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Sex Differences in Risk Factors for Incident Type 2 Diabetes Mellitus
The MONICA Augsburg Cohort Study
Christa Meisinger, MD, MPH;
Barbara Thorand, PhD, MPH;
Andrea Schneider;
Jutta Stieber, MD;
Angela Döring, MD;
Hannelore Löwel, MD
Arch Intern Med. 2002;162:82-89.
ABSTRACT
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Objective To examine sex-specific associations between cardiovascular risk factors,
a parental history of diabetes, and type 2 diabetes mellitus (DM).
Methods The study is based on 3052 men and 3114 women (aged 35 to 74 years)
who participated in one of the 3 MONICA (Monitoring of Trends and Determinants
in Cardiovascular Disease) Augsburg surveys between 1984 and 1995, who were
free of DM at baseline and returned a follow-up questionnaire in 1998. Sex-specific
hazard ratios (HRs) were estimated from Cox proportional hazard models.
Results A total of 128 cases of incident DM among men and 85 cases among women
were registered during the follow-up period. The age-standardized incidence
rate was 5.8 per 1000 person-years for men and 4.0 per 1000 person-years for
women. In multivariable survival analyses, age, body mass index, and a positive
parental history of diabetes were important independent risk factors for DM
in both sexes. High-density lipoprotein cholesterol level was inversely associated
with DM in men and women. For other risk factors, sex-related differences
were observed. Systolic blood pressure (HR per 10 mm Hg increase, 1.16), regular
smoking (HR, 1.75), and high daily alcohol intake (HR, 1.95) predicted the
development of DM in men only, whereas uric acid (HR per 1 mmol/L increase,
2.05) and physical inactivity during leisure time (HR, 1.80) were associated
with diabetes development in women only.
Conclusions In men and women, most variables predicting future diabetes in the present
study are also known to be important risk factors for cardiovascular disease
and arteriosclerosis. However, there are sex-related dissimilarities that
seem to be involved in disease development.
INTRODUCTION
WORLDWIDE, there are at present approximately 110 million people with
diabetes, the majority of them with type 2 diabetes, and it is estimated that
this number will reach more than 220 million by 2010.1
In Germany, at least 4 million people have diabetes mellitus.2
In the German National Health Interview and Examination Survey 1998, the prevalence
rate for diabetes was 4.7% for men and 5.6% for women in the 18- to 79-year-old
population.3 However, observations from other
countries have shown that the real prevalence is probably even higher because
of a high proportion of persons with undetected diabetes.4-5
Type 2 diabetes has a strong genetic component, which is much greater
than in type 1 diabetes.6 However, considerable
evidence indicates that environmental and lifestyle factors, mainly obesity
and physical inactivity, are important in inducing type 2 diabetes mellitus
in people with genetic susceptibility.6 It
is well established that even newly diagnosed diabetic subjects have an increased
atherogenic cardiovascular risk profile.7-8
Recent evidence suggests that type 2 diabetes and cardiovascular disease,
rather than being related as underlying disease and complication, share common
genetic and environmental antecedents.9-10
Furthermore, cardiovascular complications are responsible for about 80% of
premature deaths in diabetic subjects. Diabetic women have a 3- to 6-fold
and diabetic men a 2- to 4-fold increased risk of myocardial infarction.7, 11-12
Still, the environment-gene interactions as mechanisms for the development
of type 2 diabetes are not fully clarified, justifying further studies on
predictors of diabetes. Moreover, prevention programs depend on the identification
of potentially modifiable risk factors. In this connection, it is of great
interest whether cardiovascular risk factors are predictors of type 2 diabetes
and whether these risk factors are similar in men and women. As shown in Table 1, few studies have provided data
on various cardiovascular risk factors and subsequent diabetes in both sexes
within the same study population.20, 25
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Table 1. Selected Prospective Cohort Studies of Risk Factors and Type
2 Diabetes*
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To our knowledge, the MONICA (Monitoring of Trends and Determinants
in Cardiovascular Disease) Augsburg Cohort Study is the first prospective
population-based study that assessed the sex-specific incidence of type 2
diabetes mellitus in a middle European population that is characterized by
a relatively low risk of cardiovascular morbidity and mortality.32
Therefore, the aim of this study was to analyze the importance of cardiovascular
risk factors and a parental history of diabetes at baseline as predictors
of the conversion to type 2 diabetes. To answer the question of whether the
risk factors for type 2 diabetes mellitus are similar in both sexes, all analyses
were performed separately for men and women.
SUBJECTS AND METHODS
STUDY POPULATION
The data were derived from the population-based MONICA Augsburg (southern
Germany) studies conducted between 1984 and 1995. The MONICA Augsburg project
was part of the multinational World Health Organization MONICA Project, and
the design of both projects has been described in detail elsewhere.33-34 Three independent cross-sectional
surveys were carried out in the city of Augsburg and the counties of Augsburg
and Aichach-Friedberg in 1984 to 1985 (survey 1), 1989 to 1990 (survey 2),
and 1994 to 1995 (survey 3) to estimate the prevalence and distribution of
cardiovascular risk factors among men and women. Altogether, 13 428 persons
(6725 men and 6703 women; response rate, 77%) aged 25 to 74 years participated
in at least 1 of the 3 cross-sectional studies.
In 1998, vital status was assessed for all sampled persons of the 3
MONICA surveys through the population registries (Einwohnermeldeämter).
In the meantime, 772 participants (531 men and 241 women) had died and vital
status could not be assessed for 56 persons (31 men and 25 women) who had
moved to a foreign country or to an unknown location. A questionnaire assessing
the health status was mailed to the remaining 12 600 living persons (6163
men and 6437 women) with known addresses in 1998. A total of 8548 subjects
(4210 men and 4338 women) returned the questionnaire (total response rate,
67.8%; for men, 68.3%; for women, 67.4%). The present analysis was restricted
to nondiabetic persons aged 35 to 74 years at baseline examination (n = 6355;
3140 men and 3215 women). Participants who did not know whether they had diabetes
at baseline examination were included in the group of nondiabetic persons.
All men and women with missing data on any of the considered risk factors
were excluded (n = 168). An additional 21 new cases of diabetes were excluded
because these participants reported a manifestation of diabetes before the
MONICA baseline study in the follow-up questionnaire. Finally, the prospective
analyses comprised 6166 nondiabetic MONICA participants (3052 men and 3114
women) aged 35 to 74 years.
DATA COLLECTION AND LABORATORY METHODS AT THE BASELINE EXAMINATION
Baseline information on sociodemographic variables, smoking habits,
physical activity level, medication use, parental history of disease, menopause,
and alcohol consumption were gathered by trained medical staff (mainly nurses)
during a standardized face-to-face interview. In addition, all participants
underwent an extensive standardized medical examination including collection
of a nonfasting blood sample. Anthropometric measurements were performed with
the subjects in light clothing and without shoes, according to the World Health
Organization MONICA protocol.35
Body mass index (BMI) was calculated as weight in kilograms divided
by the square of height in meters. Systolic and diastolic blood pressure was
measured on the right arm in a sitting position by means of a random-zero
sphygmomanometer (Hawksley & Sons Ltd, Lancing, England),36
adhering to the World Health Organization MONICA protocol37
and the recommendations of the American Heart Association.38
After the subject had been at rest for approximately 30 minutes, 3 measurements
were taken with 3-minute intervals between the measurements. For the present
analysis, the results of the second and third measurements were averaged.
Persons who were aware of having hypertension, who were taking antihypertensive
medication, and/or who had blood pressure of 160/95 mm Hg or higher at baseline
were defined as having actual hypertension.39
Education level was categorized as low (<12 years of schooling) and
high ( 12 years of schooling). Angina pectoris was defined as pain after
exercise retrosternally, in the left arm, and in the left side of the chest
and was categorized according to Rose et al.40
Subjects were assigned to the positive parental history category if
at least 1 parent had diabetes. If neither parent had diabetes, subjects were
assigned to the negative parental history category. Subjects who answered
"I don't know" for both parents or those who answered "I don't know" for one
parent and "no" for the other parent were assigned to the unknown parental
history category.
A regular smoker was defined as a subject who currently smoked at least
1 cigarette per day. Each subject was asked how much beer, wine, and spirits
he or she had drunk on the previous workday and during the previous weekend.
This information was used to calculate the alcohol consumption in grams per
day. Alcohol intake in men came mainly from beer, whereas wine was the main
contributor of alcohol intake in women; intake of distilled spirits was very
low in both sexes. The detailed method has been described elsewhere.41-42 Alcohol intake was classified into
3 categories: 0, 0.1 to 19.9, and 20.0 or more g/d for women; and 0, 0.1 to
39.9, and 40 or more g/d for men.
The physical activity level was estimated by means of 2 separate 4-category
interview questions asking about the time per week spent on sports activities
during leisure time in summer and winter. The winter and summer responses
were combined to define one sport variable, whereby a participant was considered
active if he or she participated in sports in summer and in winter and for
more than 1 hour per week in at least 1 season. A participant was classified
as inactive if he or she was less active during leisure time.
Total cholesterol and high-density lipoprotein (HDL) cholesterol analyses
were carried out with an autoanalyzer using an enzymatic method (CHOD-PAP;
Boehringer Mannheim, Mannheim, Germany). The HDL cholesterol was precipitated
with phosphotungstic acid and magnesium ions. Regular internal and external
quality control measures for serum total cholesterol and HDL cholesterol measurements
were performed before and during the data-gathering phase of the survey. The
external quality control was performed by the World Health Organization MONICA
Quality Control Centre for Lipids in Prague, Czechoslovakia.43
Serum uric acid was measured by the uricase method in surveys 1 and
2. In survey 3, serum uric acid was determined with an enzymatic colorimetric
reaction (Uric Acid PAP; Boehringer Mannheim).
FOLLOW-UP AND END POINT
The main outcome was the development of type 2 diabetes mellitus during
the follow-up period. Subjects were classified as diabetic if they reported
a diagnosis of diabetes or if they were taking antidiabetic medication. The
same definition was used to exclude subjects with preexisting diabetes from
enrollment. A total of 210 persons (127 men and 83 women) reported the development
of diabetes during the follow-up period. Another 3 persons (1 man and 2 women)
reported having no diabetes although they took antidiabetic drugs; these subjects
were classified as diabetic for the analyses presented in this article.
Although type 1 diabetes can occur at any age, it is rare beyond 35
years of age. In this study, all participants were 35 years old or older at
study entry, and only 12 diabetic persons were treated with insulin only;
therefore, it can be assumed that most of the newly diagnosed diabetes in
this study population was type 2 diabetes. Thus, the term type 2 diabetes is used throughout this article.
The mean follow-up period was 7.6 years, with a minimum of 46 days and
a maximum of 13.8 years.
STATISTICAL ANALYSIS
All analyses were performed separately for men and women. Incidence
rates were based on person-years from the date of baseline examination until
the diagnosis of diabetes or the date when the questionnaire was filled in
as the censoring date. They were calculated by dividing the number of incident
cases by person-years in each age group. Age-standardized incidence was calculated
by direct standardization with the use of the population of the Federal Republic
of Germany in 1989 as the standard population (weights: 35-44 years, 0.2791;
45-54 years, 0.3125; 55-64 years, 0.2397; 65-74 years, 0.1687). General linear
models were used for comparison of diabetic and nondiabetic subjects (means
and prevalences were adjusted for age and survey). Cox proportional hazards
analysis was used44 to determine the age-,
survey- and BMI-adjusted as well as the multivariable adjusted relative risk
of type 2 diabetes mellitus. As a potential confounder, the variable survey was forced into the multivariable models. Variables
were analyzed by means of a backward stepwise procedure (P value for inclusion of variables <.20).
We plotted the log [-log(survival)]
curves for each risk factor to assess the proportional hazard assumptions.
This assumption was met for all variables. Results are presented as hazard
ratios (HRs) and 95% confidence intervals. Significance tests were 2-tailed,
and P values less than .05 are stated as statistically
significant. All analyses were performed with SAS software (version 6.12;
SAS Institute Inc, Cary, NC).
RESULTS
In total, 128 incident cases of diabetes among men and 85 cases among
women were registered in the 35- to 74-year-old study population between 1984
and 1998; 2924 men and 3029 women remained nondiabetic. The diabetic persons
were treated as follows: 12 persons received insulin only; 118 received tablets
only; 16 received insulin and tablets; and 62 were only following a specific
diet. Two diabetic persons declared that they received no antidiabetic treatment,
and an additional 3 had missing values for antidiabetic treatment. There was
a male predominance in the incidence of diabetes; the age-standardized incidence
rate of diabetes was 5.8 per 1000 person-years in men aged 35 to 74 years
and 4.0 per 1000 person-years in women of the same age range (Table 2).
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Table 2. Diabetes Incidence per 1000 Person-Years by Age and Sex: MONICA
Augsburg Cohort Study*
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Table 3 describes the age-
and survey-adjusted baseline characteristics of subjects by conversion status
to type 2 diabetes mellitus at follow-up separately in men and women. In both
sexes, subjects who converted to type 2 diabetes were significantly older
and had higher BMI, systolic and diastolic blood pressure, and uric acid values
than subjects who remained nondiabetic. In addition, future diabetic subjects
had lower HDL cholesterol levels. Significantly more prediabetic subjects
were actual hypertensive, and significantly more reported angina pectoris
and a positive parental history of diabetes. Prediabetic men had significantly
higher total cholesterol values and were more often regular smokers, and the
percentage with a high daily alcohol intake was also increased compared with
nondiabetic men. Significantly more prediabetic women drank no alcohol and
were physically inactive during leisure time in comparison with nondiabetic
women.
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Table 3. Sex-Specific Mean Levels (SE) and Prevalence of Baseline Characteristics
(Age- and Survey-Adjusted) by Diabetic Status at Follow-up: MONICA Augsburg
Cohort Study*
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Since age and BMI are important predictors of diabetes and were strongly
correlated with most other potential risk factors, age and BMI- and of the
remaining risk factors that was independent of age and BMI (Table 4). A positive parental history of diabetes showed a strong
positive association with diabetes in both sexes. Actual hypertension was
also associated with diabetes in both sexes but the effect was stronger in
women. The HDL cholesterol level was inversely associated with diabetes in
men and women. Systolic as well as diastolic blood pressure was related to
diabetes in men only. Total cholesterol level, an unknown parental history
of diabetes, smoking, and a high daily alcohol intake were also associated
with a higher risk of diabetes in men only. In contrast, uric acid level and
physical inactivity during leisure time were related to diabetes in women
only (Table 4).
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Table 4. Age-, Survey-, and BMI-Adjusted Hazard Ratios for the Risk
of Incident Diabetes by Sex: MONICA Augsburg Cohort Study*
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To investigate which of the baseline characteristics identified as risk
factors in the previous analysis were also independent predictors of diabetes,
a backward stepwise multiple logistic regression analysis was performed. Table 5 shows the results from the fully
adjusted models for men and women. Diastolic blood pressure was not included
in the multivariable model because of a high correlation with systolic blood
pressure (Pearson r = 0.68) and a weaker association
with diabetes in the age-, BMI-, and survey-adjusted analysis in comparison
with systolic blood pressure. Furthermore, the variable actual hypertension was also omitted in the multivariable model. Age
(men and women: HR per 1 year increase, 1.04) and BMI (men: HR per 4 kg/m2 increase, 1.98; women: HR, 1.49) were independently related to the
risk of diabetes in men and women. A positive parental history of diabetes
was also a strong predictor for the development of type 2 diabetes in both
sexes (men: HR, 2.06; women: HR, 2.37). In men, the association with an unknown
parental history of diabetes was no longer significant in the multivariable
model. The HDL cholesterol level showed an inverse association with disease
development in men (HR per 15-mg/dL [0.4-mmol/L] increase, 0.72) and women
(HR, 0.60). Systolic blood pressure was independently associated with diabetes
in men only (HR per 10–mm Hg increase, 1.16). Furthermore, regular smoking
(HR, 1.75) as well as a daily alcohol intake of 40 g or more compared with
occasional drinkers (HR, 1.95) were also independently related to diabetes
in men only. On the contrary, uric acid level (HRE [1 mmol/L] per 17 mg/dL
increase, 2.05) and physical inactivity during leisure time (HR, 1.80) were
independent predictors in women only.
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Table 5. Predictors of Type 2 Diabetes Mellitus in Multivariable Analysis
by Sex*
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These findings were unchanged if the factors shown to be independently
associated with diabetes were examined in a separate analysis in which 77
men and 61 women with preexisting coronary heart disease, ie, persons with
a diagnosis of either myocardial infarction or angina pectoris at baseline
examination, were excluded (data not shown).
COMMENT
To our knowledge, the MONICA Augsburg Cohort Study is the first prospective
population-based study to assess the sex-specific incidence of type 2 diabetes
mellitus in a middle European population characterized by a relatively low
risk of cardiovascular morbidity and mortality.32
The Augsburg study identified age, BMI, a parental history of diabetes, and
low HDL cholesterol values as independent determinants of type 2 diabetes
mellitus in both sexes. High systolic blood pressure, regular cigarette smoking,
and high daily alcohol intake predicted diabetes in men only, whereas high
uric acid values and physical inactivity during leisure time were associated
with a higher risk of diabetes in women only.
The MONICA Augsburg Cohort Study is one of the few studies that examined
the association between a variety of cardiovascular risk factors and the incidence
of diabetes in both sexes in the same study population. This facilitates the
comparison between men and women, since one can be sure that the same methods
have been used to determine risk factors in both sexes. While both men and
women have been examined in some other studies,20-21,25, 31
the Framingham Study20 and the Finnmark Study25 were the only ones that assessed the impact of several
risk factors on the incidence of diabetes. Thus, for most risk factors, one
has to rely on results from different studies to compare the effects in men
and women, which makes comparisons more difficult.
Like the MONICA Augsburg Cohort Study, the Framingham Study20 and the Finnmark Study25
demonstrated a strong positive association between BMI and diabetes in both
sexes. However, in the Finnmark Study,25 the
effect of a high BMI was much stronger in men. Concerning the predictive importance
of low HDL cholesterol levels, contradictory results were reported from the
Framingham Study,20 which showed significant
effects in men only, and from the Finnmark Study,25
which demonstrated a significant predictive relevance in women only.
In the MONICA Augsburg Cohort Study, systolic blood pressure was positively
associated with diabetes in men, but not in women. Similar results have been
observed in 3 other prospective cohort studies in men.13, 17, 26
In the Framingham Study,20 systolic blood pressure
was associated with the incidence of diabetes in the univariate analysis,
but this effect lost significance after multiple adjustment in both sexes.
In contrast to systolic blood pressure, in the present study, actual hypertension
was strongly associated with diabetes in men and women. Thus, the low impact
of systolic blood pressure in women might be attributed to the fact that more
women with actual hypertension had controlled blood pressure values in comparison
with men.45
In accordance with the present study, several prospective studies conducted
in men—the Honolulu Heart Program,16
the Pennsylvania Alumni Health Study,14 and
a study from Dallas, Tex19—also observed
a high impact of parental history on diabetes incidence. No prospective studies
investigating the association between a parental history of diabetes and the
incidence in their female offspring were found in the literature; thus, the
Augsburg results of an approximately 2.5 times higher risk of incident diabetes
in women with a positive parental history of diabetes compared with women
without such parental history have to be confirmed by further studies.
The positive association between cigarette smoking and incident diabetes
in men shown in the present analysis confirmed the results of the Zutphen
Study13 and the Health Professionals' Follow-up
Study.29 The nonsignificant impact of smoking
in women is in contrast to the results of the large American Nurses' Health
Study,22 which showed a significant dose-response
trend between the number of cigarettes smoked and the incidence of diabetes
for 30- to 55-year-old nurses. However, it is possible that the smoking behavior
of nurses does not represent the smoking behavior of the "normal" female population,
since the high stress level typical of nurses may have an impact on their
smoking behavior. In the present analysis, the number of cigarettes smoked
was not taken into account; however, it is known that the number of cigarettes
smoked is higher among men than among women in the Augsburg population.46 Furthermore, the prevalence of regular cigarette
smoking among men was considerably greater than among women. Because of this
sex difference in smoking behavior, it is possible that smoking as a risk
factor had an effect in men but not in women. The Framingham Study20 and the Finnmark Study25
observed that cigarette smoking was not a risk factor among men or women.
In accordance with the Rancho Bernardo Cohort,21
a significant association between heavy alcohol intake and incident diabetes
in men was observed in the Augsburg study. Other prospective studies suggested
an inverse association between alcohol consumption and risk of type 2 diabetes
mellitus in men26-27,29
and women23 or reported no significant impact
on disease development in men17 and women.21 The apparent lack of association between alcohol
intake and type 2 diabetes in women may be due to the fact that there were
too few heavy drinkers among women or the fact that women consumed wine more
often than men did in the present study.
In the MONICA Augsburg Cohort Study, physical inactivity during leisure
time was associated with an 80% increased risk of type 2 diabetes only in
women. In general, a positive association between physical inactivity and
type 2 diabetes independent of obesity has been noted in many prospective
studies in men14, 28, 31
and women.24, 30-31
In the Nurses' Health Study, women who engaged in vigorous exercise at least
once per week had a relative risk of type 2 diabetes mellitus of 0.8 (P = .005) compared with women who did not exercise weekly.24 In contrast to the Augsburg study, the Physicians'
Health Study documented that male physicians who exercised at least once per
week had a relative risk of type 2 diabetes of 0.71 (P
= .006) compared with those who exercised less frequently; the relative risk
of diabetes decreased with increasing frequency of exercise.28
The physical activity measure used in the present study categorized individuals
on the basis of their regular participation in leisure time activity. In general,
men from a population-based study engage in more strenuous physical activity
at work in comparison with women; thus, men are altogether more physically
active, if both occupational and leisure time physical activity is taken into
consideration. Therefore, the sex-related dissimilarities between physical
activity and type 2 diabetes in the Augsburg study could be due to the fact
that men who are classified as inactive are in fact quite active at work.
Uric acid was a strong independent risk factor of diabetes in women
in the present study. As far as we know, no prospective analysis of uric acid
and incident type 2 diabetes has been published for women, but significant
associations between uric acid values and risk of diabetes in men were established
by British,26 Swedish,18
and Israeli studies.15 Whether the observed
sex-related differences in the present study are due to genetically determined
sex-specific metabolic processes or to other factors, such as different dietary
patterns in men and women, for example, warrant further investigations.
The MONICA Augsburg Cohort Study has a number of strengths. The study
is characterized by its large number of subjects drawn from the general population,
the availability of data on multiple cardiovascular risk factors, and the
ability to examine risk factors measured an average of 7.6 years earlier as
potential predictors of subsequent type 2 diabetes. Furthermore, in comparison
with most other prospective cohort studies, a larger number of relevant variables
could be examined simultaneously in men and women. However, several limitations
of this study also need to be considered. First, in the present study only
self-reported information on diabetes status of the subjects was available;
however, validation studies have shown that self-reported diabetes reflects
the true situation reasonably well.47-49
Nevertheless, it is likely that the group of nondiabetic persons may include
subjects with undetected diabetes mellitus. This implies that the observed
hazard ratios in the present study may underestimate the effect of risk factors
on total diabetes incidence. Second, we were unable to differentiate between
persons with normal glucose metabolism and those with borderline hyperglycemia
at baseline examination and at follow-up. Moreover, it was impossible to investigate
the influence of fasting plasma glucose on the development of diabetes because
baseline examination included collection of a nonfasting blood sample. Third,
in the present study only risk factors that were collected in all of the 3
cross-sectional studies could be taken into consideration. Therefore, important
risk factors, such as low-density lipoprotein cholesterol level, triglyceride
level, and waist-to-hip ratio, could not be included in this analysis. Fourth,
incomplete follow-up could also bias the study results. One can suppose that
persons who have diabetes are under regular physician care and might therefore
be less interested in participating in studies like the Augsburg study. Since
diabetic patients have an increased risk of dying of cardiovascular disease,7, 11-12 they could also be
lost by selective mortality during follow-up. Thus, the incidence rates for
men and women in the Augsburg study are most likely underestimated. Moreover,
the follow-up rate of our study was 68%; both male and female nonrespondents
had a slightly higher risk factor profile at baseline in comparison with the
respondents.50 Thus, response bias cannot be
excluded in the present study. However, it seems unlikely that the low response
rate would be responsible for the fact that several risk factors work in one
sex but not the other, since very similar response rates were observed for
both sexes and similar differences in risk factors between participants and
nonparticipants were observed among men and women.
In conclusion, most variables predicting future diabetes in men and
women in the present study are also known to be important risk factors for
cardiovascular disease and arteriosclerosis. Thus, early diagnosis of persons
who are at high risk will be of greatest importance for the prevention of
type 2 diabetes mellitus as well as atherosclerotic vascular disease. However,
further studies are needed to explore the sex-related dissimilarities that
seem to be involved in disease development.
AUTHOR INFORMATION
Accepted for publication April 18, 2001.
This study was supported by grants from the Federal Ministry of Research
and Technology, Bonn, Germany (BMBF-FKZ: 01ER9701/4; survey 1984-1985: BMFT
07064279).
We thank Socialdata (Munich, Germany; MONICA Augsburg survey 1984-1985)
and the company Bernhard Schwertner (Augsburg; MONICA Augsburg surveys 1989-1990
and 1994-1995) for the organization and realization of the surveys and the
follow-up questionnaire in 1998. We also thank Anita Schuler (medical data
manager, KORA [Cooperative Research in the Region of Augsburg] myocardial
infarction registry, Augsburg), Rafael Banos (chemical engineer, laboratory
analyses, Central Hospital of Augsburg, Augsburg), Ulrich Keil, PhD, MPH (University
of Münster, Münster, Germany), as principal investigator of the
study, and, last but not least, all the 13 428 study participants of
the MONICA Augsburg studies.
Corresponding author: Christa Meisinger, MD, MPH, Central Hospital
of Augsburg, MONICA/KORA Augsburg Herzinfarktregister, Stenglinstr 2, D-86156
Augsburg, Germany (e-mail: kora.augsburg{at}t-online.de).
From the GSF National Research Center for Environment and Health, Institute
of Epidemiology, Neuherberg (Drs Meisinger, Thorand, Stieber, Döring,
and Löwel and Ms Schneider), and Central Hospital of Augsburg, KORA-Herzinfarktregister,
Augsburg (Dr Meisinger), Germany.
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