Effects of Smoking and Smoking Cessation on Endothelial Function 1-Year Outcomes From a Randomized Clinical Trial

University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA.
Journal of the American College of Cardiology (Impact Factor: 16.5). 03/2010; 55(18):1988-95. DOI: 10.1016/j.jacc.2010.03.002
Source: PubMed


The purpose of this study was to determine whether smoking cessation improves flow-mediated dilation (FMD) of the brachial artery.
The long-term effects of continued smoking and smoking cessation on endothelial function have not been described previously.
This was a 1-year, prospective, double-blind, randomized, placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies. FMD was measured by B-mode ultrasonography before and 1 year after the target smoking cessation date. Cessation was verified by exhaled carbon monoxide levels. DeltaFMD was compared among study arms and between subjects who successfully quit smoking and those who continued to smoke. Predictors of baseline FMD and DeltaFMD were identified by multivariable regression.
The 1,504 current smokers (58% female, 84% white) were 44.7 +/- 11.1 years of age and smoked 21.4 +/- 8.9 cigarettes/day. Baseline FMD was similar in each treatment arm (p = 0.499) and was predicted by BA diameter (p < 0.001), reactive hyperemia blood flow (p < 0.001), high-density lipoprotein cholesterol (p = 0.001), and carbon monoxide (p = 0.012) levels. After 1 year, 36.2% quit smoking. FMD increased by 1% (6.2 +/- 4.4% to 7.2 +/- 4.2%) after 1 year (p = 0.005) in those who quit, but did not change (p = 0.643) in those who continued to smoke. Improved FMD among quitters remained significant (p = 0.010) after controlling for changes in brachial artery diameter, reactive hyperemia, low-density lipoprotein cholesterol, and the presence of a home smoking ban.
Despite weight gain, smoking cessation leads to prolonged improvements in endothelial function, which may mediate part of the reduced cardiovascular disease risk observed after smoking cessation. (Smoking Cessation Medications: Efficacy, Mechanisms and Algorithms; NCT00332644).

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    • "and others [9] have previously shown that active cigarette smoking and even exposure to secondhand smoke [6] leads to acute impairment of endothelial function and might also have a longer-lasting effects by negatively impacting vascular repair mechanisms, including the migratory function of endothelial cells. Endothelial dysfunction is a major mechanism by which cigarette smoking promotes atherosclerosis [10] [11]. "
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    ABSTRACT: Objectives: To investigate the effect of smoking on vascular response to transradial coronary angiography (TCA). Background: Cigarette smoking is the most important modifiable cardiovascular risk factor associated with endothelial dysfunction. Methods: Radial artery flow-mediated vasodilation (RA-FMD), local stiffness (fractional diameter change), intima-media thickness (IMT), luminal and external arterial diameter were measured in 40 current smokers (CS) and former smokers (FS) at 6-14 months at the site of previous TCA and contralateral control artery. Vascular regenerative capacity was studied as chemotactic cell migration in vitro and ex vivo (n=10) and the time course of endothelial functional recovery following RA-FMD up to 72 h after TCA (n=10). Results: At 10 ± 3 months after TCA, subjects exhibited significant local stiffening and increased IMT as compared to the control arm. These late structural changes were significantly more pronounced in CS as compared to FS. IMT thickening correlated with packyears, number of daily cigarettes, and inversely with RA-FMD. Nitric oxide synthase (NOS)-dependent chemotaxis of CS' circulating angiogenic cells was impaired. Ex vivo incubation of endothelial cells with CS' plasma inhibited NOS-dependent endothelial wound closure and chemotaxis. In vivo, TCA acutely decreased RA-FMD. At 24 h, RA-FMD had recovered in FS but remained impaired at 24 h and only recovered at 48 h in CS. Conclusion: In active smokers, transradial coronary angiography is associated with delayed early recovery from transient endothelial dysfunction, decreased NOS-dependent vascular regeneration, and late arterial remodeling pointing towards potential harmful effects of transradial coronary angiography on vascular function in distinct subsets of patients.
    American Journal of Cardiovascular Disease 07/2014; 4(2):47-57.
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    • "While smoking cessation was related to increased incident diabetes mellitus, particularly amongst the heaviest smokers, it is vital to recognize that smoking cessation has tremendous health benefits despite its relation with incident diabetes mellitus and IFG. For instance, in this same cohort, we previously demonstrated that despite weight gain, smoking cessation leads to improvements in lipids, lipoproteins, and endothelial function, each of which are established markers of CVD risk [17], [18]. Recently, longitudinal analyses from the Framingham Heart Study and Women's Health Initiative showed that weight gain after a quit attempt did not significantly attenuate the CVD risk reduction after quitting smoking [12], [13]. "
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    ABSTRACT: Weight gain after smoking cessation may increase diabetes mellitus and impaired fasting glucose (IFG) risk. This study evaluated associations between smoking cessation and continued smoking with incident diabetes and IFG three years after a quit attempt. The 1504 smokers (58% female) were mean (standard deviation) 44.7 (11.1) years old and smoked 21.4 (8.9) cigarettes/day. Of 914 participants with year 3 data, the 238 abstainers had greater weight gain, increase in waist circumference, and increase in fasting glucose levels than the 676 continuing smokers (p≤0.008). In univariate analyses, Year 3 abstinence was associated with incident diabetes (OR = 2.60, 95% CI 1.44–4.67, p = .002; 4.3% absolute excess) and IFG (OR = 2.43, 95% CI 1.74–3.41, p<0.0001; 15.6% absolute excess). In multivariate analyses, incident diabetes was associated independently with older age (p = 0.0002), higher baseline body weight (p = 0.021), weight gain (p = 0.023), baseline smoking rate (p = 0.008), baseline IFG (p<0.0001), and baseline hemoglobin A1C (all p<0.0001). Smoking more at baseline predicted incident diabetes among eventual abstainers (p<0.0001); weighing more at baseline predicted incident diabetes among continuing smokers (p = 0.0004). Quitting smoking is associated with increased diabetes and IFG risk. Independent risk factors include older age, baseline body weight, baseline glycemic status, and heavier pre-quit smoking. These findings may help target smokers for interventions to prevent dysglycemia. Trial Registration NCT00332644
    PLoS ONE 06/2014; 9(6):e98278. DOI:10.1371/journal.pone.0098278 · 3.23 Impact Factor
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    • "Therefore, we suggest that, in patients not receiving cell therapy, active smoking-related EPC alterations participate in the impairment of cardiac function recovery after acute reperfused ST elevation MI in smokers as compared to non/former smokers. Alternatively, the absence of change in EPC levels associated with myocardial infarction and smoking status could be related to the presence of endothelial dysfunction in chronic smokers [19], as both may be related [20]. Moreover, EPCs from heavy smokers die prematurely during the early phase of culture [21]. "
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    ABSTRACT: Although autologous bone marrow cell (BMC) therapy has emerged as a promising treatment for acute myocardial infarction (AMI), trials reported mixed results. In the BONAMI trial, active smoking reduced cardiac function recovery after reperfused AMI. Therefore, we hypothesized that variability in the functionality of BMCs retrieved from patients with cardiovascular risk factors may partly explain these mixed results. We investigated the characteristics of progenitor cells in active smokers and non-smokers with AMI and their potential impact on BMC therapy efficacy. Bone marrow and blood samples from 54 smoking and 47 non-smoking patients enrolled in the BONAMI cell therapy trial were analyzed. The white BMC and CD45dimCD34+ cell numbers were higher in active smokers (P = 0.001, P = 0.03, respectively). In marked contrast, either bone marrow or blood endothelial progenitor CD45dimCD34 + KDR + cells (EPCs) were decreased in active smokers (P = 0.005, P = 0.04, respectively). Importantly, a multivariate analysis including cardiovascular risk factors confirmed the association between active smoking and lower EPC number in bone marrow (P = 0.04) and blood (P = 0.04). Furthermore, baseline circulating EPC count predicted infarct size decrease at three months post-AMI in non-smokers (P = 0.01) but not in active smokers. Interestingly, baseline circulating EPCs were no longer predictive of cardiac function improvement in the BMC therapy group. These data suggest that circulating EPCs play an important role in cardiac repair post-AMI only in non-smokers and that active smoking-associated EPC alterations may participate in the impairment of cardiac function recovery observed in smokers after AMI, an effect that was overridden by BMC therapy.
    Stem Cell Research & Therapy 12/2013; 4(6):152. DOI:10.1186/scrt382 · 3.37 Impact Factor
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