Low smoking exposure and development and prognosis of COPD over four decades: a population-based cohort study.

BACKGROUND: A diagnosis of COPD is mainly considered in individuals with >10 pack-years of smoking. We tested the hypothesis that low smoking exposure, below the critical threshold of 10 pack-years, increases risk of COPD and leads to poor prognosis. METHODS: We followed non-obstructed adult smokers from the Copenhagen City Heart Study for COPD, defined as a forced expiratory volume in 1 s (FEV1)/forced vital capacity <0.70 and FEV1 <80% predicted, and for related clinical outcomes. First, we followed individuals for 5 years according to baseline smoking for risk of developing COPD, and thereafter for up to four decades for severe exacerbations and death. RESULTS: In 6098 non-obstructed smokers, 1781 (29%) developed COPD after 5 years of follow-up: 23% of individuals with <10 pack-years of smoking at baseline, 26% of those with 10-19.9 pack-years, 30% of those with 20-39.9 pack-years and 39% of those with ≥40 pack-years. During four decades of follow-up, we recorded 620 exacerbations and 5573 deaths. Compared to individuals without COPD with <10 pack­years of smoking, multivariable adjusted hazard ratios (HRs) for exacerbations were 1.94 (95% CI 1.36-2.76) in those without COPD and ≥10 pack-years, 2.83 (95% CI 1.72-4.66) in those with COPD and <10 pack-years, 4.34 (95% CI 2.93-6.43) in those with COPD and 10-19.9 pack-years, 4.39 (95% CI 2.98-6.46) in those with COPD and 20-39.9 pack-years and 4.98 (95% CI 3.11-7.97) in those with COPD and ≥40 pack-years. Corresponding HRs for all-cause mortality were 1.20 (95% CI 1.10-1.32), 1.31 (95% CI 1.13-1.53), 1.59 (95% CI 1.40-1.79), 1.81 (95% CI 1.62-2.03) and 1.81 (95% CI 1.55-2.10). CONCLUSION: Low smoking exposure below the critical threshold of 10 pack-years increases risk of COPD in middle-aged adults within 5 years, and these individuals have increased risk of severe exacerbation and early death over four decades.

Plasma immunoglobulin E and risk of exacerbation and mortality in chronic obstructive pulmonary disease: A contemporary population-based cohort.

BACKGROUND: Novel biomarkers and targeted treatments are needed for patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To test the hypothesis that high plasma immunoglobulin (Ig)E concentrations associate with increased risk of exacerbation and mortality in individuals with COPD in the general population. METHODS: Among 46,598 adults in the Copenhagen General Population Study, we included 1559 with COPD, defined as forced expiratory volume in 1 second/forced vital capacity < 0.70 and forced expiratory volume in 1 second < 80% predicted in individuals aged ≥ 40 years with chronic respiratory symptoms and smoking exposure ≥ 10 pack-years, and without asthma. We assessed risk of future severe exacerbation and all-cause mortality according to baseline plasma IgE ≥ 76 IU/mL, a clinical cutoff for omalizumab treatment in severe asthma. RESULTS: During 14 years of follow-up (median, 6.9; interquartile range, 3.4), we recorded 224 severe exacerbations and 434 deaths in 1559 individuals with COPD. Individuals with COPD with IgE ≥ 76 IU/mL vs those with < 76 IU/mL had a multivariable adjusted hazard ratio (HR) of 1.43 (95% confidence interval, 1.07-1.89) for severe exacerbation and 1.30 (1.05-1.62) for all-cause mortality. Compared with individuals with IgE < 76 IU/mL and blood eosinophils < 300 cells/µL, the multivariable adjusted HR for severe exacerbation was 1.12 (0.76-1.67) for those with IgE < 76 IU/mL and blood eosinophils ≥ 300 cells/µL, 1.62 (1.17-2.24) for IgE ≥ 76 IU/mL and blood eosinophils < 300 cells/µL, and 1.06 (0.63-1.77) for those with IgE ≥ 76 IU/mL and blood eosinophils ≥ 300 cells/µL. Corresponding HRs for all-cause mortality were 1.27 (0.99-1.63), 1.47 (1.14-1.88), and 1.17 (0.83-1.64), respectively. CONCLUSION: High plasma IgE was associated with an increased risk of severe exacerbation and all-cause mortality in individuals with COPD in the general population, independent of blood eosinophils.

Occupational lifting and risk of hypertension, stratified by use of anti-hypertensives and age - a cross-sectional and prospective cohort study.

BACKGROUND: Heavy occupational lifting is prevalent in the general working population and is sparsely reported to associate with hypertension, especially among older and hypertensive workers. We investigated if heavy occupational lifting is associated with hypertension and blood pressure (BP) in both cross-sectional and prospective study designs in the Copenhagen General Population Study, stratified by age, and use of anti-hypertensives. METHODS: Participation was conducted following the declaration of Helsinki and approved by the ethical committee (H-KF-01-144/01). By multivariable logistic and linear regression models, we investigated the association between heavy occupational lifting and hypertension, in a cross-sectional design (n = 67,363), using anti-hypertensives or BP ≥140/≥90 mmHg as outcome, and in a prospective design (n = 7020) with an above-median change in systolic BP (SBP) from baseline to follow-up and/or a shift from no use to use of anti-hypertensives as outcome, with and without stratification by age and use of anti-hypertensives. RESULTS: The odds ratio for hypertension was estimated at 0.97 (99% CI: 0.93-1.00) in the cross-sectional analysis, and at 1.08 (99% CI: 0.98-1.19) in the prospective analysis. The difference in SBP among workers with versus without heavy occupational lifting was estimated at - 0.29 mmHg (99% CI -0.82 - 0.25) in the cross-sectional and at 1.02 mmHg (99% CI -0.41 - 2.45) in the prospective analysis. No significant interaction between heavy occupational lifting and age, nor use of anti-hypertensives were shown. CONCLUSIONS: Only the prospective analysis indicated heavy occupational lifting to increase the risk of hypertension. Further research on the association between occupational lifting and hypertension are needed.

Effect of Predeployment Psychiatric Diagnoses on Postdeployment Long-Term Sickness Absence and Mental Health Problems Among Danish Military Personnel.

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.

Combined value of exhaled nitric oxide and blood eosinophils in chronic airway disease: the Copenhagen General Population Study.

We investigated whether the combination of increased exhaled nitric oxide fraction (FeNO) 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 FeNO <25 ppb and blood eosinophils <0.3×109 cells·L-1, age- and sex-adjusted odds ratios (95% CI) for wheezing were 1.54 (1.29-1.84) for individuals with FeNO ≥25 ppb or blood eosinophils ≥0.3×109 cells·L-1 and 2.14 (1.47-3.10) for individuals with FeNO ≥25 ppb and blood eosinophils ≥0.3×109 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 FeNO 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.

Ranking of psychosocial and traditional risk factors by importance for coronary heart disease: the Copenhagen City Heart Study.

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.

Fibrinogen and α1-antitrypsin in COPD exacerbations.

BACKGROUND: We tested the hypotheses that fibrinogen and α1-antitrypsin are observationally and genetically associated with exacerbations in COPD. METHODS: We studied 13,591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455 (rs1800790, G>A) and FGB -448 (rs4220, G>A) and had plasma fibrinogen measured. Furthermore, 13,405 individuals were genotyped for the SERPINA1 S-allele (rs17580) and the Z-allele (rs28929474) and had measurements of plasma α1-antitrypsin. Exacerbations were defined as hospital admissions or treatments with systemic corticosteroids. We studied observational associations between plasma measurements and exacerbations in Cox regression analyses, associations between genotypes and exacerbations in logistic regression analyses and associations between genetically determined plasma levels and exacerbations in instrumental variable analyses. RESULTS: Elevated fibrinogen and α1-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p<0.001) and 1.18 (1.11 to 1.25, p<0.001), respectively, per SD increase. Presence of the Z-allele was associated with increased odds of exacerbations, OR=1.25 (1.05 to 1.48, p=0.01), as was α1-antitrypsin level genetically lowered by the Z-allele, OR=1.07 (1.02 to 1.13, p=0.004), per SD decrease. Fibrinogen elevating genotypes, FGB -455 (AA) and FGB -448 (AA), were not associated with exacerbations, OR=0.96 (0.73 to 1.25, p=0.77) and OR=1.01 (0.75 to 1.33, p=0.90), respectively, and neither was genetically elevated fibrinogen level, OR=1.11 (0.76 to 1.63, p=0.58) per SD increase. CONCLUSIONS: Fibrinogen and α1-antitrypsin were observationally associated with increased risk of exacerbations. However, genetically, fibrinogen per se was not associated with exacerbations, while lowered α1-antitrypsin was associated with increased odds of exacerbations.

Statin use and exacerbations in individuals with chronic obstructive pulmonary disease.

BACKGROUND: We tested the hypothesis that statin use in individuals with COPD is associated with a reduced risk of exacerbations. METHODS: We identified 5794 individuals with COPD and a measurement of C reactive protein (CRP) in the Copenhagen General Population Study (2003-2008). During 3 years of follow-up we recorded exacerbations with hospital admissions or oral corticosteroid treatment. In a nested case-control design, matching on age, gender, smoking, COPD severity and comorbidity, we estimated the association between statin use and exacerbations. In addition, we examined the association between statin use and high CRP (>3 mg/L), and the association between high CRP and exacerbations during follow-up. RESULTS: Statin use was associated with reduced odds of exacerbations in crude analysis, OR=0.68 (95% CI 0.51 to 0.91, p=0.01), as well as in multivariable conditional logistic regression analysis, OR=0.67 (0.48 to 0.92, p=0.01). However, in the subgroup with the most severe COPD and without cardiovascular comorbidity, we observed a null association between statin use and exacerbations, OR=1.1 (0.5 to 2.1, p=0.83). Furthermore, statin use was associated with reduced odds of a high CRP, OR=0.69 (0.56 to 0.85, p<0.001), and a high CRP was associated with an increased risk of exacerbations, HR=1.62 (1.35 to 1.94, p<0.001). We estimated the percentage of excess risk of the association of statin use with exacerbations possibly mediated through a reduction of CRP to be 14% (4-51%). CONCLUSIONS: Statin use was associated with reduced odds of exacerbations in individuals with COPD from the general population, although this was not apparent in those with the most severe COPD without cardiovascular comorbidity. Statins may thus only associate with reduced risk of exacerbations in patients with COPD with coexisting cardiovascular disease.

Low use and adherence to maintenance medication in chronic obstructive pulmonary disease in the general population.

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.

Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). METHODS: Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. RESULTS: Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P < 0.001), and more of them had a history of respiratory infections (6.8 vs 1.4%, P < 0.001) than individuals with COPD but without gastro-esophageal reflux disease. Among individuals with COPD and gastro-esophageal reflux disease, those who did not use acid inhibitory treatment regularly had an increased risk of COPD exacerbations during follow-up, hazards ratio (HR): HR = 2.7 (1.3-5.4, P = 0.006). Individuals with gastro-esophageal reflux disease, using acid inhibitory treatment regularly did not have an increased risk of exacerbations, HR = 1.2 (0.6-2.7, P = 0.63). CONCLUSIONS: Gastro-esophageal reflux disease was associated with an increased risk of medically treated exacerbations of COPD, but only in those individuals who did not use acid inhibitory treatment regularly.

Changes in physical activity and all-cause mortality in COPD.

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.

Predictive value of casual ECG-based resting heart rate compared with resting heart rate obtained from Holter recording.

BACKGROUND: Elevated resting heart rate (RHR) is associated with cardiovascular mortality and morbidity. Assessment of heart rate (HR) from Holter recording may afford a more precise estimate of the effect of RHR on cardiovascular risk, as compared to casual RHR. Comparative analysis was carried out in an age-stratified subsample of 131 subjects in the Copenhagen City Heart Study (CCHS). METHODS: Casual RHR was assessed from electrocardiograms recorded during clinical assessment. Hourly daytime HRs were mapped by Holter recording. Holter RHR was defined as the average of the lowest 3 hourly HRs recorded and mean HR calculated from all daytime HRs. Follow-up was recorded from public registers. Outcome measure was hazard rate for the combined endpoint of cardiovascular mortality, non-fatal heart failure and non-fatal acute myocardial infarction. Comparison of casual RHR, Holter RHR and mean HR by Multivariate Cox regression was performed. RESULTS: A total of 57 composite endpoints occurred during 17.1 years of follow-up. Regression analysis suggests correlation between Casual RHR and Holter RHR. Multivariate Cox regression analysis adjusted for gender and age demonstrated hazard rates of 1.02 (p = 0.079) for casual RHR, 1.04 (p = 0.036*) for Holter RHR, and 1.03 (p = 0.093) for mean HR for each 10 beat increment in HR. CONCLUSIONS: In a comparative analysis on the correlation and significance of differing RHR measurement modalities RHR measured by 24-hour Holter recording was found to be marginally superior as a predictor of cardiovascular morbidity and mortality. The results presented here do not however warrant the abandonment of a tested epidemiological variable.

Longevity in male and female joggers: the Copenhagen City Heart Study.

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.

Resting heart rate is a predictor of mortality in COPD.

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.

Soluble urokinase plasminogen activator receptor for risk prediction in patients admitted with acute chest pain.

BACKGROUND: Plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non-ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain. METHODS: suPAR concentrations were measured on admission in 449 consecutive chest pain patients in a single center between January 3, 2005, and February 14, 2006. Patients were followed for all-cause mortality from discharge until July 28, 2011. RESULTS: The diagnoses at discharge comprised high-risk NSTEACS [non-ST elevation myocardial infarction or unstable angina with electrocardiogram (ECG) abnormalities] in 77 patients (17.2%) and low-risk NSTEACS without evidence of myocardial ischemia in 257 (57.2%) of patients. Another 115 (25.6%) of patients received other diagnoses. During a median follow-up of 5.7 years (range, 0.01-6.6 years) there were 162 (36.1%) deaths. suPAR was predictive of mortality independent of age, sex, smoking, final diagnosis for the hospitalization, comorbidities (diabetes, hypertension, previous myocardial infarction, and heart failure), and variables measured on the day of admission (renal function, inflammatory markers, and markers of myocardial ischemia) with a hazard ratio (95% CI) of 1.93 (1.48-2.51) per SD increase in log-transformed suPAR, P < 0.0001. The use of suPAR improved the predictive accuracy of abnormal ECG findings and increased troponin concentrations regarding all-cause mortality (c statistics, 0.751-0.805; P < 0.0001). CONCLUSIONS: suPAR is a strong predictor of adverse long-term outcomes and improves risk stratification beyond traditional risk variables in chest pain patients admitted with suspected NSTEACS.

Use of sugar in coffee and tea and long-term risk of mortality in older adult Danish men: 32 years of follow-up from a prospective cohort study.

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.

Combined effect of lung function level and decline increases morbidity and mortality risks.

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.

The physical activity health paradox and risk factors for cardiovascular disease: A cross-sectional compositional data analysis in the Copenhagen City Heart Study.

BACKGROUND: Studies indicate that physical activity during leisure and work have opposite associations with cardiovascular disease (CVD) risk factors, referred to as the physical activity health paradox. We investigated how sedentary behaviour and physical activity types during leisure and work are associated with systolic blood pressure (SBP), waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) in an adult general population sample using compositional data analysis. METHODS: Participants wore accelerometers for 7 days (right thigh and iliac crest; 24 h/day) and had their SBP, WC, and LDL-C measured. Accelerometer data was analysed using the software Acti4 to derive daily time spent in sedentary behaviour and physical activity types. The measure of association was quantified by reallocating time between sedentary behaviour and 1) walking, and 2) high-intensity physical activity (HIPA; sum of climbing stairs, running, cycling, and rowing), during both domains. RESULTS: In total, 652 participants were included in the analyses (median wear time: 6 days, 23.8 h/day). During leisure, the results indicated that less sedentary behaviour and more walking or more HIPA was associated with lower SBP, while during work, the findings indicated an association with higher SBP. During both domains, the findings indicated that less sedentary behaviour and more HIPA was associated with a smaller WC and lower LDL-C. However, the findings indicated less sedentary behaviour and more walking to be associated with a larger WC and higher LDL-C, regardless of domain. CONCLUSIONS: During leisure, less sedentary behaviour and more walking or HIPA seems to be associated with a lower SBP, but, during work, it seems to be associated with a higher SBP. No consistent differences between domains were observed for WC and LDL-C. These findings highlight the importance of considering the physical activity health paradox, at least for some risk factors for CVD.

Decreasing systolic blood pressure and declining mortality rates in an untreated population: results from the Copenhagen City Heart Study.

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.

Interaction between leptin and leisure-time physical activity and development of hypertension.

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.