Study design and study population
The present study was derived from the population-based MONICA (Monitoring Trends and Determinants in Cardiovascular Diseases)/KORA (Cooperative Health Research in the Region of Augsburg) Augsburg surveys conducted between 1984 and 1995 [5, 13]. The World Health Organization (WHO) MONICA Project was initiated in the early 1980s in 26 countries to monitor the risk factors for cardiovascular diseases, such as hypertension, smoking, hypercholesterolemia and obesity . The MONICA Augsburg Study, a part of the multinational WHO MONICA project, was initiated in 1984 in the city of Augsburg and two adjacent counties in southern Germany. The study was approved by the local authorities: The MONICA surveys S1 and S2 with the baseline examination were approved by the data protection commission following the rules at the time of the examinations (1984/85 and 1989/90). The follow-up examinations within the KORA framework were approved by the ethics committee of the Bavarian Medical Association. All participants provided a written informed consent.
Overall, a number of 8,802 persons participated in the first survey (S1) conducted in 1984/85 (age range 25 to 64 years, response 79%) or in the second survey (S2) conducted in 1989/90 (age range 25 to 74 years, response 77%). After excluding 506 participants with a history of MI or with incomplete information on any of the considered variables, the study population of the present analysis comprised of 8,296 subjects (4,099 men and 4,197 women).
Baseline information on socio-demographical and lifestyle characteristics as well as medical examinations including collection of a nonfasting venous blood sample was assessed by trained medical staff in a standardized manner following the WHO MONICA recommendations .
Definition of incident MI
Within the framework of KORA study participants were followed up until 2002. The outcome incident MI was defined as the first event of a non-fatal or fatal MI including coronary death before the age of 75 years and was assessed by the MONICA/KORA Augsburg coronary event registry . Until December 2000, the diagnosis of a major non-fatal MI event was based on the MONICA algorithm taking into account symptoms, cardiac enzymes and electrocardiography (ECG) changes. Since January 1, 2001 MI was diagnosed according to ESC and ACC criteria. Vital status of all cohort members was assessed regularly through the population registries. Deaths from MI were validated by autopsy reports, death certificates, chart review, and information from the last treating physician.
Mean duration of follow-up was 13.3 years (standard deviation (SD) 4.4) and ranged from 0.03 to 18.2 years. During the follow-up period, a number of 307 men and 80 women developed an incident MI event.
Definition of smoking status, tar and nicotine intake
Smoking status was assessed by a face-to-face interview by asking "Do you currently smoke cigarettes?". In case of answering "yes", participants were further asked if they smoke regularly or occasionally; in case of answering "no", participants were asked "Have you ever smoked cigarettes?". Moreover, the average amount of cigarettes smoked per day among regular smokers was assessed in the questionnaire by the question "How many cigarettes do you smoke on average per day?" and age at smoking onset by the question "How old have you been when you started to smoke cigarettes?".
Participants were classified into four categories: regular smokers, occasional smokers, ex-smokers and never-smokers. Regular smokers are defined as those who reported to smoke currently at least one cigarette per day; while occasional smokers smoked less than one cigarette per day on average. Ex-smokers are those subjects who smoked cigarettes daily before the time of baseline examination but not currently. Never-smokers reported to have not consumed any cigarettes before the time of baseline examination. The number of cigarettes smoked on average per day (cig/day) was divided into light smokers (1-19 cig/day) and heavy smokers (≥ 20 cig/day).
Information on tar and nicotine contents of cigarette for each brand was obtained from annual reports by the respective cigarette manufactures. Among the regular smokers, nicotine intake per day (mg/day) was calculated by multiplying the nicotine yield per cigarette smoked with the number of cigarettes smoked per day, and tar intake per day (mg/day) was calculated by multiplying the tar yield per cigarette smoked with the number of cigarettes smoked per day. Using tertiles of the distribution of nicotine yield per cigarette, nicotine intake per day was divided into groups of low (≤ 8 mg/day), medium (9 - 16 mg/day), and high nicotine intake per day (≥ 17 mg/day) among regular smokers. Using tertiles of the distribution of tar yield per cigarette, tar intake per day then was grouped into groups of low (≤129 mg/day), medium (130 - 259 mg/day), and high tar intake per day (≥ 260 mg/day) among regular smokers.
Definition of cardiovascular risk factors
Venipuncture was performed on the sitting subjects with minimal tourniquet use. Further blood handling followed strict standardization. Total serum cholesterol and high density lipoprotein cholesterol (HDL-C) were measured by enzymatic methods (CHOD-PAP, Boehringer Mannheim, Germany). HDL-C was precipitated with phosphotungstic acid and magnesium ions. For the present analyses, we used the ratio of total cholesterol and HDL-C (total cholesterol/HDL-C). Alcohol intake was assessed by a recall method and alcohol consumption was calculated in grams/day (g/day). Alcohol consumption was classified into three categories: non-drinkers (0 g/d), intake of 0.1-39.9 g/day and ≥ 40.0 g/day for men and intake of 0.1-19.9 g/day and ≥ 20.0 g/day for women. To assess physical activity, participants were considered as active during leisure time if they regularly participated in sports in summer and in winter and if they were active for at least one hour per week in either season. All other participants were considered as inactive. Actual hypertension was defined as blood pressure values ≥ 140/90 mmHg and/or use antihypertensive medication, given that the subjects were aware of being hypertensive. Diabetes was defined if participants reported a history of diabetes or if they reported use of anti-diabetic medication.
We conducted a descriptive analysis by baseline characteristics and risk factors separately for men and women to give a description of the study population. Multivariable analyses were performed by Cox proportional hazards models to assess the effect of smoking habits, tar and nicotine intake on incident MI with controlling for potential confounding by other cardiovascular risk factors. Never-smokers were chosen as reference category. All models were calculated separately for men and women. A first basic model was adjusted for age (continuous) and survey (S1 or S2); a second multivariable model was adjusted additionally for the following variables: alcohol consumption (men: 0, 1-39, ≥ 40 g/day, women: 0, 1-19, ≥ 20 g/day), actual hypertension (yes or no), ratio of total cholesterol and HDL-C (<3.0, 3.0-5.4, ≥ 5.5), physical inactivity (yes or no) and history of diabetes (yes or no). Results are presented as hazard ratio (HR) with 95% confidence interval (95% CI). Significance tests were 2-tailed. For all statistical analysis a p value less than 0.05 was considered to be statistically significant. The evaluations were performed with the statistical software package SAS (Version 9.1, SAS-Institute Inc., Cary, NC, USA).