Aortic Root Dimension Using Transthoracic Echocardiography: Results from the Copenhagen City Heart Study.

Findings regarding the relation between aortic size and risk factors are heterogeneous. This study aimed to generate new insights from a population-based adult cohort on aortic root dimensions and their association with age, anthropometric measures, and cardiac risk factors and evaluate the incidence of acute aortic events. Participants from the fifth examination round of the Copenhagen City Heart study (aged 20 to 98 years) with applicable echocardiograms and no history of aortic disease or valve surgery were included. Aorta diameter was assessed at the annulus, sinus of Valsalva, sinotubular junction, and the tubular part of the ascending aorta. The study population comprised 1,796 men and 2,316 women; mean age: 56.4 ± 17.0 and 56.9 ± 18.1 years, respectively. Men had larger aortic root diameters than women regardless of height indexing (p <0.01). Age, height, weight, systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, hypertension, diabetes, ischemic heart disease, and smoking were positively correlated with aortic sinus diameter in the crude and gender-adjusted analyses. However, after full adjustment, only height, weight, and diastolic blood pressure remained significantly positively correlated with aortic sinus diameter (p <0.001). For systolic blood pressure and pulse pressure, the correlation was inverse (p <0.001). During follow-up (median 5.4 [quartile 1 to quartile 3 4.5 to 6.3] years), the incidence rate of first-time acute aortic events was 13.6 (confidence interval 4.4 to 42.2) per 100,000 person-years. In conclusion, beyond anthropometric measures, age, and gender, diastolic blood pressure was the only cardiac risk factor that was independently correlated with aortic root dimensions. The number of aortic events during follow-up was low.

Cohort study of postural sway and low back pain: the Copenhagen City Heart Study.

PURPOSE: Low back pain is a significant health problem with a high prevalence. Studies of smaller cohorts of low back pain patients have indicated increased body sway. The present paper tests the hypothesis of an association between low back pain and postural sway in a large randomly selected population. METHODS: The current study used the fifth examination (2011-2015) of The Copenhagen City Heart Study where 4543 participated. The participants answered a self-administered questionnaire regarding pain, physical activity, smoking, alcohol consumption, education, and other lifestyle factors. Measurement of postural body sway was performed using the CATSYS system. RESULTS: Totally 1134 participants (25%) reported to have low back pain. Subjects with low back pain had higher sway area and sway velocity than subjects without. CONCLUSION: When using multivariate statistical analysis, confounding factors such as male gender, higher age, larger body height, low education level, smoking, and low activity level explained the association between low back pain and postural sway.

Changes in cardiac time intervals over a decade and the risk of incident heart failure: The Copenhagen City Heart Study.

BACKGROUND: The cardiac time intervals include the isovolumic contraction time (IVCT), the left ventricular ejection time (LVET), the isovolumic relaxation time (IVRT) and the combination of all the cardiac time intervals in the myocardial performance index (MPI) (defined as [(IVCT+IVRT)/LVET)]. Whether the cardiac time intervals change over time and which clinical factors that accelerate these changes is not well-established. Additionally, whether these changes are associated with subsequent heart failure (HF), remains unknown. METHODS: We investigated participants from the general population (n = 1064) who had an echocardiographic examination including color tissue Doppler imaging performed in both the 4th and 5th Copenhagen City Heart Study. The examinations were performed 10.5 years apart. RESULTS: The IVCT, LVET, IVRT and MPI increased significantly over time. None of the investigated clinical factors were associated with increase in IVCT. Systolic blood pressure (standardized ß= - 0.09) and male sex (standardized ß= - 0.08) were associated with an accelerated decrease in LVET. Age (standardized ß=0.26), male sex (standardized ß=0.06), diastolic blood pressure (standardized ß=0.08), and smoking (standardized ß=0.08) were associated with an increase in IVRT, while HbA1c (standardized ß= - 0.06) was associated with a decrease in IVRT. Increasing IVRT over a decade was associated with an increased risk of subsequent HF in participants aged <65 years (per 10 ms increase: HR 1.33; 95%CI (1.02-1.72), p = 0.034). CONCLUSION: The cardiac time increased significantly over time. Several clinical factors accelerated these changes. An increase in IVRT was associated with an increased risk of subsequent HF in participants aged <65 years.

Physical activity in leisure time and at work and risk of dementia: A prospective cohort study of 117,616 individuals.

BACKGROUND AND AIMS: Up to 40% of all dementia cases may be preventable, primarily by treating or acting on well-established cardiovascular risk factors such as diabetes, hypertension, smoking, and physical inactivity. Whether physical inactivity is associated with risk of non-Alzheimer's dementia - a disease influenced by cardiovascular risk factors - and whether a given association differs for physical activity in leisure time and at work remains unknown. METHODS: We conducted a prospective cohort study including 117,616 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study with up to 43 years of follow-up. RESULTS: Multifactorially adjusted hazard ratios for low versus high physical activity at leisure time was 1.60 (95% confidence interval 1.40-1.83) for non-Alzheimer's dementia and 0.94 (0.80-1.11) for Alzheimer's disease. Corresponding values for non-Alzheimer's dementia after additional adjustment for physical activity at work or apolipoprotein E (APOE) genotype were 1.60 (1.40-1.83) and 1.82 (1.34-2.15). Multifactorially and APOE adjusted hazard ratios for high versus low physical activity at work were 1.50 (1.10-2.05) for non-Alzheimer's dementia and 1.62 (1.14-2.31) for Alzheimer's disease. When combining the two types of physical activity, physical activity in leisure time had the strongest relationship with risk of non-Alzheimer's dementia. CONCLUSIONS: Physical inactivity in leisure time was associated with increased risk of non-Alzheimer's dementia, independent of modifiable risk factors and physical activity at work. The present study thus provides evidence for public health advice on physical activity in leisure time for the vascular part of dementia.

AHRR (cg05575921) Methylation Safely Improves Specificity of Lung Cancer Screening Eligibility Criteria: A Cohort Study.

BACKGROUND: Screening reduces lung cancer mortality, but specificities of eligibility criteria are low. We tested if leukocyte AHRR(cg05575921) methylation improves specificity of lung cancer screening eligibility criteria. METHODS: A total of 9,206 and 5,370 individuals of the 1991 to 1994 and 2001 to 2003 examinations of the Copenhagen City Heart Study, Denmark, were followed for lung cancer within 5 years after examination and mortality. Screening eligibility criteria (DANTE, DLCST, ITALUNG, LUSI, NELSON, NLST, and PLCOM2012) were evaluated, and AHRR (cg05575921) methylation extent at different methylation cut points was added. The model with the lowest number of eligible individuals per 5-year lung cancer was validated within the 2001 to 2003 examination. RESULTS: Eligibility criteria identified risk-groups ranging from 3,182 (DANTE) to 1,641 (ITALUNG) individuals. The positive predictive value was highest for PLCOM2012 (3.2%), while DANTE showed the highest negative predictive value (99.7%). Adding AHRR (cg05575921) methylation led to higher specificities for all criteria. Number of eligible individuals per 5-year lung cancer varied from 38 (NELSON) to 27 (NLST) with AHRR (cg05575921) methylation <55%. This last model led to a 21.9% lower screening burden and increased (P < 0.05) specificity of 84.0%. Findings were reproduced among the 5,334 individuals of the 2001 to 2003 examination. CONCLUSIONS: Adding AHRR (cg05575921) methylation on top of current eligibility criteria for lung cancer screening improves specificity by excluding those individuals with the lowest risk. IMPACT: The results point toward a potential clinical use of AHRR (cg05575921) methylation, which is a cost-effective measurement compared with lung CT scanning, to provide additional predictive risk information to identify eligible smokers for lung cancer screening. See related commentary by Hung, p. 698.

Association between Isometric and Allometric Height-Indexed Left Atrial Size and Atrial Fibrillation.

BACKGROUND: Height-based indexations for the evaluation of left atrial (LA) volumes have been proposed as an alternative method to account for body stature when body composition is abnormal. The aim of this study was to derive reference values for these indexation methods and to examine their association with atrial fibrillation (AF). METHODS: A healthy population was randomly split into derivation and validation cohorts (n = 493 each). The derivation cohort was used to derive reference values for iso- and allometric height-indexed LA volumes. Echocardiography included measurement of maximal LA volume (LAVmax) and minimal LA volume (LAVmin). Associations between these measures and AF were investigated in the validation cohort. Cox proportional-hazards regression was performed, adjusting for CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation) risk score. RESULTS: From 986 healthy subjects, allometric height-indexed exponents were determined to 1.72 and 1.56 for LAVmax and LAVmin, respectively. Upper reference values were determined to be LAVmax > 22.1 mL/m1.72 and LAVmin > 12.7 mL/m1.56. In the validation cohort, 41 patients (8%) developed AF during follow-up (median, 14.7 years). In unadjusted analyses, both isometric and allometric indexed LAVmax were associated with AF (hazard ratio, 1.07 [95% CI, 1.03-1.11; P < .001] and 1.11 [95% CI, 1.05-1.18; P < .001] per 1 mL/m and 1 mL/m1.72 increase, respectively) with equal C statistics of 0.63. Height-indexed LAVmin was also associated with AF, with higher C statistics than for LAVmax. All findings were consistent after multivariable adjustment. LAVmax > 22.1 mL/m1.72 posed an increased risk for AF (hazard ratio, 4.65; 95% CI, 1.83-11.86), but LAVmin > 12.7 mL/m1.56 carried a higher risk (hazard ratio, 6.33; 95% CI, 2.66-15.07). CONCLUSIONS: Both isometric and allometric height-indexed LA volumes are associated with AF in the general population. LAVmin is more strongly associated with AF than LAVmax regardless of indexation.

Association between exposure to heavy occupational lifting and cardiac structure and function: a cross-sectional analysis from the Copenhagen City Heart Study.

To investigate cross-sectional associations between heavy occupational lifting and cardiac structure and function. Participants from the 5th round of the Copenhagen City Heart Study, aged < 65 years old, answering a questionnaire regarding occupational physical activity, heavy occupational lifting, use of anti-hypertensive and heart medication, and data on blood pressure, cardiac structure and function, from an echocardiographic examination, were included. Adjusted linear regressions and logistic regressions were applied to estimate the cross-sectional association between heavy occupational lifting and cardiac structure and function across all included participants and in groups stratified by hypertension status, and the risk for having abnormal values of cardiac structure and function. 2511 participants were included. The cross-sectional standardized associations between heavy occupational lifting and measures of cardiac structure and function showed a trends for raised left ventricular mass index (LVMi) (ß 0.14, 99% CI - 0.03 to 0.31). The standardized associations stratified by hypertensive status showed significant associations between exposure to heavy occupational lifting and LVMi (ß 0.20, 99% CI - 0.002 to 0.40) and a trend of a raised end-diastolic interventricular septal thickness (IVSd) (ß 0.15, 99% CI - 0.03 to 0.33) among normotensives. Exposure to heavy occupational lifting increased the odds for an abnormal IVSd (OR 1.42, 99% CI 1.07-1.89). This cross-sectional study shows heavy occupational lifting to associate with indices of abnormal cardiac structure and function among normotensives, indicating an increased risk for cardiovascular disease.

Non-adherence to established dietary guidelines associated with increased mortality: the Copenhagen General Population Study.

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.

U-Shaped Association Between Duration of Sports Activities and Mortality: Copenhagen City Heart Study.

OBJECTIVE: To investigate the association between the duration of weekly leisure-time sports activity and all-cause mortality. METHODS: As part of the prospective Copenhagen City Heart Study, 8697 healthy adults completed a comprehensive questionnaire about leisure-time sports activities. Duration (minutes per week) of leisure-time sports activities was recorded for tennis, badminton, soccer, handball, cycling, swimming, jogging, calisthenics, health club activities, weightlifting, and other sports. The primary end point was all-cause mortality, and the median follow-up was 25.6 years. The association between duration of leisure-time sports activities and all-cause mortality was studied using multivariable Cox proportional hazards regression analysis. RESULTS: Compared with the reference group of 2.6 to 4.5 hours of weekly leisure-time sports activities, we found an increased risk for all-cause mortality for those with 0 hours (hazard ratio [HR], 1.51; 95% CI, 1.29 to 1.76), for those with 0.1 to 2.5 hours (HR, 1.24; 95% CI, 1.05 to 1.46), and for those with more than 10 hours (HR, 1.18; 95% CI, 1.00 to 1.39) of weekly leisure-time sports activities. These relationships were generally consistent with additional adjustments for potential confounders among subgroups of age, sex, education, smoking, alcohol intake, and body mass index, when the first 5 years of follow-up were excluded, and for cardiovascular disease mortality. CONCLUSION: We observed a U-shaped association between weekly duration of leisure sports activities and cardiovascular and all-cause mortality, with lowest risk for those participating in 2.6 to 4.5 weekly hours, being consistent across subgroups. Participation in sport activities should be promoted, but the potential risk of very high weekly hours of sport participation should be considered for inclusion in guidelines and recommendations.

Diastolic function assessed with speckle tracking over a decade and its prognostic value: The Copenhagen City Heart Study.

BACKGROUND: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) may be a more accurate measure of LV filling pressure then ratio of early filling pressure to early tissue velocity. The aim of the study was to investigate the impact of age, sex, obesity, smoking, hypertension, hypercholesterolemia, diabetes, physical activity level, socioeconomic, and psychosocial status on E/e'sr over a decade. Additionally, the predictive value of ΔE/e'sr on future major adverse cardiovascular events (MACE) has never been explored. METHOD: The study included 623 participants from the general population, who participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5). Examinations were median 10 years apart. MACE was the composite endpoint of heart failure, myocardial infarction, and all-cause death. RESULTS: Follow-up time was median 5.7 years, and 43 (7%) experienced MACE. Mean age was 51 ± 14 years, and 43% were male. Mean ΔE/e'sr was 2.1 ± 23.0 cm. After multivariable adjustment for demographic, clinical, and biochemistry variables, high age (stand. ß-coef. = .24, P < .001) and mean arterial blood pressure (MAP) (stand. ß-coef. = .17, P < .001) were significantly associated with an accelerated increase in E/e'sr In multivariable Cox regression, E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of MACE (HR = 1.20, 95% CI [1.01; 1.42] per 10 cm increase for both). ΔE/e'sr did only provide incremental prognostic value to change in left atrial volume index of the conventional diastolic measurements. CONCLUSION: In the general population, age and MAP were predictors of an accelerated increase in E/e'sr over a decade. E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of future MACE.

Kidney function and the prognostic value of myocardial performance index.

A decreased glomerular filtration rate (GFR) is a risk factor for cardiovascular disease even after adjustment for conventional risk factors. The myocardial performance index (MPI) is defined as (isovolumetric relaxation time (IVRT) + isovolumetric contraction time (IVCT))/ejection time (ET). It has been shown to be an independent predictor of cardiovascular events. We hypothesized the MPI could prove valuable for assessing cardiac risk in subjects of the general population with decreased estimated GFR (eGFR). MPI was measured in 1915 subjects from a large general population prospective cohort study using color tissue Doppler imaging (TDI) M-mode through the mitral valve. We compared the prognostic capabilities of the MPI between subjects with eGFR ≥ 75 mL/min/1.73 m2 and subjects with eGFR < 75 mL/min/1.73 m2 using multivariable adjusted Cox regression models. The composite endpoint was heart failure, myocardial infarction or cardiovascular death. Mean age was 58 years (SD 16.2), 58% were women, 42% had hypertension and 8.3% diabetes. During a median follow-up time of 12.4 years [IQR 10.6-12.7 years] 269 participants reached the combined endpoint. eGFR modified the prognostic capability of MPI (p-value for interaction < 0.001): After multivariable adjustment, MPI remained an independent predictor of the composite endpoint only in participants with eGFR < 75 mL/min/1.73 m2: HR 1.18 (95% CI 1.02-1.38), p = 0.03, vs. in subjects with eGFR ≥ 75 mL/min/1.73 m2: HR 1.14 (95% CI 0.94-1.39), p = 0.17. These results suggest the MPI could be particularly valuable for identifying elevated cardiac risk in individuals from the general population with decreased eGFR.

Echocardiographic predictors of cardiovascular morbidity and mortality in women from the general population.

AIMS: Global longitudinal strain (GLS) is a strong predictor of adverse cardiovascular outcome in men. However, studies have indicated that GLS may not predict cardiovascular outcomes as effectively in women. The aim of this study was to identify echocardiographic predictors of cardiovascular morbidity and mortality in women from the general population. METHODS AND RESULTS: A total of 1245 women from the general population free of heart failure (HF) and atrial fibrillation had an echocardiographic examination performed including tissue Doppler imaging. In this subset, 747 women had images eligible for strain analysis. Endpoint was a composite of acute myocardial infarction, HF, and cardiovascular death. During follow-up (median 12.5 years), 162 women (13.0%) reached the composite outcome. These women had higher left ventricular (LV) mass index (LVMI), more LV hypertrophy, lower E/A, higher E/e', larger LV dimensions, and longer deceleration time. LVMI and e' remained as significant predictors of the composite outcome [LVMI: hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.03-1.17, P = 0.004, per 5 g/m2 increase] (e': HR 1.53, 95% CI 1.07-2.20, P = 0.020, per 1 cm/s decrease) after adjusting for age, hypertension, systolic blood pressure, diabetes mellitus, total cholesterol, smoking status, prevalent ischaemic heart disease, LV ejection fraction, E/e', E, E/A, interventricular septum thickness in diastole, left ventricular posterior wall in diastole, a', body surface area, and pro-brain natriuretic peptide. GLS was not an independent predictor of outcome after multivariable adjustment. CONCLUSION: The degree of LV hypertrophy assessed as LVMI and diastolic dysfunction evaluated by e' are associated with adverse cardiovascular outcome in women from the general population.

The impact of cardiovascular risk factors on global longitudinal strain over a decade in the general population: the copenhagen city heart study.

Global longitudinal strain (GLS) declines throughout adult-life as the LV remodels and adapts. Information on the impact of cardiac risk factors such as male sex, obesity, smoking status, hypertension, hypercholesterolemia, and diabetes on GLS. over time has not yet been investigated. The present prospective longitudinal study included 689 participants of the 4th and 5th Copenhagen City Heart Study who had GLS measured at both timepoints. Mean age was 51 years and 45% were male. All participants underwent two echocardiographic examinations median 10.4 (IQR: 10.2, 10.9) years apart. Average decline in GLS during follow-up was -0.7%. High age, male sex, high body mass index, and mean arterial blood pressure (MAP) proved to be significantly associated with an accelerated decline in GLS. In a multivariable regression model including all the investigated cardiovascular risk factors, age (stand. ß-coef. = -0.10, P = 0.005), male sex (stand. ß-coef. = -0.16, P < 0.001), and MAP (stand. ß-coef. = -0.07, P = 0.009) were independent predictors of an accelerated decline in GLS during a 10-year period. Finally, the investigated risk factors had different regional impact after the same multivariable adjustments. Male sex had a significant impact on changes in longitudinal strain at the apical, mid-wall and basal segments, meanwhile MAP and age only accelerated changes in the mid-wall and basal longitudinal strain. In the general population age, male sex, and MAP are independent predictors of an accelerated decline in GLS over a 10-year period. Furthermore, MAP, male sex and age had different regional impact.

Does occupational lifting affect the risk of hypertension? Cross-sectional and prospective associations in the Copenhagen City Heart Study.

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.

Dose-Response Association Between Level of Physical Activity and Mortality in Normal, Elevated, and High Blood Pressure.

It has been a challenge to verify the dose of exercise that will produce the maximum health benefits in hypertension. This study aimed to explore the association between level of daily physical activity, all-cause mortality and cardiovascular outcome at different blood pressure levels. A random sample of 18 974 white men and women aged 20 to 98 years were examined in a prospective cardiovascular population study. Self-reported activity level in leisure-time was drawn from the Physical Activity Questionnaire (level I: inactivity; II: light activity; and III: moderate/high-level activity). Blood pressure was defined as normal blood pressure: <120/<80 mm Hg; Prehypertension: 120-139/80-89 mm Hg; Stage I hypertension: 140-159/90-99 mm Hg; Stage II hypertension ≥160/≥100 mm Hg. The mean follow-up time was 23.4±11.7 years. At all levels of blood pressure, higher levels of physical activity were associated with lower all-cause mortality in a dose-response pattern. The pattern remained unchanged after adjustment for following confounders: sex, age, smoking status, education, diabetes mellitus, previous cardiovascular disease, body mass index, and calendar time. Compared with inactivity, following hazard ratios were found for stage I hypertension: light activity, hazard ratio 0.78 (0.72-0.84; P<0.001), moderate/high-level activity, hazard ratio 0.69 (0.63-0.75; P<0.001). At all levels of blood pressure, the risk of cardiovascular events was significantly reduced independent of the level of physical activity. In conclusion, the association between physical activity and all-cause mortality was present in an inverse dose-response pattern at all levels of blood pressure. Physical activity was associated with reduction in cardiovascular events independent of the level of physical activity.

The Copenhagen Sarcopenia Study: lean mass, strength, power, and physical function in a Danish cohort aged 20-93 years.

BACKGROUND: Despite no international consensus on the diagnostic criteria for sarcopenia, low lean mass, muscle strength, and physical function are important risk factors for disability, frailty, and mortality in older individuals, as well as in a wide range of patients with muscle loss. Here, we provide a population-based reference material of total and regional lean body mass, muscle strength/power parameters, and physical function in a healthy cohort of Danish men and women across the lifespan. METHODS: Volunteers aged 20-93 years from the Copenhagen City Heart Study were invited to establish a Danish reference material (Copenhagen Sarcopenia Study) on lean mass characteristics [appendicular lean mass (ALM), iDXA, GE Lunar], muscle function [handgrip strength (HGS), Jamar dynamometer and leg extension power (LEP), Nottingham Power Rig], and physical function [30 s sit-to-stand test (STS), 10-m maximal and habitual gait speed (GS)]. RESULTS: A total of 1305 participants [729 women (age: 56.4 ± 18.9 years, height: 1.66 ± 0.01 m, body mass index: 24.6 ± 4.3 kg/m2 and 576 men, age: 57.0 ± 17.5 years, height: 1.80 ± 0.07 m, body mass index: 26.0 ± 3.9 kg/m2 ] completed all measurements and were included in the present analysis. Lean mass characteristics (TLM, ALM, and ALM/h2 ) decreased with increasing age in both men and women (P < 0.001). Men demonstrated larger absolute and relative total ALM and higher HGS and LEP compared with women at all age intervals (P < 0.001). HGS and LEP decreased progressively with age in both men and women (P < 0.01); 30 s STS performance, habitual GS, and maximal GS decreased at an accellerated rate of decline with increasing age in both men and women (P < 0.001). Habitual GS was reduced in men and women aged ≥70 years, while maximal GS was reduced from the age of ≥60 years compared with young adults (P < 0.001). Regardless of sex, 30 s STS was reduced from the age of ≥50 years compared with the young reference group (P < 0.001) CONCLUSIONS: While the power-based measurements (LEP and 30 s STS) started to decline already at age +50 years, less power-based parameters (GS and HGS) and lean mass characteristics (TLM, ALM, and ALM/h2 ) remained unaltered until after the age of +70 years. Notably, the cut-off thresholds derived in the present study differed from earlier reference data, which underlines the importance of obtaining updated and local reference materials.

Physical activity and risk of instant and 28-day case-fatality in myocardial infarction.

BACKGROUND: While physical activity reduces risk of developing myocardial infarction (MI), it is unknown whether a history of physical activity is also protective of fatal arrhythmia and case-fatality in patients who have suffered an acute MI. METHODS: 104,801 individuals included in 2003-2014 in the Copenhagen General Population Study (CGPS), a prospective population-based study with self-reported leisure time physical activity (LTPA) in three categories measured at baseline, were followed until 2014 through national registries. The 1,517 individuals who suffered a first time MI during follow-up constituted the study population. Outcomes were fatal MI, defined as date of death same as date of MI (including out-of-hospital deaths) and 28-day fatality. Through multivariable analyses the association between baseline LTPA and outcomes were assessed adjusted for CVD risk factors. RESULTS: Of 1,517 MI events, 117 (7.7%) were fatal and another 79 (5.6%) lead to death within 28 days. Median time from baseline to MI was 3.6 years (IQR 1.7-5.8). LTPA was associated with lower risk of fatal MI with odds ratios of 0.40 (95% CI: 0.22-0.73) for light and 0.41 (0.22-0.76) for moderate/high LTPA after multivariable adjustment with sedentary LTPA as reference. Age, alcohol-intake, education and smoking were identified as other predictors for fatal MI. We found no association between LTPA and 28-day case fatality. CONCLUSIONS: Among individuals with MI, those that have engaged in any light or moderate physical activity were more likely to survive their MI. Results are consistent with effect of exercise preconditioning on risk of fatal arrhythmia.

Self-reported occupational physical activity and cardiorespiratory fitness: Importance for cardiovascular disease and all-cause mortality.

OBJECTIVES: This study aimed to investigate whether workers with the combination of high occupational physical activity (OPA) and low cardiorespiratory fitness have an increased risk of cardiovascular disease (CVD) and all-cause mortality. METHODS: Using multivariable Cox proportional hazards regression, we analyzed 2190 males and 2534 females from the Copenhagen City Heart Study, aged 20-67 years and with no known CVD at study entry in 1991-1994, for the risk of CVD and all-cause mortality from independent, stratified and combinations of self-reported OPA (ie, low, moderate and high) and cardiorespiratory fitness (low, same and higher as peers) at baseline. RESULTS: During a median follow-up of 18.5 years, 257 and 852 individuals died from CVD and any cause, respectively. In the fully-adjusted model, an increased risk for CVD mortality was found for those with low compared to high self-reported cardiorespiratory fitness [hazard ratio (HR) 2.17, 95% confidence interval (95% CI) 1.40-3.38), for those with high compared to low OPA (HR 1.45, 95% CI 1.05-2.00), and for those with high compared to low OPA within the strata of low self-reported cardiorespiratory fitness (HR 2.83, 95% CI 1.24-6.46). Moreover, those with the combination of high OPA and low self-reported cardiorespiratory fitness had an increased risk for CVD mortality compared to those with the combination of low OPA and high self-reported cardiorespiratory fitness (HR 6.22, 95% CI 2.67-14.49). Rather similar, but lower risk estimates were found for all-cause mortality. CONCLUSION: These findings may have important implications for CVD prevention among workers with excessive cardiovascular strain at work.

Morbidity and Mortality in 7,684 Women According to Personal Hair Dye Use: The Copenhagen City Heart Study followed for 37 Years.

BACKGROUND: Permanent hair dye contains aromatic amines which are carcinogenic, and can cause allergic skin reactions. In the long term personal use of hair dye might therefore influence both morbidity and mortality. OBJECTIVES: We tested the hypothesis that personal use of hair dye in women is associated with increased morbidity and mortality in the general population. METHODS: We included 7,684 women from the Copenhagen City Heart Study with information on the use of personal hair dye. We assessed the risk of cancer, skin diseases, other morbidities, and mortality during a median follow-up of 27 years (range 0-37). RESULTS: The multivariable adjusted hazard ratio for malignant melanoma in women with versus without personal use of hair dye was 2.07 (95% confidence interval 1.25-3.42). There was no increased risk of other cancer types. For other skin diseases and other major causes of morbidity we found no differences between the two groups, except for a minor excess of digestive diseases and increased risk of Parkinson's disease among women using hair dye. Finally, we found no difference in all-cause mortality comparing women using personal hair dye or not. After correction for multiple comparisons, none of the results remained significant. However, in sensitivity analysis the excess risk of malignant melanoma remained increased with a hazard ratio of 2.58 (95%CI 1.33-5.03) among users of personal hair dye. CONCLUSIONS: Personal use of hair dye does not have major influences on morbidity and mortality. Our finding of a 2-fold risk of malignant melanoma in women using hair dye is hypothesis generating.

Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. METHODS: We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. RESULTS: Among 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27±18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONS: Our study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.).