Associations of occupational and leisure-time physical activity with all-cause mortality: an individual participant data meta-analysis.

OBJECTIVE: Health effects of different physical activity domains (ie, during leisure time, work and transport) are generally considered positive. Using Active Worker consortium data, we assessed independent associations of occupational and leisure-time physical activity (OPA and LTPA) with all-cause mortality. DESIGN: Two-stage individual participant data meta-analysis. DATA SOURCE: Published and unpublished cohort study data. ELIGIBILITY CRITERIA: Working participants aged 18-65 years. METHODS: After data harmonisation, we assessed associations of OPA and LTPA with all-cause mortality. In stage 1, we analysed data from each study separately using Cox survival regression, and in stage 2, we pooled individual study findings with random-effects modelling. RESULTS: In 22 studies with up to 590 497 participants from 11 countries, during a mean follow-up of 23.1 (SD: 6.8) years, 99 743 (16%) participants died. Adjusted for LTPA, body mass index, age, smoking and education level, summary (ie, stage 2) hazard ration (HRs) and 95% confidence interval (95% CI) for low, moderate and high OPA among men (n=2 96 134) were 1.01 (0.99 to 1.03), 1.05 (1.01 to 1.10) and 1.12 (1.03 to 1.23), respectively. For women (n=2 94 364), HRs (95% CI) were 0.98 (0.92 to 1.04), 0.96 (0.92 to 1.00) and 0.97 (0.86 to 1.10), respectively. In contrast, higher levels of LTPA were inversely associated with mortality for both genders. For example, for women HR for low, moderate and high compared with sedentary LTPA were 0.85 (0.81 to 0.89), 0.78 (0.74 to 0.81) and 0.75 (0.65 to 0.88), respectively. Effects were attenuated when adjusting for income (although data on income were available from only 9 and 6 studies, for men and women, respectively). CONCLUSION: Our findings indicate that OPA may not result in the same beneficial health effects as LTPA.

Continuous monitoring is superior to manual measurements in detecting vital sign deviations in patients with COVID-19.

BACKGROUND: Patients admitted to the emergency care setting with COVID-19-infection can suffer from sudden clinical deterioration, but the extent of deviating vital signs in this group is still unclear. Wireless technology monitors patient vital signs continuously and might detect deviations earlier than intermittent measurements. The aim of this study was to determine frequency and duration of vital sign deviations using continuous monitoring compared to manual measurements. A secondary analysis was to compare deviations in patients admitted to ICU or having fatal outcome vs. those that were not. METHODS: Two wireless sensors continuously monitored (CM) respiratory rate (RR), heart rate (HR), and peripheral arterial oxygen saturation (SpO2 ). Frequency and duration of vital sign deviations were compared with point measurements performed by clinical staff according to regional guidelines, the National Early Warning Score (NEWS). RESULTS: SpO2 < 92% for more than 60 min was detected in 92% of the patients with CM vs. 40% with NEWS (p < .00001). RR > 24 breaths per minute for more than 5 min were detected in 70% with CM vs. 33% using NEWS (p = .0001). HR ≥ 111 for more than 60 min was seen in 51% with CM and 22% with NEWS (p = .0002). Patients admitted to ICU or having fatal outcome had longer durations of RR > 24 brpm (p = .01), RR > 21 brpm (p = .01), SpO2 < 80% (p = .01), and SpO2 < 85% (p = .02) compared to patients that were not. CONCLUSION: Episodes of desaturation and tachypnea in hospitalized patients with COVID-19 infection are common and often not detected by routine measurements.

Artificial intelligence enabled ECG screening for left ventricular systolic dysfunction: a systematic review.

Screening for left ventricular systolic dysfunction (LVSD), defined as reduced left ventricular ejection fraction (LVEF), deserves renewed interest as the medical treatment for the prevention and progression of heart failure improves. We aimed to review the updated literature to outline the potential and caveats of using artificial intelligence-enabled electrocardiography (AIeECG) as an opportunistic screening tool for LVSD.We searched PubMed and Cochrane for variations of the terms "ECG," "Heart Failure," "systolic dysfunction," and "Artificial Intelligence" from January 2010 to April 2022 and selected studies that reported the diagnostic accuracy and confounders of using AIeECG to detect LVSD.Out of 40 articles, we identified 15 relevant studies; eleven retrospective cohorts, three prospective cohorts, and one case series. Although various LVEF thresholds were used, AIeECG detected LVSD with a median AUC of 0.90 (IQR from 0.85 to 0.95), a sensitivity of 83.3% (IQR from 73 to 86.9%) and a specificity of 87% (IQR from 84.5 to 90.9%). AIeECG algorithms succeeded across a wide range of sex, age, and comorbidity and seemed especially useful in non-cardiology settings and when combined with natriuretic peptide testing. Furthermore, a false-positive AIeECG indicated a future development of LVSD. No studies investigated the effect on treatment or patient outcomes.This systematic review corroborates the arrival of a new generic biomarker, AIeECG, to improve the detection of LVSD. AIeECG, in addition to natriuretic peptides and echocardiograms, will improve screening for LVSD, but prospective randomized implementation trials with added therapy are needed to show cost-effectiveness and clinical significance.

Experiences from COVID-19-driven use of telephone consultations in a cardiology clinic-The CoviTel study.

INTRODUCTION: The COVID-19 pandemic triggered a rapid shift towards telephone consultations (TC) in the out-patient clinic setting with little knowledge of the consequences. The aims of this study were to evaluate patient-centred experiences with TC, to describe patterns in clinical outcomes from TC and to pinpoint benefits and drawbacks associated with this type of consultations. METHODS: This mixed methods study combined an analysis of quantitative and qualitative data. A quantitative, retrospective observational study was conducted employing data from all 248 patients who received TC at an out-patient cardiology clinic during April 2020 with a one-month follow-up. Semi-structured interviews were conducted; Ten eligible patients were recruited from the outpatient clinic by purposive sampling. RESULTS: Within the follow-up period, no patients died or were acutely hospitalised. Approximately one in every four patients was transferred to their general practitioner, while the remaining three-quarter of the patients had a new examination or a new consultation planned. The cardiologist failed to establish contact with more than a fifth of the patients, often due to missing phone numbers. Ten patients were interviewed. Five themes emerged from the interviews: 1) Knowing an estimated time of the consultation is essential for patient satisfaction, 2) TC are well perceived when individually adapted, 3) TC can be a barrier to patient questions, 4) Video consultations should only be offered to patients who request it, and 5) Prescriptions or instructions made via TC do not cause uncertainty in patients. CONCLUSIONS: The TC program was overall safe and the patients felt comfortable. Crucial issues include precise time planning, the patient's availability on the phone and a correct phone number. Patients stressed that TC are unsuitable when addressing sensitive topics. A proposed visitation tool is presented.

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

INTRODUCTION: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. METHODS AND ANALYSIS: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022. ETHICS AND DISSEMINATION: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible. TRIAL REGISTRATION NUMBER: NCT04121949; Pre-results.

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.

Relationship between peripheral neuropathy, diastolic function and adverse cardiovascular outcome in individuals with type 1 diabetes mellitus without known cardiovascular disease: Results from the Thousand & 1 Study.

AIMS: To investigate the association between measures of peripheral neuropathy (PN) and impaired left ventricular diastolic function, and the prognosis in patients with type 1 diabetes (T1DM) and no known cardiovascular disease (CVD), and to test the incremental prognostic value of including measures of PN and diastolic function to the established Steno T1 Risk Engine. METHODS: Echocardiography and quantitative biothesiometry was performed to evaluate diastolic function and PN. The participants were categorized according to severity of diastolic function and PN. The study endpoint was combined cardiovascular (CV) events and all-cause death. Associations were analysed using multivariable regression models. The prognostic capability was assessed with Harrell's C-statistics and tested against the Steno T1 Risk Engine. RESULTS: A total of 946 individuals (51.5% men) were included. The mean (SD) follow-up was 6 (1.3) years. The total number of CV events and all-cause death were 100. In the multi-adjusted analysis, both PN and impaired diastolic function were associated with increased risk of CV events and all-cause death: severe PN versus no PN: hazard ratio (HR) 2.23 (95% confidence interval [CI] 1.06-4.68; P = 0.035); severe diastolic impairment versus normal function: HR 2.27 (95% CI 1.16-4.44; P = 0.016). Measures of diastolic function improved prognostic capability when added to the Steno T1 Risk Engine: C-statistic 0.797 (95% CI 0.793-0.817) versus 0.785 (95% CI 0.744-0.825; P = 0.006). CONCLUSION: Peripheral neuropathy and impaired diastolic function are associated with an increased risk of CV events and all-cause death in patients with T1DM. Measures of diastolic function improved prediction of prognosis by the Steno T1 Risk Engine.

Cardiovascular prognostic value of echocardiography and N terminal pro B-type natriuretic peptide in type 1 diabetes: the Thousand & 1 Study.

AIMS: Patients with type 1 diabetes have a high risk of cardiovascular disease. Yet, the importance of routine assessment of myocardial function in patients with type 1 diabetes is not known. Thus, we examined the prognostic importance of NT-proBNP and E/e', an echocardiographic measure of diastolic function, in type 1 diabetes patients with preserved left ventricular ejection fraction (LVEF) and without known heart disease. METHODS AND RESULTS: Type 1 diabetes patients without known heart disease and LVEF ≥45% enrolled in the Thousand and 1 study were included and followed through nationwide registries. The risk of major cardiovascular events (MACE) and death associated with levels of NT-proBNP and E/e' was examined. Of 960 patients, median follow-up of 6.3 years (Q1-Q3: 5.7-7.0), 121 (12%) experienced MACE and 51 (5%) died. Increased levels of both NT-proBNP and E/e' were associated with worse outcomes (adjusted hazard ratios for MACE = 1.56 (1.23-1.98) and 4.29 (2.25-8.16) per Loge increase for NT-proBNP and E/e', respectively). NT-proBNP and E/e' combined significantly improved the discrimination power of the Steno T1D risk engine (MACE, C-index: 0.813 (0.779-0.847) vs 0.779 (0.742-0.816); P = 0.0001; All-cause mortality, C-index 0.855 (0.806-0.903) vs 0.828 (0.776-0.880); P = 0.03). CONCLUSION: In patients with type 1 diabetes, preserved ejection fraction, and no known heart disease, NT-proBNP and E/e' were associated with increased risk of MACE and all-cause mortality. The risks associated with NT-proBNP and E/e' combined identified patients at remarkably high risk.

Metoprolol Versus Carvedilol in Patients With Heart Failure, Chronic Obstructive Pulmonary Disease, Diabetes Mellitus, and Renal Failure.

This study compared the survival and the risk of heart failure (HF), chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), hypoglycemia, and renal failure (RF) hospitalizations in geriatric patients exposed to carvedilol or metoprolol. Data sources were Danish administrative registers. Patients aged ≥65 and having HF, COPD, and DM were followed for 1 year from the first ß-blocker prescription redemption. Patients' characteristics were used to 1:1 propensity score match carvedilol and metoprolol users. A Cox regression model was used to compute the hazard ratio (HR) of study outcomes. For statistically significant associations, a conditional inference tree was used to assess predictors most associated with the outcome. In total, 1,424 patients were included. No statistically significant differences were observed for survival (HR 0.86; 95% confidence interval [CI] 0.67 to 1.11, p = 0.240) between carvedilol/metoprolol users. The same applied to COPD (HR 0.88; 95% CI 0.75 to 1.05, p = 0.177), DM (HR 0.95; 95% CI 0.82 to 1.10, p = 0.485), hypoglycemia (HR 0.88; 95% CI 0.47 to 1.67, p = 0.707), and RF (HR 1.25; 95% CI 0.93 to 1.69, p = 0.142) hospitalizations. Carvedilol users had a 38% higher hazard then metoprolol users of HF hospitalization during the follow-up period (HR 1.38; 95% CI 1.19 to 1.60, p <0.001). Artificial intelligence identified carvedilol exposure as the most important predictor for HF hospitalization. In conclusion, we found an increased risk of HF hospitalization for carvedilol users with this triad of diseases but no statistically significant differences in survival or risk of COPD, DM, hypoglycemia, and RF hospitalizations.

Beta-blocker, aspirin, and statin usage after first-time myocardial infarction in patients with chronic obstructive pulmonary disease: a nationwide analysis from 1995 to 2015 in Denmark.

AIMS: To determine whether beta-blockers, aspirin, and statins are underutilized after first-time myocardial infarction (MI) in patients with chronic obstructive pulmonary disease (COPD) compared with patients without COPD. Further, to determine temporal trends and risk factors for non-use. METHODS AND RESULTS: Using Danish nationwide registers, we performed a cross-sectional study investigating the utilization of beta-blockers, aspirin, and statins after hospitalization for first-time MI among patients with and without COPD from 1995 to 2015. Risk factors for non-use were examined in multivariable logistic regression models. During 21 years of study, 140 278 patients were included, hereof 13 496 (9.6%) with COPD. Patients with COPD were less likely to use beta-blockers (53.2% vs. 76.2%, P < 0.001), aspirin (73.9% vs. 78.8%, P < 0.001), and statins (53.5% vs. 61.9%, P < 0.001). Medication usage increased during the study period but in multivariable analyses, COPD remained a significant predictor for non-use: odds ratio (95% confidence interval) for non-use of beta-blockers 1.86 (1.76-1.97); aspirin 1.24 (1.16-1.32); statins 1.50 (1.41-1.59). Analyses stratified by ST-segment elevation myocardial infarction (STEMI) and non-STEMI showed similar undertreatment of COPD patients. Risk factors for non-use of beta-blockers in COPD included increasing age, female sex, and increasing severity of COPD (frequent exacerbations, use of multiple inhaled medications, and low lung function). Similar findings were demonstrated for aspirin and statins. CONCLUSION: Beta-blockers, and to a lesser extent aspirin and statins, were systematically underutilized by patients with COPD following hospitalization for MI despite an overall increase in the utilization over time. Increasing severity of COPD was a risk factor for non-use of the medications.

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.

Beta-blocker choice and exchangeability in patients with heart failure and chronic obstructive pulmonary disease: an Italian register-based cohort study.

Clinical guidelines suggest that for patients with heart failure and concurrent chronic obstructive pulmonary disease (COPD), metoprolol/bisoprolol/nebivolol should be preferred over carvedilol. However, studies suggest a high proportion of carvedilol usage that remains unexplained. Therefore, we aimed to investigate the predictors of carvedilol choice in patients with heart failure and COPD that were naïve to carvedilol or metoprolol/bisoprolol/nebivolol. Caserta Local Health Unit databases (Italy) were used as data sources. Age, sex, chronic/acute comorbidities, and co-medications were included in a logistic regression model to assess predictors of carvedilol choice. Chronic comorbidities include those defined in the Elixhauser comorbidity index and all hospitalizations within two years prior to the first beta-blocker prescription. Comedications include all redeemed prescriptions within one year prior to the beta-blocker prescription. Kernel density estimations were used to assess the overlap in propensity and preference scores distributions for receiving carvedilol and thereby potential beta-blocker exchangeability. Totally, 10091 patients composed the study population; 2011 were exposed to carvedilol. The overlapping of propensity scores distributions was 57%. Accordingly, the exchangeability was not reached. Atrioventricular block (Odds Ratio, OR 8.20; 95% Confidence Interval, 95% CI 1.30-51.80), cerebrovascular thrombosis (OR 7.06; 95% CI 1.14-43.68), chronic kidney disease (OR 4.32; 95% CI 1.16-16.02), and acute heart failure (OR 1.97; 95% CI 1.28-3.03) hospitalizations were statistically significantly associated with carvedilol choice. Analogously, human insulin (OR 3.00; 95% CI 1.24-7.24), fondaparinux (OR 2.47; 95% CI 1.17-5.21) or strontium ranelate (OR 2.03; 95% CI 1.06-3.90) redeemed prescriptions. In conclusion, this study suggests the absence of beta-blockers exchangeability and a preferential choice of carvedilol in patients with heart failure, COPD and concurrent chronic kidney disease, atrioventricular block, cerebrovascular thrombosis, acute heart failure or redeeming human insulin, fondaparinux or strontium ranelate prescriptions. Therefore, it suggests that choice of prescribing carvedilol over metoprolol/bisoprolol/nebivolol is driven by differences in comorbidities and co-treatments.

Objectively Measured Sitting and Standing in Workers: Cross-Sectional Relationship with Autonomic Cardiac Modulation.

Excessive sitting and standing are proposed risk factors for cardiovascular diseases (CVDs), possibly due to autonomic imbalance. This study examines the association of objectively measured sitting and standing with nocturnal autonomic cardiac modulation. The cross-sectional study examined 490 blue-collar workers in three Danish occupational sectors. Sitting and standing during work and leisure were assessed during 1⁻5 days using accelerometers. Heart rate (HR) and heart rate variability (HRV) were obtained during nocturnal sleep as markers of resting autonomic modulation. The associations of sitting and standing still (h/day) with HR and HRV were assessed with linear regression models, adjusted for age, gender, body mass index, smoking, and physical activity. More sitting time during leisure was associated with elevated HR (p = 0.02), and showed a trend towards reduced HRV. More standing time at work was associated with lower HR (p = 0.02), and with increased parasympathetic indices of HRV (root mean squared successive differences of R-R intervals p = 0.05; high-frequency power p = 0.07). These findings, while cross-sectional and restricted to blue-collar workers, suggest that sitting at leisure is detrimental to autonomic cardiac modulation, but standing at work is beneficial. However, the small effect size is likely insufficient to mitigate the previously shown detrimental effects of prolonged standing on CVD.

Left ventricular concentric geometry predicts incident diabetes mellitus independent of established risk factors in the general population: the Copenhagen City Heart Study.

BACKGROUND: Subtle impairments in left ventricular (LV) function and geometry are common findings in individuals with diabetes. However, whether these impairments precede the development of diabetes mellitus (DM) is not entirely clear. METHODS: Echocardiograms from 1710 individuals from the general population free of prevalent diabetes mellitus were analyzed. Left ventricular (LV) concentric geometry was defined as either LV concentric remodeling or LV concentric hypertrophy as directed in contemporary guidelines. The severity of LV concentricity was assessed by relative wall thickness (RWT) calculated as posterior wall thickness (PWT) indexed to left ventricular internal diameter at end diastole (LVIDd) (RWT = 2 * PWT/LVIDd). End-point was incident DM. RESULTS: Median follow-up time was 12.6 years (IQR: 12.0-12.8 years). Follow-up was a 100%. A total of 55 participants (3.3%) developed DM during follow-up. At baseline, the prevalence of a concentric LV geometric pattern was significantly higher (41.8% vs 20.3%, p < 0.001) in individuals who developed DM during follow-up. In a final multivariable model adjusting for established DM risk factors including HbA1c, BMI and plasma glucose, LV concentric geometry and RWT remained significantly associated with incident DM (LV concentric geometry: HR 1.99, 95% CI 1.11-3.57, p = 0.021) (RWT: HR 1.41, 95% CI 1.06-1.86, p = 0.017, per 0.1 increase). This association remained despite adjustment for established risk factors for DM. CONCLUSION: Altered LV geometry may precede the development of DM. LV concentric geometry determined by echocardiography and the severity of LV concentricity evaluated as RWT are associated with incident DM in the general population.

Comparison of Long-Term Clinical Implications of Beta-Blockade in Patients With Obstructive Airway Diseases Exposed to Beta-Blockers With Different ß1-Adrenoreceptor Selectivity: An Italian Population-Based Cohort Study.

Rationale: Long-term clinical implications of beta-blockade in obstructive airway diseases remains controversial. We investigated if within the first 5 years of treatment patients with heart failure and obstructive airway diseases using non ß1-adrenoreceptor selective beta-blockers have an increased risk of being hospitalized for all-causes, heart failure, and chronic obstructive pulmonary disease (COPD) when compared to patient using selective beta-blockers. Methods: Carvedilol users were propensity matched 1:1 for co-treatments, age, gender, and year of inclusion in the cohort with metoprolol/bisoprolol/nebivolol users. Cox proportional hazard regression model was used to compare all causes, COPD, and heart failure hospitalization or the beta-blocker discontinuation between cohorts. For statistically significant associations, we computed the rate difference and the attributable risk. Results: Overall, 11,844 patients out of the 51,214 (23.1%) were exposed to carvedilol and 39,370 (76.9%) to metoprolol/bisoprolol/nebivolol. Carvedilol users had a higher hazard for heart failure hospitalization (HR 1.29; 95% Confidence Interval [CI] 1.18-1.40) with 106 (95%CI 76-134; p-value < 0.001) additional cases of heart failure hospitalization per 10000 person-years if compared to metoprolol/bisoprolol/nebivolol users. In all, 26.8% (95%CI 22.5-30.9%; p-value < 0.001) of heart failure hospitalizations in the study population could be attributed to being exposed to carvedilol. Carvedilol users had a higher hazard (HR 1.06; 95%CI 1.02-1.10) of discontinuing the pharmacological treatment with 131 (95%CI 62-201; p-value < 0.001) additional cases of beta-blocker discontinuation per 10000 person-years metoprolol/bisoprolol/nebivolol users. In all, 6.5% (95%CI 3.9-9.0%; p-value < 0.001) of beta-blocker discontinuation could be attributed to being exposed to carvedilol. Conclusion: On long-term follow-up period, carvedilol was associated with a higher risk of heart failure hospitalization and discontinuation if compared to metoprolol/bisoprolol/nebivolol users among patients with heart failure and obstructive airway diseases.

Burden of Uncontrolled Metabolic Risk Factors and Left Ventricular Structure and Function in Patients With Type 2 Diabetes Mellitus.

Background Type 2 diabetes mellitus is closely associated with metabolic risk factors that all contribute to impairment of the left ventricle. The implications of having type 2 diabetes mellitus with well-controlled metabolic risk factors compared to an increasing burden of uncontrolled metabolic risk factors on left ventricular structure and function are not known. Methods and Results We compared patients with type 2 diabetes mellitus (n=751) with different degrees of uncontrolled metabolic risk factors present with a control group of individuals without present uncontrolled metabolic risk factors as recommended by the World Health Organization (n=80). In patients with well-controlled metabolic risk factors, only diastolic but neither structural nor systolic measures were impaired compared to the control group: the (early diastolic mitral inflow velocity)/(atrial diastolic mitral inflow velocity) ratio (median 0.94 [interquartile range 0.80, 1.08] versus 1.11 [0.85, 1.38], P<0.001), lateral early diastolic myocardial velocity at the level of the mitral annulus (mean 9.6 m/s [SD 2.5] versus 10.8 [3.5], P<0.001) and lateral (early diastolic mitral inflow velocity)/(early diastolic myocardial velocity at the level of the mitral annulus) (7.7 [6.5, 10.2] versus 6.3 [4.9, 7.8], P<0.001). With an increasing burden of uncontrolled metabolic risk factors, there were increased left ventricular mass index and wall thicknesses and impaired systolic function measured as global longitudinal strain: control group -15.9 (2.0); 0 uncontrolled risk factors -15.3 (2.4); 1 to 2 -14.6 (2.8); and ≥3 -14.0 (2.8), P<0.001. Within the diabetes mellitus group, there were uni- and multivariable associations of left ventricular measures and systolic blood pressure, body mass index, hemoglobin A1c, and HDL -cholesterol. Conclusions In patients with type 2 diabetes mellitus, having well-controlled metabolic risk factors was associated with only left ventricular diastolic impairment but not with either structural or even subtle measures of systolic function. Increasing burden of uncontrolled metabolic risk factors was associated with structural and functional impairments.

[Heart failure often accompanies diabetes mellitus].

There are 320,000 diabetes patients in Denmark. Heart failure (HF) is a major cardiovascular complication to diabetes mellitus with increasing prevalence. HF occurs 2-4 times more frequently in diabetes patients, but patients may go undiagnosed for years. Diabetes patients typically suffer from diastolic dysfunction caused by myocardial hyper-trophy and "stiffness" of the left ventricle. This frequent finding has prompted the term "diabetic cardiomyopathy". Echocardiography is a key examination in diagnosing HF and may be warranted to a greater degree in diabetes patients at particular risk.

Main and interactive effects of physical activity, fitness and body mass in the prevention of cancer from the Copenhagen Male Study.

Little knowledge exists about the role of cardiorespiratory fitness (CRF) or its interaction with excess adiposity determined by body mass index (BMI) in cancer prevention. A total of 5,128 middle-aged men, without a history of cancer at baseline in 1970-71, were examined for subsequent incidence and mortality of several cancer types. Participants' data were linked with cancer registration and mortality data to March 2017. During 47 years of follow-up, a total of 1,920 incident cases and 1,638 cancer-related deaths were ascertained. BMI, particularly obesity, was associated with (i) incidence and (ii) mortality from respiratory/thoracic cancers; and (iii) all cancer-cause mortality. The respective adjusted hazard ratios (HRs) were: (i) 0.51 (95%CI:0.32-0.79), (ii) 0.48 (95%CI:0.30-0.75) and (iii) 0.73 (95%CI:0.59-0.89) when compared obese men (BMI ≥30 kg/m2) to men with healthy-BMI (<25 kg/m2). Increasing CRF was inversely associated with incidence and mortality of respiratory/thoracic cancers, HRs 0.78 (95%CI:0.67-0.90) and 0.73 (95%CI:0.63-0.84) respectively; and all cancer-cause incidence 0.92 (95%CI:0.86-0.98) and mortality 0.85 (95%CI:0.79-0.91). Physical activity (PA) was not associated with most outcomes. We found no evidence of interactions between CRF or PA and BMI on cancer risk. This evidence suggests that midlife CRF is associated with lowered risk of cancer incidence and mortality with no evidence of cancer risk modification by BMI.

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.

Cardiorespiratory fitness, fatness and incident diabetes.

AIMS: Increases in prevalence have led to a diabetes pandemic. Obesity and low cardiorespiratory fitness (CRF) are considered to be central mechanisms. We investigated if the effect of CRF on diabetes risk was equivalent across levels of fatness among healthy men. METHODS: In total 4988 middle-aged Caucasian employed men free of cardiovascular disease, diabetes and cancer were included from the Copenhagen Male Study starting in 1970-71. CRF was assessed using a sub-maximal bicycle ergometer test and body mass index (BMI) was measured by height and weight. Their interaction and stratified associations with diabetes incidence were estimated in multivariable Cox-models including conventional risk factors and social class. Diabetes incidence was assessed through a national register. RESULTS: During 44 years of follow-up, 518 (10.4%) incident cases of diabetes occurred. In the multi-adjusted model, the obese had a significantly higher risk of diabetes compared to normal weight men (Hazard Ratio (HR):4.89; 95% CI: 3.62-6.61) and CRF was significantly inversely associated with diabetes (HR:0.86; 95% CI: 0.75-0.98 per 10-unit increase in ml/kg/min1 CRF). A significant multi-adjusted interaction between CRF, BMI and diabetes was found (p=0.009). The stratified multi-adjusted analyses on BMI showed a significantly stronger reduced risk of diabetes per 10-unit increase in ml/kg/min1 of CRF among the obese (HR:0.58; CI: 0.38-0.89), but a weaker association among overweight (HR:0.86; CI: 0.71-1.03) and normal weight (HR:0.97; CI: 0.76-1.23). CONCLUSION: High CRF has a stronger protective effect on diabetes among obese than among normal weight men, supporting the recommendation of fitness-enhancing physical activity for preventing diabetes among the obese.