a Cigarette Yield and the Risk of Myocardial Infarction in Smokers William H. Sauer, MD; Jesse A. Berlin, SeD; Brian L. Strom, MD, MPH: Carolyn Miles, MPH: Jeffrey L. Carson, MD; Stephen E. Kimme Background: Although cigarette smoking is amajorrisk factor for acute myocardial infarction (MI), cigarette tar yield has not been clearly demonstrated to affect MI risk, Methods: A case-control study of first MI in smokers aged 30 through 65 years was conducted among 68 hos- pilals in an 8-county area during a 28-month period. Case subjects were smokers hospitalized at any ofthe area hos- pitals with a first ML. Approximately 4 community con- trol smokers percase subject were randomly selected from the same geographic area using random digit dialing. De- tailed data on smoking history and cigarette brand were collected Results: We identified 587 case subjects and 2685 con- trols who smoked cigarettes with known tar yields. AE ter adjustment using multivariable logistic regression, the ‘xs ratios (ORs) for subjects smoking medium-and high- I, MD, MSCE compared with low-tar-yield cigarettes were 1.86 (05% confidence interval [Cl], 1.21-2.87) and 2.21 (05% C 1.47-3.34), respectively. The adjusted OR increased as tar per day intake increased (P<.001 for the trend): compared with the lowest category of tar per day, the ORs (05% Cls) for increasing tar per day were 1-16 (0.83-1.62), 1.85 (1.35-2.52),2.42 (1.54-3.78), and 2.50 (1.78-3.52), There was a similar trend of increasing (ORs as tar per day increased in smokers of lower-yield cigarettes (P<.001 for the trend) and when low-yield, ‘cigarette smokers were excluded (P<.001 forthe trend). Conclusions: Smoking higher-yield cigarettes is asso- ciated with an inereased risk of MI, and there isa dost response relationship between total tar consumption per day and ML “Arch Intern Med. 2002;162:300-306 From the Department of. Medicine, Cardiovascular Divison (Drs Sauer and Kimmel), Division of General Internal Medicine (Dr Strom), and the Cente or Clinical Epidemiology and Biostatistics ‘and Department of Biostatistics ‘and Epdemiology (Drs Beri, ‘Strom, and Kimmel and Ms Miles), University of Pemsylvania School of Medicine, Philadelphia Department of Medicine Divison of General internal Medicine, University of Medicine and Dentistry of New Jersey, New Brunswick (Dr Carson) list of study participants appears on page 5a. (aepnureD) SRCHINTERN WEDIVOL 1, FENTT SmT INCE THE FIRST observational study linking tobacco and heart disease In 1940," nu- merous studies have con- firmed the association be- tween cigarette smoking and an increased risk of myocardial infarction (MD) Smok- ing cessation dramatically decreases this risk to the level of nonsmokers within 3 years.** Despite these compelling data ‘and great ellorts by public health offi- cials io educate smokers, an estimated 1.1 billion people worldwide continue to smoke.” Regulatory efforts to limit the tar and nicotine content of cigarettes have been proposed in many countries," based primarily on the effects of higher ciga- rete yield on the risk of malignancy” and mortality rom some smoking-related di ceases, Several countries have recently adopted or proposed legislation that lim- its the amount of arand nicotine in eiga- retes,"*"" and the European Union, which already has a 12-mg tar limit, recently passed legislation that will reduce the up- per limit of tar to 10 mg.” Similar regu- lations have not heen enacted in the United Slates: While reductions in cigarette yield (cg, reductions in nicotine, carbon mon- oxide, and tar) may reduce the risk ofsome smoking-related malignancies," the fects on Mlare unknown, Because the ab- solute increase in risk of MI from eiga- rette smoking is greater than that for lung cancer, a better understanding of the fects of cigarette yield on MI risk is eriti- cally important to worldwide regulatory efforts. Although prior investigations have failed to identily a clear difference in MI risk by cigarette yield,"2""! most of these studies were performed more than a de- cade ago, belore low-tar cigarettes be- ‘came popular, and therefore may have hhad limited ability to detect an hhigher- vs lower-yield cigarettes." only study to suggest an increase in the oc- currence of nonfatal MI {rom higher- lar-yield cigarettes did not specifically include data for smokers of the lowest- yleld cigarettes.* Therefore, the specific ‘ims of this case-control study were to (©2002 American Medical Association, All rights reserved. ‘Downloaded From: http:/archinte jamanetwork.com/pdfaccess.ashx?urt=/data/journals/intemed/S304/ on 0309/2017SUBJECTS AND METHODS SOURCE POPULATION We performed a case-control study of Ml in smokers from an 8-county region of eastern Pennsylvania (Philadelphia, Montgomery, Bucks, Chester, Delaware, Camden, Glouces” ter, and Burlington counties) The primary objective ofthe study was to examine the effect of nicotine patch expo- sure and the risk of ML in smokers" This study also col- lected detailed information on smoking habits and there- fore permitted a secondary posthoc evaluation ofthe role of tar yield in ML IDENTIFICATION AND DEFINE (OF CASE SUBJECTS 1ON Cave subjects werebetween the agesof30and 65 years with Sis Ml who were hospitalized at any ofthe 68 acute care hospitals inthe & county region from September 1995 through December 31,1997. To maximize the complete ness of case subject identification, hosptal-specii sys tems of ase subject ascertainment were developed, andthe erson responsible for cae subject ascertainment a each Rospital was comacted on atleast a monthly bass. ‘Acute Al was defined using the citeri from the Min- nesota Heatt Survey” Of potentially eligible subjects (N=778), 84% had thelr medical records reviewed for con- fnmaton oftheir Ml. and 85% had Mis that met the study titra, Given this high rate of confirmation, the 140 el- file subjects for whom charts were not avalale are i Eladed inthe primary analyses; a separate analyse ex- cluded these subjects. Subjects were excluded if (1) they were not current smokers (defined as abstinence fom cigarettes or at less T'veek prior to their Ml); (2) they had the ML as 2 com plication ofa hospalization fra different condition Cg, posopeatve) ©) they had roe MI: they were preg fant or currently nursing (an exclusion criterion used tn the primary dataset"). (3) they did not have telephones ordid not speak English; () they didnot vein Lathe 8 Counties of (7) the brand of cigarette smoked by the par ticipant was not tested bythe Federal Trade Commission “Th prtcpation rte among elighle ace subjects wa ‘69%; among all potential ease subjects (known eligible and potently eligi) patipation vas extimated to Be 01%." ‘Thecharts of 49 nonpatepant cligblecase subjects (79% ofthe known eligible nonpartcipans) were reviewed to collect ase demographic information (age, sex, and insurance) The ony diference between percipants and sionparticipants wae insurance status (P01), wth non- Pattlipante more likely tobe receiving medical asistance {sass 5.10) IDENTIFICATION AND SELECTION OF CONTROLS Approximately 4 community control subjects were se- lected fr each case subject using a modification ofthe Wales berg random digit dialing method.” Each randomly de- rived telephone number was dialed up to 9 times attempts ‘each during the day, evening, and weekend) to maximize participation and avoid th bis of using daytime only cll Any household with 9 subject who relused to participate received up to 2 follow-up “conversion” telephone calls, AT there was more than 1 cligble person living in a single household, one was chosen st random. Contels were be- tween the ages of 30 and 65 yeas and were subject tothe same exclusion criteria as cave subjects “The participation rate among known cligible con trols was 51%, A study was prforined to esuimate the use of nicotine patches (one marker of trying to qult smoke ing) among nonparipants Of the 214 subjects who r= fused to parclpae, 85 agred to answer 2 questions, which wwerenot specited untl the subject agreed, shout patch use Two (4%, 95% confidence interval [Cl], 03%8,2%) of theBhad uscd a nicotine patch within the prior wee com- pared with 1.0% (95% Cl, 0.7%) of participant Controle = DATA COLLECTION Exposure and covariate data were collected using a struc tured telephone interview for both cae subjects and con- trols, The study hypothesis was not revealed o subject t anytime. To maximize the vallty of exposure informa tion, case subjects were interviewed ony if they could be reached within 6 months of thei Ml. Controle were also interiewed only within 6 months of being denied to pre- tent the potent selection Bas that could result i sub- jects who could not be reached within this ime frame dif- fered from those who could. Detailed information wis chained regedingcbaceo use including most recent brand of egarette smoked, frequency and duration of smoking, and prior atemps to qui) and other clinical and demo- fraphic characteristics all data were collected relative to thndex dat: the date of Ml for cae subjects and the date of the telephone interview for controls CIGARETTE YIELD CLASSIFICATION, ‘Tar yield was used asa measute of cigarette yield because (D tis direely proportional to the amount of nicotine catbon monoxide, and other potentially toxic substances produced by a cigarette; (2) isthe measure being used for regulatory limitations in many countries"; and (3) itis the basis forthe labeling of cigarettes as ultralight, light, oF regular The tar yield of each brand of eigarettes smoked by. patients was determined from data published by the Fed tral Trade Commission” From these data, 3 categories of cigarettes (low tar, medium tr, and high tat) were derived which correspond to ultralight (=6 mg of tar), light (7-12 mg), and regular (>12mg)-A measure of ar consumed per day also was calculated foreach participant by multiplying the tar yield ofthe cigarette smoked by the quantity of cigs reltes smoked per day during the week prio to the index date. Quintiles were created to ensure an equal number of control group participants in each eategoy. STATISTICAL ANALYSIS, The odds ratio (OR) was used to estimate the relative risk. of MI from smoking higher-yield cigarettes vs lowe Yield cigarettes, Multivariable logistic regression analysis was performed to control for possible confounding. The method of Hosmer and Lemeshow" demonstrated good fit for all models (P>.05). The multivariable model included. Continued on next page (wePRINTED) RRCHINTERN WEDIVOU 16, ENT oOo (©2002 American Medical Association, All rights reserved. ‘Downloaded From: http:/archinte jamanetwork.com/pdfaccess.ashx?urt=/data/journals/intemed/S304/ on 0309/2017variables that are known risk factors for Ml and any potential confounding variable that changed the rude OR by more than 10% after adjustment ‘These covariates included sociodemographic and Iiestyle traits (age, sex, race, any degree of exercise within the past year, vitamin use, education, years smoking, and number of cigarettes smoked per day luring the index week) and clinical characteristics (body mass index; history of coronary disease, hypertension, diabetes mellitus, or hypercholesterok- ‘emia; and any family history of coronary disease). (Other potential confounding variables tested (total household income, marital status, caffeine and alco- hol consumption, type of insurance, prior attempts to quit, use of any nicotine replacement therapy, aspirin or B-blocker use, patient concerns for MI and a validated physical activity score) did not sig- nificantly affect any of the tar-yield ORS and were therefore not included, Dose-response relationships were tested by in- cluding the tar variables, both as continuous and eat- tegorical variables, in multivariable models. Addi- tonal quadratic terms were included to test for nonlinearity. Separate analyses using nicotine or car- hhon monoxide instead of tar asa marker for cigarette yield produced similar results. Analyses including any Subject who smoked within the last year, sing the ie- time average smoking frequency asa.covariate and ex cluding the 140 case subjects with unverified ML, were performed with no meaningful change in the results Ih addition, interactions were tested between each variable and ar yields; none was significant (P>.10) Satistcal analyses were performed using the SPSSsta- Ustcal program (version 9.0, SPSS Inc, Chicago I) and statistical significance was defined as a 2-sided Prvalue lower than 5. determine if smoking higher-yield cigarettes is associ ‘ated with an increased risk of first nonfatal MI and to ex famine the contribution of tar yield to MI risk. HZ! (CHARACTERISTICS OF STUDY PARTICIPANTS A total of 609 eligible case subjects and 2739 eligible con- trols were identified. Of these, 22 case subjects and 54 controls were excluded because they smoked cigarettes with unknown tar yields. The characteristics of smok- cersin the control group, listed by type of cigarette smoked, are given in Table 1 ASSOCIATION BETWEEN CIGARETTE TYPE AND MI Inthe unadjusted analysis, smokers of medium- and high- yleld cigarettes had a higher OR for MI than low-yield, smokers (Table 2). The confounding variables that in- creased the ORs alter adjustment were age, quantity smoked per day, and history of diabetes, coronary ar- tery disease, hypertension, or hypercholesterolemia. The (aepnureD) SRCHINTERN WEDIVOL I, FENTT SOT ‘confounders that decreased the ORs afleradjustment were vitamin use, education, and exercise, After adjustment for all confounders, the ORs increased for smokers of medium-and high-yield cigarettes, and the associations remained significant (Table 2). When we controlled for all sociodemographic and lifestyle factors, the ORs for smokers of medium- and high-yield cigarettes in- creased relative to the unadjusted results: 1.61 (95% C 1.09-2.39) and 2.00 (95% Cl, 1.38-2.01), respectively. When we controlled forall clinical factors, the ORs also Increased (medium-yield OR, 1.95; 95% Cl, 1.29-2.95; high-yield OR, 2.67; 05% Cl, 1.81-3.02) DOSE-RESPONSE RELATIONSHIP BETWEEN TAR AND MI Tar Yield per Cigarette The association between tr yield per cigarette (using quin- tiles) and MI is given in Table 3. Compared with the lowest group (=5 mg tar), the multivariable-adjusted ORs for each of the categories of tar were sequentially higher (P<.001 for the trend). When tar yield was treated as a ‘continuous variable, the estimated risk for ML increased, by 496 for each I-mg increase in tar yield (adjusted OR, 1.04; 05% C1, 1.01-1.06; P=.002). In addition to this lin- ‘ear association, there was a nonlinear relationship for con- tinuous tar (adjusted for quadratic term, B=-0.003; SE=0.0015; P=.05), Tar Dose Per Day There was a significant increase in ORs with increasing lar consumption per day within each subgroup of eiga- rette type (Figure). This trend was also seen in the un- adjusted analysis for each individual subgroup of smok- ters (low, P=.002; medium, P<.001; high, P<.001). Multivariable adjustment did not alter the results for ‘smokers of medium-tar (P=,005) or high-tar (P=.01) ciga- rettes; however, we could not fit reliable multivariable models for smokers of low-tar cigarettes because of the small number of exposed individuals in the higher-tar- per-day categories within this group, iim STUDY RESULTS, Using tar as a marker for cigarette yield, the results of| this study show that smoking higher-yield cigarettes is associated with an increase in the odds of MI. In addi lion, increasing amounts of tar inhaled per day was as- sociated with increased risk. Although a dose-response relationship between smoking and risk for MI has been clearly demonstrated in previous studies,** this reation- ship was only explained in terms of the number of ciga- rettes smoked per day. The results of our study demon- strate that, among people smoking the same number of cigarettes per day, tar yield isan independent risk factor for MI, and that people who consume more tar, egard- less of cigarette type, have an increased risk for ML (©2002 American Medical Association, All rights reserved. ‘Downloaded From: http:/archinte jamanetwork.com/pdfaccess.ashx?urt=/data/journals/intemed/S304/ on 0309/2017Table 1. Characteristics of Smokers Inthe Control Group gare Nae charter (w= 302) (2927) (a= 1430) gma 4423 138 Ost. 107 1637208 Nite, mg 048 20130 07700088 1.188 0.40, Catbon mani, mg S17 148 toa «1.60, 187541485, Tar dos par dy, m9 9025 26248 s7o7 «10468 2073021106 (Gguets smoked por dy naa 12.10 1806 1067 18120 1201 ‘Smoking dain, 7535067 23102085 2420004 Ever atemptd to quit 253 (87 4) 7 (24) 1117 770) Age.y 45014816 42012882 wssaee Face Wie 275,014) 802 85.9) 951 (658) Back 2170) 97 (105) 438,202) Other 517) 24/28) 5840) fomae sex 1 (642) 580 61.4 731 (638) koi? 2514516 2586.25.03 2645 526, Calg aducation 214,709) 492,631) 617 44) farce inthe pst year 1 632) 575 (620) 800 65.8) History of CAD 10133) (15) 34/23) Hypercolestrlomia 58192) 158165) 2201157) Hypertension 521172) 10 (15.1) 230 192) Diabetes meus 1560) 33,38) 5185) Family tory of A 125 (81. 354,82) su @74) Vian se 125 (618) 335 (5.1) 25 299) Asptin use for reventon of 13143) 38,41) 128) Nica asitans recent 0 15118) ni) Patent conrad about 120207) 228 (5.4) 498 242) “Daa are gen a5 mean «SD or number (percenage) of ska, Bl ndcates body ass index CAD, coronary aay dase: andl myocardial farcton. Murer of subjects for some arabes may ot upto tell stu poplaban because of messing or unknown dt Table 2. Assocation Between Cigarette Type and Myocardial Infarction, cases contre veibie® Mutvarabet iow ar (=8 m9) 2 302 10 Retrnca) 10 Retrnce) Medina (7-12 me) 163 or 125 088-182), 1.86 121-287) High tar (>12 mg) 32 156 189(138268) 2a (1ar33) *P.001 fr avr carparion, {Mode clude th fling peti confounding vera: pe cx rca bad massindo history of cranty sae, hypertension dabtes mais, cor yparchosttlemia ay amy story of coronary ies: nse itn the pst eat amin duran es mag, ad mnt garetts smoked per day. P= 00 or veal comparison. PRIOR INVESTIGATIONS OF TAR YIELD AND MI addition, because this study. as well as other Euro- pean studies," did not specifically include data on Thereare relatively few,and somewhat contradictory, epi-_the lowest-yield cigarettes (<6 mg), the effects of demiological data on the association between tarand MI, lower-yield cigarettes could not be studied ‘One large case-control study conducted in England Two prior studies examining yield of American ciga- concluded that smokers of medium-tar cigarettes rettes did not demonstrate an association between in- (210 mg, the highest tar yield studied) had modestly creasing yields of nicotine or carbon monoxide and MI!" increased (10%) odds for MI when compared with relative to nonsmokers, Although tar was not specili- smokers of low-tar cigarettes (=10 mg).*! Our study cally studied, the results for ta yield would be expected demonstrates not only a greater increase in risk from to be related to nicotine and carbon monoxide, as the greater than 10-mg tar yield, but also an increased risk tar yield is proportional to these compounds in all Irom even a 6-to 10-mg tar yield. The lesser OR in the cigarettes. The apparent diserepancy with our study previous study" may have resulted [rom the selection could be explained by the use of hospital-based controls of controls who were relatives of the case subjects. and of nonsmokers as the reference group in the prior These controls may have heen more likely to smoke studies." Hospitalized patients may not accurately re- similar tar-yield cigarettes because of their relation flect the general population from which our case sub- ship, potentially biasing the results toward the null. In jects were drawn, and the comparison with those who (aePRueD) ARCHINTERN WEDIVOL IE, FETT aNOE WWW ARCINTERSINED.COM, (©2002 American Medical Association, All rights reserved. ‘Downloaded From: http:/archinte jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/S304/ on 0309/2017Table 3, Assocation Between Tar Veld pe Cigarette and MyocardalInfartion servlet. m9 cases Contos utara 35 78 110 (teres) “10 (trace) Ww uo 134 091-197) 205 (1303.23), 1115 14 400 2is(14e32y 216 (13448) 1620 27 ‘008 174(120.25% 236(151-360), 0 8 51 651 (3821110) 242128456), +P. 001 fr avr comparison, “std forth ume confounding varies atin tho second fot ta Table 2. P= 006 for veal comparison; P01 fr and rettes, than participants, Although response bias is dif= ficult to assess, the information that was obtained from nonparticipant controls and case subjects suggests that this bias is unlikely. Because the prevalence of nicotine patch use among nonparticipant controls seemed to be higher than that of participants (although this could be chance finding), nonparticipant controls may have been, mote likely to attempt to quit, a characteristic associ- ated with smokers of lower-yield cigarettes in our data, In addition, although insurance status of nonpartici- pant controls is unknown, nonparticipant case subjects ‘a Rabo ‘Azle cng Eng — Hig Tare ‘owe "igh ° were more likely to be receiving medical assistance, a char- Crate acteristic that was strongly associated with smoking higher-yield cigarettes in our study. These characteris: tics of nonparticipants would falsely diminish an asso- ciation between tar yield and ML utvarabl ds ratios ware adjusted forthe same confounding varias cluding Cgaetes smoker dy. The raerance group ets who consume st han 190m apa 3. 01 forthe rnd P= 01 for alt levels; P= 001 fo the eager, excluding lon greta, P01 forthe eatpary excluding high figuras; and P00 or ightar cartes ony. Bacal neat 05% anfdane mara (Cs). The asterisk cata a th pe i ofthe {8 lor the group canauring more than 450 mg ofr per day nth, catagory excluding hightareqareta smokers is 179 Uncontrolled confounding (eg, lifestyle factors and depression) is another potential limitation of our study. thas been postulated that the low-yield-cigarette smok- ing population is likely to choose this type of cigarette as 4 way to minimize the damaging health conse- ‘quences of smoking” and that the marketing of low-tar cigarettes targets more educated and health-conscious have never smoked may have diminished any relative smokers." However, adjustment for numerous markers dose-response relationship that cigarette yield has among, smokers. Inaddition, these studies were conducted more than 10 years ago, when low-tar cigarettes were only be- sinning to gain popularity. Most of the smokers of the lowest-yield cigarettes were likely to have recently switched to these brands, pethaps preventing.a clear dis- Lunction from smokers of higher-yield cigarettes. POTENTIAL LIMITATIONS The potential limitations of observational research and secondary post hoc analyses must be considered in in- terpreting the results ofthis study. Because this study only included patients with nonfatal MI, we cannot draw con- clusions regarding fatal Mis. A false association could be created if smokers of lower-yield cigarettes were more likely to develop silent MI oF sudden death after an ML However, there are no data to suggest that lower-yield cigarettes would increase the likelihood of developing ei ther of these clinical outcomes, and thus this potential bias is unlikely. A low participation rate could have created a false association if nonparticipant controls were more likely tosmoke higher-yield cigarettes, or ifnonparticipant case subjects were more likely to smoke lower-yleld ciga- (@epnureD) SRCHINTERN WEDIVOL I, FENTT SOT of low-risk individuals (eg, vitamin use, education, ex- cercise) did not alter the study results. In addition, low- Yield smokers may have been at higher, rather than lower, risk because they tended to have more traditional risk factors for MI. In fact, adjustment for all measured po- tential confounders increased, rather than decreased, the ORs for smokers of medium-tar and high-tar cigarettes In addition, several subanalyses, including those that ex- cluded smokers of low- and medium-yield cigarettes, con- Uinued to demonstrate a clear association between in- ‘creasing tarand ML. Therefore, uncontrolled confounding is unlikely to have explained the study results. The inability to accurately measure the amount of lar exposure of an individual smoker could have affected our results in several ways. First, we only collected information on the most recent brand of cigarette. However, we believe it is more likely that high-yield smokers would have switched to low-yield brands, diminishing the association between tar and ML Second, individual smoking behavior can alter the d livery ofthe proposed dose of ta," especially among those who switch to lower-yield cigarettes but titrate the amount of tar delivered through “vent-blocking” and other smok- ing behavior modifications.”»” This may be of greater im- (©2002 American Medical Association, All rights reserved. ‘Downloaded From: http:/archinte jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/S304/ on 0309/2017Advisory Board Members Robert Wallace, MD, chair: The University of lowa, owa City. Neal L Benowitz, MD: University of California, San Francisco Michael Crigu, MD, MPH: University of California San Diego School of Medicine, La Jolla. Paul D.Stlley, MD, MPH: Uni- versity of Maryland School of Medicine, Baltimore. Stephen Walter, PD: MeMaster University Health Sciences Center, Hamil- ton, Ontario. Participating Hospitals and Sponsors Abingion Memorial Hospital, Abington, Pa: James Robertson, MD. Albert Einstein Medical Center, Philadelphia, Pa: Mortis N Koller, MD. Allegheny University Hospitals, Bucks County, Warminster, Pa: David Waldstein, MD. Allegheny University Hos- pital, Cty Ave, Philadelphia, Pa Albert F-D’Alonzo, DO. Allegheny University Hospitals, Elkins Park, Jenkintown, Pa: Gilbert, Grossman, MD. Allegheny University Hospitals, Graduate Philadelphia, Pa: Robert Lester, MD. Allegheny University Hospitals, Hahnemann, Philadelphia: Wiliam G. Kussmaul, MD. Allegheny University Hospitals, Medical Collegeof Pennsylvania, Phila: delphia: Steven Meister, MD. Allegheny University Hospitals, Parkview, Philadelphia: David Masiak, DO. Brandywine Hospital, Thorndale, Pa: Arthur B. Hodess, MD. Bryn Mawr Hospital, Bryn Mawr, Pa: Jack Martin, MD. Chester County Hospital, West Chester, Pa: Azam Husain, MD. Chestnut Hill Hospital, Philadelphia: Raymond Rodriguez, MD. Cooper Hospital-University Medical Center, Camden, NJ: Williaa H. Mattha, Je, MD. Crozer Chester Medical Center, Upland, Pa: R. David Mishalove, ‘MD. Deborah Heart and Lung Center, Browns Mills, Nj: Charles Dennis, MD. Delaware County Memorial Hospital, Drexel Hil, Pa: William Beckwith, MD- Delaware Valley Medical Center, Langhorne, Pac Morris |. Rossman, DO. Doylestown Hospital, Doylestown, Pa: James J. Kmetz0, MD. Episcopal Heart Insitute, Philadelphia: Nirmal De, MD. Frankford Hospital, Torresdale and Frankford Campus, Philadelphia: Robert Krause, MD. Germantown Hospital and Medical Center, Philadelphia: Erank S James, MD. Grand View Hospital, Sellersville, Pa: Paul Hermany, MD. Holy Redeemer Hospital, Meadowbrook, Pa: William Haaz, MD. Hospital ofthe University of Pennsylvania, Philadelphia: Evan Loh, MD. Jeanes Hospital, Philadelphi: Richard A Narvaez, MD. John F. Kennedy Memorial Hospital, Jenkintown, Pa: Gilbert Grossman, MD. Kennedy Memorial Hospital Stratford, Voorhees, NJ: Louis Papa, DO. Kennedy Niemorial Hospital-Washington Township, Sewell, NJ: Mario Maiese, DO. Kennedy Memorial Hospital-Cherry Hill, Cherry ill, NJ- Norman P. Silvers, MD. Lankenau Hesptal, Wynnewood, Pa: Peter R. Kowey, MD. Lower Bucks Hospital, Langhorne, Pa: Jonathan Gold, MD. Memorial Hospital of Burlington County, Mt Laurel, NJ Steven Lederman, MD. Mercy Catholic Medical Centers Fitzgerald Misericordia, Philadelphia: Clifford E. Schott, J, MD. Mercy Haverford, Broomall, Pa: Julian L Gladstone, MD. Methodist Hospital, Philadelphia: David Elbaum, DO. Montgomery Hospital, Norristown, Pa: Edward Buonocore, MD. Nazarcth Hospital, Philadelphia: Richard Vassallo, MD. Neumann Medical Center, Philadelphia: Nirmal De, MD. North Fenn Hospital, Lansdale, Pa: Joseph Kraynak, MD. North Philadelphia Health System-St Joseph's Hospital, Philadelphia David Knox, MD. Northeastern Hospital, Philadelphia: Donald L. Kahn, MD. Our Lady of Lour- des Medical Centr, Voorhees, NJ: Donald W. Orth, MD. Paoli Memorial Hospital, Paoli, Pa: Elliot M. Gerber, MD. Pennsylva- nia Hospital, Philadelphia: John U. Doherty, MD. Phoenisville Hospital, Phoeniville, Pa: Kathleen E. Magness, MD. Pottstown Memorial Medical Center, Potstown, Pa: Joseph Krantzler, MD. Presbyterian Medical Gener of Philadelphia, Philadelphia: Stephen E Kimmel, MD. Quakertown Community Hospital, Quakertown, Pa: Ric Baxter, MD. Rancocas Hospital, Willingboro, Nf: Wvan Rudolph, MD. Riddle Memorial Hospital, Media, Pa: Vsevolod Kohutiak, MD. Rexborough Memorial Hospital, Philadelphia: Michael DeAngelis, MD. Southern Chester County Medical Center, West Grove, Pa: David Callahan, DO. Springfield Hospital, Springfield, ar Dominic Pisano, DO. St Agnes Medical Center, Philadelphia: Pasquale Procacci, MD. St Mary's Medical Center, Levittown, Pa: Rajnikant Shab, MD. Suburban General Hospital, Norristown, Pa: John Fornace, DO. Taylor Hospital, Ridley ark, Pa: Roger Weiner, MD. Temple University Hospital, Philadelphia: David Wiener, MD. Thomas Jefferson University Hos- pita, Philadelphia Perry Weinstock, MD. Underwood Memorial Hospital, Woodbury, NJ Jon S. Owens, MD. Veterans Affairs Medical Center, Philadelphia: Lawrence H. Frame, MD. West Jersey Hespital-Berin, Berlin, NJ Richard Perlman, MD, PhD. West Jersey Hospital-Camden, Camden, Nf Richard Perlman, MD, PRD. West Jersey Hospital-Marlion, Marlton, NJ: Richard Perlman, MD, PRD. Wes Jersey Hospital-Voorhees, Voorhees, NJ: Richard Perlman, MD, PhD. portance right after switching than with longer-term above 6 mg, were associated with a significant increase use." Regardless, individual smoking behavior that in- in ML Therefore, legislation aimed at reducing the amount creased actual exposure to tarin the lower-yield groups, _of tar in cigarettes could have additional benefits, above relative to what was predicted, would have biased our and beyond reducing smoking-related cancers and other results toward the null. Finally, smokers may have morbidities. Of course, smoking cessation should re- changed their quantity of smoking in the index week; main the goal of all smokers, as itis the only way to abol- however, calculations of tar per day using lifetime aver _ish the increased risk of Ml [rom smoking,”" even among ages did not alter the results. smokers of low-yield cigarettes.” co Accepted for publication April 14, 2001 This study was supported by grants from Aventis Phar- This study demonstrated a significant association be-__maceuticals (formerly Hoechst Marion Roussel Inc), Par- tween smoking higher-yield cigarettes and first nonfatal __sippany, NJ: Novartis Consumer Health, Summit, NJ: and ML, independent of the quantity of cigarettes smoked,and McNeil Consumer Products Co, Fort Washington, Pa. ‘consistent dose-response relationship between tar in- Corresponding author: Stephen E. Kimmel, MD, MSCE, take per day and Ml, regardless of the type of cigarette University of Pennsylvania School of Medicine, Center for smoked. Tar yields above 10 mg per cigarette, and even Clinical Epidemiology and Biostatistics, 717 Blockley Hall, (@epnurED) SRCHINTERN WEDIVOL I, FEDTT ann WWW ARCHINTERNNED COM (©2002 American Medical Association, All rights reserved. ‘Downloaded From: http:/archinte jamanetwork.com/pdfaccess.ashx?urt=/data/journals/intemed/S304/ on 0309/2017423 Guardian Dr, Philadelphia, PA 19104-6021 (e-mail skimmel@cceb.med upenn.edu). —_ i iy_¥_—_ 1. Engh. ii A Berton Toba an cron sn JAMA, 040: seta, 2, Dall Peto Morya alton smoking 20 yet eben on ile teh dts AU. 18762-1525-506 8 Cet for ies Gono. eduing the Heath Cooequncs of Smoking: 125 eae of rors oot ofthe Surgeon General ockil S Opt eth and Human Sarvs, Publ Healy Sei, 980, COE peo anu 4 Wen Wo, Geen , Stamler Ml et Reb and bso exes ris of ernay hw aseac among waren uho Smokes, Wg Med 1987, srr-300 65 Ramberg, avian DL, Hlnch SP. Sapir Thais of myocar ‘scion ser ting smoking men under Sys fap. Engh ied 185 SrErstti5is 6. RasrbegL ar J, Shap S. 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Wald Hele, Sipe Wh Tusal-Peos H oraly in ‘ton ta yl of gues prospective stud ofa cabars, BIL 105 srv0-588 Neln Warring: an-tozo raves, Mew Yor Times DecanBer,186 a FTAs aigance ie, Antismoking capsignrs srg ight oer, ‘tine dlrs Post Dear 17000 Dansk Teg ar-smaking masses approved or Europ, Washington Past May 16, 200117 ogi, raros MG, La Vesa, Sara Nob A, Toppan. Tar yd ot ions ar ik of eat myocar fron B44 1985 305:187 1570, ‘nan, Hench SP Raster Metin OS, ShapeoS. Wezing and carbon monoie content of caret smoke andthe kt myocar infare- an in young men Eng Med. 865308400413. 0 0. w ” u 6 1% ". * 0 (wePRINTED) RRCHINTERN WED VOU 16, ENT oOo 2 2 Palmar JR RasebeL, Shape S. “Low iurates andthe kof mo ‘al myocar ncn in wen Eng J Med. 1833208601573 Parh, Clin Peta alr tnt Sts ot nr! Sia (S18) Claboraors. gue smoking aryl, nd ont mya in {acn: 1400 cae nd 22000 are te Unted ego, 4 155 aan vl SE. 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Spetansous ite brand ewtshng: cose ‘uanes foie and extn moni exposure Ar Pub eth 187 fenor-rad Zany P, Sioa ML Crete band uth: in rake epee and sakag bhava J Phamazal Exp Ther WEE 2ISS1B 627 Fest Fulton A Stepen AM ea The recon sy andomised ‘alot teat of ue tyre on crs smoking The ar a5 S038, an: arevewat ele Pay (©2002 American Medical Association, All rights reserved. ‘Downloaded From: http:/archinte jamanetwork.com/pdfaccess.ashx?urt=/data/journals/intemed/S304/ on 0309/2017