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.

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.

A Review of Major Danish Biobanks: Advantages and Possibilities of Health Research in Denmark.

Biobank research may lead to an improved understanding of disease etiology and advance personalized medicine. Denmark (population ~5.9 million) provides a unique setting for population-based health research. The country is a rich source of biobanks and the universal, tax-funded healthcare system delivers routinely collected data to numerous registries and databases. By virtue of the civil registration number (assigned uniquely to all Danish citizens), biological specimens stored in biobanks can be combined with clinical and demographic data from these population-based health registries and databases. In this review, we aim to provide an understanding of advantages and possibilities of biobank research in Denmark. As knowledge about the Danish setting is needed to grasp the full potential, we first introduce the Danish healthcare system, the Civil Registration System, the population-based registries, and the interface with biobanks. We then describe the biobank infrastructures, comprising the Danish National Biobank Initiative, the Bio- and Genome Bank Denmark, and the Danish National Genome Center. Further, we briefly provide an overview of fourteen selected biobanks, including: The Danish Newborn Screening Biobank; The Danish National Birth Cohort; The Danish Twin Registry Biobank; Diet, Cancer and Health; Diet, Cancer and Health - Next generations; Danish Centre for Strategic Research in Type 2 Diabetes; Vejle Diabetes Biobank; The Copenhagen Hospital Biobank; The Copenhagen City Heart Study; The Copenhagen General Population Study; The Danish Cancer Biobank; The Danish Rheumatological Biobank; The Danish Blood Donor Study; and The Danish Pathology Databank. Last, we inform on practical aspects, such as data access, and discuss future implications.

Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study.

AIMS: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19. METHODS AND RESULTS: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. CONCLUSION: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.

Possible Modifiers of the Association Between Change in Weight Status From Child Through Adult Ages and Later Risk of Type 2 Diabetes.

OBJECTIVE: We investigated the association between changes in weight status from childhood through adulthood and subsequent type 2 diabetes risks and whether educational attainment, smoking, and leisure time physical activity (LTPA) modify this association. RESEARCH DESIGN AND METHODS: Using data from 10 Danish and Finnish cohorts including 25,283 individuals, childhood BMI at 7 and 12 years was categorized as normal or high using age- and sex-specific cutoffs (<85th or ≥85th percentile). Adult BMI (20-71 years) was categorized as nonobese or obese (<30.0 or ≥30.0 kg/m2, respectively). Associations between BMI patterns and type 2 diabetes (989 women and 1,370 men) were analyzed using Cox proportional hazards regressions and meta-analysis techniques. RESULTS: Compared with individuals with a normal BMI at 7 years and without adult obesity, those with a high BMI at 7 years and adult obesity had higher type 2 diabetes risks (hazard ratio [HR]girls 5.04 [95% CI 3.92-6.48]; HRboys 3.78 [95% CI 2.68-5.33]). Individuals with a high BMI at 7 years but without adult obesity did not have a higher risk (HRgirls 0.74 [95% CI 0.52-1.06]; HRboys 0.93 [95% CI 0.65-1.33]). Education, smoking, and LTPA were associated with diabetes risks but did not modify or confound the associations with BMI changes. Results for 12 years of age were similar. CONCLUSIONS: A high BMI in childhood was associated with higher type 2 diabetes risks only if individuals also had obesity in adulthood. These associations were not influenced by educational and lifestyle factors, indicating that BMI is similarly related to the risk across all levels of these factors.

Resting heart rate and mortality in the very old.

The number of very old individuals in the population is rapidly increasing. Previous studies have indicated that many factors known to be strongly associated with survival among middle-aged and elderly show no association among the oldest old. Resting heart rate (RHR) is associated with increased risk of death in the general population as well as in patients with various types of heart disease. The association between RHR and mortality in the very old is the subject of this report. The study population was identified in The Nationwide Danish 1905 Cohort Study (n = 1086) and comprised 854 subjects with a median age of 95.2 years (range 94.7-95.9), in whom RHR was measured by radial pulse palpation. Participants were followed until death through the civil registration system, and remaining lifespan after RHR measure was used as outcome. Participants were divided into six groups according to RHR (≤50, 51-60, 61-70, 71-80, 81-90 and ≥91) with the largest group used as the reference group (61-70 beats per minute (bpm)). Survival analyses using Cox' proportional hazards models were performed to study the association between RHR and mortality. Median RHR was 68 bpm in males (IQR 62-76) and 70 bpm (IQR 64-78) in females. After stratifying both sexes into six groups according to RHR, we found no significant difference in remaining lifespan between groups in either males or females. No significantly increased risk was demonstrated in groups with higher RHR. In very old people, elevated RHR is not associated with increased mortality.

Secular trends in risk of stroke according to body mass index and blood pressure, 1976-2017.

OBJECTIVE: To test the hypothesis that the associations of body mass index (BMI) and BMI-related risk factors with risk of stroke have attenuated over time using cohorts recruited from the general population over 4 decades. METHODS: We undertook prospective studies of 2 cohorts enrolled in 1976 to 1978 (13,567 participants from the Copenhagen City Heart Study) and 2003 to 2015 (107,040 participants from the Copenhagen General Population Study). Each cohort was recruited randomly from the Danish general population 20 to 100 years of age. Participants were followed up from the date of examination to date of emigration, death, or stroke event, whichever occurred first. Follow-up ended in March 2017. We did not lose track of any individual. BMI and blood pressure were modeled with splines and in categories. Main outcome was incident stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. RESULTS: The crude incidence of stroke declined in extreme categories of BMI and blood pressure from 1977 to 2017. The multivariable-adjusted hazard ratios for stroke in participants with BMI ≥30 vs 18.5 to 24.9 kg/m2 were 1.4 (95% confidence interval 1.2-1.6) in the 1976-1978 cohort and 1.1 (1.0-1.2) in the 2003-2015 cohort (p = 0.008 for 1976-1978 vs 2003-2015). The corresponding hazard ratios (confidence intervals) in participants with blood pressure ≥160/100 vs <140/90 mm Hg were 2.1 (1.9-2.3) and 1.5 (1.4-1.7), respectively (p < 0.001). Similar secular trends were observed for diabetes mellitus but were not obvious for other risk factors. CONCLUSION: The associations of high BMI and high blood pressure with higher risk of stroke were attenuated across 2 Danish cohorts enrolled from 1976 through 2015.

Attitudes to and experiences with body weight control and changes in body weight in relation to all-cause mortality in the general population.

BACKGROUND AND AIMS: Increased body mass index (BMI = weight/height2; kg/m2) and weight gain is associated with increased mortality, wherefore weight loss and avoided weight gain should be followed by lower mortality. This is achieved in clinical settings, but in the general population weight loss appears associated with increased mortality, possibly related to the struggles with body weight control (BWC). We investigated whether attitudes to and experiences with BWC in combination with recent changes in body weight influenced long-term mortality among normal weight and overweight individuals. POPULATION AND METHODS: The study population included 6,740 individuals attending the 3rd cycle in 1991-94 of the Copenhagen City Heart Study, providing information on BMI, educational level, health behaviours, well-being, weight half-a-year earlier, and answers to four BWC questions about caring for body weight, assumed benefit of weight loss, current and past slimming experiences. Participants reporting previous unintended weight loss (> 4 kg during one year) were excluded. Cox regression models estimated the associations of prior changes in BMI and responses to the BWC questions with approximately 22 years all-cause mortality with age as 'time scale'. Participants with normal weight (BMI < 25.0 kg/m2) and overweight (BMI ≥ 25.0 kg/m2) were analysed separately, and stratified by gender and educational level, health behaviours and well-being as co-variables. RESULTS: Compared with stable weight, weight loss was associated with significantly increased mortality in the normal weight group, but not in the overweight group, and weight gain was not significantly associated with mortality in either group. Participants with normal weight who claimed that it would be good for their health to lose weight or that they were currently trying to lose weight had significantly higher mortality than those denying it. There were no other significant associations with the responses to the BWC questions in either the normal weight or the overweight group. When combining the responses to the BWC questions with the weight changes, using the weight change as either a continuous or categorical variable, there were no significant interaction in their relation to mortality in either the normal weight or the overweight group. CONCLUSION: Attitudes to and experiences with BWC did not notably modify the association of changes in body weight with mortality in either people with normal weight or people with overweight.

Relationship Between Left Atrial Functional Measures and Incident Atrial Fibrillation in the General Population: The Copenhagen City Heart Study.

OBJECTIVES: This study sought to investigate whether left atrial (LA) functional measures predict atrial fibrillation (AF) in the general population. BACKGROUND: Increasing evidence suggests LA functional measures are predictors of AF in several patient groups. METHODS: In a community-based cohort study, approximately 2,000 individuals underwent a transthoracic echocardiogram. Conventional echocardiographic measures and extended LA measures, including the minimal and maximal LA volumes (LAVmin and LAVmax, respectively) and left atrial emptying fraction (LAEF), were performed. The endpoint was incident AF, and participants with known AF were excluded, which left 1,951 for inclusion. RESULTS: Over 11.0 years of follow-up, 184 (9.4%) developed AF. Those who developed AF had significantly larger LA volumes and lower LAEF than participants free of AF. These LA measures were univariable predictors of AF (LAVmax hazard ratio [HR]: 1.10 [95% confidence interval (CI): 1.08 to 1.12] per 1-ml increase, p < 0.001; LAVmin HR: 1.14 [95% CI: 1.12 to 1.16] per 1-ml increase, p < 0.001; LAEF HR: 1.03 [95% CI: 1.02 to 1.04] per percent decrease, p < 0.001). All LA measures remained predictors independent of clinical risk scores, with LAVmin providing the highest C-statistics when added to these risk scores (C-statistic for CHADS2 0.728 vs. CHADS2 + LAVmin 0.778; C-statistic for CHARGE-AF 0.815 vs. CHARGE-AF + LAVmin 0.830). However, hypertension modified the relationship between the measures of LA function (both LAVmin and LAEF) and risk of AF (p for interaction < 0.001), which was not the case for LAVmax (p = 0.22). The measures of LA function mainly provided prognostic information regarding risk of AF in participants without hypertension. Even when we restricted our analysis to individuals without hypertension and nondilated LA (LAVmax<34 ml/m2), the LAVmin and LAEF remained significantly independent predictors of AF after multivariable adjustments (LAVmin HR: 1.12 [95% CI: 1.01 to 1.24], p = 0.028, and LAEF HR: 1.03 [95% CI: 1.00 to 1.06], p = 0.021, respectively). CONCLUSIONS: LA functional measures predict AF in the general population and provide prognostic information incremental to clinical risk scores. In individuals without hypertension and nondilated LA, these measures indicate an increased risk of AF.

Resting Heart Rate Is Not Associated with Cognitive Function.

AIMS: In order to examine the hypothesis that elevated resting heart rate (RHR) is associated with impaired cognitive score, we investigated the relationship between RHR and cognitive score in middle-aged, elderly and old Danish subjects from the general population. METHODS: Composite cognitive scores derived from the result of 5 age-sensitive cognitive tests for a total of 7,002 individuals (Middle-aged Danish twin: n = 4,132, elderly Danish twins: n = 2,104 and Danish nonagenarian: n = 766) divided according to RHR and compared using linear regression models adjusted for sex, age, previous heart conditions and hypertension. RHR was assessed by palpating radial pulse. Genetic and shared environmental confounding was addressed in intrapair analyses of 2,049 twin pairs. RESULTS: In unadjusted multivariate models and in multivariable models adjusting for age, sex, heart conditions and hypertension, RHR was not associated with cognitive function. Furthermore, the intrapair analyses showed that RHR was not associated with cognitive score testing within twin pairs, as measured by the proportion of twin pairs in which the twin with higher RHR also was the twin with the lowest composite cognitive score (1,049 pairs of 2,049 pairs [51% (95% CI 49-53), p < 0.289]). CONCLUSION: While elevated RHR has been shown to be associated with adverse health events and poor fitness level, RHR has no relation to cognitive function in the general population.

Heritability of resting heart rate and association with mortality in middle-aged and elderly twins.

OBJECTIVE: Resting heart rate (RHR) possibly has a hereditary component and is associated with longevity. We used the classical biometric twin study design to investigate the heritability of RHR in a population of middle-aged and elderly twins and, furthermore, studied the association between RHR and mortality. METHODS: In total, 4282 twins without cardiovascular disease were included from the Danish Twin Registry, hereof 1233 twin pairs and 1816 'single twins' (twins with a non-participating co-twin); mean age 61.7 (SD 11.1) years; 1334 (31.2%) twins died during median 16.3 (IQR 13.8-16.5) years of follow-up assessed through Danish national registers. RHR was assessed by palpating radial pulse. RESULTS: Within pair correlations for RHR adjusted for sex and age were 0.23 (95% CI 0.14 to 0.32) and 0.10 (0.03 to 0.17) for RHR in monozygotic (MZ) and dizygotic (DZ) twin pairs, respectively. Overall, heritability estimates were 0.23 (95% CI 0.15 to 0.30); 0.27 (0.15 to 0.38) for males and 0.17 (0.06 to 0.28) for females. In multivariable models adjusting for age, gender, body mass index, diabetes, hypertension, pulmonary function, smoking, physical activity and zygosity, RHR was significantly associated with mortality (eg, RHR >90 vs 61-70 beats per min: all-cause HR 1.56 (95% CI 1.21 to 2.03); cardiovascular 2.19 (1.30 to 3.67). Intrapair twin comparison revealed that the twin with the higher RHR was significantly more likely to die first and the probability increased with increase in intrapair difference in RHR. CONCLUSIONS: RHR is a trait with a genetic influence in middle-aged and elderly twins free of cardiovascular disease. RHR is independently associated with longevity even when familial factors are controlled for in a twin design.

Left Ventricular Systolic Function Assessed by Global Longitudinal Strain is Impaired in Atrial Fibrillation Compared to Sinus Rhythm.

BACKGROUND: Atrial fibrillation (AF) is the most common aberrant cardiac arrhythmia. Many AF patients present with symptoms of dyspnea and fatigue, but have normal left ventricular ejection fraction (LVEF). PURPOSE: To determine the reproducibility of measurements of global longitudinal strain (GLS) and strain rate in patients with AF and examine if the arrhythmia is associated with abnormal LV strain and strain rate independent of age, sex, heart rate, LVEF and LV mass. We hypothesized that AF independently reduces ventricular systolic performance. METHODS: The study was conducted as a retrospective analysis of images from 150 randomly selected patients with AF compared to an equal number of subjects with sinus rhythm (SR) matched for age, sex, heart rate, LVEF and LV mass. Half of the patients had normal LVEF (LVEF > 50%) and half had reduced LVEF (LVEF < 50%). GLS and strain rate were measured in each group, as were quantitative LV volumes and standard systolic and diastolic parameters. Results: GLS was significantly impaired in patients with AF compared to subjects with SR, both in the overall population (-12.25 ± 4.1% vs. -16.13 ± 4.7%, p<0.0001), in patients with normal LVEF (-14.41 ± 3.9% vs. -19.42 ± 3.1%, p<0.0001) and in patients with reduced LVEF (-10.10 ± 3.1% vs. -12.85 ± 3.5%, p<0.0001).Linear regression and Bland Altman analyses demonstrated good intraobserver and interobserver agreement for measurements of GLS and strain rate parameters even in patients with AF.

Occupational physical activity, but not leisure-time physical activity increases the risk of atrial fibrillation: The Copenhagen City Heart Study.

BACKGROUND: Previous findings regarding physical activity and risk of incident atrial fibrillation (AF) are controversial, focusing on leisure-time physical activity (LTPA) and without distinguishing it from occupational physical activity (OPA). Our aim was to study the association between physical activity and risk of AF, with special attention to the possible divergent effects of OPA and LTPA. METHODS AND RESULTS: In a prospective, observational cohort study, 17,196 subjects were included from the Copenhagen Population Register. All participants had a physical examination, a 12-lead electrocardiogram (ECG), and answered a questionnaire regarding health and physical activity. Participants without previously diagnosed AF who answered adequately regarding OPA and LTPA were included. LTPA and OPA were each graded into four levels. Follow-up were carried out between 1981-1983, 1991-1994, and 2001-2003. Information regarding hospitalization and mortality was drawn from the National Patient Registry and the Registry of Causes of Death. Outcome was incident AF as determined by follow-up ECG or register diagnosis. In univariable Cox regression analysis all sub-groups of OPA had a significant higher risk of AF compared to moderate OPA. When adjusting for confounders, the risk remained significantly increased for high OPA (hazard ratio (HR) 1.21 (95% confidence interval (CI) 1.02-1.43), p = 0.028), and very high OPA (HR 1.39 (95% CI 1.03-1.88), p = 0.034). We found no significant association between LTPA and incident AF. CONCLUSIONS: High and very high OPA were associated with a significantly increased risk of incident AF. LTPA was not associated with risk of incident AF.

Change in Body Mass Index Associated With Lowest Mortality in Denmark, 1976-2013.

IMPORTANCE: Research has shown a U-shaped pattern in the association of body mass index (BMI) with mortality. Although average BMI has increased over time in most countries, the prevalence of cardiovascular risk factors may also be decreasing among obese individuals over time. Thus, the BMI associated with lowest all-cause mortality may have changed. OBJECTIVE: To determine whether the BMI value that is associated with the lowest all-cause mortality has increased in the general population over a period of 3 decades. DESIGN, SETTING, AND PARTICIPANTS: Three cohorts from the same general population enrolled at different times: the Copenhagen City Heart Study in 1976-1978 (n = 13,704) and 1991-1994 (n = 9482) and the Copenhagen General Population Study in 2003-2013 (n = 97,362). All participants were followed up from inclusion in the studies to November 2014, emigration, or death, whichever came first. EXPOSURES: For observational studies, BMI was modeled using splines and in categories defined by the World Health Organization. Body mass index was calculated as weight in kilograms divided by height in meters squared. MAIN OUTCOMES AND MEASURES: Main outcome was all-cause mortality and secondary outcomes were cause-specific mortality. RESULTS: The number of deaths during follow-up was 10,624 in the 1976-1978 cohort (78% cumulative mortality; mortality rate [MR], 30/1000 person-years [95%CI, 20-46]), 5025 in the 1991-1994 cohort (53%; MR, 16/1000 person-years [95%CI, 9-30]), and 5580 in the 2003-2013 cohort (6%;MR, 4/1000 person-years [95%CI, 1-10]). Except for cancer mortality, the association of BMI with all-cause, cardiovascular, and other mortality was curvilinear (U-shaped). The BMI associated with the lowest all-cause mortality increased by 3.3 from the 1976-1978 cohort compared with the 2003-2013 cohort. [table: see text] The multivariable-adjusted hazard ratios for all-cause mortality for BMI of 30 or more vs BMI of 18.5 to 24.9 were 1.31 (95%CI, 1.23-1.39;MR, 46/1000 person-years [95%CI, 32-66] vs 28/1000 person-years [95%CI, 18-45]) in the 1976-1978 cohort, 1.13 (95%CI, 1.04-1.22; MR, 28/1000 person-years [95%CI, 17-47] vs 15/1000 person-years [95%CI, 7-31]) in the 1991-1994 cohort, and 0.99 (95%CI, 0.92-1.07;MR, 5/1000 person-years [95%CI, 2-12] vs 4/1000 person-years [95%CI, 1-11]) in the 2003-2013 cohort. CONCLUSIONS AND RELEVANCE Among 3 Danish cohorts, the BMI associated with the lowest all-cause mortality increased by 3.3 from cohorts enrolled from 1976-1978 through 2003-2013. Further investigation is needed to understand the reason for this change and its implications.

Educational inequality in cardiovascular disease depends on diagnosis: A nationwide register based study from Denmark.

BACKGROUND: Social inequality is present in the morbidity as well as the mortality of cardiovascular diseases. This paper aims to quantify and compare the level of educational inequality across different cardiovascular diagnoses. DESIGN: Register based study. METHODS: Comparison of the extent of inequality across different cardiovascular diagnoses requires a measure of inequality which is comparable across subgroups with different educational distributions. The slope index of inequality and the relative index of inequality were applied for measuring inequalities in incidence of six cardiovascular diagnoses: ischaemic heart disease, acute myocardial infarction, valvular heart disease, congestive heart failure, atrial fibrillation and stroke in the period 2005-2009. All individuals in the general Danish population aged 35-84 years were followed in national registers regarding hospitalisation, death and education from 1985 to 2009 (annual average of 2.9 million people) to define incident cases. RESULTS: Marked educational inequality was found in the incidence of ischaemic heart disease, acute myocardial infarction, heart failure and stroke (relative index of inequality: 0.37 (95% confidence interval 0.34; 0.40) to 0.60 (0.57; 0.63), absolute index of inequality: -241 (-254.4; -227.4) to -37 (-42.7; -31.1)) while inequality in atrial fibrillation and, in particular, in valvular heart disease was small and insignificant (relative index of inequality: 0.57 (0.49; 0.65) to 0.97 (0.88; 1.08), absolute index of inequality: -29 (-35.1; -21.9) to -1 (-4.8; -3.8)). CONCLUSION: The degree of educational inequality in cardiovascular diseases depends on the diagnosis, with the highest inequality in ischaemic heart disease, acute myocardial infarction, heart failure and stroke. Small differences were found between men and women.

Sex Hormones and Ischemic Stroke: A Prospective Cohort Study and Meta-Analyses.

CONTEXT AND OBJECTIVE: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear. We tested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. DESIGN, SETTING, AND PARTICIPANTS: Adult men (n = 4615) and women (n = 4724) with measurements of endogenous sex hormones during the 1981-1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through potential mediators. Present and previous findings were summarized in meta-analyses. MAIN OUTCOME MEASURES: Plasma total testosterone and total estradiol were measured by competitive immunoassays. Diagnosis of IS was ascertained from the national Danish Patient Registry and the national Danish Causes of Death Registry and verified by experienced neurologists. RESULTS: During follow-up, 524 men and 563 women developed IS. Men with testosterone concentrations ≤10th percentile compared to the 11th-90th percentiles had a hazard ratio for IS of 1.34 (95% confidence interval, 1.05-1.72); 21% of this risk was mediated by body mass index (P = .002) and 14% by hypertension (P = .02). In accordance with this, the corresponding hazard ratio was 1.46 (1.09-1.95) in overweight/obese and hypertensive men. The corresponding hazard ratio in the meta-analysis was 1.43 (1.21-1.70). Other extreme concentrations of testosterone or estradiol were not associated with risk of IS in men or women. CONCLUSIONS: Extremely low endogenous testosterone concentrations were associated with high risk of IS in men, a risk mediated in part by body mass index and hypertension. Whether or not low testosterone is a causal factor for IS or merely a biomarker of poor metabolic health is still not known.

Long-Term Clinical Impact of Coronary CT Angiography in Patients With Recent Acute-Onset Chest Pain: The Randomized Controlled CATCH Trial.

OBJECTIVES: The aim of the CATCH (CArdiac cT in the treatment of acute CHest pain) trial was to investigate the long-term clinical impact of a coronary computed tomographic angiography (CTA)-guided treatment strategy in patients with recent acute-onset chest pain compared to standard care. BACKGROUND: The prognostic implications of a coronary CTA-guided treatment strategy have not been compared in a randomized fashion to standard care in patients referred for acute-onset chest pain. METHODS: Patients with acute chest pain but normal electrocardiograms and troponin values were randomized to treatment guided by either coronary CTA or standard care (bicycle exercise electrocardiogram or myocardial perfusion imaging). In the coronary CTA-guided group, a functional test was included in cases of nondiagnostic coronary CTA images or coronary stenoses of borderline severity. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), hospitalization for unstable angina pectoris (UAP), late symptom-driven revascularizations, and readmission for chest pain. RESULTS: We randomized 299 patients to coronary CTA-guided strategy and 301 to standard care. After inclusion, 24 patients withdrew their consent. The median (interquartile range) follow-up duration was 18.7 (range 16.8 to 20.1) months. In the coronary CTA-guided group, 30 patients (11%) had a primary endpoint versus 47 patients (16%) in the standard care group (p = 0.04; hazard ratio [HR]: 0.62 [95% confidence interval: 0.40 to 0.98]). A major adverse cardiac event (cardiac death, MI, hospitalization for UAP, and late symptom-driven revascularization) was observed in 5 patients (2 MIs, 3 UAPs) in the coronary CTA-guided group versus 14 patients (1 cardiac death, 7 MIs, 5 UAPs, 1 late symptom-driven revascularization) in the standard care group (p = 0.04; HR: 0.36 [95% CI: 0.16 to 0.95]). Differences in cardiac death and MI (8 vs. 2) were insignificant (p = 0.06). CONCLUSIONS: A coronary CTA-guided treatment strategy appears to improve clinical outcome in patients with recent acute-onset chest pain and normal electrocardiograms and troponin values compared to standard care with a functional test. (Cardiac-CT in the Treatment of Acute Chest Pain [CATCH]; NCT01534000).