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Since 1970, jogging has become an increasingly popular form of exercise, but concern about harmful effects has been raised following reports of deaths during jogging. The purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women. Jogging habits were recorded in a random sample of 17,589 healthy men and women aged 20–98 years, invited between 1976 and 2003 to the Copenhagen City Heart Study. The expected lifetime was calculated by integrating the predicted survival curve estimated in the Cox model. In this study 1,878 persons (1,116 men and 762 women) were classified as joggers. During the 35-year maximum follow-up period, we registered 122 deaths among joggers and 10,158 deaths among nonjoggers. The age-adjusted hazard ratio of death among joggers was 0.56 (95% confidence interval: 0.46, 0.67) for men and 0.56 (95% confidence interval: 0.40, 0.80) for women. The age-adjusted increase in survival with jogging was 6.2 years in men and 5.6 years in women. This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women. [ABSTRACT FROM PUBLISHER]

BackgroundLeptin and adiponectin are hormones secreted by adipose tissue, and both hormones are candidate intermediaries between adipose tissue and overweight-related diseases. So far, no prospective study has been published where the independent effects of these two hormones on the development of hypertension have been directly compared. The objective of this study was to investigate the relationships between plasma levels of leptin and adiponectin and new-onset hypertension in the Copenhagen City Heart Study (CCHS).MethodsIn a prospective study design, we examined new-onset hypertension in 620 women and 300 men who were normotensive in the third CCHS examination, which was performed in 1991–1994.ResultsBetween the third and the fourth CCHS examination, which was performed in 2001–2003, 254 had developed hypertension, defined as systolic blood pressure (SBP) ≥140 mm Hg, or diastolic blood pressure (DBP) ≥90 mm Hg, or use of antihypertensive medication. Using logistic regression analysis, adjusting for age, sex, estimated glomerular filtration rate, triglycerides, high-density lipoprotein cholesterol (HDL-C), fibrinogen, and glucose, and with leptin and adiponectin included in the same model, leptin was significantly associated with new-onset hypertension with an odds ratio (95% confidence interval) of 1.28 (1.08–1.53; P < 0.005) for 1 s.d. higher level of log-transformed leptin, whereas adiponectin was not significantly associated with new-onset hypertension having an odds ratio of 1.02 (0.84–1.24; P = 0.83) for 1 s.d. higher level of log-transformed adiponectin.ConclusionsIn the CCHS, leptin, but not adiponectin, was a significant independent predictor of new-onset hypertension.American Journal of Hypertension 2010; doi:10.1038/ajh.2009.244 [ABSTRACT FROM AUTHOR]

Objective: To examine the assumption that postdeployment incidence of sickness and other absence from work are higher among Gulf War Veterans compared with nonveterans.Methods: A prospective registry study including a cohort of 721 Danish Gulf War Veterans and a control cohort of 3,629 nonveterans selected from the general Danish population. Outcome measures were up to 23 years postdeployment incidence of (1) long-term sickness absence and (2) long-term all types of absence from work. Long term with regard to sickness and other absence was defined as exceeding 8 weeks. The association between outcomes and information on deployment history was studied using time-to-event analysis. The index date was the return date from the last deployment to the Gulf. The follow-up period was the time from index date until April 27, 2014.Results: As the main finding, no difference was found between veterans and nonveterans in the incidence rate of long-term sickness absence. After an initial short period (3 months) with elevated incidence rate of long-term absence from work among veterans, there was no difference between the cohorts.Conclusion: Among Danish Gulf War Veterans, no postdeployment increased risk of long-term sickness absence or long-term absence from work was found as compared with nonveterans. [ABSTRACT FROM AUTHOR]

Background: Tea and coffee are the most consumed beverages worldwide and very often sweetened with sugar. However, the association between the use of sugar in tea or coffee and adverse events is currently unclear., Objectives: To investigate the association between the addition of sugar to coffee or tea, and the risk of all-cause mortality, cardiovascular mortality, cancer mortality and incident diabetes mellitus., Methods: Participants from the prospective Copenhagen Male Study, included from 1985 to 1986, without cardiovascular disease, cancer or diabetes mellitus at inclusion, who reported regular coffee or tea consumption were included. Self-reported number of cups of coffee and tea and use of sugar were derived from the study questionnaires. Quantity of sugar use was not reported. Primary outcome was all-cause mortality and secondary endpoints were cardiovascular mortality, cancer mortality and incident diabetes mellitus, all assessed through the Danish national registries. The association between adding sugar and all-cause mortality was analyzed by Cox regression analysis. Age, smoking status, daily alcohol intake, systolic blood pressure, body mass index, number of cups of coffee and/or tea consumed per day and socioeconomic status were included as covariates. Vital status of patients up and until 22.03.2017 was assessed. Sugar could be added to either coffee, tea or both., Results: In total, 2923 men (mean age at inclusion: 63±5 years) were included, of which 1007 (34.5%) added sugar. In 32 years of follow-up, 2581 participants (88.3%) died, 1677 in the non-sugar group (87.5%) versus 904 in the sugar group (89.9%). Hazard ratio of the sugar group compared to the non-sugar group was 1.06 (95% CI 0.98;1.16) for all-cause mortality. An interaction term between number of cups of coffee and/or tea per day and adding sugar was 0.99 (0.96;1.01). A subgroup analysis of coffee-only drinkers showed a hazard ratio of 1.11 (0.99;1.26). The interaction term was 0.98 (0.94;1.02). Hazard ratios for the sugar group compared to the non-sugar group were 1.11 (95% CI 0.97;1.26) for cardiovascular disease mortality, 1.01 (95% CI 0.87;1.17) for cancer mortality and 1.04 (95% CI 0.79;1.36) for incident diabetes mellitus., Conclusion: In the present population of Danish men, use of sugar in tea and/or coffee was not significantly associated with increased risk of mortality or incident diabetes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Treskes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim of this study was to estimate the association between self-reported perceived danger during deployment, measured as combat exposure or witnessing the consequences of war, and post-deployment suicide attempts among military personnel. Furthermore, the effect of post-deployment symptoms of posttraumatic stress disorder (PTSD) and/or depression on the risk of suicide attempts was also evaluated., Methods: This observational cohort study included Danish Army military personnel who returned from deployment in international missions from 1998 to 2016 and had completed a post-deployment questionnaire. Perceived exposure to danger was ascertained by self-report. Data on suicide attempt were retrieved from national registers. Adjusted Cox regression analyses were used to evaluate if military personnel indicating high level of combat exposure were more likely to have attempted suicides post-deployment than military personnel with lower levels of combat exposure., Results: Eighty-three suicide attempts were registered after homecoming among 12,218 military personnel. Perceived higher exposure to combat was associated with the risk of suicide attempt (hazard ratio = 1.08; 95% CI, 1.01-1.16). Furthermore, the association between combat exposure and suicide attempt was fully mediated by post-deployment symptoms of PTSD and/or depression. No association was found between witnessing consequences of war and the risk of post-deployment suicide attempt., Conclusions: This nationwide study found that combat exposure was associated with an increased risk of suicide attempt among military personnel. This association was, however, fully mediated by mental disorders (PTSD and/or depression). These findings suggest that better psychological follow-up of military personnel identified as having PTSD and/or depression may be warranted., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Aims: The relevance of adherence to established dietary guidelines is repeatedly challenged. We hypothesised that non-adherence to established dietary guidelines is associated with an excess risk of cardiovascular, non-cardiovascular and all-cause mortality., Methods: We studied 100,191 white adult Danes aged 20-100 years recruited in 2003-2015 and followed up until December 2018. During follow-up equalling 865,600 person-years, 9273 individuals died. Participants' diets were assessed at baseline by a food frequency questionnaire focusing on key foods defining a healthy diet according to Danish dietary guidelines. Individuals were divided into five categories ranging from very high to very low adherence to dietary guidelines and studied with Cox and Fine-Gray regression models. At study inclusion, we collected demographic and lifestyle characteristics by questionnaire, made a physical examination and took a blood sample., Results: Cardiovascular, non-cardiovascular and all-cause mortality increased gradually with increasing non-adherence to dietary guidelines. Cardiovascular mortality was 30% higher (95% confidence interval 7-57%), non-cardiovascular mortality 54% higher (32-79%) and all-cause mortality 43% higher (29-59%) in individuals with very low adherence to dietary guidelines compared with those with very high adherence after adjustments for age, sex, education, income, smoking, leisure time physical activity and alcohol intake. Mortality risk estimates were similar in all strata of adjusted variables., Conclusion: Non-adherence to Danish food-based dietary guidelines is associated with up to 43% increased all-cause mortality in a dose-response manner. The mortality excess was seen for both cardiovascular and non-cardiovascular causes. The public has good reasons to have confidence in and to adhere to established dietary guidelines., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Military personnel may withhold information on mental health problems (MHPs) for fear of not being permitted to deploy. Past or current MHPs may, however, increase the risk of postdeployment MHPs. Using psychiatric diagnoses rather than self-report assessments in predeployment screening may be a more effective screening strategy for determining deployment fitness. This retrospective follow-up study investigated (a) the extent to which predeployment childhood and adult psychiatric diagnoses predicted postdeployment MHPs, measured as psychiatric diagnosis and the purchase of psychiatric drugs, and long-term sickness absence among formerly deployed Danish military personnel and (b) whether perceived combat exposure moderated or mediated the effect of predeployment psychiatric diagnoses. Complete data were available for 7,514 Danish military personnel who answered questions on perceived combat exposure between 6-8 months after returning from their first deployment to the Balkans, Iraq, or Afghanistan. Data on all psychiatric diagnoses given at Danish hospitals, all medicine purchases, and all sickness absences were retrieved from nationwide research registers. Personnel with predeployment psychiatric diagnoses had a statistically significant higher risk for both postdeployment long-term sickness absence, hazard ratio (HR) = 2.06, 95% CI [1.52, 2.80]; and postdeployment MHPs, HR = 2.38, 95% CI [1.73, 3.27], than personnel without a predeployment psychiatric diagnosis. Personnel with a predeployment psychiatric diagnosis demonstrated a higher risk of reporting high levels of perceived combat exposure. Perceived combat exposure was not found to moderate or mediate the effect of a predeployment psychiatric diagnosis on the two outcomes. Additional findings, limitations, and implications are discussed., (© 2020 International Society for Traumatic Stress Studies.)

Objective The aim of this study was to investigate cross-sectional and prospective associations between heavy occupational lifting and hypertension. Methods Data from the third, fourth and fifth examinations of the Copenhagen City Heart Study were included. Multivariable logistic regression models were applied to adjust for sex, age, body mass index (BMI), smoking, education, self-rated cardiorespiratory fitness, vital exhaustion and baseline blood pressure, and were used to estimate (i) the cross-sectional association between heavy occupational lifting and hypertension, defined as using anti-hypertensives or having a systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg, and (ii) the prospective association between heavy occupational lifting and risk of becoming a systolic blood pressure case, defined as an above median change (from baseline to follow-up) and/or a shift from no use of anti-hypertensives at baseline to use of anti-hypertensives at a ten-year follow-up. Results Both cross-sectional [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.94-1.20] and prospective (OR 1.10, 95% CI 0.92-1.31) analysis indicated no relations. Explorative prospective analyses suggested linear associations between heavy occupational lifting and systolic blood pressure among participants using anti-hypertensives. Exposure to heavy occupational lifting tended to increase the incidence of hypertension (OR 1.30, 95% CI 0.97-1.73) among participants ≥50 years. Conclusions No associations were seen among the general population. Positive associations were seen among users of anti-hypertensives and participants ≥50 years, indicating these groups as vulnerable to increases in blood pressure when exposed to occupational lifting.

Objective Prolonged seated immobility during long-distance flights is related to an increased risk of venous thromboembolism (VTE), but little, if anything, is known about the risk related to sedentary work. The objective of this paper was to examine the risk of VTE according to sitting posture at work. Methods This prospective study includes a total of 78 936 participants from the Copenhagen City Heart Study and the Copenhagen General Population Study, all without previous thromboembolic events and aged <65 years. An assessment of the number of hours spent in sitting position at work was assigned each participant at baseline using a job exposure matrix. VTE was identified through national patient registries. Survival analyses were performed to determine the risk of VTE according to sedentary position at work with adjustment for a range of known determinants including lifestyle and coagulation factors. Results During the follow-up period of 582 411 person years (mean follow-up, 7.4 years) 911 participants experienced their first VTE event. Multivariable adjusted analyses showed no difference in risk of VTE between occupational sitting ≥6.5 hours/day and occupational sitting ≤3.5 hours/day (hazard ratio 1.11, 95% confidence interval 0.92-1.34). Conclusion This study does not support the hypothesis that sedentary work is a risk factor for VTE in the general population. Whether certain occupations with particularly high exposure to immobilized sitting positions are associated with thromboembolic events is not addressed.

Aims: As a consequence of modern urban life, an increasing number of individuals are living alone. Living alone may have potential adverse health implications. The long-term relationship between living alone and all-cause and cardiovascular mortality, however, remains unclear., Methods and Results: Participants from The Copenhagen Male Study were included in 1985-86 and information about conventional behavioural, psychosocial, and environmental risk factors were collected. Socioeconomic position (SEP) was categorized into four groups. Multivariable Cox-regression models were performed with follow-up through the Danish National Registries. A total of 3346 men were included, mean (standard deviation) age 62.9 (5.2) years. During 32.2 years of follow-up, 89.4% of the population died and 38.9% of cardiovascular causes. Living alone (9.6%) was a significant predictor of mortality. Multivariable risk estimates were [hazard ratio (95% confidence interval)] 1.23 (1.09-1.39), P = 0.001 for all-cause mortality and 1.36 (1.13-1.63), P = 0.001 for cardiovascular mortality. Mortality risk was modified by SEP. Thus, there was no association in the highest SEP but for all other SEP categories, e.g. highest SEP for all-cause mortality 1.01 (0.7-1.39), P = 0.91 and 0.94 (0.6-1.56), P = 0.80 for cardiovascular mortality; lowest SEP 1.58 (1.16-2.19), P = 0.004 for all-cause mortality and 1.87 (1.20-2.90), P = 0.005 for cardiovascular mortality. Excluding participants dying within 5 years of inclusion (n = 274) did not change estimates, suggesting a minimal influence of reverse causation., Conclusions: Living alone was an independent risk factor for all-cause and cardiovascular mortality with more than three decades of follow-up. Individuals in middle- and lower SEPs were at particular risk. Health policy initiatives should target these high-risk individuals., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

We investigated whether the combination of increased exhaled nitric oxide fraction ( F eNO ) level and blood eosinophil count had an additive value in chronic airway disease in the general population.We included 4677 individuals aged 20-100 years from the Copenhagen General Population Study. Based on pre- and post-bronchodilator spirometry, self-reported asthma and smoking history, participants were subdivided into healthy never-smokers (n=1649), healthy ever-smokers (n=1581), asthma (n=449), chronic obstructive pulmonary disease (COPD) (n=404), asthma-COPD overlap (ACO) (n=138) and nonspecific airflow limitation (n=456).Compared to individuals with F  cells·L eNO <25 ppb and blood eosinophils <0.3×10 9  cells·L -1  cells·L F eNO ≥25 ppb or blood eosinophils ≥0.3×10 9  cells·L -1 and 2.14 (1.47-3.10) for individuals with F eNO ≥25 ppb and blood eosinophils ≥0.3×10 9  cells·L -1 Corresponding odds ratios were 1.13 (0.91-1.41) and 1.83 (1.20-2.79) for sputum production, 1.54 (1.22-1.94) and 3.26 (2.16-4.94) for asthma, 1.03 (0.80-1.32) and 0.67 (0.36-1.27) for COPD and 1.32 (0.88-1.96) and 2.14 (1.05-4.36) for ACO. Among individuals reporting respiratory symptoms, predicting the type of chronic airway disease did not differ between the two biomarkers and did not improve by combining them.Combination of F eNO and blood eosinophils may have an additive value in characterising chronic airway disease in the general population but still needs to be investigated further with regard to clinical application., Competing Interests: Conflict of interest: Y. Çolak reports personal fees from Boehringer Ingelheim and AstraZeneca outside the submitted work. Conflict of interest: P. Lange reports grants from AstraZeneca and GlaxoSmithKline, and personal fees from Boehringer Ingelheim, AstraZeneca, Novartis and GlaxoSmithKline, outside the submitted work., (Copyright ©ERS 2018.)

Aim: We hypothesized that medically treated exacerbations in COPD defined as treatments with oral corticosteroids alone or in combination with antibiotics by register linkage with a nationwide prescription registry is a valid, robust and low-biased measure of exacerbations., Methods: A total of 13,591 individuals with COPD in the Copenhagen General Population Study (2003-2013) were linked to the Danish prescription registry. Exacerbations were defined as dispensing of oral corticosteroids alone or in combination with antibiotics, dispensed less than four weeks apart during three years of follow-up. Construct validity of this definition of medically treated exacerbations was assessed by studying baseline determinants as well as by studying the association between GOLD 1 through 4 grades and time to first exacerbation during follow-up., Results: Among individuals with COPD, 964 individuals (7.1%) had at least one exacerbation during follow-up. At baseline, comparing those with versus without exacerbations during follow-up, FEV1, 72% of predicted vs. 85% (p < 0.001), previous exacerbations, 43% vs. 11% (p < 0.001), breathlessness, 33% vs. 14% (p < 0.001), and use of inhaled medications, 54% vs. 14% (p < 0.001) were associated with exacerbations. Compared to individuals with GOLD 1, the multivariable hazard ratio (HR) for exacerbations was HR = 17.4 (12.3-24.5, p < 0.001) for GOLD 4, HR = 4.8 (3.9-5.9, p < 0.001) for GOLD 3, and HR = 2.0 (1.7-2.3, p < 0.001) for GOLD 2. In sensitivity analyses, our definition of exacerbations was robust and without major biases., Conclusions: Compared to individuals with GOLD 1, the risk of exacerbations was 17-fold for GOLD 4, 5-fold for GOLD 3, and 2-fold for GOLD 2. Medically treated exacerbations defined by register linkage seem a valid, robust, and low-biased measure of exacerbations in COPD., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: To rank psychosocial and traditional risk factors by importance for coronary heart disease., Methods and Results: The Copenhagen City Heart Study is a prospective cardiovascular population study randomly selected in 1976. The third examination was carried out from 1991 to 1994, and 8882 men and women free of cardiovascular diseases were included in this study. Events were assessed until April 2013. Forward selection, population attributable fraction, and gradient boosting machine were used for determining ranks. The importance of vital exhaustion for risk prediction was investigated by C-statistics and net reclassification improvement. During the follow-up, 1731 non-fatal and fatal coronary events were registered. In men, the highest ranking risk factors for coronary heart disease were vital exhaustion [high vs. low; hazard ratio (HR) 2.36; 95% confidence interval (CI), 1.70-3.26; P < 0.001] and systolic blood pressure (≥160 mmHg or blood pressure medication vs. <120 mmHg; HR 2.07; 95% CI, 1.48-2.88; P < 0.001). In women, smoking was of highest importance (≥15 g tobacco/day vs. never smoker; HR 1.74; 95% CI, 1.43-2.11; P < 0.001), followed by vital exhaustion (high vs. low; HR 2.07; 95% CI, 1.61-2.68; P < 0.001). Vital exhaustion ranked first in women and fourth in men by population attributable fraction of 27.7% (95% CI, 18.6-36.7%; P < 0.001) and 21.1% (95% CI, 13.0-29.2%; P < 0.001), respectively. Finally, vital exhaustion significantly improved risk prediction., Conclusion: Vital exhaustion was one of the most important risk factors for coronary heart disease, our findings emphasize the importance of including psychosocial factors in risk prediction scores., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objective: We tested the hypothesis that use of and adherence to maintenance medication is low among individuals in the general population who have chronic obstructive pulmonary disease (COPD) , even in cases of severe and very severe COPD., Design and Participants: We identified 5,812 individuals with COPD from the Copenhagen General Population Study, and classified them according to the Global Initiative for Obstructive Lung Disease (GOLD) airflow limitation grades 1-4. Dispensing of fixed-dose combinations of inhaled corticosteroids with long-acting beta2-agonists, long-acting anti-cholinergics, or long-acting beta2-agonists was identified in a nationwide registry. Use of medication was defined as medication dispensed during a one-year period , and adherence was calculated from dosages available in one year., Key Results: Use of fixed-dose combinations of inhaled corticosteroids with long-acting beta2-agonists varied from 2 % to 61 % (p < 0.001, test for trend), long-acting anti-cholinergics varied from 0.4 % to 36 % (p < 0.001), and long-acting beta2-agonists varied from 0.3 % to 11 % (p < 0.001. Among utilizers of these medications, adherence varied from 29 % to 56 % (p < 0.001, test for trend) across GOLD 1-4 for fixed-dose combinations of inhaled corticosteroids with long-acting beta2-agonists, from 51 % to 68 % (p = 0.11) for long-acting anti-cholinergics, and from 25 to 62 % (p = 0.01) for long-acting beta2-agonists., Conclusions: Use of and adherence to maintenance medication for COPD in the general population was associated with the severity of COPD as defined by GOLD, but even in severe and very severe COPD, use and adherence was low.

Little is known about changes in physical activity in subjects with chronic obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we aimed to study changes in physical activity in subjects with and without COPD and the impact of physical activity on mortality risk. Subjects from the Copenhagen City Heart Study with at least two consecutive examinations were selected. Each examination included a self-administered questionnaire and clinical examination. 1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1 s 67±18 and 91±15% predicted, respectively) were included. COPD subjects with moderate or high baseline physical activity who reported low physical activity level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35, respectively; both p<0.001). In COPD subjects with low baseline physical activity, no differences were found in survival between unchanged or increased physical activity at follow-up. In addition, subjects without COPD with low physical activity at follow-up had the highest hazard ratio of mortality, irrespective of baseline physical activity level (p≤0.05). A decline to low physical activity at follow-up was associated with an increased mortality risk in subjects with and without COPD. These observational data suggest that it is important to assess and encourage physical activity in the earliest stages of COPD in order to maintain a physical activity level that is as high as possible, as this is associated with better prognosis., (©ERS 2014.)

Background: We wished to characterize undertreatment in COPD., Methods: Among 5,812 individuals with COPD defined by FEV1/FVC &lt; 0.7 participating in the Copenhagen General Population Study, we identified 920 individuals with FEV1 &lt; 60% predicted. Prescriptions were identified in an all-inclusive nationwide registry. For each individual, we examined treatment with medication in the year before the day of the baseline examination, as well as treatment in the first year after the examination. Multivariable logistic regression analyses were applied in individuals with FEV1 &lt; 60% predicted to identify predictors of treatment in the first year after baseline., Results: Only 30% of individuals with COPD and FEV1 &lt; 60% predicted were treated with medication in the year before the examination, whereas 42.2% were treated with medication in the first year after. Reporting six to 10 previous respiratory infections during the preceding 10 years that required consulting a doctor and/or staying home from work was the strongest predictor of treatment with medication (OR, 7.9; 95% CI, 3.5-19.8; P &lt; .001). Breathlessness, low FEV1, previous admissions with a discharge diagnosis of COPD, and former smoking were also predictors of treatment with medication, whereas comorbidity predicted lack of treatment. In subgroup analysis, among individuals with FEV1 &lt; 50% predicted, visits to the general practitioner and age were additional predictors of treatment, whereas male sex and being a widow/widower predicted lack of treatment., Conclusions: In this study, we observed important characteristics of a major undertreatment in individuals with COPD in the general population. Previous reported respiratory infections were the strongest predictors of treatment with medications, which indicates that most COPD treatment is initiated because of acute exacerbations.

Background: The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined., Methods: From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality., Results: During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08-2.81, p=0.027) and men a 2.09-fold (95% CI: 1.37-3.18, p<0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36-7.99, p<0.01) increase for women and a 3.53-fold (1.78-7.02, p<0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10-20% based on FRS, to low (<10%) or high (>20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p=0.034) and borderline significant for women (p=0.054), while the integrated discrimination improvement was highly significant (P≤0.001) for both genders., Conclusions: suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The clinical significance of high heart rate in chronic obstructive pulmonary disease (COPD) is unexplored. We investigated the association between resting heart rate, pulmonary function, and prognosis in subjects with COPD. 16 696 subjects aged ≥40 years from the Copenhagen City Heart Study, a prospective study of the general population, were followed for 35.3 years, 10 986 deaths occurred. Analyses were performed using time-dependent Cox-models and net reclassification index (NRI). Resting heart rate increased with severity of COPD (p<0.001). Resting heart rate was associated with both cardiovascular and all-cause mortality across all stages of COPD (p<0.001). Within each stage of COPD, resting heart rate improved prediction of median life expectancy; the difference between <65 bpm and >85 bpm was 5.5 years without COPD, 9.8 years in mild (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), 6.7 years in moderate (GOLD stage II) and 5.9 years in severe/very severe COPD (GOLD stage III/IV), (p<0.001). Resting heart rate significantly improved risk prediction when added to GOLD stage (categorical NRI 4.9%, p = 0.01; category less NRI 23.0%, p<0.0001) or forced expiratory volume in 1 s % predicted (categorical NRI 7.8%, p = 0.002; category less NRI 24.1%, p<0.0001). Resting heart rate increases with severity of COPD. Resting heart rate is a readily available clinical variable that improves risk prediction in patients with COPD above and beyond that of pulmonary function alone. Resting heart rate may be a potential target for intervention in COPD.

Lung function level and decline are each predictive of morbidity and mortality. Evaluation of the combined effect of these measurements may help further identify high-risk groups. Using Copenhagen City Heart Study longitudinal spirometry data (n = 10,457), 16-21 year risks of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease mortality, and all-cause mortality were estimated from combined effects of level and decline in forced expiratory volume in one second (FEV(1)). Risks were evaluated using Cox proportional hazards models for individuals grouped by combinations of baseline predicted FEV(1) and quartiles of slope. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using stratified analysis by gender, smoking status, and baseline age (≤45 and >45). For COPD morbidity, quartiles of increasing FEV(1) decline increased HRs (95 % CI) for individuals with FEV(1) at or above the lower limit of normal (LLN) but below 100 % predicted, reaching 5.11 (2.58-10.13) for males, 11.63 (4.75-28.46) for females, and 3.09 (0.88-10.86) for never smokers in the quartile of steepest decline. Significant increasing trends were also observed for mortality and in individuals with a baseline age ≤45. Groups with 'normal' lung function (FEV(1) at or above the LLN) but excessive declines (fourth quartile of FEV(1) slope) had significantly increased mortality risks, including never smokers and individuals with a baseline age ≤45.

Aims: To investigate the association between resting heart rate (RHR) and markers of chronic low-grade inflammation. Also, to examine whether elevated resting heart rate is independently associated with cardiovascular and all-cause mortality in the general population, or whether elevated RHR is merely a marker of chronic low-grade inflammation., Methods and Results: A group of 6518 healthy subjects from the the Danish general population were followed for 18 years during which 1924 deaths occurred. Subjects underwent assessment of baseline RHR, conventional cardiovascular risk factors, high-sensitivity C-reactive protein (hsCRP), and fibrinogen. RHR was associated with hsCRP and fibrinogen in uni- and multivariate models (p < 0.0001). A 10 beats per minute increase in RHR was associated with increased cardiovascular and all-cause mortality in univariate models - HR (95%CI) (1.21 (1.14-1.29) and 1.15 (1.11-1.19); multivariate models adjusted for conventional risk factors - 1.16 (1.09-1.24) and 1.10 (1.06-1.14); multivariate models including hsCRP - 1.14 (1.07-1.22) and 1.09 (1.05-1.14); fibrinogen - 1.15 (1.07-1.22) and 1.09 (1.05-1.14); and both hsCRP and fibrinogen - 1.14 (1.07-1.22) and 1.09 (1.05-1.14)., Conclusion: RHR was associated with markers of chronic low-grade inflammation. However, RHR remained associated with both cardiovascular and all-cause mortality after adjusting for markers of chronic low-grade inflammation. This suggests that RHR is an independent risk factor for cardiovascular and all-cause mortality, and not merely a marker of chronic low-grade inflammation.

Background: Current recommendations prescribe that every adult should accumulate 30 minutes or more of moderate physical activity in leisure time, preferably every day of the week. The optimal intensity, duration, and frequency still have to be established. The aim of this study was to examine the impact of intensity versus duration of cycling on all-cause and coronary heart disease mortality., Design: Relative intensity and duration of cycling were recorded in 5106 apparently healthy men and women aged 21-90 years drawn from the general population of Copenhagen, and followed for an average of 18 years. Total number of deaths during follow-up was 1172, of these 146 were coronary heart disease deaths. For both sexes we found a significant inverse association between cycling intensity and risk of all-cause and coronary heart disease death, but only a weak association with cycling duration. The difference in expected lifetime in relation to intensity of cycling was calculated. Men with fast intensity cycling survived 5.3 years longer, and men with average intensity 2.9 years longer than men with slow cycling intensity. For women the figures were 3.9 and 2.2 years longer, respectively., Conclusion: Our findings indicate that the relative intensity, and not the duration of cycling, is of more importance in relation to all-cause and coronary heart disease mortality. Thus our general recommendations to all adults would be that brisk cycling is preferable to slow.

OBJECTIVE. The mechanisms by which overweight and physical inactivity lead to hypertension are complex. Leptin, an adipocyte-derived hormone, has been linked with hypertension. We wanted to investigate the relationship between leptin, physical activity and new-onset hypertension. METHODS. The study was a prospective cohort study of 744 women and 367 men, who were normotensive in the third Copenhagen City Heart Study (CCHS) examination, performed 1991−94. Based on questionnaire items, the participants were divided into two groups with low (n = 674) and high (n = 437) levels of leisure-time physical activity, respectively. RESULTS. Between the third and the fourth CCHS examination, performed 2001?03, 304 had developed hypertension, defined as systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or use of antihypertensive medication. In a logistic regression model, including age, sex, body mass index, SBP, DBP, level of physical activity and leptin, we found a significant interaction between leptin and level of physical activity with new-onset hypertension as outcome variable (p = 0.012). When we entered the interaction variables, effect of leptin with low level of physical activity and with high level of physical activity, respectively, in the original model, leptin predicted new-onset hypertension in participants with low level of physical activity [odds ratio (95% confidence interval): 1.16 (1.01−1.33) for one unit increase in log-transformed leptin levels, p = 0.038], but not in participants with high level of physical activity [0.88 (0.74−1.05), p = 0.15]. CONCLUSION. We found that leptin predicted new-onset hypertension but only in participants with low level of physical activity.

Background: Elevated resting heart rate is associated with mortality in general populations. Smokers may be at particular risk. The association between resting heart rate (RHR), smoking status and cardiovascular and total mortality was investigated in a general population., Methods: Prospective study of 16,516 healthy subjects from the Copenhagen City Heart Study. 8709 deaths, hereof 3821 cardiovascular deaths, occurred during 33 years of follow-up., Results: In multivariate Cox models with time-dependent covariates RHR was significantly associated with both cardiovascular and total mortality. Current and former smokers had, irrespective of tobacco consumption, greater relative risk of elevated RHR compared to never smokers. The relative risk of all-cause mortality per 10 bpm increase in RHR was (95% CI): 1.06 (1.01-1.10) in never smokers, 1.11 (1.07-1.15) in former smokers, 1.13 (1.09-1.16) in moderate smokers, and 1.13 (1.10-1.16) in heavy smokers. There was no gender difference. The risk estimates for cardiovascular and all-cause mortality were essentially similar. In univariate analyses, the difference in survival between a RHR in the highest (> 80 bpm) vs lowest quartile (< 65 bpm) was 4.7 years in men and 3.6 years in women. In multivariate analyses, the difference was about one year in never smokers and about two years in current and former smokers., Conclusions: In a healthy population resting heart rate is associated with total and cardiovascular mortality. Elevated resting heart rate is associated with greater risk in subjects with a history of smoking than in never smokers., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of the present study was to evaluate developments in 30 years mortality risk that may be associated with developments in population systolic blood pressure (SBP) and to evaluate possible secular trends in BP-associated mortality risk in the untreated population., Design: The Copenhagen City Heart Study is a prospective longitudinal epidemiological study. The present analysis comprised participants from survey 1 (1976-78) and 3 (1991-94)., Methods: BP measurements and other methods were fully standardized and unchanged throughout the observation period. Questionnaires were completed by the participants and double checked by the technicians while they were interviewing the participants., Results: 18 077 persons participated. Age, systolic BP, diastolic BP, cholesterol, BMI, diabetes, gender and habitual physical activity were significant predictors of all-cause death in all age groups. Risk factor adjusted risk for all-cause death was significantly lower in survey 3 compared with survey 1. Among elderly people, there was no development in mortality risk. In the age groups 40-49 years and 50-59 years there were survey differences indicating a significant trend towards longer life expectancy compared with their age-matched counterparts in survey 1. The association between BP and mortality remained unchanged., Conclusion: A declining risk of all-cause death was observed in the younger and middle-aged cohorts of the population. The decrease in systolic BP and decline in mortality risk in the same age groups points to a role of systolic BP in age-cohort differentiated improvements of life expectancy. The effect of systolic BP on mortality did not change during follow-up.

Background: Low-grade chronic inflammation has been proposed to play a major role in the pathogenesis of hypertension. Low-grade chronic inflammation is also closely associated with obesity, an established causative factor in the development of hypertension. The purpose of this study was to investigate the relationship between two markers of inflammation, C-reactive protein (CRP) and fibrinogen, and blood pressure (BP) and other hemodynamic variables in obese subjects., Methods: From a large cardiovascular study based in the general population, we selected subjects with a body mass index (BMI) > or =30 kg/m2, free of major cardiovascular diseases, not taking BP-lowering or lipid-lowering drugs (n = 487; women = 51.1%; median (5th to 95th percentile) age = 62 years (36-80)). The cardiovascular study included measurements of traditional and new risk factors, including ankle brachial BP index, a measure of subclinical atherosclerosis. CRP was determined by a high-sensitive assay., Results: In partial Spearman rank correlation analysis, adjusted for age and sex, we found no significant relationships between either CRP or fibrinogen and systolic BP, diastolic BP, pulse pressure, or ankle brachial index (rho: -0.057 to 0.068; P > 0.13). However, fibrinogen and CRP were found to be significantly related to heart rate (rho: 0.127-0.169; P < 0.01)., Conclusions: In this study of generally healthy obese subjects from the general population, we found no significant relationships between markers of inflammation and systolic BP or diastolic BP, showing that obese subjects with higher levels of inflammatory markers do not have higher BP levels than their obese counterparts with lower levels of inflammatory markers.