who quit cigarette smoking

Rapid reduction in coronary risk for those who quit cigarette smoking Patrick McElduff and Annette Dobson Department of Statistics, University of Newcastle, New South Wales Robert Beaglehole and Rodney Jackson Department of Community Health, School of Medicine, University of Auckland, New Zealand M any studies have shown that the increased risk of myocardial infarction in smokers compared with never smokers declines after quitting smoking.i-l0 Debate continues on how quickly this decline occurs, and whether or not ex-smokers eventually reach the same level of risk as people who never smoked. Well-designed cohort studies have a number of advantages over case-control studies and they are useful for estimating the long-term benefit of quitting cigarette smoking. However, the number of adverse outcomes in cohort studies is small and wide time intervals are needed to register enough outcomes to show a significant difference in risk between ex-smokers and never smokers. Wide time intervals are appropriate when the rate of change in risk is slow but they hide important information when the rate of change is rapid. Case-control studies have the advantage of involving a larger number of adverse outcomes. They can therefore use narrower time intervals and can describe the changing pattern in risk with greater precision. Previous case-control studies have suggested that the risk of a major coronary event.educes rapidly after quitting cigarette smoking and returns to the risk of a never smoker within periods ranging from two to five year^.^.^.' These studies have reported estimates of risk with wide confidence intervals and therefore have had insufficient power to detect relatively small differences in risk. This large population-based case-control study was conducted in the context of the World Health Organization MONICA Project which monitored trends and determinants of cardiovascular disease in well defined populations." Using data collected in Newcastle, Australia, and Auckland, New Zealand, including data reported by Dobson et al4 we compared the risk of a major coronary event (i.e. non-fatal definite myocardial infarction or coronary death) among current smokers and people in different categories of time since quitting smoking with the risk among never smokers. The large number of cases and controls in this study has enabled us to describe the change in risk more accurately than previous studies. Method The study populations were people aged 35-69 years living in Newcastle and the surrounding area of the Hunter region of New South Wales and residents of Auckland (excluding Maoris and Pacific Islanders) aged 35-64 years. Cases and controls were identified in the MONICA Project. The MONICA Project involved registration of all suspected coronary events occurring in the study population through continuous surveillance of all hospitals and scrutiny of all death certificates. Cases were defined as those people who had coronary events which satisfied the MONICA criteria for non-fatal definite myocardial infarction or coronary death." In both centres, patients with non-fatal events were interviewed while they were still in hospital to obtain information on symptoms, medical history and other variables. Cardiac enzyme results were extracted from hospital notes and electrocardiographs were copied and subsequently coded according to the Minnesota code. Details of fatal cases were obtained from death certificates, post mortem records and from doctors, relatives or other informants. For this study, cases were included if the Abstract The objective of this study was to determine the rate of the decline in risk of a major coronary event after quitting cigarette smoking. It was a populationbased case-control study of men and women aged 35 to 69 years in Newcastle, Australia, and men and women aged 35 to 64 years in Auckland, New Zealand, between 1986 and 1994. Cases were 5,572 people identified in population registers of coronary events and controls were 6.268 participants in independent community-based risk factor prevalence surveys from the same study populations. There was a rapid reduction in risk after quitting cigarette smoking. The risk of suffering a major coronary event for men who were current cigarette smokers was 3.5 (95Y0 CI 3.0-4.0) times higher than the risk for never smokers but this fell to 1.5 (95Y0 CI 1.l-1.9) for men who had quit for 1-3 years. who were current cigarette smokers were 4.8 (95% CI 4.0-5.9) times more likely to suffer a major coronary event than never smokers and this fell to 1.6 (95%0 CI 1.O-2.5) for women who had quit for 1-3 years. Those who had quit cigarette smoking for 4-6 years or more had a similar risk to never smokers. These results reinforce the importance of smoking cessation. The public health message is that the benefit of giving up smoking occurs rapidly. (Aust NZJ Public Health 1998; 22: 787-91) Correspondence to: Mr Patrick McElduff, Department of Statistics, University of Newcastle, Callaghan, NSW 2308. Fax: (02) 4921 7063; e-mail: stmonicapm@cc.newcastle.edu.au 1998 VOL. 22 NO. 7 AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH 787

McElduff et al. coronary event occurred in the periods 1987-94 in Newcastle and 1986-88 or 1992 in Auckland, coinciding approximately with community-based risk factor prevalence studies. There was close to complete case ascertainment in both centres but 16.7% of cases in Newcastle and 2.6% of cases in Auckland were not included in the analyses because of insufficient information on smoking status or time since quitting. Cases who died accounted for 92% of the missing data in Newcastle. Controls were participants in risk factor prevalence studies also conducted as part of the MONICA Project. In Newcastle, the risk factors studies were conducted in June-December 1988, June- November 1989 and June-December 1994. In Auckland, the risk factor studies were conducted from February 1986 to January 1988 and from January 1993 to March 1994. In both centres, the sampling frame was the electoral roll. (In Australia, registration on the electoral roll is compulsory for most people and more than 95% of eligible people are enrolled. In New Zealand registration is compulsory for all people.)there were 86,764 men and 87,164 women in the Newcastle study population at the 1991 Census and 171,260 men and 176,380 women in the study population in Auckland at the 1986 Census (excluding Maoris and Pacific Islanders). For the risk factor studies in Newcastle, stratified random samples of the study population were selected, with the sampling fraction being greater for the older age strata. People chosen for the sample were invited to attend study centres to complete a self-administered questionnaire and to have physical measurements made. In Auckland in 1993, stratified random sampling was used to select subjects but in 1986-1988 controls were group matched to cases on age and sex with case-control ratios of 1 : 1.5 in men and 1.3 in women planned. Controls attended a study centre where they had physical measurements taken and completed an interviewer-administered questionnaire. Extensive systems of reminders and follow up were used to encourage participation. The response rate for Newcastle in 1988-89 was 63%, and in 1994 was 64%, for Auckland in 1986-88 it was 83%, and in 1993 it was 75%. Questions about smoking history differed between datasets. In Newcastle in 1994 the controls were asked Have you ever smoked cigarettes?, Have you ever smoked cigars or cigarillos? and Have you ever smoked a pipe?, with each allowing for answers of now regularly, now occasionally, no and used to. In 1988-89, controls were asked Do you smoke now? and If you don t smoke now, did you smoke in the past?. Cases in Newcastle were asked, Have you ever smoked cigarettes, cigars or a pipe regularly?. In Auckland cases and controls were asked the same questions, Do you smoke cigarettes?, Did you ever smoke cigarettes? and Do you smoke a pipe or cigars?. To determine time since quitting, similar questions were used for cases and controls for all datasets: in Newcastle the response option for the cases was categorical, whereas for all other datasets it was continuous. Subjects were classified as current regular smokers if they currently smoked on average at least one cigarette per day or had quit for less than one month. Subjects who were once regular smokers and had quit smoking were categorised according to the Newcastle categories of time since quitting: 1-5 months, 6-1 1 months, 1-3 years, 4-6 years, 7-9 years, 10-12 years and more than 12 years. Subjects who had never been regular smokers were classified as never smokers. Age was categorised into five-year groups from 35-39 to 65-69 for Newcastle and from 35-39 to 60-64 forauckland. InAuckland, data were not collected for 65-69 year olds. The highest level of education attained was used as an indicator of socioeconomic status and was categorised as: no tertiary education, technical college or professional institution (including university and college of advanced education). Information on medical history was ascertained by asking the subjects if they had been told by a doctor or medical person that they had had: a heart attack, angina, high blood pressure or diabetes. Subjects were deemed to have had a history of coronary heart disease if they answered yes to either a heart attack or angina. Body mass index was calculated as weight in kilograms divided by the square of height in metres. The initial analysis involved calculating age standardised prevalences of coronary heart disease risk factors by the direct method using the age distribution of all cases from both centres as the standard. Levels of risk factors were compared between cases and controls within each centre and for men and women separately using a z-test for the difference between two age standardised proportions. The same test was used to compare the prevalence of risk factors between cases inauckland and cases in Newcastle. To test if there was a reduction in risk of a major coronary event associated with years since quitting, logistic regression was used to calculate age adjusted (using five-year age groups) odds ratios and 95% confidence intervals for each of the categories. Odds ratios were also calculated after adjusting for the effects of age, education, body mass index, and history of coronary heart disease, diabetes and hypertension. Results are presented separately for men and women and by non-fatal definite myocardial infarction and coronary death. Analyses that involved the combined data from Auckland and Newcastle included interaction terms to adjust for the different age and body mass index distribution of the controls from the two centres. Logistic regression was performed using Proc Genmod in SAS.I3 Results There were three times more men than women among the cases and there was a rapid increase in the number of cases with age. In the control groups, there was a similar number of men and women and there was slightly more older people in the control groups in both Auckland and Newcastle. In both Auckland and Newcastle cases were more likely than controls to be current smokers, have no tertiary education, and have a history of coronary heart disease, hypertension and diabetes (Table 1). Cases in Newcastle were more likely than cases in Auckland to have no tertiary education and less likely to have a history of coronary heart disease. Table 2 gives the adjusted odds ratios of suffering a major 788 AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH 1998 VOL. 22 NO. 7

~ ~~~ ~~ Rapid reduction in coronary risk for those who quit cigarette smoking Table 1. Age standardised prevalences of factors associated with risk of a major coronary event in Newcastle, Australia, and Auckland, New Zealand, for people aged 35-64 years. Newcastle (1 987-94) Auckland (1986-93) Case Control Case Control Pa Current smokers 44.8 23.8 43.1 21.4 0.35 No tertiary education 69.9 62.6 47.2 37.1 co.01 Body mass index >25kg/m2 57.4 78.0 59.3 50.9 0.30 History of coronary heart disease 38.0 12.0 42.1 8.4 0.02 History of hypertension 45.1 33.8 42.4 29.5 0.14 History of diabetes 11.2 3.3 10.4 3.2 0.47 Current smokers 41.7 15.3 47.9 17.2 0.06 No tertiary education 85.5 79.8 74.7 51.6 <0.01 Body mass index >25kg/m2 50.5 61.O 53.2 38.6 0.43 History of coronary heart disease 33.4 6.6 40.2 8.2 0.04 History of hypertension 60.8 41.O 56.6 33.1 0.22 History of diabetes 19.4 1.9 20.8 3.1 0.61 Note: (a) p-value from a test of the difference in the prevalence of risk factors between cases in Auckland and cases in Newcastle. All differences between cases and controls are statistically significant (p4.0 1). coronary event for each category of the variable describing time since quitting compared with never smokers. After adjusting for age, education, body mass index, and history of coronary heart disease, diabetes and hypertension, Newcastle had larger odds ratios than Auckland for the 1-5 month group in both men and women but the differences were not statistically significant. In fact, men in Newcastle who had quit for 1-5 months had a nonsignificantly higher risk of a event compared with current Table 2: Adjusted odds ratios (95% CI) for the risk of a major coronary event associated with time since quitting cigarette smoking. Newcastle Auckland Time since quitting Odds ratio Odds ratios adjusted Odds ratio Odds ratios adjusted adjusted for age for age, history, education, adjusted for age for age, history, education, hypertension, diabetes hypertension, diabetes and bodv mass index and bodv mass index Never smoker 1.oo 1.oo 1.oo 1.oo Current smoker 3.6 (3.1-4.3) 3.3 (2.8-4.0) 3.9 (3.2-4.8) 3.8 (3.0-4.7) 1-5 months 14.1 (6.7-29.8) 10.1 (4.7-21.6) 4.7 (2.4-9.5) 4.7 (2.2-10.0) 6-12 months 4.4 (2.6-7.5) 3.2 (1.8-5.6) 3.8 (1.8-8.0) 2.9 (1.2-6.7) 1-3 years 1.9 (1.4-2.6) 1.6 (1.1-2.3) 2.3 (1.6-3.3) 1.6 (1.1-2.4) 4-6 years 1.5 (1.1-2.0) 1.2 (0.8-1.7) 1.8 (1.2-2.7) 1.2 (0.8-2.0) 7-9 years 1.6 (1.1-2.2) 1.3 (0.9-1.9) 1.1 (0.8-1.7) 0.8 (0.5-1.2) 10-1 2 years 1.7 (1.2-2.4) 1.6 (1.1-2.3) 1.O (0.7-1.6) 0.9 (0.5-1.4) >12 years 1.O (0.9-1.3) 1.O (0.8-1.2) 1.O (0.8-1.3) 1.O (0.7-1.3) Never smoker 1.oo 1.oo 1.oo 1.oo Current smoker 4.7 (3.7-5.9) 5.3 (4.1-6.8) 5.4 (4.0-7.4) 6.2 (4.3-8.9) 1-5 months 7.4 (3.5-15.8) 6.4 (2.7-1 4.9) 2.7 (1.l-6.8) 2.7 (0.9-7.9) 6-12 months 3.2 (1.5-6.9) 3.1 (1.2-7.9) 5.0 (1.9-13.5) 3.7 (1.2-1 1.7) 1-3 years 1.9 (1.3-3.0) 1.9 (1.2-3.3) 2.4 (1 3-4.5) 2.7 (1.3-5.6) 4-6 years 1.3 (0.8-2.4) 1.3 (0.7-2.6) 1.5 (0.6-3.5) 0.9 (0.3-2.4) 7-9 years 1.2 (0.7-2.1) 1.3 (0.6-2.7) 2.1 (1.0-4.5) 1.9 (0.8-4.7) 10-1 2 years 1.7 (1.O-3.0) 1.4 (0.7-2.8) 3.0 (1.3-6.8) 2.3 (0.8-6.7) 212 years 0.9 (0.6-1.2) 0.9 (0.6-1.3) 0.8 (0.5-1.5) 0.8 (0.4-1.5) 1998 VOL. 22 NO. 7 AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH 789

~ ~ ~ ~ ~ ~ McElduff et al. Figure 1: Adjusted odds ratio and 95% confidence intervals for the reduction in risk of a major coronary event associated with time since quitting smoking. Odds ratio 12 I 0 Current 0-5 mths 6-12 mths 1-3 yrs 4-6 yrs 7-9 yrs 10-12 yrs > I2 yrs smoker Time since quitting smokers. The adjusted odds ratios show that the risk of a major coronary event for ex-smokers compared with never smokers declined as the period of quitting cigarette smoking increased. The results for men and women were similar in both centres although results for women in Auckland were slightly erratic because of the smaller number of cases. Using the combined data for Newcastle and Auckland, Figure 1 illustrates that men and women had a similar reduction in risk of a major coronary event after quitting cigarette smoking and the risk returned to the level of a never smoker after approximately five years. Adjusted odds ratios for the risk of a non-fatal definite myocardial infarction were similar to the adjusted odds ratios for the risk of a coronary death for each of the categories of time since quitting (Table 3). The confidence intervals were wider than the Table 3: Adjusted odds ratios (95% CI) for non-fatal definite myocardial infarction and fatal coronary events associated with time since quitting smoking. ~~ Non-fatal definite myocardial infarction Coronary death Newcastle Auckland Combined Newcastle Auckland Combined Never smoker 1.oo 1.oo 1.oo 1.oo 1.oo 1.oo Current smoker 3.2 (2.6-3.9) 4.0 (3.1-5.1) 3.5 (3.0-4.1) 3.1 (2.4-4.1) 3.0 (2.1-4.1) 3.1 (2.5-3.8) 1-5 months 10.6 (4.9-23.0) 5.6 (2.6-12.3) 7.4 (4.4-12.6) 7.5 (3.1-18.4) 3.3 (0.9-11.7) 5.3 (2.7-10.7) 6-12 months 3.4 (1.9-6.1) 2.7 (1.0-7.2) 3.1 (1.9-5.2) 2.7 (1.2-6.0) 4.4 (1.4-13.8) 3.2 (1.6-6.1) 1-3 years 1.6 (1.1-2.3) 1.6 (1.0-2.5) 1.6 (1.2-2.1) 1.8 (1.1-2.9) 1.2 (0.7-2.2) 1.6 (1.1-2.3) 4-6 years 1.1 (0.8-1.6) 1.2 (0.7-2.1) 1.1 (0.8-1.5) 1.1 (0.7-1.9) 1.2 (0.6-2.4) 1.2 (0.8-1.7) 7-9 vears 1.2 (0.8-1.8) 0.7 (0.4-1.3) 1.0 (0.7-1.4) 1.6 (0.9-2.6) 0.8 (0.4-1.4) 1.2 (0.8-1.7) 10-1 2 years 1.5 (1.0-2.3) 1.0 (0.6-1.7) 1.3 (0.9-1.8) 1.6 (1.0-2.7) 0.7 (0.3-1.5) 1.2 (0.8-1.8) >12 years 1.1 (0.9-1.3) 1.1 (0.8-1.5) 1.1 (0.9-1.3) 0.8 (0.6-1.1) 0.7 (0.5-1.1) 0.8 (0.6-1.0) Never smoker 1.oo 1.oo 1.oo 1.oo 1.oo 1.oo Current smoker 5.4 (4.0-7.1) 6.0 (4.0-9.0) 5.6 (4.5-7.0) 4.4 (2.9-6.6) 5.0 (2.8-8.9) 4.5 (3.3-6.3) 1-5 months 6.2 (2.5-15.0) 3.1 (1.0-10.0) 4.7 (2.4-9.1) 6.1 (1.7-20.3) 2.1 (0.3-15.1) 4.1 (1.5-11.0) 6-12 months 2.3 (0.8-7.0) 3.2 (0.8-12.3) 2.7 (1.2-6.4) 5.0 (1.3-18.4) 5.7 (1.2-27.4) 5.4 (2.0-14.7) 1-3 years 1.9 (1.1-3.3) 2.5 (1.1-5.9) 2.1 (1.3-3.3) 1.8 (0.8-4.3) 3.3 (1.0-10.5) 2.1 (1.1-4.3) 4-6 years 1.3 (0.6-2.7) 0.6 (0.2-2.2) 1.0 (0.6-1.9) 1.5 (0.5-4.1) 1.3 (0.3-5.1) 1.3 (0.6-3.0) 7-9 years 1.6 (0.7-3.4) 1.8 (0.6-5.0) 1.6 (0.9-3.1) 0.7 (0.2-3.1) 1.3 (0.3-5.2) 1.0 (0.4-2.7) 10-1 2 years 1.7 (0.8-3.4) 1.9 (0.5-6.5) 1.7 (0.9-3.1) 1.2 (0.4-4.0) 2.2 (0.4-13.5) 1.4 (0.5-3.8) >12 years 1.0 (0.7-1.6) 0.9 (0.4-1.8) 1.0 (0.7-1.4) 0.5 (0.2-1.1) 0.7 (0.2-2.0) 0.5 (0.3-1.0) Note: Odds ratios were calculated after adjusting for the effects of age, sew, education, body mass index, and history of coronary heart disease, diabetes and hyperiension. 790 AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH 1998 VOL. 22 NO. 7

Rapid reduction in coronary risk for those who quit cigarette smoking combined analyses because there were fewer events in each category of time since quitting, but the trends were consistent with those observed in Table 2. Discussion This study shows there is a rapid reduction in the risk of a major coronary event after quitting cigarette smoking. The risk returns to the level of never smokers within 4-6 years. Narrow categories of time since quitting cigarette smoking were used to determine how quickly the reduction in risk occurs. Only a few other studies have used similar categ~ries,~-~ but this study has more cases and controls and therefore more power to detect small differences in the risk between ex-smokers and never smokers. The reduction in risk was apparent within 6-12 months and was substantial by 1-3 years. Early case-c'ontrol studies reported the risk returned to that of a never smoker after periods of quitting ranging from two to five year^,^.^.' but some cohort s t ~ d i eand s ~ one ~ case-control ~ ~ ~ ~ ~ study1 found a residual increased risk lasting for more than 10 years. Later cohort studies have concluded that the risk for ex-smokers does reduce to that of never smokers, although this process takes longer than reported by the case-control studies.hj" This large case-control study used data collected from two countries and found no statistical difference in risk between ex-smokers and never smokers after about five years. It should be noted however, that as the risk of a major coronary event for ex-smokers approaches the risk of never smokers, the power to detect a difference in risk between the two groups decreases. Studies that showed a lasting increased risk relied on the relative risk estimates for the subgroup of people who were heavy smokers (>20 cigarettes per day) for long periods of time (>20 years).'** The possible mechanisms for a decrease in risk after quitting smoking are both short term and long term. In the short term there is a reduction in fibrinogen levels and platelet ~tickiness.~~.~~ Smoking an individual cigarette causes an acute increase in blood 6. pressure that can lead to the rupture of an existing atherosclerotic plaque. When people quit smoking this potential trigger for an 7. acute event is removed. However, there is a slight short-term increase in diastolic blood pressure, possibly due to weight increase. 8. These biological changes are all consistent with quite rapid re- 9. ductions in risk. Atherosclerosis which is related to lower high density lipoprotein and other metabolic effects may take longer 10. to regress.15 Many of the studies on quitting and risk of coronary heart disease demonstrate a dose response relationship with 11. amount smoked. and it is plausible that the atherosclerotic effects are more severe for heavier smokers and therefore take longer to diminish.1-3,7,x This would explain why some studies showed an elevated risk in ex-smokers who had been heavy smokers, even after they had quit smoking for more than 10 years. This study shows a non-significant increased risk of coronary heart disease in men, particularly in Newcastle, in the period 1-5 months after quitting, although a similar effect was not found in women. This possible short-term increase in risk has not been reported before., even in the few studies that have examined risk in the immediate period after q~itting.~.~ One possible explanation is that men with symptoms of coronary heart disease gave up smoking because they felt unwell. The effect was still present after adjusting for history of coronary heart disease and in an analysis (not shown) including only subjects with no history of coronary heart disease. However, these adjustments would not control for subclinical symptoms. An alternative explanation might be that the effect is due to biological changes such as increased weight and increased diastolic blood pressure which seem to occur after quitting smoking.16 The effect, however, was seen mainly in men in Newcastle, and even if it were real, the significance of the finding is unclear. One of the weaknesses of this study is that questions on smoking history differed slightly between centres and over time, possibly causing some misclassification of exposure and resulting in a dilution of the true difference in risk between ex-smokers and those who never smoked. This study has provided further evidence of a reduction in risk of-a major coronary event appearing within the first year of quitting cigarette smoking. For those who quit smoking, the risk of a major coronary event reduces to the level of a never smoker within five years. The public health message is clear: the benefits of quitting cigarette smoking occur rapidly. References 1. 2. 3. 4. 5. 15. 16. Negn E, LaVecchia C, D'Avanzo B, et al. Acute myocardial infarction: Association with time since stopping smoking in Italy. J Epidemiol Communify Health 1994; 48: 129-33. Ben-Shlomo Y, Smith GD, Shipley MJ, Marmot MG. What determines mortality risk in male former cigarette smokers? Am J Public Health 1994; 84: 1235-42. Paganini-Hill A, Hsu G. Smoking and mortality among residents of a California retirement community. Am J Public Health 1994; 84: 992-5. Dobson AJ, Alexander HM, Heller RF, Lloyd DM. How soon after quitting smoking does risk of heart attack decline? J Clin Epidemiol 1991; 44: 1247-53. Rosenberg L, Palmer JR, Shapiro S. Decline in the risk of myocardial infarction among women who stop smoking. N Engl J Med 1990; 322: 213-7. Tverdal A. Thelle D. Stensvold I, et al. Mortality in relation to smoking history: 13 years' follow-up of 68,000 Norwegian men and women 35-49 years. J Clin Epidemiol 1993; 46: 475-87. Rosenberg L, Kaufman DW, Helmrich SP, Shapiro S. The risk of myocardial infarction after quitting smoking in men under 55 years of age. N Engl J Med 1985; 313: 1511-4. Cook DG. Shaper AG, Pocock SJ, Kussick SJ. Giving up smoking and the nsk of heart attacks. Lancet 1986; 2: 1376-80. Cook DG, Shaper AG. Stopping smoking and risk of ischaemic heart disease. Lancet 1989; 1: 895. Ockene JK, Kuller LH, Svendsen KH, Meilahn E. The relationship of smoking cessation to coronary heart disease and lung cancer in the Multiple Risk Factor Intervention Trial (MRLlT). Am J Public Health 1990; 80: 954-8. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, et al. Myocardial infarction and coronary deaths in the World Health Organisation MONICA Project. Circu- lation 1994; 90: 583-612. 12. Keil U. Kuulasmaa K. WHO MONICA Project: risk factors [published emturn appears in Int J Epidemiol 1990; 19: 7761. Int J Epidemiol 1989; 18(1): S46-SS5. 13. SAS Institute Inc. SAS Technical Report P-243, SAYSTAT, Software: The GENMOD Procedure, Release 6.09. Cary(NC): SAS Institute Inc; 1993. 14. Meade TW. Imeson I, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet 1987; 2: 986-8. Sleight P. Smoking and hypertension. Clin Exp Hypenens 1993; 15: 1181-92. Terres W, Becker P, Rosenberg A. Changes in cardiovascular risk profile during the cessation of smoking. Am J Med 1994; 97: 242-9. 1998 VOL. 22 NO. 7 AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH 791