Elevated resting heart rate, physical fitness and all-cause mortality: a 16-year follow-up in the Copenhagen Male Study.

OBJECTIVE: To examine whether elevated resting heart rate (RHR) is an independent risk factor for mortality or a mere marker of physical fitness (VO2Max). METHODS: This was a prospective cohort study: the Copenhagen Male Study, a longitudinal study of healthy middle-aged employed men. Subjects with sinus rhythm and without known cardiovascular disease or diabetes were included. RHR was assessed from a resting ECG at study visit in 1985-1986. VO2Max was determined by the Åstrand bicycle ergometer test in 1970-1971. Subjects were classified into categories according to level of RHR. Associations with mortality were studied in multivariate Cox models adjusted for physical fitness, leisure-time physical activity and conventional cardiovascular risk factors. RESULTS: 2798 subjects were followed for 16 years. 1082 deaths occurred. RHR was inversely related to physical fitness (p < 0.001). Overall, increasing RHR was highly associated with mortality in a graded manner after adjusting for physical fitness, leisure-time physical activity and other cardiovascular risk factors. Compared to men with RHR ≤ 50, those with RHR > 90 had an HR (95% CI) of 3.06 (1.97 to 4.75). With RHR as a continuous variable, risk of mortality increased with 16% (10-22) per 10 beats per minute (bpm). There was a borderline interaction with smoking (p = 0.07); risk per 10 bpm increase in RHR was 20% (12-27) in smokers, and 14% (4-24) in non-smokers. CONCLUSIONS: Elevated RHR is a risk factor for mortality independent of physical fitness, leisure-time physical activity and other major cardiovascular risk factors.

Occupational noise exposure, social class, and risk of ischemic heart disease and all-cause mortality--a 16-year follow-up in the Copenhagen Male Study.

OBJECTIVE: Long-term exposure to occupational noise may be associated with an increased risk of ischemic heart disease (IHD) and all-cause mortality. However, the issue remains unsettled. Only a small number of longitudinal studies have been carried out, and control for potential confounders including a strong correlate of noise exposure namely social class may have been insufficient. METHODS: We carried out a 16-year follow-up of 2998 men aged 53-75 years without overt cardiovascular disease. RESULT: Overall, 197 men (6.6%) died due to IHD and 1192 (39.8%) from all-causes. Of the 2998 men, 1008 (33.6%) reported exposure to occupational noise for ≥5 years [mean 25.4, standard deviation (SD) 12.5 years]; among these men, 47.3% reported hearing impairment versus only 24.8% among unexposed men (63.0%). Referencing unexposed men, the hazard ratio (HR) for IHD mortality was 0.97 [95% confidence interval (95% CI) 0.71-1.33], and the HR for all-cause mortality was 1.01 (95% CI 0.89-1.15) when adjusting for potential confounders: age, hearing impairment, blood pressure, diabetes, fasting serum triglycerides and high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucosuria, cancer, body mass index, alcohol, tobacco, leisure-time physical activity, and social class. Stratified analyses of high and low social classes confirmed the overall results. CONCLUSION: Cumulative occupational exposure to noise was strongly associated with hearing impairment, but not with death from either IHD or all-cause mortality in a long-term follow-up adjusting for established cardiovascular risk factors including low social class.

Serum selenium level and risk of lung cancer mortality: a 16-year follow-up of the Copenhagen Male Study.

Serum selenium has been implicated as a risk factor for lung cancer, but the issue remains unsettled. In a cohort of 3,333 males aged 53-74 yrs, we tested the hypothesis that a low serum selenium concentration would be associated with an increased risk of lung cancer mortality. Over 16 yrs, 167 (5.1%) subjects died of lung cancer: 48 (5.0%) out of 965 with low serum selenium (0.4-1.0 µmol · L(-1)), 57 (5.1%) out of 1,141 with medium serum selenium (1.1-1.2 µmol · L(-1)) and 62 (5.1%) out of 1,227 with high serum selenium (1.3-3.0 µmol · L(-1)). After adjustment for age, referencing the lowest level of serum selenium, hazard ratios (HRs) for medium and high levels of serum selenium were 0.97 (95% CI 0.66-1.43) and 0.99 (95% CI 0.68-1.45), respectively. Taking into account pack-years of smoking, spirits intake, dietary markers (salt and fat preferences) and health measures (chronic bronchitis and peak flow), referencing the lowest level of serum selenium, HRs were 1.17 (95% CI 0.79-1.75) and 1.43 (95% CI 0.96-2.14), for medium and high levels respectively. Among heavy smokers, a high serum selenium concentration was associated with a significantly increased risk of lung cancer mortality after taking into account all potential confounders. The hypothesis that low serum selenium is an independent risk factor for lung cancer was not supported.

Determinants of obesity among men with the lewis double-negative blood group: a genetic marker of obesity-the Copenhagen Male Study.

OBJECTIVE: Middle-aged and elderly men with the Lewis blood group phenotype Le(a-b-), have a two-fold higher prevalence of obesity than others. We investigated if the association could be ascribed to differences in lifestyle, or if obesity determinants had a different impact in this group. METHOD: This was a cross-sectional study of 3,290 men aged 53-74 years with a mean of 63 years drawn from the Copenhagen Male Study. The main outcome measure was prevalence of obesity [body mass index (BMI) ≥30 (kg/m(2))]. RESULTS: Among men with the Le(a-b-) phenotype (n = 315), the prevalence of obesity was 15.6%; it was 8.1% among men with other phenotypes (n = 2,975, p < 0.001). Obesity-related life style habits did not differ between Le(a-b-) and other men. In multiple logistic regression analyses, the role of obesity covariates was conspicuously different between men with the Le(a-b-) phenotype and men with other Lewis phenotypes. However, among Le(a-b-) men, a much stronger inverse association was found between high coffee consumption (>7 cups/day vs. less) and obesity, and between lacking fat avoidance and obesity; the odds ratio [95% confidence interval (CI)] for high coffee consumption was 0.2(0.1-0.7) and for avoidance of fatty foods 2.0(1.04-3.7). The association of obesity with leisure time physical activity, smoking, alcohol use, use of sugar in hot beverages, and tea consumption, did not differ between Le(a-b-) men and others. CONCLUSIONS: Our findings suggests a gene-environment interaction between lifestyle and obesity. Because some ethnic groups have up to 40% with the Le(a-b-) phenotype, the above observations may be of significant public health interest.

Antihypertensive treatment, high triglycerides, and low high-density lipoprotein cholesterol and risk of ischemic heart disease mortality: a 16-year follow-up in the Copenhagen male study.

OBJECTIVE: The aim of this study was to test the hypothesis that metabolic syndrome dyslipidemia is a major risk factor for ischemic heart disease (IHD) mortality among men taking antihypertensive medication. METHODS: This was a 16-year follow up of 2,986 men 53-75 years old without overt cardiovascular disease; 357 men used antihypertensive medicine. Potential risk factors were type of baseline medication, blood pressure, diabetes, fasting serum triglycerides (TG), high-density lipoprotein (HDL-C) and total cholesterol, glucosuria, electrocardiogram (ECG) changes, cancer history, body mass index, alcohol and tobacco use, leisure time physical activity, social class, and age. The main outcome was IHD mortality. RESULTS: Men treated for hypertension had a two-fold higher cumulative incidence of IHD mortality during the follow up compared to other men (12.0% vs, 5.8%). Dyslipidemia was defined as TG >or=1.70 mmol/L or HDL-C

Sugar in coffee or tea and risk of obesity: A neglected issue.

AIM: In the Copenhagen Male Study sugar intake in coffee or tea is inversely associated with obesity. We analyzed the association of sugar intake with obesity among men with and without lifestyle factors indicating health awareness. METHODS: A cross-sectional study of 3,290 men aged 53-75 years including information about smoking, alcohol, physical activity, tea and coffee use, avoidance of fatty food, social class, self-assessed health, and family obesity. RESULTS: Overall, 291 men (8.8%) were obese, body mass index > or =30. Among men using sugar in coffee or tea (36%), the prevalence was 6.2%; among others, 10.3% (odds ratio [95% confidence interval]=0.6 [0.4-0.8]). An inverse association between use of sugar in hot beverages and prevalence of obesity was consistent in subgroups, and most pronounced among the least health-conscious [odds ratio [95% confidence interval]=0.4 [0.2-0.8]). INTERPRETATION: The results indicate a weight-controlling or reducing effect of small amounts of sucrose ingested several times a day.

Metabolic and lifestyle predictors of ischemic heart disease and all-cause mortality among normal weight, overweight, and obese men: a 16-year follow-up in the Copenhagen Male Study.

AIM: The aim of this study was to identify metabolic and lifestyle risk factors for ischemic heart disease (IHD) and all-cause mortality (ACM) among normal weight, overweight, and obese men. METHODS: This was a 16-year follow up of 2982 men 53 to 75 years without overt cardiovascular disease. POTENTIAL RISK FACTORS: These were blood pressure, diabetes, fasting serum triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucosuria, cancer, body mass index (BMI), alcohol, tobacco, leisure-time physical activity, social class, and age. MAIN OUTCOME: This was to determine mortality during 16 years of follow-up. RESULTS: A total of 194 men (6.5%) died due to IHD and 1184 (39.8%) from all causes. All lifestyle factors and clinical/metabolic risk factors were associated with BMI, positively or negatively. Risk of IHD and ACM increased gradually from the normal weight (BMI 20.0-25.0) to higher BMI groups. With respect to IHD, compared to normal weight men, obese men (BMI > or = 30.0) had an age-adjusted hazard ratio (HR) (95%CI) of 1.67(1.04-2.68); adjusted for potential confounders HR was 0.99 (0.59-1.66); corresponding estimates for ACM were 1.21 (0.98-1.49) and 0.86 (0.68-1.09). High TG (>1.70 mmol/L) was an independent risk factor for IHD mortality only among men with BMI < or = 27.5 kg/m(2); low HDL-C (< or =1.03 mmol/L) was an independent risk factor for IHD mortality only among men with BMI > 27.5 kg/m(2). Cumulative smoking and type 2 diabetes/glucosuria were the strongest risk factors of ACM among men with a BMI < or = 27.5 as well as men with a BMI > 27.5. CONCLUSION: The importance of risk factors for IHD mortality, in particular serum TG and serum HDL-C, depends on BMI.

Wine intake, ABO phenotype, and risk of ischemic heart disease and all-cause mortality: the Copenhagen Male Study--a 16-year follow-up.

The association of alcohol intake with ischemic heart disease (IHD) and all-cause mortality may depend on ABO phenotype. We tested this hypothesis in a 16-year follow-up of 3,022 Caucasian men aged 53-74 years without overt cardiovascular disease. Potential risk factors and confounders included were ABO phenotypes, alcohol intake (wine, beer, and spirits), tobacco smoking history, leisure-time physical activity, social class, and age. During 16 years, 1985-1986 to end of 2001, 197 subjects (6.5%) died due to IHD, and 1,204 (39.8%) from all causes. Among non-O phenotypes (A, B, and AB) significantly fewer men who died due to IHD were wine consumers, 43.9% versus 55.7%, P<.01; with respect to all-cause mortality corresponding figures were 47.0% versus 60.1%, P<.001. No difference was found among men with phenotype O. Among men with phenotype A, compared to alcohol abstainers, in Cox analysis, the hazard ratio (HR) (95% confidence limit) for men drinking up to 8 beverages/wk was 0.5 (0.3-1.02), and among men consuming >8 beverages/wk (the highest quintile) the HR was 0.3 (0.2-0.8), P<.01. Among men with phenotype O, the association of wine intake with IHD mortality was slightly and not significantly U-shaped. The difference in the predictive role of wine intake between phenotype O and phenotype A men was supported in a statistical test for interaction. A similar association was found for all-cause mortality. The results suggest that the effect of wine intake on IHD and all-cause mortality among middle-aged and elderly men may depend on ABO phenotypes.

Occupational organic solvent exposure, smoking, and prevalence of chronic bronchitis-an epidemiological study of 3387 men.

OBJECTIVE: To investigate the interaction of smoking and history of long-term occupational exposure to organic solvents on the prevalence of chronic bronchitis (CB) among middle aged and elderly men. METHODS: A questionnaire on health, lifestyle, and working conditions, and a clinical examination including measurements of height, weight, and peak-flow. Self-reported occupational solvent exposure for 5 years or more was compared to never exposed. Three thousand two hundred eight men aged 63 +/- 10 years were included. RESULTS: Four hundred sixty one men had CB (14.4%). Current smoking and the interaction of smoking and long-term occupational exposure to organic solvents (> 5 years) were the factors most strongly associated with prevalence of CB. In the solvent exposed group odds ratio for CB was 7.0 (95% confidence interval [CI]: 3.4 to 14.5) comparing current smokers with non-smokers against only 3.7 (95% CI: 2.8 to 4.8) in the nonexposed group, also after control for potential confounders. Among nonsmokers only, long-term exposure to organic solvents was not associated with an increased prevalence of CB. CONCLUSION: Current or previous occupational exposure to organic solvents doubles the smoking related risk of CB, probably due to an additional irritative effect in the alveolar and bronchial mucosa.

Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age >or=55 years.

Increased ventricular ectopic activity and even more complex arrhythmias are not uncommon in subjects without apparent heart disease. However, their prognostic significance has been controversial and not updated in recent years. The prevalence and prognostic significance of different ventricular arrhythmias were studied in a cohort of middle-aged and elderly subjects without apparent heart disease. Six hundred seventy-eight men and women aged 55 to 75 years without a history of heart disease or stroke were included. Baseline examinations included physical examinations, fasting laboratory testing, and 48-hour ambulatory electrocardiographic monitoring. All patients were followed for up to 5 years. Combined events were defined as all-cause mortality or acute myocardial infarction. A cardiovascular event was defined as cardiovascular death or acute myocardial infarction. In total, 84% had 0 to 10 ventricular premature complexes (VPCs)/hour, 8% had 11 to 30 VPCs/hour, and 8% had >30 VPCs/hour; 10.8% had >or=1 run of >or=3 VPCs. Frequent VPCs (>or=30/hour) was a significant predictor of combined (hazard ratio 2.47, 95% confidence interval 1.29 to 4.68, p = 0.006) and cardiovascular (hazard ratio 2.85, 95% confidence interval 1.16 to 7.0, p = 0.023) event rates, after adjustment for conventional risk factors. Runs of >or=4 VPCs/day or >or=2 doublets/day were also associated with a poor prognosis, but only in the presence of frequent VPCs. The detection of a single VPC on standard electrocardiography was a significant predictor of frequent VPCs and an independent predictor of events (hazard ratio 2.6, 95% confidence interval 1.02 to 6.66, p = 0.045). In conclusion, apparently healthy, middle-aged and elderly subjects with frequent VPCs (>or=30/hour) have a poor prognosis. According to current guidelines, strict risk-factor modification and primary prevention are justified in these high-risk subjects.

Physical activity in leisure-time and risk of cancer: 14-year follow-up of 28,000 Danish men and women.

AIM: The preventive effect of physical activity on risk of cancer in general remains controversial. This study aimed at assessment of the associations between leisure- time physical activity and incidence of cancer in the general population of adult men and women. METHODS: 13,216 women and 18,718 men aged 20-93 years selected from the general population participated in a health examination including a questionnaire with information on physical activity, smoking, alcohol intake, postmenopausal hormones, and socioeconomic status. Incident cases of cancers where recorded during a follow-up period of 14 years. The six most frequent cancer cases in both sexes were included in this analysis. RESULTS: A highly significant inverse association was seen between vigorous physical activity in leisure time and cancer of the ovary, adjusted rate ratio being 0.33 (95% CI 0.16-0.67; p = 0.001) for the most physical active women. In men there was a highly significant increase for non-melanoma skin cancer, with adjusted rate ratio of 1.72 (95% CI 1.23-2.40; p = 0.001), for the most active men and vigorous activity was associated with a non-significant lower risk of colon cancer, the adjusted rate ratio being 0.72 (95% CI 0.47-1.11; p = 0.06). CONCLUSION: Generally, there were no, or only weakly, inverse associations between physical activity in leisure time and incidence of cancer, except for cancer of the ovary.

Prevalence and prognostic significance of daily-life silent myocardial ischaemia in middle-aged and elderly subjects with no apparent heart disease.

AIMS: We aimed to determine the prevalence and prognostic significance of daily-life silent myocardial ischaemia (SMI) in healthy middle-aged and elderly subjects with no previous heart disease. METHODS AND RESULTS: Six hundred and seventy-eight healthy men and women between 55 and 75 years of age and with no history of cardiovascular disease or stroke were included. Baseline examinations included physical examination, fasting laboratory testing, and 48 h ambulatory electrocardiogram monitoring. An episode of ischaemia was defined by a down-sloped or horizontal ST depression of at least 1 mm at a duration of at least 1 min. Seventy-seven subjects (11.4%) had SMI. All participants were followed for up to 5 years. In 77 subjects with SMI, 16 (20.7%) had an event (death or myocardial infarction). In 601 subjects without SMI, 50 (8.3%) had an event. The hazard ratios for SMI in relation to cardiac and combined events after correction for conventional risk factors were 3.1 [(1.24-7.97), P=0.016] and 1.97 [(1.06-3.69), P=0.033], respectively. CONCLUSION: SMI as detected by Holter monitoring was detected in 11.4% of these subjects and was associated with more than three-fold increase in the cardiac event rate after correction for risk factors, implying that this test could be used to identify high-risk individuals among these subjects.

Changes in alcohol intake and mortality: a longitudinal population-based study.

BACKGROUND: Using alcohol intake at one point in time, numerous studies have shown a J- or U-shaped relation with all-cause mortality. Mortality is lowest among the light to moderate drinkers, with the risk of dying from coronary heart disease higher among nondrinkers and the risk of dying from cancer higher among heavy drinkers. We studied whether changes in individual alcohol intake result in corresponding changes in mortality. METHODS: In a longitudinal study of 6644 men and 8010 women, age 25 to 98 years, who had attended at least 2 health surveys with a 5-year interval between them, we addressed the risk of death after combinations of changes in alcohol intake. RESULTS: Mortality after changes in alcohol intake was consistent with the mortality observed among those who reported stable drinking. Stable drinkers showed a U-shaped all-cause mortality, with relative risks of 1.29 (95% confidence interval [CI] = 1.13-1.48) for nondrinkers (< 1 drink per week) and 1.32 (1.15-1.53) for heavy drinkers (> 13 drinks per week) compared with light drinkers (1 to 6 drinks per week). For coronary heart disease mortality, stable nondrinkers had a relative risk of 1.32 (0.97-1.79) compared with stable light drinkers and those who had reduced their drinking from light to none increased their risk (1.40; 1.00-1.95), and those who had increased from nondrinking to light drinking reduced their relative risk ratio (0.71; 0.44-1.14). Cancer mortality was increased in all groups of heavy drinkers. CONCLUSION: Persons with stable patterns of light and moderate alcohol intake had the lowest all-cause mortality. Individual changes in alcohol intake were followed by corresponding changes in mortality.

Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease.

AIM: Elevation of inflammation markers, high heart rate, and reduced heart-rate variability are all strong markers of mortality in a broad spectrum of patients. The association between these markers has not been clarified thoroughly. We investigated the associations between markers of inflammation, heart rate, and heart-rate variability. METHODS AND RESULTS: Six hundred and forty-three healthy men and women between 55 and 75 years of age and with no prior history of cardiovascular disease or stroke were included in the study. The baseline study included a physical examination, fasting laboratory tests, and 24-h ambulatory ECG monitoring. We selected the time-domain components of heart-rate variability for further analyses. C-reactive protein concentration and white blood cell count were selected as markers of inflammation. After identifying parameters related to measures of heart-rate variability, we used regression analyses to evaluate independent associations. Heart-rate variability, as measured by the standard deviation of the time between normal-to-normal complexes or the standard deviation of the average of normal-to-normal intervals for each 5-min period, was negatively associated with smoking, C-reactive protein, white blood cell count, blood sugar and triglyceride concentration, female gender, and diabetes. In contrast, physical activity was strongly associated with higher heart-rate variability. In multivariate regression analyses, increased heart-rate and reduced heart-rate variability were significantly and independently related to white blood cell count or C-reactive protein concentration. CONCLUSION: Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in healthy middle-aged and elderly subjects. The increased mortality that has been reported in these settings may thus have a common aetiology. An autonomic imbalance in favour of the sympathetic system may interact with inflammatory processes to play a more important role in the process of atherosclerosis than previously thought.

High triglycerides/low high-density lipoprotein cholesterol, ischemic electrocardiogram changes, and risk of ischemic heart disease.

BACKGROUND: High triglycerides (TG)/low high-density lipoprotein cholesterol (HDL-C)(TG > or =1.60 and HDL-C < or =1.18 mmol/L) and ischemic ST-T changes in the resting electrocardiogram (ECG) are both strong risk factors of ischemic heart disease (IHD) in men without clinical cardiovascular diseases. This study tested the hypothesis that men free of clinical IHD with high TG/low HDL-C and resting ischemic ECG changes would have a particularly poor prognosis with respect to IHD. METHODS: We conducted a cohort study of 2906 men, aged 53 to 74 years, without overt IHD at baseline. RESULTS: During 8 years, IHD developed in 229 men; 61 cases were fatal. Of the risk factors recorded, ischemic ECG changes and high TG/low HDL-C were the strongest risk factors of IHD. Compared with men without high TG/low HDL-C and without ischemic ECG changes, age-adjusted relative risk of total IHD (95% CI) was 3.5 (1.7-7.2) in men with both high TG/low HDL-C and ischemic ECG changes; the corresponding value for fatal IHD was 11.2 (4.9-25.8). Adjusted for conventional risk factors, the interaction term high TG/low HDL-C x ischemic ECG changes was a significant predictor of IHD death, with a relative risk of 2.6 (1.0-6.9). CONCLUSIONS: In men free of clinical IHD, ischemic ECG changes were significantly more predictive of fatal IHD in men with high TG/low HDL-C, indicating an adverse synergistic effect of these 2 risk factors.

[Airborne contact allergy provoked by kathon in water-based plastic paint]. / Luftbåren kathonkontaktallergi udløst af vandbaseret plasticmaling.

We describe two cases of airborne contact allergy to plastic paint containing Kathon. Two women with known kathon allergy, aged 33 and 50 years, developed severe dermatitis and systemic reactions after painting their homes with water-based plastic paint with Kathon as preservative. Both required treatment with systemic steroids. On return to their homes, the symptoms immediately recurred, and they were forced to stay away for several weeks afterwards. Patients allergic to Kathon should be informed of the risk of airborne contact allergy when exposed to paints preserved with Kathon.

[Mortality associated with physical activity in leisure time, at work, in sports and cycling to work]. / Dødelighed associeret med fysisk aktivitet i fritiden, på arbejdet, sport og cykling til arbejde.

INTRODUCTION: Previous studies have shown that high levels of physical activity are associated with lower mortality in middle-aged men. Few studies have investigated this association in women and the independent effects of cycling to work and participation in sports. MATERIAL AND METHODS: The participants were 13,445 women and 17,441 men aged 20 to 93 years. Self-reported physical activity included general questions about leisure time physical activity and physical activity at work, sports participation, and cycling to work. Adjustment was made for blood pressure, total cholesterol, triglyceride, body mass index, smoking, and educational level. RESULTS: During 433,000 person-years of observation, 2738 women and 4672 men died. Physical inactivity during leisure time predicted mortality in both men and women in all age groups. In women and men, the most physically active in leisure time experienced only half the mortality of the sedentary. Even in the moderately and highly active persons, sports participants experienced only half the mortality of non-participants. Physical activity at work predicted mortality in women only. The men and women who rode a bicycle to work had a 39% lower risk of mortality after multivariate adjustment including leisure time physical activity. DISCUSSION: Leisure time physical activity was inversely associated with all-cause mortality in both men and women in all age groups. Benefit was found from moderate leisure time physical activity with further benefit from sports activity and bicycling as transportation. Benefit from physical activity at work was found in women only.