Coronary Heart Disease Cardiovascular Disease

CAEPA฀and฀1.23฀Scientiic฀Committee฀on฀Tobacco฀and฀Health,฀SCOTH฀ [90] .฀Platelet฀ aggregation฀ induced฀ by฀ tobacco฀ smoke฀ products฀ has฀ been฀ proposed฀ as฀ the฀ mechanism฀ responsible฀for฀this฀non-linear฀dose–response฀anomaly฀ [90] . The฀purpose฀of฀studies฀by฀Pitsavos฀et฀al.฀performed฀in฀Greece฀was฀to฀investigate฀the฀ association฀between฀passive฀smoking฀and฀the฀risk฀of฀acute฀coronary฀syndromes฀ACS฀ among฀non-smokers฀ [91] .฀In฀total,฀848฀patients฀with฀the฀irst฀event฀of฀ACS฀and฀1,078฀car- diovascular฀disease-free฀matched฀controls฀completed฀a฀detailed฀questionnaire฀regarding฀ 1.5 1.0 P = 0.006 for linear trend 1.23 95 CI, 1.13−1.34 1.29 95 CI, 1.21−1.42 1.00 0.5 Level of Exposure to cigarettes [cpd] Relative Risk 1 − 19 20 1.00 P = 0.01 for linear trend 1.18 95 CI, 0.98 − 1.42 1.31 95 CI, 1.11 − 1.55 1.29 95 CI, 1.16 − 1.43 1.5 1.0 0.5 Duration of Exposure to Smoking [years] 1 − 9 10 − 19 20 Fig. 9.5 ฀฀฀Relative฀risk฀of฀ coronary฀heart฀disease฀ associated฀with฀passive฀ smoking฀among฀non-smokers฀ [84] .฀Number฀of฀cigarettes฀ smoked฀above฀and฀duration฀ of฀exposure฀below.฀95฀CI฀ 95฀conidence฀interval Studies฀included฀in฀the฀meta-analysis฀ Number฀ Relative฀risk฀95฀CI฀ p-value All฀studies 18 1.25฀1.17–1.32 0.001 Peer-reviewed฀studies 15 1.25฀1.17–1.33 0.001 Studies฀using฀death฀from฀AMI฀or฀CHD฀฀ as฀an฀outcome฀measure 14 1.24฀1.17–1.32 ฀ 0.001 Studies฀controlling฀for฀important฀risk฀฀ factors฀for฀CHD 10 1.26฀1.16–1.38 ฀ 0.001 Table 9.5 ฀฀฀Relative฀risk฀of฀coronary฀heart฀disease฀associated฀with฀passive฀smoking฀among฀non- smokers฀ [84] their฀ exposure฀ to฀ environmental฀ smoke.฀ Two฀ hundred฀ and฀ ninety-seven฀ 35฀ of฀ the฀ patients฀and฀259฀24฀of฀the฀controls฀were฀deined฀as฀non-smokers฀and฀passive฀smokers,฀ respectively.฀After฀controlling฀for฀several฀potential฀confounders,฀the฀results฀showed฀that฀ non-smokers฀exposed฀to฀cigarette฀smoke฀increased฀the฀risk฀of฀ACS฀by฀51฀OR,฀1.51;฀ 95฀CI,฀1.21–2.99฀compared฀with฀non-smokers฀not฀exposed฀to฀smoke.฀It฀was฀estimated฀ that฀34฀coronary฀events฀per฀134฀subjects฀would฀occur฀as฀a฀result฀of฀passive฀smoking฀during฀ their฀ lifetime.฀ Consequently,฀ this฀ study฀ supported฀ the฀ hypothesis฀ that฀ passive฀ smoking฀ increases฀the฀risk฀of฀developing฀ACS฀ [91] . A฀ British฀ study฀ examined฀ the฀ associations฀ between฀ a฀ biomarker฀ of฀ overall฀ passive฀ exposure฀to฀tobacco฀smoke฀serum฀cotinine฀concentration,฀and฀risk฀of฀CHD฀and฀stroke฀by฀ the฀use฀of฀a฀prospective฀population-based฀study฀design฀the฀British฀regional฀heart฀study฀ [92] .฀In฀total,฀4,729฀men฀in฀18฀towns,฀who฀provided฀baseline฀blood฀samples฀for฀cotinine฀ assay฀and฀a฀detailed฀smoking฀history฀in฀1978–1980,฀it฀was฀shown฀that฀2,105฀men฀who฀said฀ they฀did฀not฀smoke฀and฀who฀had฀cotinine฀concentrations฀14.1฀ngml฀were฀divided฀into฀ four฀equal-sized฀groups฀on฀the฀basis฀of฀cotinine฀concentrations.฀Relative฀hazards฀95฀CIs฀ for฀CHD฀in฀the฀second฀0.8–1.4฀ngml,฀third฀1.5–2.7฀ngml,฀and฀fourth฀2.8–14.0฀ngml฀ quarters฀ of฀ cotinine฀ concentration฀ compared฀ with฀ the฀ irst฀ ³0.7฀ ngml฀ were฀ 1.45฀฀ 1.01–2.08,฀ 1.49฀ 1.03–2.14,฀ and฀ 1.57฀ 1.08–2.28,฀ respectively,฀ after฀ adjustment฀ for฀ established฀risk฀factors฀for฀CHD.฀Hazard฀ratios฀for฀cotinine฀0.8–14.0฀nu฀³0.7฀ngml฀were฀ particularly฀increased฀during฀the฀irst฀3.73,฀1.32–10.58฀and฀second฀5-year฀follow-up฀peri- ods฀1.95,฀1.09–3.48฀compared฀with฀later฀periods.฀There฀was฀no฀consistent฀association฀ between฀cotinine฀concentration฀and฀risk฀of฀stroke.฀In฀conclusion,฀this฀study฀indicated฀that฀ the฀studies฀based฀on฀reports฀of฀smoking฀in฀a฀partner฀alone฀seem฀to฀underestimate฀the฀risks฀ of฀exposure฀to฀passive฀smoking.฀Further฀prospective฀studies฀relating฀biomarkers฀of฀passive฀ smoking฀to฀the฀risk฀of฀CHD฀are฀needed฀ [92] . However,฀all฀ETS-studies฀clearly฀show฀that฀ETS฀represents฀a฀smaller฀risk฀than฀active฀ smoking฀in฀terms฀of฀the฀development฀of฀CHD.฀The฀indings฀from฀a฀cancer฀prevention฀ study฀indicate฀that฀the฀risk฀of฀CHD฀for฀smokers฀is฀1.7฀times฀higher฀than฀for฀non-smokers,฀ and฀for฀women฀the฀factor฀is฀1.6฀ [93] .฀Related฀lifestyle฀variables฀in฀passive฀smokers฀must฀ be฀taken฀into฀account฀in฀a฀consistent฀manner฀if฀the฀conclusions฀reached฀are฀to฀be฀usable฀ [94,฀95] .฀Various฀studies฀suggest฀that฀passive฀smokers฀differ฀from฀non-smokers฀in฀terms฀of฀ diet฀less฀fruit฀and฀vegetables,฀more฀fat฀and฀meat฀ [96–99] .฀ETS฀causes฀increases฀in฀CO฀ and฀CO-Hb,฀whereas฀heart฀rate฀and฀blood฀pressure฀rise฀only฀minimally฀ [37] .

9.4.2 Arteriosclerosis

Cigarette฀smoking฀is฀beyond฀doubt฀a฀major฀factor฀in฀the฀development฀of฀cardiovascular฀ disease฀ [100] .฀A฀direct฀association฀has฀been฀established฀between฀carotid฀artery฀calciication฀ and฀smoking฀ [71,฀101] .฀However,฀crossover฀studies฀indicate฀that฀ETS฀exposure฀also฀corre- lates฀ with฀ atherosclerotic฀ changes฀ [71,฀ 102] .฀ The฀ Atherosclerosis฀ Risk฀ in฀ Communities฀ ARIC฀Study฀investigated฀the฀impact฀of฀active฀smoking฀and฀of฀ETS฀exposure฀on฀atheroscle- rosis฀progression฀in฀10,914฀subjects฀between฀1987฀and฀1989.฀Carotid฀intima-media฀thick- ness฀IMT฀was฀measured฀by฀ultrasound฀at฀baseline฀and฀again฀after฀3฀years,฀and฀correlations฀ were฀investigated฀with฀other฀risk฀factors฀and฀lifestyle฀variables.฀After฀adjustment฀for฀these฀ factors,฀it฀was฀compared฀with฀a฀carotid฀IMT฀in฀never-smokers฀of฀28.7฀µm;฀current฀cigarette฀ smokers฀had฀a฀50฀increase฀43.0฀µm฀and฀passive฀smokers฀had฀a฀20฀increase฀35.2฀µm฀ Fig.฀ 9.6 ฀ [103] .฀The฀most฀pronounced฀impact฀was฀detected฀in฀subjects฀with฀hypertension฀ and฀diabetes฀and฀in฀smokers฀of฀more฀than฀one฀packday.฀In฀these฀subjects,฀the฀changes฀were฀ found฀to฀be฀irreversible฀even฀after฀smoking฀cessation฀ [103] .฀Atherosclerosis฀progression฀has฀ therefore฀been฀demonstrated฀in฀response฀to฀ETS฀and฀the฀process฀is฀irreversible฀in฀heavy฀ smokers฀ [104] .฀The฀extent฀of฀atherosclerosis฀progression฀due฀to฀ETS฀is฀reported฀to฀be฀34฀ 5.9฀µm฀compared฀with฀17.1฀µm฀in฀smokers฀ [103] .฀The฀ARIC฀Study฀was฀the฀irst฀to฀dem- onstrate฀in฀a฀large฀patient฀population฀that,฀in฀contrast฀with฀non-smoking,฀ETS฀causes฀an฀11฀ progression฀in฀atherosclerosis. Differences฀in฀the฀proile฀of฀cardiovascular฀risk฀factors฀may฀potentially฀be฀due฀to฀differ- ences฀ in฀ atherosclerosis฀ progression฀ between฀ active฀ smokers฀ and฀ passive฀ smokers฀ [72,฀105] .฀All฀cardiovascular฀and฀lifestyle฀variables฀are฀less฀implicated฀than฀smoking฀in฀the฀ progression฀of฀atherosclerosis.฀After฀a฀prolonged฀smoking฀career,฀smoking฀cessation฀pos- sibly฀has฀no฀inluence฀on฀progression฀ [106] ,฀although฀other฀observations฀suggest฀that฀3–5฀ years฀after฀smoking฀cessation฀the฀risk฀of฀cardiovascular฀events฀approximates฀to฀that฀in฀ non-smokers฀ [107] . In฀terms฀of฀IMT,฀diabetic฀patients฀show฀marked฀atherosclerosis฀progression฀because฀ their฀underlying฀diabetes฀is฀already฀associated฀with฀vascular฀damage฀ [108] .฀The฀relative฀ risk฀of฀death฀from฀cardiac฀arrest฀is฀2.5฀times฀higher฀for฀smoking฀than฀for฀non-smoking฀ diabetic฀patients฀ [109] .฀Other฀studies฀also฀indicate฀that฀the฀smoking฀diabetic฀patient฀is฀at฀ extreme฀risk฀in฀terms฀of฀morbidity฀and฀mortality฀see฀Sect.฀7.4.2.2฀in฀ Chap.฀7 ฀ [110–112] . To฀date,฀however,฀no฀correlation฀has฀been฀shown฀between฀ETS฀exposure฀number฀of฀ hours฀and฀atherosclerosis฀progression฀ [113] .฀Pack-years฀of฀smoking฀are฀not฀crucial฀for฀ ex-smokers,฀especially฀since฀no฀differences฀in฀atherosclerosis฀progression฀have฀been฀found฀ in฀this฀group฀between฀ETS-exposed฀and฀non-ETS-exposed฀individuals.฀By฀comparison฀ with฀non-smokers,฀the฀effect฀of฀ETS฀exposure฀has฀been฀demonstrated.฀IMT฀is฀an฀excellent฀ marker฀of฀atherosclerosis฀progression฀ [114] . IM thickness [µm 3 years] N–E N+E P–E P+E C 5 10 20 30 40 45 25 35 15 Fig. 9.6 ฀฀฀Atherosclerosis฀ progression,฀assessed฀in฀ terms฀of฀the฀increase฀in฀ intima-media฀thickness฀of฀ the฀carotid฀artery฀within฀3฀ years,฀in฀non-smokers฀N,฀ past฀smokers฀P฀and฀current฀ smokers฀C฀and฀taking฀ETS฀ exposure฀+E฀into฀account.฀ Mean฀values฀and฀95฀ CIs฀ [103]