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1、吸煙與心血管疾病,吸煙是中國人心血管疾病的重要危險因素,高血壓 160M血脂異常 160M 糖尿病 20MIFG 20M肥胖 60M超重 200M吸煙 350M被動吸煙

2、 540M,中國NEHNS IV,冠心病—是吸煙致死疾病的前三位之一,由吸煙引起死亡的前三位疾?。簢赓Y料為:COPD>冠心?。痉蜟a國內(nèi)資料為:COPD>肺Ca>冠心病,1. Surgeoen General’s Report. Health Consequences of Smoking; 2004. 2. J Natl Cancer Inst. 1993;85(24):1994. 3.

3、 Crane. Cancer Epidemiol Biomarkers Prev. 1996;5(8):639. 4. Miligi. Am J Ind Med. 1999;36(1):60. 5. Roman. Cerebrovasc Dis, 2005;20(Suppl 2):91. 6. Willigendael. J Vasc Surg. 2004;40:1158. 7. Yang. BMJ. 1999;319:143,

4、內(nèi)皮功能紊亂血栓生成增加炎癥反應(yīng)加強(qiáng)氧化修飾,Lavi et al. Circulation. 2007;115:2621-2627; http://www.texasheartinstitute.org/HIC/Topics/Diag/diangio.cfm. Accessed June 14, 2007.,右冠狀動脈粥樣硬化,吸煙促發(fā)心血管疾病的發(fā)病機(jī)理,組織因子(TF)在動脈粥樣硬化斑塊有高表達(dá),這可能在血栓形成中發(fā)揮重要作

5、用TF 水平以 Xa因子 (FXa)進(jìn)行評價吸煙者與非吸煙者比,循環(huán)中TF活性遠(yuǎn)高于后者,Sambola et al. Circulation. 2003;107:973-977.,Factor Xa (FXa) pmol/L/min,P=.003,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

6、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,217,283,0,100,200,300,400,吸煙者吸煙前(2支煙),吸煙者吸煙后(2支煙),,吸煙使血栓生成增加,Barua et al. Circulation. 2001;104:1905-1910.,吸煙使一氧化氮生物合成減少,Zeiher et al. Circulation. 1995;92:109

7、4-1100.,P<.01,P<.001,P<.01,,,,,吸煙者,P<.01,,,不吸煙者,P<.01,,,與不吸煙者相比,吸煙者根據(jù)流量調(diào)節(jié)的內(nèi)皮血管舒張功能明顯減弱,,,動脈造影正常的吸煙者,動脈造影不正常的吸煙者,,,動脈造影正常的不吸煙者,動脈造影不正常的不吸煙者,,流量調(diào)節(jié)的內(nèi)皮血管舒張功能%,吸煙使血管內(nèi)皮舒張功能受損,Lavi et al. Circulation. 2007;115:26

8、21-2627.,與不吸煙者相比,吸煙者更容易發(fā)生心外膜內(nèi)皮功能障礙,46%,34%,35%,內(nèi)皮功能障礙%,吸煙致心外膜血管內(nèi)皮功能障礙,,,,,,,,,白細(xì)胞計(jì)數(shù)升高與更高心血管事件風(fēng)險相關(guān)與不吸煙者相比,吸煙者的白細(xì)胞計(jì)數(shù)明顯升高,Lavi et al. Circulation. 2007;115:2621-2627; Stewart et al. Circulation. 2005;111:1756-1762,,,,,,,P&

9、lt;.0001,P=.03,P<.0001,P<.0001,吸煙者,戒煙者,白細(xì)胞,中性粒細(xì)胞,淋巴細(xì)胞,單核細(xì)胞,,,,,,不吸煙者,,細(xì)胞計(jì)數(shù),109/L,吸煙使白細(xì)胞計(jì)數(shù)升高,ns=not significant. a Unless marked as “ns,” differences for each value between groups were statistically significant at

10、a level of P<.05. Schmid et al. Thromb Res. 1996;81:451-460.,不吸煙者,吸煙者,,,,,pg/mLa,11-脫氫血栓烷素B2,,,ns,ns,ns,Min/10° Plateletsa,丙二醛,天,,,ns,ns,ns,ns,ns,ns,ns,ns,ns,ns,天,被動吸煙的人血小板聚集功能與吸煙者接近,吸煙使血小板聚集功能增強(qiáng),異構(gòu)前列腺素F2 水平是體內(nèi)脂

11、質(zhì)過氧化反應(yīng)的指標(biāo)The dots representing subjects who smoked are each connected to a dot representing a nonsmoker matched to the subject for age and sex.Adapted from Morrow et al. N Engl J Med. 1995;332(18):1198-1203.,,,,640,,56

12、0,,480,,400,,320,,240,,160,,80,,吸煙者,,不吸煙者,,,,1000,,900,,800,,700,,600,,500,,400,,300,,吸煙者,,不吸煙者,自由異構(gòu)前列腺素F2,pmol/L,酯化異構(gòu)前列腺素F2,pmol/L,吸煙增加氧化修飾,吸煙與心血管疾病的流行病學(xué),,吸煙流行10年后出現(xiàn)吸煙相關(guān)疾病的流行,吸煙與冠心病 (CAD),Waters et al. Circulation. 1996

13、;94:614-621.,已有病變加重的發(fā)生率,吸煙者,非吸煙者,新病變發(fā)生率,吸煙者,P=.002,P=.007,57,37,36,20,非吸煙者,患者百分率%,患者百分率%,吸煙加重動脈粥樣硬化,aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the eve

14、nt in nonexposed people. Adjusted for age.Willett et al. N Engl J Med. 1987;317(1):1303-1309.,1.0,1.6,2.6,2.0,1-14/日,非吸煙者,15-24/日,?25/日,吸煙者每日吸煙量,,相對風(fēng)險可信區(qū)間,95%,吸煙增加心絞痛風(fēng)險,與非吸煙者相比,吸煙者發(fā)生急性非致死性心梗的風(fēng)險增加3倍。,aThe ratio of the

15、odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.Teo. Lancet. 2006;368:647-658.,年齡<40 y,年齡40-49 y,年齡50-59 y,年齡60-69 y,年齡>70 y,,,,,,,,支/日?20,非吸煙者,戒煙者,1-1

16、9支/日,,,,,,,,風(fēng)險比可信區(qū)間,95%,吸煙增加急性非致死性心梗的風(fēng)險,Y usuf S et al . Lancet. 2004;364:937-52,OR (99% CI),每日吸煙量與心肌梗死發(fā)生有量效關(guān)系,a The probability of an event (developing a disease) occurring in exposed people compared with the prob

17、ability of the event in nonexposed people. Adjusted for age.Willett et al. N Engl J Med. 1987;317(21):1303-1309.,致死冠心病的相對風(fēng)險,1-14/日,非吸煙者,15-24/日,?25/日,吸煙者每日吸煙量,,相對風(fēng)險可信區(qū)間,95%,吸煙增加冠心病死亡風(fēng)險,aThe probability of an event (de

18、veloping a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age.Wannamethee et al. Circulation. 1995;91:1749-1756.,,,,,,,,,,,,,,,,,,,,,,,,,,,1.0,2.3,0.0,

19、1.0,2.0,3.0,4.0,不吸煙者,吸煙者,吸煙增加心源性猝死的風(fēng)險,aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for the baseline variables s

20、ignificantly associated with each end point.Hasdai et al. N Engl J Med. 1997;336:755-761.,Q波心梗 (MI),,,,1.0,1.28,2.08,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0.

21、0,1.0,2.0,3.0,4.0,不吸煙者,戒煙者,吸煙者,吸煙使冠脈介入治療后發(fā)生Q波心梗的風(fēng)險增高,被動吸煙與冠心病,Adjusted for age, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL cholesterol, FEV, height, preexisting CAD, body mass index, trigly

22、cerides, white cell count, diabetes, physical activity, alcohol intake, and social class. aLight active refers to men smoking 1-9 cigarettes a day. bHeavy passive refers to upper three quarters of cotinine concentration

23、 combined (0.8 to 14.0 ng/mL). cLight passive refers to lowest quarter of cotinine concentration among nonsmokers (0-0.07 ng/mL). Whincup et al. BMJ. 2004;329:200-205.,被動吸煙增加冠心病發(fā)生風(fēng)險,aThe ratio of the odds of development

24、 of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for age, sex, region, physical activity, and consumption of fruits, vegetables, and alcohol. Adapted from Teo et al. La

25、ncet. 2006;368:647-658.,被動吸煙暴露持續(xù)時間(小時/周),無,1-7,8-14,15-21,?22,4,2,1,0.75,,,,,,,,被動吸煙使發(fā)生非致死性心梗的風(fēng)險量級增加,被動吸煙增加急性心梗發(fā)生風(fēng)險,吸煙與腦卒中,大量吸煙后急性作用:腦血管急性血栓形成,腦核磁共振像 急性缺血性腦卒中,Goldstein et al. Stroke. 2006;37:1583-1633; http://www.ucih

26、s.uci.edu/stroke/whatisastroke.shtml. Accessed October 19, 2007.,吸煙增加急性缺血性卒中風(fēng)險,無論是主動還是被動吸煙都會加快頸動脈粥樣硬化,aAdjusted for demographic characteristics, cardiovascular risk factors, and lifestyle variables (risk factor model and

27、 Keys score, education, leisure activity, body mass index, and alcohol use). bTo environmental tobacco smoke.Howard et al. JAMA. 1998;279(2):119-124.,吸煙者,不吸煙者且無被動吸煙b,43.0,38.8,31.6,32.8,25.9,不吸煙者但有被動吸煙b,戒煙者且無被動吸煙b,戒煙者有被

28、動吸煙b,頸動脈內(nèi)膜中層厚度增加,μm/3年,吸煙促進(jìn)頸動脈粥樣硬化進(jìn)展,aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age, follow-up period, hi

29、story of diabetes, hypertension, high cholesterol levels, and relative weight (in 5 categories).Colditz et al. N Engl J Med. 1988;318(15):937-941.,青年、中年女性,發(fā)生腦卒中的風(fēng)險可能與吸煙量相關(guān),吸煙增加致命性和非致命性腦卒中風(fēng)險,aThe probability of an event

30、(developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people.Adjusted for age, exercise, alcohol consumption, body mass index, history of hypertension, and history o

31、f diabetes. Kurth et al. Stroke. 2003;34:2792-2795.,,,,不吸煙者 (n=20,339),每日吸煙量少于15支 (n=1914),每日吸煙量多于15支 (n=3265),吸煙增加出血性卒中風(fēng)險,aTwenty-year age-adjusted mortality per 10,000 person-years for men. P<.014 for trend. Ha

32、rt et al. Stroke. 1999;30:1999-2007.,吸煙增加腦卒中死亡風(fēng)險,吸煙與外周血管疾病 (PVD),吸煙使發(fā)生PVD的時間早10年吸煙使發(fā)生PVD的風(fēng)險增加10-16倍,高于冠心病的發(fā)生風(fēng)險吸煙與下列血管疾病的風(fēng)險增加有關(guān):無癥狀的 PVD間歇性跛行PVD的進(jìn)展因PVD并發(fā)癥引起的截肢股幗動脈旁路失敗血管手術(shù)后的死亡,,Freund KM, The Framingham Study: 3

33、4 years of follow-up. Ann Epidemiol 1993; 3:417-424,吸煙增加外周血管疾病危險,吸煙促進(jìn)主動脈擴(kuò)張吸煙增加主動脈瘤死亡風(fēng)險,Witteman JC,. Circulation 1993; 88:2156-2162Wilmink TB, J Vasc Surg 1999; 30:1099-1105,吸煙與主動脈瘤發(fā)生有量效關(guān)系,戒煙對心血管的益處,戒煙對心血管益處的病理生理

34、機(jī)制,長期吸煙者戒煙2周后,纖維蛋白原濃度和纖維蛋白原的合成速率均明顯減低,ASR=absolute rate of fibrinogen synthesis. aAbstention period of 2 weeks. Hunter et al. Clin Sci (Lond). 2001;100(4):459-465.,P<.001,P<.001,吸煙,戒煙a,16.1,24.1,2.49,3.06,吸煙,戒煙a,血

35、漿纖維蛋白原濃度,g/L,纖維蛋白原絕對合成速率,(ASR),mg/kg,戒煙使纖維蛋白原下降,aAbstention period of 17 weeks.Eliasson et al. Nicotine Tob Res. 2001;3(3):249-255.,戒煙使白細(xì)胞計(jì)數(shù)明顯降低,aQuit smoking for 28 days. bResumed smoking after quitting for 14 days.AD

36、P=adenosine diphosphate. ADP is a platelet aggregation agonist.Morita et al. J Am Coll Cardiol. 2005;45:589-594.,戒煙使血小板聚集率下降,HDL=high-density lipoprotein; LDL=low-density lipoprotein. aAbstention period of 17 weeks. E

37、liasson et al. Nicotine Tob Res. 2001;3(3):249-255.,低密度脂蛋白 (mmol/L),戒煙使血脂改善,戒煙可改善脂蛋白構(gòu)成,包括高密度脂蛋白升高,低密度脂蛋白降低,增強(qiáng)指數(shù) (%)b,,aProvides an assessment of small arteriolar compliance. bThe amplitude of the reflected wave depends o

38、n the stiffness of the small vessels and large arteries and thus provides a measure of systolic arterial stiffness.cAbstention period of 6 months. Oren et al. Angiology. 2006;57(5):564-568.,P<.05,63.1,50.6,吸煙,戒煙c,戒煙使

39、動脈順應(yīng)性改善,a Abstention period of 6 months. Oren et al. Angiology. 2006;57(5):564-568.,心率 (Beats/min),P<.05,吸煙,戒煙a,戒煙使血液動力學(xué)改善,戒煙對心血管益處的流行病學(xué),1. CDC. Surgeon General Report 2004 2. American Cancer Society. Guide to Quitt

40、ing Smoking2006,,肺功能改善減少咳嗽鼻竇充血呼吸急促等,3個月,,肺Ca發(fā)生率是繼續(xù)吸煙者的30-50%,CAD危險減少50%,CAD危險與正常不吸煙者相似,卒中危險恢復(fù)到正常不吸煙者水平,,,,,,1年,5 年,10 年,15 年,戒煙,戒煙使冠心病風(fēng)險減少,aThe ratio of the odds of development of disease in exposed persons to the odds o

41、f development of disease in nonexposed persons. Adjusted for sex, region, diet, alcohol, physical activity, consumption of fruits, vegetables, and alcohol.Adapted from Teo. Lancet. 2006;368:647-658.,P<.0001,吸煙者,>1

42、-3,>5-10,>10-15,?20,戒煙者 (戒煙年數(shù)),>3-5,>15-20,,4,2,1,,,,,,,,戒煙數(shù)年后,發(fā)生急性心梗的風(fēng)險明顯降低,戒煙使急性心梗風(fēng)險降低,與吸煙者相比,冠狀動脈介入治療后戒煙者整體死亡風(fēng)險明顯下降,生存率 (%),100,80,60,40,20,0,,,時間(年),,,Hasdai. N Engl J Med. 1997;336(11):755-761.,戒煙者,,持續(xù)吸煙

43、者,,戒煙使冠狀動脈介入治療后死亡率下降,對戒煙的生存收益進(jìn)行評估,戒煙5年,生存率提高3%,戒煙5年可提高10%,戒煙15年則可提高15%。,Adapted from van Domburg et al. J Am Coll Cardiol. 2000;36(3):878-883.,生存概率 (%),0,5,10,15,,,,,,,,20,年,P<.0001 (戒煙者 vs 吸煙者),,,,不吸煙者,持續(xù)吸煙者,,,100,80

44、,60,40,20,0,,戒煙者,,戒煙使冠狀動脈旁路移植術(shù)后死亡率減低,對于心梗后左心室功能異常的患者,戒煙可使心律失常造成死亡風(fēng)險降低,Peters et al. J Am Coll Cardiol. 1995;26(5):1287-1292.,P=.040,生存時間(年),,,戒煙者,,吸煙,,生存率%,戒煙使心律失常死亡風(fēng)險減少,戒煙者與持續(xù)吸煙者相比,反復(fù)發(fā)生心臟驟停風(fēng)險明顯降低,aAbstention period of 3

45、 years. Hallstrom et al. N Engl J Med. 1986;314:271-275.,,3年內(nèi)發(fā)生率 (%),P=.038,,心臟驟停反復(fù)發(fā)作,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,27,19,0,5,10,15,20,25,30,吸煙者,戒煙者,a,戒煙使心臟驟停風(fēng)險減低,Jonason et al. Acta Med Scand. 1987;221:253-260.,年,,,累積靜息

46、痛 (%),30,20,10,0,,,,,,,,,P=.049,,,,,,戒煙,,吸煙,,對于間歇性跛行(IC)患者,戒煙可減緩?fù)庵苎懿〉倪M(jìn)一步加重。,戒煙使外周血管疾病癥狀改善,aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in non

47、exposed people. Adjusted for age and treatment assignment.Robbins et al. Ann Intern Med. 1994;120(6):458-462.,與持續(xù)吸煙的患者比較,戒煙者非致死性腦卒中的發(fā)生風(fēng)險降低,戒煙使卒中風(fēng)險降低,,全因死亡降低約15-20%,CVD死亡降低約25-35%,1。Kawachi, 1993. 2. Lievre, 2000. 3. Vr

48、cer, 2003,戒煙1,降壓2,降膽固醇l3,,,,,,,,,,戒煙1,,0,.,1,0,.,4,0,.,7,1,.,0,1,.,3,1,.,6,1,.,9,,,,,,,,,,,,,,,,,,全因死亡,降膽固醇3,降壓2,CVD死亡,戒煙、降壓、降膽固醇對無CVD史者死亡的影響,全因死亡降低約12-35%戒煙所致的風(fēng)險降低最大,戒煙1,降壓2a,降壓2b,降膽固醇4,,0,.,1,0,.,4,0,.,7,1,.,0,1,.,3

49、,1,.,6,1,.,9,,,,,,,,,,,,,,,,,,,,,,,,,,,降膽固醇3,,1. Critchley, 2003. 2. BPLTTC, 2003. 3. Vrercer, 2003. 4. CTT, 2005,全因死亡,,戒煙、降壓、降膽固醇對有CVD史者死亡的影響,戒煙$ 2,000 – 6,000降血壓藥物$ 9,000 – 26,000降血脂藥物$ 50,000 – 196,000,平均

50、每挽救一個生命年(人年)的成本:,Benowitz, Prog Cardiovasc Dis, 2003;46:91,戒煙是降低心血管風(fēng)險最經(jīng)濟(jì)的干預(yù)方式,短期益處? 纖維蛋白原濃度下降? 纖維蛋白原合成速率減低? 白細(xì)胞計(jì)數(shù)下降高密度/低密度脂蛋白比例改善? 卒中風(fēng)險降低? 高密度脂蛋白增加? 低密度脂蛋白下降動脈壓? 心率下降動脈順應(yīng)性改善? 心梗后心律失常所致猝死風(fēng)險減低? 血小板體積減小血小板環(huán)磷酸腺苷

51、反應(yīng)增強(qiáng),促使前列腺素E1 發(fā)生腺苷酸環(huán)化? 吸煙導(dǎo)致的血小板聚集減少,長期益處減少下列風(fēng)險卒中 重復(fù)冠脈搭橋術(shù) 心梗后反復(fù)發(fā)生冠脈事件心梗后心律失常所致猝死繼發(fā)心血管疾病 冠脈搭橋術(shù)后血運(yùn)重建術(shù)減少 冠脈搭橋術(shù)后的死亡率經(jīng)皮冠狀動脈成形術(shù)后死亡率與心血管疾病進(jìn)展相關(guān)的炎癥標(biāo)志分子水平(C反應(yīng)蛋白, 白細(xì)胞, 纖維蛋白原),Twardella et al. Eur Heart J. 2004;25:2101-2

52、108; Morita et al. J Am Coll Cardiol. 2005;45:589-594; Oren et al. Angiology. 2006;57:564-568; Terres et al. Am J Med. 1994; 97:242-249; Nilsson et al. J Int Med. 1996; 240:189-194; Peters et al. J Am Coll Cardiol. 1995;

53、26:1287-1292; Rea et al. Ann Intern Med. 2002;137: 494-500; Hasdai et al. N Engl J Med. 1997;336:755-761; van Domburg et al. J Am Coll Cardiol. 2000; 36:878-883; Bakhru et al. PLoS Med. 2005;2:e160; Eliasson et al. Nicot

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