1、 Key PointSmoking is causally linked to a host of cardiovascular, respiratory, reproductive, and other conditions, as well as many types of cancer. The top 3 smoking-attributable causes of death in the United States are lung cancer, ischemic heart disease, and chronic obstructive pulmonary disease (
2、COPD).BackgroundIn 2004, the US Surgeon General published a report on the health effects of active smoking, focusing specifically on the evidence for a causal relationship between smoking and disease and death. According to the research summarized in the report, many serious conditions are caused by
3、 smoking, including cardiovascular, respiratory, reproductive, and other conditions, as well as cancer affecting diverse areas and organs of the body. In addition to the widely-known consequences of lung cancer and respiratory disease, smoking has been causally linked to such diverse morbidities as
4、low-bone density, nuclear cataract, bladder cancer, and reduced fertility.1 Other studies have linked smoking to vascular dementia2 and peripheral arterial disease.3 These conditions can affect young and middle-aged smokers and, in general, as a smokers age increases, the frequency of smoking-caused
5、 diseases rises.1References1. US Department of Health and Human Services. The Health Consequences of Smoking. A Report of the Surgeon General. Atlanta, Ga: Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health P
6、romotion, Office on Smoking and Health; 2004. 2. Roman GC. Vascular dementia prevention: a risk factor analysis. Cerebrovasc Dis. 2005;20(Suppl 2):91-100. 3. Willigendael EM, Teijink JA, Bartelink ML, et al. Influence of smoking on incidence and prevalence of peripheral arterial disease. J Vasc Surg
7、. 2004;40:1158-1165. 4. Ezzati M, Lopez AD. Regional, disease specific patterns of smoking-attributable mortality in 2000. Tobacco Control. 2004;13:388-395.Slide 1 Smoking has been implicated as a cause of both peripheral and coronary endothelial dysfunction and has been shown to be a predictor of l
8、ong-term cardiovascular events, but its mechanism is not fully understood. Potential mechanisms by which smoking may play a role in cardiovascular events prior to the development of significant coronary artery disease (CAD) include induction of endothelial dysfunction, oxidative stress, increased bl
9、ood thrombogenicity, and an enhanced inflammatory response.Slide 2Key PointCurrent smokers have elevated levels of tissue factor (TF), which may be one of the mechanisms by which smoking is associated with increased atherothrombotic complications. TF is highly expressed in atherosclerotic plaques an
10、d its presence has been related to plaque thrombogenicity. TF may be present in the blood as well, and plays a role in the propagation of thrombosis. Acute coronary syndromes are associated with atherosclerotic lesion disruption and thrombus formation. Smoking has been implicated in both atheroscler
11、otic progression and atherothrombotic complications. The objective of this study was to evaluate whether the increased rate of atherothrombotic complications observed in current smokers, is mediated through increased circulating levels of TF. Levels of TF were assessed by adding factor X, factor VII
12、a, and calcium to plasma, and then quantifying the concentration of factor Xa (FXa). Circulating TF was reported as changes in factor FXa per unit time (pmol/L/min). Subjects who smoke 10 cigarettes per day with a smoking history of 10 years were evaluated before and 2 hours after smoking 2 cigarett
13、es. Baseline levels of circulating TF were significantly increased 2 hours after smoking 2 cigarettes (21772 pmol/L before and 283106 pmol/L/min FXa after; P=.003). The authors concluded that smoking has significant modulatory effects on plasma levels of circulating TF. Slide 3Key PointSmoking is as
14、sociated with reduced nitric oxide (NO) biosynthesis. NO is the primary vasodilatory substance produced by endothelial cells. Smokers have been noted to have impaired endothelium-dependent vasodilation (EDV). Barua et al hypothesized that reduction in NO biosynthesis contributes to the impaired EDV
15、noted in current smokers. Twenty-three male patients (15 current smokers, 8 nonsmokers) had fasting bloodwork drawn, while abstaining from smoking for a 6 to 8 hour period. Human umbilical vein endothelial cells (HUVECs) were incubated with serum from participants, and after 12 hours basal NO produc
16、tion in the supernatant was determined. NO production in the cell culture supernatant was evaluated by chemiluminscence. HUVECs incubated with current smokers serum showed significantly lower basal NO production compared with HUVECs incubated with nonsmokers serum (P30% stenosis in the left anterior
17、 descending (LAD) coronary artery or a history of variant angina, valvular heart disease, clinical evidence of heart failure, or diabetes. Intracoronary ultrasound examination was performed in 24 patients. LAD diameter was evaluated angiographically before and after a 7-mg papaverine infusion. Papav
18、erine maximally increases coronary blood flow without affecting global hemo-dynamics. Changes in LAD diameter were utilized to assess flow-dependent dilation. Flow-dependent dilation was significantly blunted in current smokers compared with nonsmokers (P.0001). When vessel segments were divided int
19、o normal and irregular segments based upon their angiographic appearance, both smoking groups demonstrated significantly blunted response in flow-dependent vasodilation compared with the nonsmoking groups (P.01). The authors concluded that long-term cigarette smoking is associated with a reduction i
20、n endothelium-dependent vasodilation, regardless of the presence or absence of coronary atherosclerotic lesions.Slide 5Key PointCurrent smokers, without evidence of significant coronary artery disease (CAD), are more likely to have epicardial endothelial dysfunction than nonsmokers. In an attempt to
21、 establish whether or not smoking is associated with coronary endothelial dysfunction and inflammation, Lavi et al evaluated 881 patients referred for evaluation of chest pain, who did not have evidence of significant CAD on diagnostic coronary angiography. Patients consisted of 115 current smokers
22、(smoking within the last month) and 766 ex-smokers and nonsmokers. Nonsmokers included both previous and never smokers. All patients underwent diagnostic coronary angiography. Microvascular coronary flow reserve was assessed after infusion with incremental doses of adenosine. Coronary vasoreactivity
23、 was assessed after infusion of incremental doses of acetylcholine. Endothelium-independent epicardial coronary artery function was assessed by the change in coronary artery diameter in response to an intracoronary bolus of nitroglycerine. All patients had baseline bloodwork prior to angiography to
24、evaluate white blood cell (WBC) count and other systemic markers of inflammation. Significantly more current smokers were found to have epicardial endothelial dysfunction, 46%, than ex-smokers, and nonsmokers, 34% and 35%, respectively. Slide 6Key PointCurrent smokers without evidence of significant
25、 coronary artery disease have significantly increased WBC counts compared with nonsmokers. Elevated WBC counts have been associated with a greater long-term cardiovascular risk. In an attempt to establish whether or not smoking is associated with coronary endothelial dysfunction and inflammation, La
26、vi et al evaluated 881 patients referred for evaluation of chest pain, who did not have evidence of significant coronary artery disease on diagnostic coronary angiography. Patients consisted of 115 current smokers (smoking within the last month) and 766 ex-smokers and nonsmokers. Nonsmokers included
27、 both previous and never smokers. All patients underwent diagnostic coronary angiography. Microvascular coronary flow reserve was assessed after infusion with incremental doses of adenosine. Coronary vasoreactivity was assessed after infusion of incremental doses of acetylcholine. Endothelium-indepe
28、ndent epicardial coronary artery function was assessed by the change in coronary artery diameter in response to an intracoronary bolus of nitroglycerine. All patients had baseline bloodwork prior to angiography to evaluate WBC count and other systemic markers of inflammation. Both total WBC count an
29、d leukocyte subtypes were higher in current smokers than in nonsmokers.Slide 7Key PointNonsmokers repeatedly exposed to cigarette smoke have platelet function similar to that of current smokers (ie, increased thrombogenicity). Schmid et al evaluated the effect of single and repeated exposure to envi
30、ronmental tobacco smoke on platelet thromboxane formation. Twenty-four subjects (12 nonsmokers, 12 current smokers) were exposed to the smoke of 30 cigarettes for 60 minutes. Blood was drawn immediately before, immediately after, and 6 hours after environmental tobacco smoke exposure, and assessed f
31、or levels of malondialdehyde, serum and plasma thromboxane B2, 11-dehydro-thrombaxane B2 as well as conversion of arachidonic acid to thromboxane B2 and hydroxy-5, 8,10-heptadecatrienoic acid . Smokers abstained from smoking for 10 hours prior to the experiment; however, they were allowed to reiniti
32、ate smoking 7 hours after the experiment was initiated. The experiment was repeated for 6 sequential days and on day 12. The above graph demonstrates that nonsmokers repeatedly exposed to cigarette smoke have platelet function similar to that of current smokers (ie, increased thrombogenicity). This
33、study also demonstrated that the effects of even brief exposure to environmental tobacco smoke (minutes to hours) are often nearly as great (averaging 80% to 90%) as the effects of chronic active smoking. Slide 8Key PointCurrent smokers have higher levels of oxidative modification in vivo than do no
34、nsmokers. F2-isoprostane level is an accurate method of detecting lipid peroxidation, and thereby oxidant injury, in vivo. In this study Morrow et al determined whether smoking induces oxidative modification by evaluating whether production of F2-isoprostanes are increased in smokers. Twenty subject
35、s (10 smokers, 10 nonsmokers) had fasting bloodwork drawn on 2 separate occasions. Participants were not allowed to smoke prior to venipuncture. The average of the 2 measurements of F2-isoprostanes are demonstrated above. Levels of free F2-isoprostanes in plasma from current smokers were significant
36、ly higher than those measured in age- and sex-matched nonsmokers (242147 and 10319 pmol/L, respectively) (P=.02). The levels of F2-isoprostanes esterified to lipids in plasma from smokers were also significantly higher than those measured in nonsmokers (574217 and 34565 pmol/L, respectively; P=.03).
37、 The authors concluded that elevated levels of F2-isoprostanes in current smokers indicate that smoking induces oxidative modification of biologic components in humans.Slide 9Key PointWhen evaluated by serial quantitative coronary arteriography, it is seen that smoking accelerates progression of exi
38、sting coronary artery disease (CAD) and new lesion formation. Waters et al evaluated 331 participants (90 current smokers, 241 nonsmokers) with angiographically documented coronary atherosclerosis and fasting cholesterol levels between 220 and 300 mg/dL, enrolled in the randomized, double-blind, pla
39、cebo-controlled Canadian Coronary Atherosclerosis Intervention Trial (CCAIT). Patients were randomized to receive either placebo or lovastatin 20 mg once daily. In an attempt to achieve a target low-density lipoprotein (LDL) cholesterol level 130 mg/dL, drug doses were increased over the initial 16
40、weeks of the trial to a maximum dose of 40 mg twice daily. Participants were evaluated over a 2-year period. Repeat angiography was performed at the conclusion of the study period (except in 21 patients in whom it was performed earlier). Baseline and follow-up coronary angiograms were compared, and
41、a change in minimal lumen diameter 0.4 mm was considered a true change (either progression or regression). A new lesion was defined as a stenosis that was not apparent on the initial angiogram or was 25% in diameter stenosis but that narrowed by 0.4 mm in minimal lumen diameter at the second angiogr
42、am. Significantly more current smokers showed evidence of progression. Progression occurred in 41 of 72 (57%) current smokers and 83 of 227 (37%) nonsmokers, P=.002. Significantly more current smokers developed new atherosclerotic lesions, 36% vs 20%, P=.007. The authors therefore concluded that coronary atherosclerosis progresses more rapidly in current smokers than in nonsmokers.
