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.

The physical activity paradox in cardiovascular disease and all-cause mortality: the contemporary Copenhagen General Population Study with 104 046 adults.

AIMS: Leisure time physical activity associates with reduced risk of cardiovascular disease and all-cause mortality, while these relationships for occupational physical activity are unclear. We tested the hypothesis that leisure time physical activity associates with reduced major adverse cardiovascular events (MACE) and all-cause mortality risk, while occupational physical activity associates with increased risks. METHODS AND RESULTS: We studied 104 046 women and men aged 20-100 years in the Copenhagen General Population Study with baseline measurements in 2003-2014 and median 10-year follow-up. Both leisure and occupational physical activity were based on self-report with four response categories. We observed 7913 (7.6%) MACE and 9846 (9.5%) deaths from all causes. Compared to low leisure time physical activity, multivariable adjusted (for lifestyle, health, living conditions, and socioeconomic factors) hazard ratios for MACE were 0.86 (0.78-0.96) for moderate, 0.77 (0.69-0.86) for high, and 0.85 (0.73-0.98) for very high activity; corresponding values for higher occupational physical activity were 1.04 (0.95-1.14), 1.15 (1.04-1.28), and 1.35 (1.14-1.59), respectively. For all-cause mortality, corresponding hazard ratios for higher leisure time physical activity were 0.74 (0.68-0.81), 0.59 (0.54-0.64), and 0.60 (0.52-0.69), and for higher occupational physical activity 1.06 (0.96-1.16), 1.13 (1.01-1.27), and 1.27 (1.05-1.54), respectively. Similar results were found within strata on lifestyle, health, living conditions, and socioeconomic factors, and when excluding individuals dying within the first 5 years of follow-up. Levels of the two domains of physical activity did not interact on risk of MACE (P = 0.40) or all-cause mortality (P = 0.31). CONCLUSION: Higher leisure time physical activity associates with reduced MACE and all-cause mortality risk, while higher occupational physical activity associates with increased risks, independent of each other.

Echocardiographic predictors of long-term adverse cardiovascular outcomes in participants with and without diabetes mellitus: A follow-up analysis of the Copenhagen City Heart Study.

BACKGROUND: Previous studies have identified several echocardiographic markers of cardiac dysfunction in participants with diabetes mellitus, including E/e'. However, previous studies have been limited by short follow-up duration or low statistical power, and none have assessed whether echocardiographic predictors of adverse cardiovascular outcome differ between individuals with DM and individuals without DM. METHODS: A total of 1997 individuals from the general population without heart disease had an echocardiogram performed in 2001 to 2003. Diabetes was defined as HbA1c ≥6.5% (≥48 mmol/mol), non-fasted blood glucose ≥11.1 mmol/L or the use of glucose lowering medication. The end-point was a composite of heart failure (HF), ischemic heart disease (IHD) and cardiovascular death (CVD). RESULTS: At baseline, a total of 292 participants (15%) had diabetes. Median follow-up time was 12.4 years (interquartile-range: 9.8-12.8 years) and follow-up was 100%. During follow-up, 101 participants (35%) with diabetes and 281 participants without diabetes (16%) reached the composite end-point. The prognostic value of E/e' was significantly modified by diabetes (p for interaction: 0.003). In participants with diabetes, only E/e' remained an independent predictor of outcome in a final multivariable model adjusted for clinical and echocardiographic parameters (HR 1.08, 95% CI 1.00-1.17, p = 0.0041, per 1 increase). In participants without diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and a' remained independent predictors of outcome when adjusted for clinical and echocardiographic parameters. In individuals with diabetes, only E/e' added incremental prognostic value to risk factors from the SCORE risk chart and the ACC/AHA Pooled Cohort Equation. CONCLUSION: In individuals with diabetes from the general population, E/e' is a stronger predictor of cardiovascular mortality and morbidity than in individuals without diabetes and contributes with incremental prognostic value in addition to established cardiovascular risk factors.

The effect of occupational physical activity on dementia: Results from the Copenhagen Male Study.

Leisure-time physical activity (LTPA) reduces the risk of dementia, while the effect of occupational physical activity (OPA) on dementia is uncertain. Therefore, the aim of this study was to investigate the effect of OPA on dementia. For comparison, also the association between LTPA and dementia was analyzed. In this longitudinal study, we used self-reported questionnaire data on OPA and LTPA collected in 1970-71 from 4721 male employees, who were 40-59 years old at baseline. Dementia was identified through national registers and participants were followed from they turned 60 years and until 2016. We estimated incidence rate ratios (IRR) and adjusted for age, socioeconomic status, marital status, and psychological stress. In additional analyses, we included health behaviors and blood pressure and mutually adjusted OPA and LTPA. We identified 697 dementia cases during 86 557 person-years. We found an IRR of 1.48 (95% CI: 1.05-2.10) among participants with high OPA compared with participants in sedentary jobs. Participants with high LTPA had a non-significantly lower IRR of dementia compared with participants with a sedentary leisure time. In conclusion, LTPA and OPA are differentially associated with dementia. Therefore, current recommendations regarding the beneficial effect of physical activity on dementia only concern LTPA, and more research on OPA and dementia is needed.

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.

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.

Can we walk away from cardiovascular disease risk or do we have to 'huff and puff'? A cross-sectional compositional accelerometer data analysis among adults and older adults in the Copenhagen City Heart Study.

BACKGROUND: It is unclear whether walking can decrease cardiovascular disease (CVD) risk or if high intensity physical activity (HIPA) is needed, and whether the association is modified by age. We investigated how sedentary behaviour, walking, and HIPA, were associated with systolic blood pressure (SBP), waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) among adults and older adults in a general population sample using compositional data analysis. Specifically, the measure of association was quantified by reallocating time between sedentary behaviour and 1) walking, and 2) HIPA. METHODS: Cross-sectional data from the fifth examination of the Copenhagen City Heart Study was used. Using the software Acti4, we estimated daily time spent in physical behaviours from accelerometer data worn 24 h/day for 7 days (i.e., right frontal thigh and iliac crest; median wear time: 6 days, 23.8 h/day). SBP, WC, and LDL-C were measured during a physical examination. Inclusion criteria were ≥ 5 days with ≥16 h of accelerometer recordings per day, and no use of antihypertensives, diuretics or cholesterol lowering medicine. The 24-h physical behaviour composition consisted of sedentary behaviour, standing, moving, walking, HIPA (i.e., sum of climbing stairs, running, cycling, and rowing), and time in bed. We used fitted values from linear regression models to predict the difference in outcome given the investigated time reallocations relative to the group-specific mean composition. RESULTS: Among 1053 eligible participants, we found an interaction between the physical behaviour composition and age. Age-stratified analyses (i.e.,

Increased Ferritin Concentration and Risk of Atrial Fibrillation and Heart Failure in Men and Women: Three Studies of the Danish General Population Including 35799 Individuals.

BACKGROUND: Moderately increased plasma ferritin, as a biomarker of iron overload, has been associated with higher rates of cardiovascular death and heart failure. However, the association of moderately increased plasma ferritin with risk of atrial fibrillation in the general population is unknown. METHODS: We examined the association of plasma ferritin concentrations with risk of atrial fibrillation and heart failure in metaanalyses of 35799 men and women from 3 studies of the Danish general population: the Copenhagen City Heart Study, the Danish General Suburban Population Study, and the Copenhagen General Population Study. RESULTS: Multivariable adjusted fixed effects odds ratios for atrial fibrillation were 1.23 (95% CI, 1.05-1.44; P = 0.005) in men for ferritin concentration ≥300 µg/L vs <300 µg/L, 1.13 (95% CI, 0.93-1.38; P = 0.22) in women for ≥200 µg/L vs <200 µg/L, and 1.19 (95% CI, 1.06-1.35; P = 0.005) in both sexes combined (P sex interaction = 0.52). Corresponding fixed effects odds ratios for heart failure were 1.16 (95% CI, 0.98-1.37; P = 0.08) in men, 0.86 (95% CI, 0.67-1.10; P = 0.23) in women, and 1.05 (95% CI, 0.91-1.21; P = 0.45) in both sexes combined (P sex interaction = 0.05). Multivariable adjusted fixed effects odds ratio for atrial fibrillation per step increase in ferritin concentrations was 1.13 (95% CI, 1.06-1.21; P trend = 0.0005) in both sexes combined (P sex interaction = 0.59); the corresponding value for heart failure was 1.03 (95% CI, 0.95-1.11; P trend = 0.47) (P sex interaction = 0.08). In sensitivity analyses, there was no evidence of U-shaped relationships between plasma ferritin concentrations and risk of atrial fibrillation or heart failure in men or women. CONCLUSIONS: Increased ferritin concentration is associated with increased risk of atrial fibrillation in the general population.

Epicardial and pericardial adipose tissues are associated with reduced diastolic and systolic function in type 2 diabetes.

The aim of this study was to investigate the association of epicardial (EAT) and pericardial (PAT) adipose tissues with myocardial function in type 2 diabetes (T2D). EAT and PAT were measured by ultrasound in 770 patients with T2D and 234 age- and sex-matched non-diabetic controls. Echocardiography was performed, including tissue Doppler imaging and 2D speckle tracking. Patients with T2D versus controls had increased EAT (4.6 ± 1.8 mm vs. 3.4 ± 1.2 mm, P < 0.0001) and PAT (6.3 ± 2.8 mm vs. 5.3 ± 2.4 mm, P < 0.0001). EAT and PAT were associated with structural cardiac measures both in T2D patients and controls (all P < 0.043), but only in T2D patients with functional measures: PAT was associated with impaired global longitudinal strain [beta coefficient (SE)] [0.11% (0.04), P = 0.002], while EAT was associated with reduced diastolic function by lateral early diastolic myocardial velocity (e'lat ) [-0.31 (0.05) cm/s, P = 0.001], mitral inflow velocities: peak early (E)/peak atrial (A) ratio [-0.02 (0.01), P = 0.001] and lateral E/e'lat [0.36 (0.10), P < 0.001]. However, no interaction was found between diabetes status and PAT (P = 0.75) or EAT (P = 0.45). Adipose tissue in intimate relation to the myocardium is higher in patients with T2D versus controls and is associated with functional myocardial measures in T2D.

Time spent cycling, walking, running, standing and sedentary: a cross-sectional analysis of accelerometer-data from 1670 adults in the Copenhagen City Heart Study : Physical behaviours among 1670 Copenhageners.

BACKGROUND: Information about how much time adults spend cycling, walking and running can be used for planning and evaluating initiatives for active, healthy societies. The objectives of this study were to describe how much time adult Copenhageners cycle, walk, run, stand and spend sedentary using accelerometers, and to describe differences between population groups. METHODS: In the fifth examination of the Copenhagen City Heart Study, 2335 individuals gave consent to wear accelerometers (skin-attached; right thigh and iliac crest; 24 h/day, 7 consecutive days) of which 1670 fulfilled our inclusion criteria (≥16 h/day for ≥5 days; median wear time: 23.8 h/day). Daily time spent cycling, walking, running, standing and sedentary was derived from accelerometer-based data using the Acti4 software, and differences between sex, age groups, level of education and BMI were investigated using Kruskal-Wallis rank sum tests. RESULTS: Among those cycling (61%), the median cycling time was 8.3 min/day. The median time walking, running, standing and sedentary was 82.6, 0.1, 182.5 and 579.1 min/day, respectively. About 88% walked fast (i.e., ≥100 steps/min) ≥30 min/day. The shortest duration and lowest prevalence of cycling, walking and running were found among older individuals, those with a low level of education, and individuals being overweight or obese. CONCLUSIONS: We found a long duration and high prevalence of cycling and walking, but also that many adult Copenhageners spent much time sedentary. Population groups with low participation in physical activities such as cycling and walking should be targeted in future initiatives towards an active, healthy society.

Increasing population height and risk of incident atrial fibrillation: the Copenhagen City Heart Study.

Aims: The incidence of atrial fibrillation (AF) has increased significantly over the last decades. Population height is changing in many countries. Height is an important risk factor for AF. The aim of the present study was to assess the role of changes in population height in the increased risk of AF. Methods and results: The Copenhagen City Heart Study comprises 18 852 randomly selected men and women aged 20-93 years, studied in four separate cross-sectional surveys in 1976-78, 1981-83, 1991-94, and 2001-03, including physical examination, electrocardiogram (ECG), and standard questionnaires. Hospitalization and mortality data were collected from public registers. Prevalent AF was determined from ECGs and incident AF from register diagnoses. During follow-up, age-standardized prevalence of AF increased significantly from 1.35% to 2.11% in men and from 0.67% to 1.07% in women (P < 0.001). Incident AF increased four-fold in both men and women [hazard ratio (HR) 4.16, 95% confidence interval (CI) 3.27-5.29; P < 0.001]. In multivariable Fine and Gray subdistribution hazards regression analyses, height was consistently an important risk factor for incident AF with HRs between 1.35 (95% CI 1.10-1.66; P = 0.004) and 1.65 (95% CI 1.40-1.93; P < 0.001). Population height increased with 3.3 cm for men and 2.1 cm for women, and population attributable risks for height was 20-30%. Conclusion: Height is a powerful risk factor for AF. Adult height is attained at age 20, while AF incidence occurs 50 years later. Given a causal relationship between height and AF incidence, increased population height in Denmark will contribute to an increase in AF occurrence for at least 25 more years.

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.).

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.

Visible age-related signs and risk of ischemic heart disease in the general population: a prospective cohort study.

BACKGROUND: Cardiovascular disease is 1 of the most common age-related diseases, and also 1 of the most common causes of death in the general population. We tested the hypothesis that visible age-related signs associate with risk of ischemic heart disease (IHD), myocardial infarction (MI), and death in the general population, independent of chronological age. METHODS AND RESULTS: 10,885 individuals aged 20 to 93 years free of IHD were followed from 1976 through 1978 until June 2011 with 100% complete follow-up. During these 35 years of follow-up, 3401 participants developed IHD and 1708 developed MI. Presence of frontoparietal baldness, crown top baldness, earlobe crease, and xanthelasmata was associated with increased risk of IHD or MI after multifactorial adjustment for chronological age and well-known cardiovascular risk factors. The risk of IHD and MI increased stepwise with increasing number of age-related signs with multifactorially adjusted hazard ratios up to 1.40 (95% confidence interval, 1.20-1.62) for IHD and 1.57 (1.28-1.93) for MI, in individuals with 3 to 4 versus no age-related signs at baseline (P for trend <0.001). In all age groups in both women and men, absolute 10-year risk of IHD and MI increased with increasing number of visible age-related signs. CONCLUSIONS: Male pattern baldness, earlobe crease, and xanthelasmata-alone or in combination-associate with increased risk of ischemic heart disease and myocardial infarction independent of chronological age and other well-known cardiovascular risk factors. This is the first prospective study to show that looking old for your age is a marker of poor cardiovascular health.

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.

Total and cause-specific mortality by moderately and markedly increased ferritin concentrations: general population study and metaanalysis.

BACKGROUND: Previous population-based studies of plasma ferritin concentration have not revealed a relationship with total mortality. We tested the possible association of increased ferritin concentrations with increased risk of total and cause-specific mortality in the general population. METHODS: We examined total and cause-specific mortality according to baseline plasma ferritin concentrations in a Danish population-based study (the Copenhagen City Heart Study) of 8988 individuals, 6364 of whom died (median follow-up 23 years). We also included a metaanalysis of total mortality comprising population-based studies according to ferritin quartiles or tertiles. RESULTS: Multifactorially adjusted hazard ratios (HRs) for total mortality for individuals with ferritin ≥200 vs <200 µg/L were 1.1 (95% CI 1.1-1.2; P = 0.0008) overall, 1.1 (1.0-1.2; P = 0.02) in men, and 1.2 (1.0-1.3; P = 0.03) in women. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10(-22)), with median survival of 55 years at ferritin concentrations ≥600 µg/L, 72 years at 400-599 µg/L, 76 years at 200-399 µg/L, and 79 years at ferritin <200 µg/L. The corresponding HR for total overall mortality for ferritin ≥600 vs <200 µg/L was 1.5 (1.2-1.8; P = 0.00008). Corresponding adjusted HRs for ferritin ≥600 vs <200 µg/L were 1.6 (1.1-2.3; P = 0.01) for cancer mortality, 2.9 (1.7-5.0; P = 0.0001) for endocrinological mortality, and 1.5 (1.1-2.0; P = 0.01) for cardiovascular mortality. The metaanalysis random effects odds ratio for total mortality for ferritin upper vs reference quartile or tertile was 1.0 (0.9-1.1; P = 0.3) (P heterogeneity = 0.5). CONCLUSIONS: Moderately to markedly increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population.

25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis.

OBJECTIVE: We tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are associated with increased risk of symptomatic ischemic stroke in the general population. METHODS: We measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, the Copenhagen City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events. RESULTS: Stepwise decreasing plasma 25-hydroxyvitamin D concentrations were associated with stepwise increasing risk of ischemic stroke both as a function of seasonally adjusted percentile categories and as a function of clinical categories of 25-hydroxyvitamin D (p for trend ≤ 2 × 10(-3)). In a Cox regression model comparing individuals with plasma 25-hydroxyvitamin D concentrations between the 1st and 4th percentiles to individuals with 25-hydroxyvitamin D concentrations between the 50th and 100th percentiles, multivariate adjusted hazard ratio of ischemic stroke was 1.82 (95% confidence interval, 1.41-2.34). Comparing individuals with clinical categories of severe vitamin D deficiency (<25.0 nmol/l [<10.0 ng/ml]) to individuals with optimal vitamin D status (≥75.0 nmol/l [≥30.0 ng/ml]), the multivariate adjusted hazard ratio of ischemic stroke was 1.36 (1.09-1.70). 25-Hydroxyvitamin D concentrations were not associated with risk of hemorrhagic stroke. In a meta-analysis comparing lowest versus highest quartile of 25-hydroxyvitamin D concentrations, the multivariate adjusted odds ratio of ischemic stroke was 1.54 (1.43-1.65) with a corresponding hazard ratio of 1.46 (1.35-1.58) in prospective general population studies. INTERPRETATION: In this large population-based prospective study, we observed stepwise increasing risk of symptomatic ischemic stroke with decreasing plasma 25-hydroxyvitamin D concentrations. This finding was substantiated in a meta-analysis.

Right ventricular free wall and four-chamber longitudinal strain in relation to incident heart failure in the general population.

AIMS: Right ventricular free wall (RVFWLS) and four-chamber longitudinal strain (RV4CLS) are associated with adverse events in various patient populations including patients with heart failure (HF). We sought to investigate the prognostic value of RVFWLS and RV4CLS for the development of incident HF in participants from the general population. METHODS AND RESULTS: Participants from the 5th Copenhagen City Heart Study (2011-2015) without known chronic ischaemic heart disease or HF at baseline were included. RVFWLS and RV4CLS were obtained using two-dimensional speckle-tracking echocardiography from the right ventricular (RV)-focused apical four-chamber view. The primary endpoint was incident HF. Among 2740 participants (mean age 54 ± 17 years, 42% male), 43 (1.6%) developed HF during a median follow-up of 5.5 years (IQR 4.5-6.3). Both RVFWLS and RV4CLS were associated with an increased risk of incident HF during follow-up independent of age, sex, hypertension, diabetes, body mass index and tricuspid annular plane systolic excursion (TAPSE), (HR 1.06, 95%CI 1.00-1.11, P = 0.034, per 1% absolute decrease and HR 1.14, 95%CI 1.05-1.23, P = 0.001, per 1% absolute decrease, respectively). Left ventricular ejection fraction (LVEF) modified the association between RV4CLS and incident HF (P for interaction = 0.016) such that RV4CLS was only of prognostic importance among those with LVEF < 55% (HR 1.21, 95%CI 1.11-1.33, P < 0.001 vs. HR 0.94, 95%CI 0.80-1.10, P = 0.43 in patients with LVEF ≥ 55%). CONCLUSION: In participants from the general population, both RVFWLS and RV4CLS were associated with a greater risk of incident HF independent of important baseline characteristics and TAPSE, and LVEF modified the relationship between RV4CLS and incident HF.

Type of Alcohol and Blood Pressure: The Copenhagen General Population Study.

BACKGROUND: Most adults ingest alcoholic beverages. Alcohol shows strong and positive associations with blood pressure (BP). We hypothesized that intake of red wine, white wine, beer, and spirits and dessert wine show similar associations with BP in the general population. METHODS: We included 104,467 males and females aged 20-100 years in the analysis of the Danish general population. Alcohol use and type of alcohol were assessed by questionnaire. Blood pressure was measured by automated digital BP manometer. Multivariable linear regression models were used when analyzing the association between number of drinks per week and BP, stratified by sex and adjusted for relevant confounders. Each alcohol type (red wine, white wine, beer, and spirits and dessert wine) was analyzed in similar models including adjustment for other alcohol types. RESULTS: Most of the subjects (76,943 [73.7%]) drank more than 1 type of alcohol. However, 12,093 (12.6%) consumed red wine only, 4288 (4.5%) beer only, 1815 (1.9%) white wine only, and 926 (1.0%) spirits and dessert wine only. There was a dose-response association between total drinks per week and systolic and diastolic BP (SBP, DBP) (P < .001). The crude difference was 11 mmHg SBP and 7 mmHg DBP between high (>35 drinks per week) and low (1-2 drinks per week) alcohol intake. Overall, SBP was increased by 0.15-0.17 mmHG, and DBP was increased by 0.08-0.15 mmHg per weekly drink. After stratification for age and sex, effects were slightly higher among females and among individuals aged less than 60 years. CONCLUSION: Alcohol intake is associated with highly significant increased SPB and DBP. The effect is similar for red wine, white wine, beer, and spirits.

Normal age- and sex-based values of right ventricular free wall and four-chamber longitudinal strain by speckle-tracking echocardiography: from the Copenhagen City heart study.

AIM: To promote the implementation of right ventricular (RV) longitudinal strain in clinical practice, we sought to propose normal values for RV free wall (RVFWLS) and four-chamber longitudinal strain (RV4CLS) and investigate the association with clinical and echocardiographic parameters in participants from the general population. METHODS AND RESULTS: Participants from the 5th Copenhagen City Heart Study (2011-2015)-a prospective cohort study-with available RV longitudinal strain measurements were included. RVFWLS and RV4CLS were assessed using two-dimensional speckle-tracking echocardiography. In total, 2951 participants were included. Amongst 1297 participants without cardiovascular disease or risk factors (median age 44, 63% female), mean values of RVFWLS and RV4CLS were - 26.7% ± 5.2 (95% prediction interval (PI) - 36.9, - 16.5) and - 21.7% ± 3.4 (95%PI - 28.4, - 15.0), respectively. Women had significantly higher absolute values of RVFWLS and RV4CLS than men (mean - 27.5 ± 5.5 vs. - 25.4 ± 4.5, p < 0.001 and - 22.3 ± 3.5 vs. - 20.6 ± 3.0, p < 0.001, respectively). Absolute values of RVFWLS but not RV4CLS decreased significantly with increasing age in unadjusted linear regression. Tricuspid annular plane systolic excursion, RV s' and left ventricular global longitudinal strain were the most influential parameters associated with both RVFWLS and RV4CLS in multiple linear regression. Participants with cardiovascular disease (n = 1531) had a higher proportion of abnormal values of RVFWLS and RV4CLS compared to the healthy population (8% vs. 4%, p < 0.001 and 8% vs. 3%, p < 0.001, respectively). CONCLUSION: This study proposed normal age- and sex-based values of RVFWLS and RV4CLS in a healthy population sample and showed significant sex differences in both measurements across ages.