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Background: We previously showed that the common Asn291Ser substitution in lipoprotein lipase is associated with elevated plasma triglyceride levels and a 2-fold increase in the risk of ischemic heart disease in women but not men. In this study, we tested the hypothesis that this substitution is also associated with an increased risk of ischemic cerebrovascular disease (ICVD)., Methods and Results: We compared 260 patients who had nonfatal ICVD and carotid stenosis >/=50% with 1560 age-matched controls and also compared 205 Copenhagen City Heart Study cases who had nonfatal ICVD with 1210 age-matched controls. All subjects were white and from Denmark. Overall, no significant difference was observed between carrier frequencies among those with and without ICVD; however, sex interacted with genotype in predicting ICVD in the ICVD and carotid stenosis cases (P=0.02). In Copenhagen City Heart Study cases, sex was not significant (P=0.18). Odds ratios for ICVD in female mutation carriers were 2.9 (95% confidence interval [CI], 1.3 to 6. 4) and 1.9 (95% CI, 0.8 to 4.6) in ICVD plus carotid stenosis cases and Copenhagen City Heart Study cases, respectively. Equivalent values in male mutation carriers were 0.8 (95% CI, 0.3 to 1.8) and 0.8 (95% CI, 0.3 to 2.0), respectively. These results were similar in analyses that also allowed for other conventional cardiovascular risk factors., Conclusions: These results suggest that the Asn291Ser substitution in lipoprotein lipase is not associated with nonfatal ICVD in men but that it possibly confers a 2-fold risk in women.

We studied the course of forced expiratory volume in one second (FEV1) in adults with self-reported asthma using data from a longitudinal epidemiological study of the general population, The Copenhagen City Heart Study. The study was conducted over a period of 15 years with three measurements of lung function. The data base consisted of 17,506 men and women including 1.095 participants with asthma. The unadjusted FEV1 decline in subjects with asthma was 38 ml/year compared to 22 ml/year in nonasthmatics. Similarly, the statistical analysis showed that the FEV1 normalised by height (FEV1/height2) was significantly poorer in subjects with asthma compared to nonasthmatics (p < 0.001). Smoking contributed significantly to lung function decline regardless of asthma status (p < 0.001). In a sample of the general population, adults with self-reported asthma have a significantly faster decline of ventilatory function than nonasthmatics.

Background: The less favorable trend in smoking prevalence in women compared to men may be due to lower cessation rates. We analyzed determinants of spontaneous smoking cessation with particular reference to gender differences., Methods: Data on smoking were collected by questionnaire in three samples of the adult population, examined for the first time at intervals between 1976 and 1984. In total 11,802 (59%) subjects were smokers, and 9085 of them attended a reexamination after 5 years. Ten to 16 years later 6053 were examined once again. Logistic regression was performed to study the relation of determinants to having quit after 5 and 10-16 years., Results: The prevalence of quitting was 12 and 22% at first and second follow-up, respectively. At both reexaminations, quitting smoking was positively associated with male sex and cigar smoking and negatively associated with the amount of tobacco smoked, inhalation, and alcohol consumption. Furthermore, in women, smoking cessation was positively associated with level of education and body mass index (BMI). Smoking cessation was not affected by cohabitation status, leisure activity, or bronchitis symptoms., Conclusions: Smoking cessation initiatives should be targeted at heavy cigarette smokers, and at women, in particular the lean and poorly educated., (Copyright 1999 American Health Foundation and Academic Press.)

Studies reporting increased mortality in smokers are abundant, but only few have included large numbers of heavily smoking women. Based on three large Danish population studies we calculated median survival in smokers and never-smokers and compared the impact of smoking in men and women. Seventeen thousand six hundred and sixty-nine men and 13,525 women were followed for up to 30 years for all-cause mortality. During follow-up there were 8644 deaths. Large differences in tobacco-exposure between men and women were found, in particular in older birth-cohorts. Despite a smaller accumulated exposure, the impact smoking had on median survival was similar in men and women. Female inhaling heavy smokers (> or = 15 cig./day) lost 9.4 and inhaling light smokers 7.4 years in comparison with female never-smokers. Corresponding loss of life-expectancy in males was 9.2 years and 6.0 years, respectively. In conclusion, this study shows survival prospects in relation to smoking in both men and women in a way that is easily communicated. The results indicate that women who smoke as much as men run a relatively higher risk in terms of reduced life expectancy.

Background: Studies of time trends in smoking prevalence provide a better understanding of the determinants of smoking. The present study analyses changes over time in the prevalence of smoking and heavy smoking in relation to sex, age, and education., Methods: Data on smoking behaviour were collected by questionnaire in random samples of the general population in the area of Copenhagen. The database used included 71,842 measurements of smoking behaviour for 32,156 subjects aged 30 years or more, who had been examined at intervals between 1964 and 1994. In bi- and multivariate analyses the effects of sex, age, education, time period, and study group on the prevalence of smoking and of heavy smoking were assessed., Results: Smoking was least prevalent in women, in the oldest age group (more than 70 years), and among those with 8 years or more of school education. During the study period (from 1964/74 to 1990/94), the prevalence of smoking decreased from 72% to 54% in men and from 52% to 46% in women. In both men and women this decrease was smallest in the least educated (less than 8 years of school education). Heavy smoking was also least prevalent in women, in the oldest age group, and among the well educated. During the study period, the unadjusted prevalence of heavy smoking decreased from 52% to 38% in men, while it increased from 17% to 21% in women. The multivariate analysis showed that the time trend for heavy smoking only depended on sex, while educational attainment and age had no impact on the trend., Conclusion: During the last 30 years the prevalence of smoking has decreased in Denmark. The decrease has been smallest in women, and among the least educated, and the increasing trend in the prevalence of heavy smoking in women is a cause for concern.

Background and Purpose: Alcohol consumption has been associated with a protective effect on risk of ischemic stroke. There may, however, be differences in the effect of beer, wine, and spirits due to properties other than ethanol, a topic that has gained only little attention in stroke research., Methods: Our analysis was a prospective cohort study of 13 329 eligible men and women, aged 45 to 84 years, participating in the Copenhagen City Heart Study. Information on alcohol habits and a number of socioeconomic and health-related factors was obtained at baseline. During 16 years of follow-up, 833 first-ever strokes occurred. Data were analyzed by means of multiple Poisson regression., Results: We found indications of a U-shaped relation between intake of alcohol and risk of stroke. In analyses adjusted for age, sex, and smoking, intake of wine on a monthly, weekly, or daily basis was associated with a lower risk of stroke compared with no wine intake (monthly: relative risk [RR], 0. 83; 95% CI, 0.69 to 0.98; weekly: RR, 0.59; 95% CI, 0.45 to 0.77; daily: RR, 0.70; 95% CI, 0.46 to 1.00). This effect of wine intake remained after complete adjustment for confounding variables (monthly: RR, 0.84; 95% CI, 0.70 to 1.02; weekly: RR, 0.66; 95% CI, 0.50 to 0.88; daily: RR, 0.68; 95% CI, 0.45 to 1.02). There was no association between intake of beer or spirits on risk of stroke., Conclusions: The differences in the effects of beer, wine, and spirits on the risk of stroke suggest that compounds in the wine in addition to ethanol are responsible for the protective effect on risk of stroke.

Objective: to assess the relation between alcohol intake and mortality among seven cohorts of middle-aged and elderly Danes., Design: Prospective population study with baseline assessment of alcohol- and tobacco consumption, educational level and body mass index, and a mean of 11.5 years follow-up of mortality., Subjects: 16304 men and women aged 50 years or more., Main Outcome Measure: number and time of deaths from 1974 to 1995 as ascertained by the national central person register., Results: the effect of alcohol intake on mortality did not differ between middle-aged (50-64 years, mean = 56.6 years) and elderly subjects (>64 years old, mean = 69.9 years). There was a U-shaped risk function in both age groups, which persisted also when adjusting for age, sex, smoking habits, level of education and body mass index. Abstaining women had a relative risk of 1.29 (95% confidence limits 1.17-1.42) as compared with light drinkers (1-6 (drinks per week), while the relative risk for abstaining men was 1.22 (95% confidence limits; 1.08 to 1.37) as compared with light drinkers. Heavy drinking women (>28 drinks per week) had a relative risk of 1.23 (95% confidence limits; 0.85 to 1.78) and heavy drinking men (more than 69 drinks per week) had a relative risk of 2.11 (95% confidence limits 1.66-2.69), both compared with light drinkers., Conclusion: among the middle-aged and elderly women and men, a light alcohol intake is associated with lower mortality than abstention or heavy drinking.

Background: Although the prevalence of asthma and morbidity related to asthma are increasing, little is known about the natural history of lung function in adults with this disease., Methods: We used data from a longitudinal epidemiologic study of the general population in a Danish city, the Copenhagen City Heart Study, to analyze changes over time in the forced expiratory volume in one second (FEV1) in adults with self-reported asthma and adults without asthma. The study was conducted between 1976 and 1994; for each patient, three measurements of lung function were obtained over a 15-year period. The final data set consisted of measurements from 17,506 subjects (8136 men and 9370 women), of whom 1095 had asthma., Results: Among subjects who participated in all three evaluations, the unadjusted decline in FEV1 among subjects with asthma was 38 ml per year, as compared with 22 ml per year in those without asthma. The decline in FEV1 normalized for height (FEV1 divided by the square of the height in meters) was greater among the subjects with asthma than among those without the disease (P<0.001). Among both men and women, and among both smokers and nonsmokers, subjects with asthma had greater declines in FEV1 over time than those without asthma (P<0.001). At the age of 60 years, a 175-cm-tall nonsmoking man without asthma had an average FEV1 of 3.05 liters, as compared with 1.99 liters for a man of similar age and height who smoked and had asthma., Conclusions: In a sample of the general population, people who identified themselves as having asthma had substantially greater declines in FEV1 over time than those who did not.

Background: We have previously reported that men who look older than their contemporaries have a significantly higher risk for myocardial infarction. The purpose of this study was to investigate whether persons with pronounced aging signs such as graying of hair, baldness, or facial wrinkles are prone to a shorter life span compared to their contemporaries., Methods: In the Copenhagen City Heart Study comprising a random sample of 20,000 men and women, we also recorded, in addition to cardiovascular risk factors, data on signs of aging: extent of gray hair, baldness, facial wrinkles, and arcus senilis (corneal arcus). During 16 years of follow-up, 3,939 persons (1,656 women and 2,283 men) had died. The Cox regression model for proportional hazards, which included age as an explanatory variable, was used for descriptive analysis of the correlation between these aging signs and all-cause mortality., Results: We found no correlation between the mortality and the extent of graying of the hair, or baldness or facial wrinkles in either of the sexes, irrespective of age. A single exception was observed in a small subgroup of men with no gray hair. They had a slightly, but significantly, lower mortality than the rest [relative risk (RR) = .81, 95% confidence interval (CI) .67-.98; p < .05]. The presence of arcus senilis was significantly correlated with a shorter life span in women (RR = 1.25, 95% CI 1.08-1.46; p < .01). For men the same tendency was found, but the correlation was not statistically significant., Conclusion: We conclude that the degrees of graying of the hair, baldness, and facial wrinkles are not predictive of a shorter life span in men and women in the Copenhagen City Heart Study.

Lipoprotein lipase degrades triglycerides in plasma and as a by-product produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9214 men and women from a general population sample and 948 patients with ischaemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with non-carriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/L), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/L and delta = 0.11 mmol/L, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischaemic heart disease in both genders. On univariate analysis, odds ratios for ischaemic heart disease in probands were 1.89 in women (95% confidence interval: 1.19-3.01) and 0.90 (0.62-1.31) in men, and on multivariate analysis 1.98 (1.11-3.53) in women and 1.02 (0.65-1.60) in men. This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischaemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides, not predisposed to ischaemic heart disease.

Background: Familial hypercholesterolemia leads to premature ischemic heart disease and is often caused by mutations in the gene for the low-density lipoprotein receptor. Mutations in the apolipoprotein B gene, which encodes a ligand for this receptor, may also result in this phenotype., Methods: We studied the genotypes of 9255 women and men from the general population, 948 patients with ischemic heart disease, and 36 patients with familial hypercholesterolemia, all from Denmark, for three mutations in the apolipoprotein B gene: Arg3500Gln, Arg3531Cys, and Arg3500Trp., Results: The prevalence of heterozygotes in the general population was 0.08 percent (95 percent confidence interval, 0.03 to 0.16 percent) for both the Arg3500Gln and the Arg3531Cys mutations, and 0.00 percent (95 percent confidence interval, 0.00 to 0.18 percent) for the Arg3500Trp mutation. Among carriers of the Arg3500Gln mutation, cholesterol levels were significantly higher than among noncarriers in the general population - by 100 mg per deciliter (2.6 mmol per liter) among carriers in the general population, 154 mg per deciliter (4.0 mmol per liter) among patients with ischemic heart disease, and 172 mg per deciliter (4.5 mmol per liter) among patients with familial hypercholesterolemia. Heterozygous carriers of the Arg3500Gln mutation were significantly more common among patients with ischemic heart disease (odds ratio, 7.0; 95 percent confidence interval, 2.2 to 22; P=0.003) and patients with familial hypercholesterolemia (odds ratio, 78; 95 percent confidence interval, 16 to 388; P=0.001) than in the general population. Heterzygous carriers of the Arg3531Cys mutation in the general population did not have higher-than-normal plasma cholesterol levels or an increased risk of ischemic heart disease (odds ratio; 1.4; 95 percent confidence interval, 0.2 to 11; P=0.54)., Conclusions: The Arg3500Gln mutation in the apolipoprotein B gene, which is responsible for familial defective apolipoprotein B-100 and is present in approximately 1 in 1000 persons in Denmark, causes severe hypercholesterolemia and increases the risk of ischemic heart disease.

Study Aim: To examine survival after admission due to chronic obstructive pulmonary disease (COPD) in a population sample over a time span of 15 years., Design: Linkage between a prospective population cohort and register information on hospitalization and mortality., Setting: The Copenhagen City Heart Study (CCHS)., Participants: A total of 267 men and 220 women who had participated in the CCHS and who were hospitalized with a discharge diagnosis of COPD (ICD-8 491-2)., Main Results: The crude 5-yr survival rate after a COPD admission was 45% (37% for men and 52% for women). Mortality risk increased with age and with decreasing forced expiratory volume in 1 s (FEV1)% predicted; for subjects with an FEV1 < or = 40% at the CCHS survey, 5-yr survival after subsequent hospitalization was only 28%. Smoking and presence of chronic mucus hypersecretion at the examination in CCHS were not strongly associated with prognosis. Survival after admission due to COPD did not change significantly over time., Conclusion: Compared to previous studies of COPD patients, the present study indicates that prognosis after hospital admission remains virtually unchanged over the last decades. FEV1 is still the strongest predictor of survival in this patient group.

Objective: To compare risk of myocardial infarction associated with smoking in men and women, taking into consideration differences in smoking behaviour and a number of potential confounding variables., Design: Prospective cohort study with follow up of myocardial infarction., Setting: Pooled data from three population studies conducted in Copenhagen., Subjects: 11,472 women and 13,191 men followed for a mean of 12.3 years., Main Outcome Measures: First admission to hospital or death caused by myocardial infarction., Results: 1251 men and 512 women had a myocardial infarction during follow up. Compared with non-smokers, female current smokers had a relative risk of myocardial infarction of 2.24 (range 1.85-2.71) and male smokers 1.43 (1.26-1.62); ratio 1.57 (1.25-1.97). Relative risk of myocardial infarction increased with tobacco consumption in both men and women and was higher in inhalers than in non-inhalers. The risks associated with smoking, measured by both current and accumulated tobacco exposure, were consistently higher in women than in men and did not depend on age. This sex difference was not affected by adjustment for arterial blood pressure, total and high density lipoprotein cholesterol concentrations, triglyceride concentrations, diabetes, body mass index, height, alcohol intake, physical activity, and level of education., Conclusion: Women may be more sensitive than men to some of the harmful effects of smoking. Interactions between components of smoke and hormonal factors that may be involved in development of ischaemic heart disease should be examined further.

Background: Mortality from smoking-related diseases in women is increasing worldwide. Studies comparing hazards associated with smoking in women and men based on a sufficient number of heavy smokers of both genders are lacking., Methods: We used pooled data from three prospective population studies conducted in Copenhagen to compare total and cause-specific mortality in relation to smoking habits. A total of 30917 subjects, 44% women, with initial examinations between 1964 and 1992 were followed until 1994 for date and cause of death., Results: During follow up, 2900 women and 5744 men died. Smoking characteristics differed considerably with gender, particularly in the older subjects. Overall mortality rates in smokers were approximately twice those in people who never smoked. Positive associations with smoking in both men and women were confirmed for all-cause mortality as well as mortality from respiratory disease, vascular disease, lung cancer, and other tobacco-related cancers. Despite large gender differences in age at smoking debut, total and cause-specific relative mortality in smokers was similar in men and women. After excluding non-inhalers, relative risks associated with smoking for respiratory and vascular disease were higher for women than men whereas there were no gender differences in smoking related risk of cancers., Conclusions: The relative risks suggest that women may be more sensitive than men to some of the deleterious effects of smoking. However, because of lower baseline mortality rates in women, rate differences may be similar and results should be interpreted with caution.

Our aim was to compare risk of lung cancer associated with smoking by gender and histologic type. A total of 30,874 subjects, 44% women, from three prospective population-based studies with initial examinations between 1964 and 1992 were followed until 1994 through the National Cancer Registry. There were 867 cases of lung cancer, 203 among women and 664 among men. Rates among female and male never-smokers were similar, although confidence intervals around rates were wide. Rate ratios (RRs) increased with number of pack-years for both men and women to a maximum of approximately 20 in inhaling smokers with more than 60 pack-years of tobacco exposure. RRs did not differ much between men and women: adjusted for pack-years, age, and study population, the ratio between female and male smokers' RRs of developing lung cancer was 0.8 (95% confidence interval = 0.3-2.1). All histologic types were associated with smoking, with the largest RR seen for squamous cell carcinoma and anaplastic carcinoma. This prospective population-based study does not confirm previous reports from case-control studies of a higher relative risk in women than in men for lung cancer associated with smoking.

Sudden cardiovascular events among well-known politicians attract much attention--from the mass media and from the public. No previous studies have assessed the job strain profile and level of known cardiovascular risk factors among parliamentary politicians. The study was carried out within the frameworks of the Copenhagen City Heart Study. Some 102 members of the Danish parliament (70 men and 32 women) agreed to participate, giving a response rate of 55%. Three sex- and age-matched participants were drawn for each politician from the Copenhagen City Heart Study. In addition to the completion of large questionnaires on health and working conditions, all participants had a thorough examination, including measurements of height and weight and blood pressure and the drawing of a venous blood sample for the determination of serum lipids, ApolipoproteinA1 and ApolipoproteinB and fibrinogen. Job strain factors and established cardiovascular risk factors were the main outcome factors. Politicians reported much higher job demands, but also much more influence on their job than others. Politicians smoked less, consumed more wine, had higher levels of ApolipoproteinA1, and were taller. With respect to other major cardiovascular risk factors, serum lipids, blood pressure and physical activity, there was no difference between politicians and controls. Politicians had greater job demands, but also more control over their job than others, indicating that the job strain phenomenon should not increase their risk of cardiovascular disease. Other cardiovascular risk factors, job related or conventional, which were unevenly distributed between politicians and controls all favoured politicians. In conclusion, politicians had a more beneficial cardiovascular risk factor profile than a matched random sample from a comparable background population.

Background: Two recent much cited publications have raised the concern that risk associated with cigarette smoking has so far been underestimated. In this study we wish to determine whether excess all-cause mortality associated with smoking has increased during the last 20-30 years in a study population representative of the general Danish population and whether any such changes relate to changes in smoking behaviour., Methods: Pooled data from three prospective population studies conducted in Copenhagen with detailed information on smoking habits. A total of 31,194 subjects, 17,669 males and 13,525 females, initially examined between 1964 and 1992 with examinations repeated at intervals from 1-10 years, were followed until 1995 for all-cause mortality. Relative mortality risk in smokers versus never-smokers was calculated within periods of five calendar years and compared throughout the study period., Results: Male smokers' exposure did not change during the study period whereas female smokers' exposure to tobacco increased in terms of age at smoking onset, quantity smoked and depth of inhalation. During follow-up 5744 males and 2900 females died. In males, death rate ratios (comparing continuous smokers with never-smokers) did not change in the study period. In females, ratios increased from 1964-1978 to 1979-1994 by a factor of 1.3 (95% confidence interval 1.0-1.8)., Conclusions: In agreement with the observed changes in smoking habits, excess mortality in male smokers did not increase whereas excess mortality in female smokers increased slightly.

Background and Purpose: Stroke incidence has increased in some countries and decreased in others. After 20 years of intensive antihypertensive treatment the latter could be expected, and we have evaluated the sex-specific temporal trends in stroke incidence using 17 years of follow-up in the Copenhagen City Heart Study., Subjects and Methods: Our cohort comprised 19,698 subjects living in Copenhagen, Denmark. They were invited for health examinations in the following time periods: 1976 through 1978, 1981 through 1983, and 1992 through 1994. Trends are presented for all persons who attended at least one of the two first examinations as well as the total cohort including nonresponders. Subjects between 45 and 84 years of age were followed from March 1, 1976 until March 1, 1993. Changes in age-specific stroke incidence were calculated by means of Poisson regression analysis., Results: For subjects aged 45 to 64 years, no significant trends were observed, with an annual incidence rate ratio of 1.00 (95% confidence interval [CI], 0.97 to 1.03) and 1.04 (95% CI, 0.99 to 1.08) for men and women, respectively. In subjects aged 65 to 84 years a significant decrease in stroke incidence was found in men, whose annual rate ratio was 0.97 (95% CI, 0.95 to 0.99), but not in women, whose annual rate ratio was 0.98 (95% CI, 0.95 to 1.00). Throughout four observed periods the stroke incidence among men remained significantly higher than that for women., Conclusions: During the period from 1976 to 1993 there has been a decline in incidence of stroke in men and women aged 65 to 84 years that was significant only in men, whereas no changes were found for persons aged 45 to 64 years.

A common mutation (G-455--> A) in the promoter region of the beta-fibrinogen gene has been associated with elevated plasma fibrinogen levels. Whether fibrinogen genotype affects plasma fibrinogen levels and risk of ischemic heart disease in the general population has not been studied. We investigated the association between fibrinogen genotype, plasma fibrinogen levels, and ischemic heart disease in a general population sample (n = 9,127). The A-allele (relative frequency, 0.20) was associated with elevated plasma fibrinogen levels in both genders (P < 0.001). While the effect of the A-allele on fibrinogen level was additive in men, the effect was dominant in postmenopausal women. The A-allele raising effect appeared to be two- to threefold greater in individuals with ischemic heart disease than in those without. An increase of 1 SD in plasma fibrinogen increased the odds ratio for ischemic heart disease by approximately 20% (P < 0.01 for women and < 0.005 for men). However, the frequency of the A-allele was similar in those with and without ischemic heart disease, and genotype was not a predictor of disease. These results demonstrate that the (G-455--> A) mutation in the promoter region of the beta-fibrinogen gene is associated with an increase in plasma fibrinogen in both genders in the general population. This increase does not appear to cause ischemic heart disease.

The association between self-reported alcohol intake and the risk of future liver disease was studied in a population-based prospective cohort of 13,285 men and women aged 30-79 years. Diagnoses indicating alcoholic liver disease (n = 261) or cirrhosis (n = 124) were obtained from the Danish National Health Registers. The cumulated observation time was 130,558 person-years. A dose-dependent increase in risk of developing liver disease was observed with increasing alcohol intake, with the steepest increase among women. At an alcohol intake of 7-13 beverages per week for women and 14-27 beverages per week for men the relative risk was significantly greater than 1. Women had a significantly higher relative risk of developing alcohol related liver disease than men for any given level of alcohol intake. In the general population, self-reported current alcohol intake is a good predictor of the future risk of alcoholic liver disease.

Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9,214 men and women from a general population sample and 948 patients with ischemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/liter), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/liter and delta = 0.11 mmol/liter, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischemic heart disease in both genders. On univariate analysis, odds ratios for ischemic heart disease in probands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0.62-1.31), and on multivariate analysis were 1.98 in women (95% CI: 1.11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides not predisposed to ischemic heart disease.

The association between self-reported alcohol intake and the risk of future liver disease was studied in a large population-based prospective cohort with 12-year follow-up. Alcohol intake was assessed in 13,285 men and women aged 30 to 79 years by a self-administered questionnaire. Diagnoses indicating alcohol-induced liver disease (n = 261) or alcohol-induced cirrhosis (n = 124) were obtained from death certificates and the hospital discharge register, and data were analyzed by multiplicative Poisson regression models. The total cumulated observation time was 130,558 person-years. The overall incidence rates of alcohol-induced cirrhosis were 0.2% per year in men and 0.03% per year in women. The nadir of the estimated relative risk of developing liver disease was observed at an alcohol intake of 1 to 6 beverages per week, and above this level a steep increase in relative risk was observed. The risk function was independent of age and stable over time. The level of alcohol intake above which the relative risk was significantly greater than 1 was observed at 7 to 13 beverages per week for women and 14 to 27 beverages per week for men. Women had a significantly higher relative risk of developing alcohol-related liver disease than men for any given level of alcohol intake. We observed a dose-dependent increase in relative risk of developing alcohol-induced liver disease for both men and women, with the steepest increase among women. In the general population, self-reported current alcohol intake is a good predictor of the future risk of alcohol-induced liver disease.

In a prospective population study of 7,234 women and 6,051 men aged 30-79 years, information on beer, wine, spirits and tobacco consumption, and on education, income and body mass index were assessed in the period 1976-1978, and the population was followed until 1.1.1988 for mortality. With increasing intake, the wine-mortality risk function steadily decreased from a relative risk of 1.00 for those who never drank wine through 0.51 (95% confidence limits; 0.32-0.81) among those who drank three to five glasses per day. In contrast, neither beer nor spirits consumption was associated with reduced risk. For spirits consumption the relative risk of dying increased from 1.00 among those who never drank to 1.34 (1.05-1.71) among those with an intake of 3-5 drinks per day. Wine drinking showed the same relation to risk of death from cardio- and cerebrovascular disease as to mortality from all causes.

To investigate a possible relation between aging signs such as graying of the hair, baldness, and facial wrinkling and myocardial infarction (MI), we analyzed data from The Copenhagen City Heart Study. During the 12-year follow-up, 750 cases of first-time MI were observed. After statistical adjustment for possible confounders, we found a correlation between graying of the hair, facial wrinkling, and frontoparietal baldness and crown-top baldness and MI in men. For example, the relative risk was 1.4 (95% CI, 0.9 to 2.0) for men with moderately gray hair compared with men with no gray hair and 1.9 (1.2 to 2.8) for men with completely gray hair (p < 0.001). With regard to gray hair, a similar although weaker and not statistically significant trend was seen in women. We conclude that, in addition to established coronary risk factors, aging signs like graying of the hair, male baldness, and facial wrinkling indicate an additional risk of MI.

Objective: To examine the association between intake of different types of alcoholic drinks and mortality., Design: Prospective population study with baseline assessment of alcohol intake, smoking habit, income, education, and body mass index, and 10-12 years' follow up of mortality., Setting: Copenhagen city heart study, Denmark., Subjects: 6051 men and 7234 women aged 30-70 years., Main Outcome Measure: Number and time of cause-specific deaths from 1976 to 1988., Results: The risk of dying steadily decreased with an increasing intake of wine--from a relative risk of 1.00 for the subjects who never drank wine to 0.51 (95% confidence interval 0.32 to 0.81) for those who drank three to five glasses a day. Intake of neither beer nor spirits, however, was associated with reduced risk. For spirits intake the relative risk of dying increased from 1.00 for those who never drank to 1.34 (1.05 to 1.71) for those with an intake of three to five drinks a day. The effects of the three types of alcoholic drinks seemed to be independent of each other, and no significant interactions existed with sex, age, education, income, smoking, or body mass index. Wine drinking showed the same relation to risk of death from cardiovascular and cerebrovascular disease as to risk of death from all causes., Conclusion: Low to moderate intake of wine is associated with lower mortality from cardiovascular and cerebrovascular disease and other causes. Similar intake of spirits implied an increased risk, while beer drinking did not affect mortality.

The aim of the study was to examine the association between self-reported alcohol intake and subsequent mortality from all causes, and to examine if the effect of alcohol intake on the risk of death was modified by sex, age, body mass index, and smoking habits. In a prospective population study of 7,234 women and 6,051 men aged 30-79 years alcohol- and tobacco consumption and body mass index were assessed in the period 1976-1978, and the population was followed until 1.1.1988 for mortality. A U-shaped curve described the relation between alcohol intake and mortality. The nadir of the risk function was observed at one to six beverages per week (relative risk set at 1.00). Abstainers had a relative risk of 1.37 (95% confidence intervals: 1.20-1.56), whereas those drinking more than 70 beverages per week had a relative risk of 2.29 (1.75-3.00). Among the drinkers, the risk was significantly higher than 1 only among those drinking more than 42 beverages per week. Neither sex, age, body mass index, nor smoking significantly modified the risk function. Our findings suggest that simple messages about the benefits of total abstinence may not be appropriate.

Objectives: To examine if increased egg consumption raises serum high-density-lipoprotein (HDL) cholesterol in healthy individuals., Design: A cross-over study., Setting: A private clinic for preventive health examinations in Copenhagen., Subjects: Twenty-four healthy adults, 12 men and 12 women, aged 23-52 (median 40) years., Interventions: After a 1-week control period each person added two boiled eggs to the usual daily diet for 6 weeks. All persons were instructed not to change the lifestyle in other ways during the whole study period., Main Outcome Measures: Serum HDL cholesterol, total cholesterol and triglycerides were measured before, during and after 6 weeks of extra egg consumption. The corresponding serum low-density-lipoprotein (LDL) cholesterol was calculated from the Friedewald formula., Results: After 6 weeks of extra egg consumption serum HDL cholesterol increased by 10% (P < 0.05) and total cholesterol increased 4% (P < 0.05), whereas the ratio total cholesterol/HDL cholesterol did not change significantly. Serum triglycerides and LDL cholesterol were also unchanged., Conclusions: A moderate egg intake should not be rigorously restricted in healthy individuals.

Background: Similar smoking-related changes in the collagen and elastin could play a role in the pathogenesis of both skin wrinkling and chronic airflow obstruction. The hypothesis was tested by analyzing whether increased facial wrinkling, especially in smokers, is associated with the presence of airflow obstruction., Methods: An age-stratified randomized sample of the general population comprising 6034 men and 7152 women between 30 and 80 years of age was analyzed. The recording of wrinkling in the crow's foot area of the right eye was performed according to an earlier described severity score. As an index of airflow obstruction, we used the ratio between forced expiratory volume in 1 s and forced vital capacity in percent (FEV1/FVC%)., Results: Multiple regression analysis comprising current and previous smokers showed that, after controlling for age, subjects with highest wrinkle scores had on average FEV1/FVC% that was 1.2-1.9% lower than in subjects with lower wrinkle scores. No association between facial wrinkling and airflow obstruction was observed among lifetime nonsmokers., Conclusions: Increased facial wrinkling is independent of age when associated with airflow obstruction in smokers, but not in never-smokers. The magnitude of this association, however, is small.

Objective: To examine the association between self reported alcohol intake and subsequent mortality from all causes and if the effect of alcohol intake on the risk of death is modified by sex, age, body mass index, and smoking., Design: Prospective population study with baseline assessment of alcohol and tobacco consumption and body mass index, and 10-12 years' follow up of mortality., Setting: Copenhagen city heart study, Denmark., Subjects: 7234 women and 6051 men aged 30-79 years., Main Outcome Measure: Number and time of deaths from 1976 to 1988., Results: A total of 2229 people died, 1398 being men. A U shaped curve described the relation between alcohol intake and mortality. The lowest risk was observed at one to six alcoholic beverages a week (relative risk set at 1). Abstainers had a relative risk of 1.37 (95% confidence interval 1.20 to 1.56) whereas those drinking more than 70 beverages a week had a relative risk of 2.29 (1.75 to 3.00). Among the drinkers, the risk was significantly increased only among those drinking more than 42 beverages a week. Sex, age, body mass index, and smoking did not significantly modify the risk function. The risk among heavy drinkers was slightly reduced when smoking was controlled for. The risk function was similar in the first and second period of six years of observation., Conclusion: Alcohol intake showed a U shaped relation to mortality with the nadir at one to six beverages a week. The risk function was not modified by sex, age, body mass index, or smoking and remained stable over 12 years.

Data from The Copenhagen City Heart Study, a prospective population study, were analysed to investigate the influence of the type of tobacco and inhalation on mortality from lung cancer and chronic obstructive pulmonary disease (COPD). The study sample comprised 2986 plain cigarette smokers, 3222 filter cigarette smokers, 1578 smokers of cheroots/cigars, 433 male pipe smokers and 773 smokers smoking more than one type of tobacco. From 1976 to the end of 1989 we observed 268 deaths from lung cancer and 195 deaths, where COPD was considered as either the main or the contributory cause of death. Current smokers of all types of tobacco had a significantly higher risk of mortality from the investigated diseases than never-smokers. In both sexes the risks of death from both lung cancer and COPD were lower in cheroot/cigar smokers and in pipe smokers than in cigarette smokers, but these differences were markedly diminished after an adjustment for the inhalation habit. The present study substantiates that tobacco smoking increases pulmonary mortality. The small differences between the various types of tobacco are probably caused by different inhalation patterns.

The effects of low-dose (350 mg daily) polyunsaturated fatty acids from fish oil, either in gelatine capsules or microencapsulated, were investigated in a non-blind, randomized, crossover study of 12 healthy male volunteers. The authors measured the incorporation of eicosapentaenoic acid (EPA) into platelets membranes, platelet aggregability by adenosine diphosphate (ADP) and adrenaline, and fibrinolytic activity as euglobulin lysis time, after two and six weeks of therapy. Both formulations resulted in increased incorporation of EPA into platelet membranes, and the microencapsulated formulation also significantly increased the platelet level of ADP for irreversible aggregation (by about 60%). Fish oil in gelatine capsules had a smaller, non-significant effect in the same direction. Both formulations reduced adrenaline-induced aggregability, but the effects did not attain significance. Neither formulation altered fibrinolysis. The data show that low doses of fish oil in microencapsulated form significantly lower platelet aggregability, without affecting fibrinolysis.

Data from The Copenhagen City Heart Study, a prospective population study, were analysed to investigate the influence of the type of tobacco and inhalation on pulmonary and total mortality. The study sample comprised 6,511 men and 7,703 women, selected randomly after age-stratification from the general population. There were 2,986 plain cigarette smokers, 3,222 filter cigarette smokers, 1,578 smokers of cheroots/cigars, 433 male pipe smokers and 773 subjects smoking more than one type of tobacco. From 1976 until the end of 1989, 2,765 subjects died. Lung cancer was considered as main death cause in 268. Chronic obstructive pulmonary disease (COPD) was considered as the main cause in 94 cases and main or contributory cause of death in 195 cases (COPD related mortality). Current smokers had a higher risk of total mortality compared to lifetime nonsmokers: the relative risks (RR) ranged between 1.2 for male pipe smokers and 2.4 for female plain cigarette smokers. With regard to lung cancer mortality, the RR ranged between 4.1 for male pipe smokers and 7.9 for female plain cigarette smokers. Even higher RR values were estimated for COPD related mortality. In both sexes, the RR for the investigated end-points were lower in cheroot/cigar smokers and in pipe smokers than in cigarette smokers, but these differences were markedly diminished after an adjustment for the inhalation habit. The present study substantiates the view that tobacco smoking increases pulmonary and total mortality. The small differences between the various types of tobacco are probably caused by different inhalation patterns.

The relationship of ventilatory function to cardiovascular events was studied in 12,511 men and women, enrolled in 1976-1978 in a prospective population study. Until the end of 1983, 388 subjects died because of a cardiovascular disease, 133 died within 30 days of developing myocardial infarction (fatal myocardial infarction), while 238 had a non-fatal myocardial infarction. Cox proportional hazards models were employed for the analysis. In the models including tobacco smoking, cholesterol level, blood pressure, diabetes mellitus and body-mass index as covariates, forced expiratory volume in one second in percentage of predicted (FEV1% pred), forced vital capacity in percentage of predicted (FVC% pred), and the ratio between FEV1 and FVC (FEV1/FVC) were significantly related to the risk of cardiovascular death, e.g. compared with subjects with FEV1% pred or FVC% pred greater than or equal to 80 the risk of death from cardiovascular disease among subjects with FEV1% pred or FVC% pred less than 60 was approximately twice as high. There was a nonsignificant trend towards an increased risk of fatal myocardial infarction with reduction of FVC% pred, but in general the regression models did not show consistent relationship between lung function impairment and risk of myocardial infarction. In the regression models, which only included age and sex as covariates, reduced FVC% pred and FEV1% pred were significantly related to both cardiovascular mortality and to fatal myocardial infarction, but not to the non-fatal infarction, whereas the FEV1/FVC ratio was not related to fatal or to non-fatal myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

On the basis of the Osterbro investigation (Copenhagen City Heart Study) which includes several thousand smokers and non-smokers, the authors have analysed the risk of developing chronic mucus hypersecretion and decrease in forced expiration volume in the first second of expiration (FEV1) in the course of a five-year period in the following groups: non-smokers, smokers of cigarettes without filters, smokers of filter cigarettes, smokers of cigarillos/cigars and pipe smokers. All of the types of tobacco investigated led to increased loss of pulmonary function and to increased risk of development of mucus hypersecretion as compared with non-smokers. The differences between the injurious effects of the types of tobacco were limited and were probably due to different inhalation habits in the various groups of smokers. It is concluded that there is no evidence that change from one type of tobacco (eg cigarettes) to another type (eg pipe or cigar tobacco) will reduce the risk of developing chronic obstructive pulmonary disease unless the change is accompanied by considerable reduction of the tobacco consumption.

When analyzing risk factors for first acute myocardial infarction in the Copenhagen City Heart Study, a large prospective population study of 20,000 men and women, smoking was found to influence risk significantly in a dose-dependent manner, the risk increasing 2% to 3% for each gram of tobacco smoked daily. Risk was particularly associated with inhalation, the risk for inhalers being almost twice that of noninhalers. No difference in risk could be demonstrated between various types of tobacco (pipe, cigar/cheroots, or plain and filtered cigarettes). The risk seemed associated with current smoking only, inasmuch as the duration of the smoking habit was not important. Ex-smokers had the same risk as those who had never smoked regardless of duration of smoking and time elapsed since quitting. Relative excess risk was significantly higher in female smokers than in male smokers, and daily alcohol intake appeared to have some protective effect on the risk of first acute myocardial infarction among heavy smokers.

The Copenhagen City Heart Study is a prospective cardiovascular population study designed to evaluate incidence of, and risk factors for, cardiovascular disease. A random sample, comprising approximately 20,000 people, were invited to participate. Initial information about potential risk factors was collected during 1976-78 (attendance rate 74%); data about 389 new cases of first acute myocardial infarction (AMI) was obtained from a second survey in 1981-83, as well as from hospital and death registers up to 31 December 1983. The average observation period was 6.5 years. Cox's regression model was used for data analysis. Some 'basic' factors, namely age, sex, family history of AMI, early parental death, height, earlobe crease, length of school education, income and living alone or with a partner were dealt with in a previous paper and are among the potential risk factors for AMI included in the Copenhagen City Heart Study. In this analysis we also include life-style characteristics, some biological traits and disease conditions. An increased risk for first AMI among smokers was graded: the estimated relative risk (ERR) for heavy smokers consuming more than 29g tobacco per day was 2.8 relative to non-smokers. Alcohol intake of five or more drinks per day was associated with a decreased risk, an ERR of 0.6 relative to those who did not drink alcohol daily. Physical inactivity during work but not at leisure was associated with increased risk (ERR 1.4) as was body mass index where the risk was mediated mainly through blood pressure and plasma triglycerides. Oral contraception was not associated with an increased risk, whereas with diabetes the risk increased (the ERR for diabetes being 1.8). Plasma cholesterol above the level of approximately 7 mmol l-1 proportionally increased risk; the ERR in the 1.5% with the highest level was 3.7. A low triglyceride level was associated with low risk; the ERR in the fifth of the study population with the lowest level was 0.6. Elevated blood pressure also proportionally increased risk. Subjects on antihypertensive drug treatment had higher risk than non-treated subjects with similar blood pressure. The effect of socioeconomic factors described in the previous paper was not mediated through their influence on the risk factors included in the present analysis.

In order to illustrate whether there is a connection between smoking and the degree of wrinkles on the face, the authors investigated an age-stratified random sample of 4,485 women and 2,485 men aged 40-69 years. The degree of wrinkles lateral to the canthus of the right eye was described without the investigator being aware of the smoking habits of the individual concerned. For both sexes, the prevalence of deep wrinkles increased with increasing age and with decreasing household income but no significant association with body mass index was demonstrated. In men, a significant association was demonstrated between the cumulated cigarette consumption and the degree of deep wrinkles while this was not the case in women. No definite explanation of this difference between the sexes could be found but a difference in exposure to sunlight and use of face cream may be the reasons.

The function and morphology of knee extension/m. vastus lateralis and elbow flexion/m. biceps brachii were studied in young (28 +/- 0.1 years, n = 7) and elderly (68 +/- 0.5 years, n = 8) sedentary subjects and in elderly swimmers (69 +/- 1.9 years, n = 6), runners (70 +/- 0.7 years, n = 5) and strength-trained subjects (68 +/- 0.8 years, n = 7). On average, the training groups had, for the 12-17 years before the measurements were taken, performed their training regimen 3 +/- 0.1 times a week. Compared with the young subjects, the maximal isometric torque of the sedentary elderly subjects was 44% (P less than 0.05) lower in knee extension and 32% (P less than 0.05) lower in elbow flexion, and speed of movement was between 20 and 26% (P less than 0.05) lower in both knee extension and elbow flexion. The cross-sectional area of m. quadriceps femoris and the elbow flexors was also 24% (P less than 0.05) and 20% lower respectively, and the specific tension was 27% (P less than 0.05) lower in m. quadriceps femoris and 14% (P less than 0.05) lower in the elbow flexors. A 27% (P less than 0.05) higher content of myosin heavy chain type I and a 39% (P less than 0.05) higher content of the slow-type myosin light chain--2 was observed in m. vastus lateralis of the sedentary elderly subjects as compared with the young subjects. The same tendency was also seen with m. biceps brachii. Since the histochemical fibre-type distribution was identical and no major co-expression of type I and type II myosin heavy-chain isoforms was observed with immunocytochemistry, the increase in slow myosin isoforms with ageing seems mainly related to a larger relative area of type I fibres, induced by a selective atrophy of type II fibre area. An increased content of the beta-isoform of tropomyosin was also demonstrated with ageing. In contrast to the swimmers and runners, the elderly strength-trained subjects had maximal isometric torques, speed of movements, cross-sectional areas, specific tensions and a content of myosin and tropomyosin isoforms in both muscles studied identical to those of the young controls. These results seem to suggest that strength training can counteract the age-related changes in function and morphology of the ageing human skeletal muscle.

Data from a prospective epidemiological study that included 2025 plain cigarette smokers were analysed to investigate the effect of phlegm production of changing to filter cigarettes or quitting smoking. During a 5-year follow-up, 189 subjects quitted smoking, 312 changed to filter cigarettes, while 1524 continued to smoke plain cigarettes. Multiple logistic regression was used to adjust for age, duration of smoking, number of cigarettes smoked, socio-economic status and alcohol consumption. Smokers with morning phlegm at enrollment, who changed to filter cigarettes during the follow-up, had a probability ratio of 1.9 of phlegm production ceasing, compared with smokers who continued to smoke plain cigarettes (P less than 0.05). However, the probability ratio of developing morning phlegm among smokers who changed to filter cigarettes compared to those who continued to smoke plain cigarettes was 1.6 (P less than 0.05). The overall prevalence of morning phlegm at the end of the follow-up was the same in smokers who changed to filter cigarettes as in persistent plain cigarette smokers. The trends for chronic phlegm were similar, although they did not reach statistical significance. The smokers who stopped smoking had a probability ratio of 0.4 of developing morning phlegm (P less than 0.01) and a ratio of 7.7 for ceasing to produce it (P less than 0.001) compared to the smokers who continued to smoke plain cigarettes. Our results suggest that changing from plain to filter cigarettes is associated with a higher frequency of cessation of phlegm production, but offers no protection against the development of phlegm.

The relation of ventilatory impairment and chronic mucus hypersecretion to death from all causes and death from obstructive lung disease (chronic bronchitis, emphysema and asthma) was studied in 13,756 men and women randomly selected from the general population of the City of Copenhagen. During the 10 year follow up 2288 subjects died. In 164 subjects obstructive lung disease was considered to be an underlying or a contributory cause of death (obstructive lung disease related death); in 73 subjects it was considered to be the underlying cause of death (obstructive lung disease death). Forced expiratory volume in one second, expressed as a percentage of the predicted value (FEV1% pred), and the presence of chronic phlegm were used to characterise ventilatory function and chronic mucus hypersecretion respectively. For mortality analysis the proportional hazards regression model of Cox was used; it included age, sex, pack years, inhalation habit, body mass index, alcohol consumption, and the presence or absence of asthma, heart disease, and diabetes mellitus as confounding factors. By comparison with subjects with an FEV1 of 80% pred or more, subjects with an FEV1 below 40% pred had increased risk of dying from all causes (relative risk (RR) = 5.0 for women, 2.7 for men), a higher risk of obstructive lung disease related death (RR = 57 for women, 34 for men), and a higher risk of obstructive lung disease death (RR = 101 for women, 77 for men). Chronic mucus hypersecretion was associated with only a slightly higher risk of death from all causes (RR = 1.1 for women, 1.3 for men). The association between chronic mucus hypersecretion and obstructive lung disease death varied with the level of ventilatory function, being weak in subjects with normal ventilatory function (for an FEV1 of 80% pred the RR was 1.2), but more pronounced in subjects with reduced ventilatory function (for an FEV1 of 40% pred the RR was 4.2). A similar though statistically non-significant trend was observed with regard to obstructive lung disease related death. This study shows that impaired lung function is very strongly related to total mortality, obstructive lung disease related mortality, and obstructive lung disease mortality and suggests that chronic mucus hypersecretion, in those with impaired ventilatory function, is also a significant risk factor for death from obstructive lung disease.

From 1974 to 1984, decreases in the mortality of ischaemic heart disease of 11% for men 30 to 69 years of age and 16% for women in the same age-group were observed. From the Copenhagen City Heart Study, a population study of 20,000 men and women, a significant decrease in per cent of smokers, a significant decrease in P-cholesterol, a significant increase in per cent of joggers, but no change in systolic blood pressure were demonstrated, between 1976-1978 and 1981-1983. The decrease in mortality of ischaemic heart disease, may be due to reduction in risk-factor levels, and to advanced medical and surgical treatment.

In this study the long-term changes of body weight during adulthood in men obese as young adults are compared to those occurring in a random sample from the underlying population. Among 362,200 Danish draftees from 1943 to 1977, 1940 were obese (body mass index greater than or equal to 31 kg/m2). A random sample, comprising 0.5 per cent (1801), was drawn from the remaining population. In 1981-83, 4-40 years later, those living in the same region were invited to a health examination, which was attended by 964 (58 per cent) obese and 1134 (75 per cent) control subjects. In the obese group median change of body weight was 1.3 kg, and in the control group 8.3 kg. Weight change was positively correlated to duration of observation in both groups. Those with lowest body mass index at first examination tended to increase most, and those with highest body mass index tended to lose weight. However, the 5th to 95th percentiles of changes in body weight extended in the obese group from -24 to 29 kg, and in the control group from -2 to 25 kg. The range in weight change increased strikingly with increasing first body mass index exceeding 27 kg/m2. The study indicates that the greater the body mass index among young adult men, the less is the median change in body weight, but the greater is the variation of the body weight changes. These results suggest that the size of the fat mass is subject to intra-individual environmental influences that change over time.

The relation of ventilatory function and chronic mucus hypersecretion to death from lung cancer has been studied in 13,946 subjects randomly selected from the general population of the city of Copenhagen, Denmark. During the 10-yr follow-up, 225 subjects died from lung cancer. Percent predicted FEV1 (%FEV1) and presence of chronic phlegm were used to characterize ventilatory function and chronic mucus hypersecretion, respectively. Mortality analysis employed the multiple regression model of Cox and included age, sex, pack-years of smoking, and inhalation as confounding factors. %FEV1 and chronic phlegm were found to be significant predictors of death from lung cancer. In both men and women with chronic phlegm, the risk of dying from lung cancer was 1.5 greater than in those without phlegm. Compared with subjects with %FEV1 greater than or equal to 80, the subjects with %FEV1 less than 40 and those with %FEV1 between 40 and 79 had a 3.9 and 2.1 higher risk of lung cancer death, respectively. A similar regression model in which %FEV1 was replaced with the ratio of FEV1 to FVC (FEV1/FVC) showed that lowered FEV1/FVC was also a significant predictor of lung cancer death, the subjects with FEV1/FVC less than 0.6 (0.6 to 0.7) having a 2.6 (1.5) higher risk for lung cancer death than those with FEV1/FVC greater than or equal to 0.7. It is concluded that lowered ventilatory function and chronic mucus hypersecretion are both significant predictors of death from lung cancer, even after standardization for smoking.

During a five year observation period, declines of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were investigated in 200 subjects with diabetes mellitus (DM), 126 subjects who developed DM during that period and 9,051 nondiabetic subjects. After statistical adjustment for age, sex, height, and tobacco consumption we found that the subjects who developed DM during the observation period had the steepest declines of ventilatory function. Their annual declines of FVC (and FEV1) were on average 29 ml (and 25 ml) greater than the declines observed among the nondiabetic subjects. The subjects who had DM during the whole observation period experienced a decline of ventilatory function which was not significantly greater than the decline among the nondiabetic subjects. Our results suggest that DM, at its onset, is associated with a significantly accelerated decline of ventilatory function. If DM has been present for some years, its impact on the decline of ventilatory function is small.

The relation of ventilatory function to overall mortality has been studied in 662 male and 2048 female never-smokers who during the period 1976-1978 participated in the Copenhagen City Heart Study, a prospective community study of more than 14,000 men and women randomly selected from the general population of the City of Copenhagen. Until the end of 1986, 195 subjects who said they were never-smokers died. Mortality was analyzed using the proportional hazards model of Cox. In addition to measures of ventilatory function, the mortality analysis included age, sex, body-mass index, alcohol consumption, school education, diabetes mellitus, heart disease and bronchial asthma as confounding factors. Forced expiratory volume in 1 second (FEV1) as a percentage of that predicted, forced vital capacity (FVC) as a percentage of that predicted and the ratio of FEV1 to FVC were significant risk factors for mortality among both sexes. The relative risk of death associated with a 50% decrease in FEV1 and FVC as a percentage of a predicted value was 1.65 and 1.81, respectively. This study confirms that lowered ventilatory function is a strong risk factor for mortality among never-smokers of both sexes.

Data from a five year follow up study on 4372 smokers and 3753 non-smokers were analysed to investigate the influence of the type of tobacco smoked and whether the subjects said they inhaled or not on the decline in forced expiratory volume in one second (FEV1). The study sample comprised 1492 smokers of plain cigarettes and 1936 smokers of filter cigarettes, 1711 smokers of cheroots or cigars, and 233 male pipe smokers. Over the five years, smokers, especially those who said that they inhaled, had a higher rate of decline of FEV1 than non-smokers, in whom the average decline in FEV1 was 25 ml/year for women and 30 ml/year for men. There was no significant difference in the decline in FEV1 between filter cigarette smokers and plain cigarette smokers. The decline in FEV1 in cigar or cheroot smokers was the highest for all the smoking groups, and associated with a very high tobacco consumption in this group. Among pipe smokers who inhaled, the decline in FEV1 was slightly higher than in the cigarette smokers, whereas non-inhaling pipe smokers had a decline in FEV1 that was similar to that of non-smokers. In general, the smokers who said that they did not inhale had a smaller decline in FEV1 than those who said that they did. The effect of inhalation varied in magnitude in different smoking groups, being most pronounced in pipe smokers.

Muscle strength was measured in 23 men and 29 women regarded as representative of the healthy urban population of about 80 years of age. Isometric and isokinetic-strengths of right knee-extension, plantar, and dorsal flexion, and the isometric strength of some upper extremity functions were measured. For knee-extension there was a decrease in strength of about 30% from the values in a population study of 70-year-old subjects ( Aniansson et al. 1980). Muscle strength was significantly lower in women than in men in all muscle groups except for plantar and dorsal flexion of the foot. Body cell mass was reduced compared to younger age groups by about the same extent as muscle strength, and correlated to knee-extension and hand grip strengths. Functional examinations such as step tests and walking tests were performed. A correlation between the results of these tests and muscle strength was not found except for knee-extension at 60 degrees/s in men. The rather low speed in comfortable walking (men 1.0 m X s-1, women 0.9 m X s-1) and the reduced capacity for step climbing diminish the possibility of using public transport and pedestrian street intersections in relatively healthy old people.