with lovastatin therapy: the Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med. 1993;119:969-976.
36.
Haskell WL, Alderman EL, Fair JM, Maron DJ, Mackey SF, Superko HR, Williams PT, Johnstone IM, Champagne MA, Krauss RM, Farquhar JW. The effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease: the Stanford Coronary Risk Intervention Project (SCRIP). Circulation. 1994;89:975-990.
37. MAAS Investigators. Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet. 1994;344:633-638.[Medline] [Order article via Infotrieve]
38.
Jukema JW, Bruschke AVG, van Boven AJ, Reiber JHC, Bal ET, Zwinderman AH, Jansen H, Boerma GJM, van Rappard FM, Lie KI, on behalf of the REGRESS Study Group. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels: the Regression Growth Evaluation Statin Study (REGRESS). Circulation. 1995;91:2528-2540.
39. Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289-1298.[Abstract]
40. Watts GF, Lewis B, Brunt JNH, Lewis ES, Coltart DJ, Smith LDR, Mann JI, Swan AV. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS). Lancet. 1992;339:565-569.
41.
Lichtlen PR, Nikutta P, Jost S, Deckers J, Wiese B, Rafflenbeul W, and the INTACT Study Group. Anatomical progression of coronary artery disease in humans as seen by prospective, repeated, quantitative coronary arteriography: relation to clinical events and risk factors. Circulation. 1992;86:828-838.
42.
Waters D, Higginson L, Gladstone P, Kimball B, LeMay M, Boccuzzi SJ, Lesperance J, CCAIT Study Group. Effects of monotherapy with an HMG CoA reductase inhibitor upon the progression of coronary atherosclerosis as assessed by serial quantitative arteriography: the Canadian Coronary Atherosclerosis Intervention Trial (CCAIT). Circulation. 1994;89:959-968.
43. Waters D, Higginson L, Gladstone P, Kimball B, LeMay M, Lesperance J. Design features of a controlled clinical trial to assess the effect of an HMG CoA reductase inhibitor on the progression of coronary artery disease. Control Clin Trials. 1993;14:45-74.[Medline] [Order article via Infotrieve]
44. Reiber JHC, van der Zwet PMJ, von Land CD, Koning G, Loois G, Zorn I, van den Brand M, Gerbrands JJ. On-line quantification of coronary angiograms with the DCI system. Medicamundi. 1989;34:89-98.
45. Waters D, Lesperance J, Craven T, Hudon G, Gillam LD. Advantages and limitations of serial coronary arteriography for the assessment of progression and regression of coronary atherosclerosis: implications for clinical trials. Circulation. 1993;87(suppl II):II-38-II-47.
46. Moise A, Lesperance J, Theroux P, Taeymans Y, Goulet C, Bourassa MG. Clinical and angiographic predictors of new total coronary occlusion in coronary artery disease: analysis of 313 nonoperated patients. Am J Cardiol. 1984;54:1176-1181.[Medline] [Order article via Infotrieve]
47. Buja LM, Willerson JT. Clinicopathologic correlates of acute ischemic heart disease syndromes. Am J Cardiol. 1981;47:343-356.[Medline] [Order article via Infotrieve]
48. Moise A, Theroux P, Taeymans Y, Descoings B, Lesperance J, Waters DD, Pelletier GB, Bourassa MG. Unstable angina and progression of coronary atherosclerosis. N Engl J Med. 1983;309:685-689.[Abstract]
49. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988;12:56-62.[Abstract]
50.
Waters D, Craven TE, Lesperance J. Prognostic significance of progression of coronary atherosclerosis. Circulation. 1993;87:1067-1075.
51.
Buchwald H, Matts JP, Fitch LL, Campos CT, Sanmarco ME, Amplatz K, Castaneda-Zuniga WR, Hunter DW, Pearce MB, Bissett JK, Edmiston WA, Sawin HS Jr, Weber FJ, Varco RL, Campbell GS, Yellin AE, Smink RD Jr, Long JM, Hansen BJ, Chalmers TC, Meier P, Stamler J, for the Program on the Surgical Control of the Hyperlipidemias (POSCH) Group. Changes in sequential coronary arteriograms and subsequent coronary events. JAMA. 1992;268:1429-1433.
52.
Azen SP, Mack WJ, Cashin-Hemphill L, LaBree L, Shircore AM, Selzer RH, Blankenhorn DH, Hodis HN. Progression of coronary artery disease predicts clinical coronary events: long-term follow-up from the Cholesterol Lowering Atherosclerosis Study. Circulation. 1996;93:34-41.
53. Moise A, Clement B, Saltiel J. Clinical and angiographic correlates and prognostic significance of the coronary extent score. Am J Cardiol. 1988;61:1255-1259.[Medline] [Order article via Infotrieve]
54.
Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988;78:1157-1166.
55.
Taeymans Y, Theroux P, Lesperance J, Waters D. Quantitative angiographic morphology of the coronary artery lesions at risk of thrombotic occlusion. Circulation. 1992;85:78-85.
56. Falk E. Why do plaques rupture? Circulation. 1992;86(suppl III):III-30-III-42.
57.
Kiowski W, Linder L, Stoschitzky K, Pfisterer M, Burckhardt D, Burkart F, Buhler FR. Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers. Circulation. 1994;90:27-34.
58.
Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993;88:2510-2516.
59.
Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish D, Yeung AC, Vekshtein VI, Selwyn AP, Ganz P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990;81:491-497.
60.
Gilligan DM, Quyyumi AA, Cannon RO, Johnson GB, Schenke WH. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994;89:2545-2551.
61. Kjekshus J, Pedersen T, Pyorala K, for the 4S Group. Impact of hypertension, diabetes, and smoking on the effect of simvastatin on coronary events in coronary heart disease patients. Circulation. 1995;92(suppl I):I-18. Abstract.
62.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-3023.
63.
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ, for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-1307.
This article has been cited by other articles:
 |
|
 |
|
  T. S. Perlstein and R. T. Lee Smoking, Metalloproteinases, and Vascular Disease Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 250 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Freedland, R. M. Carney, and J. A. Skala Depression and Smoking in Coronary Heart Disease Psychosom Med, May 1, 2005; 67(Supplement_1): S42 - S46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Gluckman, M. Sachdev, S. P. Schulman, and R. S. Blumenthal A Simplified Approach to the Management of Non-ST-Segment Elevation Acute Coronary Syndromes JAMA, January 19, 2005; 293(3): 349 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Gluckman, B. Baranowski, M. D. Ashen, C. A. Henrikson, M. McAllister, J. B. Braunstein, and R. S. Blumenthal A Practical and Evidence-Based Approach to Cardiovascular Disease Risk Reduction Arch Intern Med, July 26, 2004; 164(14): 1490 - 1500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Ambrose and R. S. Barua The pathophysiology of cigarette smoking and cardiovascular disease: An update J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1731 - 1737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zitzmann, M. Brune, B. Kornmann, J. Gromoll, S. von Eckardstein, A. von Eckardstein, and E. Nieschlag The CAG Repeat Polymorphism in the AR Gene Affects High Density Lipoprotein Cholesterol and Arterial Vasoreactivity J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4867 - 4873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. van Domburg, K. Meeter, D. F. M. van Berkel, R. F. Veldkamp, L. A. van Herwerden, and A. J. J. C. Bogers Smoking cessation reduces mortality after coronary artery bypass surgery: a 20-year follow-up study J. Am. Coll. Cardiol., September 1, 2000; 36(3): 878 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pelkonen, H. Tukiainen, M. Tervahauta, I.-L. Notkola, S.-L. Kivelä, Y. Salorinne, and A. Nissinen Pulmonary function, smoking cessation and 30 year mortality in middle aged Finnish men Thorax, September 1, 2000; 55(9): 746 - 750. [Abstract] [Full Text]
|
|
|
|
|
|
S. D. Ross, I. E. Allen, J. E. Connelly, B. M. Korenblat, M. E. Smith, D. Bishop, and D. Luo Clinical Outcomes in Statin Treatment Trials: A Meta-analysis Arch Intern Med, August 9, 1999; 159(15): 1793 - 1802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Werner and T. A. Pearson What's So Passive About Passive Smoking?: Secondhand Smoke as a Cause of Atherosclerotic Disease JAMA, January 14, 1998; 279(2): 157 - 158. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hasdai, K. N. Garratt, D. E. Grill, A. Lerman, and D. R. Holmes Effect of Smoking Status on the Long-Term Outcome after Successful Percutaneous Coronary Revascularization N. Engl. J. Med., March 13, 1997; 336(11): 755 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 CHOLESTEROL REDUCTION LOWERS CORONARY RISK IN SMOKERS Journal Watch (General), September 3, 1996; 1996(903): 4 - 4. [Full Text]
|
|
|
|
 |
|
 S. A. Glantz and W. W. Parmley Passive and Active Smoking: A Problem for Adults Circulation, August 15, 1996; 94(4): 596 - 598. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||