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Introduction: Patients with chronic obstructive pulmonary disease (COPD) are undertreated with beta-blockers following myocardial infarction (MI), possibly due to fear for acute exacerbations of COPD (AECOPD). Is beta-blocker use associated with increased risk of AECOPD in patients following first-time MI?Methods: Danish nationwide study of patients with COPD following hospitalisation for MI from 2003 to 2015. Multivariable, time-dependent Cox regression accounting for varying beta-blocker use based on claimed prescriptions during up to 13 years of follow-up.Results: A total of 10 884 patients with COPD were discharged after first-time MI. The 1-year rate of AECOPD was 35%, and 65% used beta-blockers at 1 year. Beta-blocker use was associated with a lower risk of AECOPD (multivariable-adjusted HR 0.78, 95% CI 0.74-0.83). This association was independent of the type of MI (HR 0.70, 95% CI 0.59-0.83 in ST-elevation MI (STEMI) and HR 0.80, 95% CI 0.75-0.84 in non-STEMI), presence or absence of heart failure (HR 0.82, 95% CI 0.74-0.90 and HR 0.77, 95% CI 0.72-0.82, respectively), beta-blocker dosage and type, as well as exacerbation severity. Results were similar in 1118 patients with full data on COPD severity and symptom burden (median forced expiratory volume in 1 s as percentage of predicted was 46 and majority had moderate dyspnoea), and in 1358 patients with severe COPD and frequent AECOPD with a high 1-year rate of AECOPD of 70%.Discussion: Beta-blocker use was not associated with increased risk of AECOPD following MI. This finding was independent of COPD severity, symptom burden and exacerbation history, and supports the safety of beta-blockers in patients with COPD, including high-risk patients with severe disease. [ABSTRACT FROM AUTHOR]

Aims Echocardiography is suggested in the diagnostic work-up of patients with Type 2 diabetes (T2D). We investigated which echocardiographic parameters that best predicted cardiovascular disease (CVD) and whether this was persistent in both genders in a large cohort of outpatients with T2D. Methods and results We performed comprehensive echocardiography in 933 patients with T2D followed at specialized out-patients clinics in Copenhagen, Denmark. Follow-up was performed using national registries and included admission with future CVD events and non-CVD death as competing risk. Median follow-up was 4.8 years and 138 CVD events occurred. In univariable and multivariable analyses, a wide range of structural, diastolic, and systolic measurements predicted CVD including mean E / e ʹ [hazard ratio (HR) 1.06, 95% confidence interval: (1.03–1.10), P  < 0.001, C-statistics 0.74 (0.70–0.78)] and global longitudinal strain (GLS) [1.10 (1.01–1.20), P  = 0.03, C-statistics 0.73 (0.69–0.77)]. However, this was modified by gender. In men, mean E / e ʹ remained the strongest predictor in multivariable analyses and performed best measured by highest C-statistics [HR 1.15, 95% confidence interval: (1.08–1.21), P  < 0.001, C-statistics 0.75 (0.71–0.80)] whereas in women this was GLS [1.39 (1.14–1.70), P  = 0.001, C-statistics 0.79 (0.70–0.87)]. These findings persisted when excluding patients with known heart disease and when regarding all-cause mortality as a competing risk. Conclusion A range of echocardiographic parameters predicted CVD in patients with Type 2 diabetes, however, in multivariable analyses, mean E / e ʹ was the strongest predictor and had the highest model performance. Importantly, this study identifies a hitherto undescribed gender interaction as mean E / e ʹ performed best in men, whereas in women this was GLS. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Mitral regurgitation (MR) can be difficult to quantify. We sought to investigate whether the MR jet area to left atrial (LA) area ratio (MR/LA ratio) method for quantifying MRs can be used to predict incident atrial fibrillation (AF) in the general population., Methods and Results: The study included 4466 participants from the 5th Copenhagen City Heart Study, a prospective general population study, who underwent transthoracic echocardiography. MR jet area was measured and indexed to LA area. The endpoint was incident AF. MR was quantified in 4042 participants (mean age: 57 years, 43% men). Of these, 198 (4.9%) developed AF during a median follow-up period of 5.3 years (interquartile range: 4.4-6.1 years). MR was present in 1938 participants (48%) including 1593 (39%) trace/mild MRs (MR/LA ratio ≤ 20% and ≤4 cm2). In unadjusted analysis, MR/LA ratio was associated with incident AF [HR: 1.06 (1.00-1.13), P = 0.042 per 5% increase] but not after adjusting for CHARGE-AF score. However, the association was modified by age (P for interaction = 0.034), such that MR/LA ratio was associated with AF only in participants ≤ 73 years. In these participants, MR/LA ratio 'was' independently associated with AF after adjusting for CHARGE-AF score [HR: 1.14 (1.06-1.24), P = 0.001, per 5% increase]. This finding persisted when restricting the analysis to participants without moderate or severe MR and normal LA size [HR: 1.35 (1.09-1.68), P = 0.005, per 5% increase]., Conclusion: MR, including even trace regurgitations quantified by MR/LA ratio, is independently associated with incident AF in individuals ≤ 73 years of age., Competing Interests: Conflict of interest: M.Y.: none. F.J.O.: none. A.S.: none. K.G.S.: advisory board: Sanofi Pasteur. M.C.H.L.: none. N.D.J.: none. M.T.J.: none. G.B.J.: none. P.S.: none. R.M.: none. T.B.-S.: Steering Committee member of the Amgen financed GALACTIC-HF trial. Chief investigator of the Sanofi Pasteur financed ‘NUDGE-FLU’ trial. Chief investigator of the Sanofi Pasteur financed ‘DANFLU-1’ trial. Chief investigator of the Sanofi Pasteur financed ‘DANFLU-2’ trial. Steering Committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial. Advisory board: Sanofi Pasteur, Amgen, and GSK. Speaker honorarium: Bayer, Novartis, Sanofi Pasteur, and GSK. Research grants: GE Healthcare, Sanofi Pasteur, Novo Nordisk, and AstraZeneca., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Treskes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D., Methods: We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6-17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP., Results: A total of 126 CV events occurred (median follow-up 4.8 [4.1-5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89-202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64-4.00] and 3.32 [1.64-6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32-56] pmol/l) did not have an increased risk (HR 2.18 [0.78-6.14])., Conclusions: Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

Aims: The ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) has recently emerged as a novel measure of left ventricular filling pressure. E/e'sr has in previous studies demonstrated to have good prognostic value in various patient populations. The aim of this study is to investigate the prognostic value of E/e'sr in a large cohort of patients with Type 2 diabetes in relation to cardiovascular morbidity and mortality., Methods and Results: In this prospective study, 848 Type 2 diabetic patients (mean age 63.6 ± 10.3 years, 64.7% male) underwent comprehensive echocardiographic examination including 2D speckle tracking in which E/e'sr along with novel and conventional echocardiographic variables were obtained. During follow-up (median: 4.8 years, interquartile range: 4.0-5.3), 122 (14.1%) met the composite outcome of cardiovascular disease, hospitalization, and mortality. Both E/e'sr and E/e' were significantly associated with the outcome [E/e'sr: hazard ratio (HR) 1.07, 95% confidence interval (CI): 1.05-1.10; P < 0.001, per 0.10 m increase] and (E/e': HR 1.07, 95% CI: 1.05-1.10; P = 0.001, per 1 unit increase). E/e'sr remained an independent predictor after multivariable adjustment for demographical, clinical, and echocardiographic parameters (HR 1.06, 95% CI: 1.01-1.12; P = 0.032, per 10 cm increase). The same was true for E/e' (HR 1.09, 95% CI: 1.04-1.14; P < 0.001, per 1 unit increase). Additionally, E/e'sr provided incremental prognostic information beyond the UK 'Prospective Diabetes Study risk engine' 0.72 (0.68-0.77) vs. 0.74 (0.70-79), P = 0.040., Conclusion: In patients with Type 2 diabetes, E/e'sr provides independent and incremental prognostic information regarding cardiovascular morbidity and mortality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Good midlife cardiorespiratory fitness (CRF) may reduce the risk of chronic obstructive pulmonary disease (COPD). Reverse causation may play a role if follow-up time is short. We examined the association between CRF and both incident COPD and COPD mortality in employed men with up to 46 years follow-up, which allowed us to account for reverse causality., Methods: Middle-aged men (n=4730) were recruited in 1970-1971. CRF was determined as VO 2 max by ergometer test. Categories of CRF (low, normal, high) were defined as ± 1 Z-score (± 1 SD) above or below the age-adjusted mean. Endpoints were identified through national registers and defined as incident COPD, and death from COPD. Multi-adjusted Cox models and restricted mean survival times (RMST) were performed., Results: Compared with low CRF, the estimated risk of incident COPD was 21% lower in participants with normal CRF (HR 0.79, 95% CI 0.63 to 0.99) and 31 % lower with high CRF (HR 0.69, 95% CI 0.52 to 0.91). Compared with low CRF, the risk of death from COPD was 35% lower in participants with normal CRF (HR 0.65, 95% CI 0.46 to 0.91) and 62% lower in participants with high CRF (HR 0.38, 95% CI 0.23 to 0.61). RMST showed a delay to incident COPD and death from COPD in the magnitude of 1.3-1.8 years in normal and high CRF vs low CRF. Test for reverse causation did not alter the results., Conclusion: In a population of healthy, middle-aged men, higher levels of CRF were associated with a lower long-term risk of incident COPD and death from COPD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiac fat is a cardiovascular biomarker but its importance in patients with type 2 diabetes is not clear. The aim was to evaluate the predictive potential of epicardial (EAT), pericardial (PAT) and total cardiac (CAT) fat in type 2 diabetes and elucidate sex differences., Methods: EAT and PAT were measured by echocardiography in 1030 patients with type 2 diabetes. Follow-up was performed through national registries. The end-point was the composite of incident cardiovascular disease (CVD) and all-cause mortality. Analyses were unadjusted (model 1), adjusted for age and sex (model 2), plus systolic blood pressure, body mass index (BMI), low-density lipoprotein (LDL), smoking, diabetes duration and glycated hemoglobin (HbA 1c ) (model 3)., Results: Median follow-up was 4.7 years and 248 patients (191 men vs. 57 women) experienced the composite end-point. Patients with high EAT (> median level) had increased risk of the composite end-point in model 1 [Hazard ratio (HR): 1.46 (1.13; 1.88), p = 0.004], model 2 [HR: 1.31 (1.01; 1.69), p = 0.038], and borderline in model 3 [HR: 1.32 (0.99; 1.77), p = 0.058]. For men, but not women, high EAT was associated with a 41% increased risk of CVD and mortality in model 3 (p = 0.041). Net reclassification index improved when high EAT was added to model 3 (19.6%, p = 0.035). PAT or CAT were not associated with the end-point., Conclusion: High levels of EAT were associated with the composite of incident CVD and mortality in patients with type 2 diabetes, particularly in men, after adjusting for CVD risk factors. EAT modestly improved risk prediction over CVD risk factors.

Background: Dyspnea is a common clinical challenge in patients with type 2 diabetes and may be a sign of heart failure (HF). We sought to evaluate the predictive value dyspnea with and without an echocardiographic substrate in patients with type 2 diabetes without known heart disease., Methods: A total of 724 patients with type 2 diabetes followed at specialized clinics participated in this prospective cohort study. Clinical evaluation, comprehensive echocardiography and follow-up through national registers were performed. An echocardiographic substrate was either left ventricular hypertrophy, increased left atrial size, E/e' > 15, or LV ejection fraction<50%. The end-points were cardiovascular (CVD) events and all-cause mortality., Results: Median follow-up was 4.8 years [Interquartile range: 4.1, 5.3] for CVD event and 77 patients suffered a CVD event. Dyspnea was significantly associated with CVD event: Hazard ratio (HR): 1.58 (95% confidence interval: 1.01-2.48), p = 0.04. Stratifying by evidence of echocardiographic substrate revealed high risk individuals: CVD event: 0.71 (0.35-1.46), p = NS in patients with dyspnea and no echocardiographic substrate and 2.85 (1.74-4.67), p < 0.001 in patients with dyspnea with echocardiographic substrate). This pattern was similar in multivariable analyses. Also, C-statistics improved from 0.66 (0.60-0.72) to 0.69 (0.63-0.75), p < 0.001 and net reclassification index was 27.5%(5.0-50.0), p = 0.01 for CVD event. The results were similar for all-cause mortality except dyspnea was only a borderline significant predictor., Conclusion: In patients with type 2 diabetes complaining of dyspnea, identifying an echocardiographic substrate - thus indicating patients with HF - accurately stratifies patients with increased risk of CV events and all-cause mortality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: As a consequence of modern urban life, an increasing number of individuals are living alone. Living alone may have potential adverse health implications. The long-term relationship between living alone and all-cause and cardiovascular mortality, however, remains unclear., Methods and Results: Participants from The Copenhagen Male Study were included in 1985-86 and information about conventional behavioural, psychosocial, and environmental risk factors were collected. Socioeconomic position (SEP) was categorized into four groups. Multivariable Cox-regression models were performed with follow-up through the Danish National Registries. A total of 3346 men were included, mean (standard deviation) age 62.9 (5.2) years. During 32.2 years of follow-up, 89.4% of the population died and 38.9% of cardiovascular causes. Living alone (9.6%) was a significant predictor of mortality. Multivariable risk estimates were [hazard ratio (95% confidence interval)] 1.23 (1.09-1.39), P = 0.001 for all-cause mortality and 1.36 (1.13-1.63), P = 0.001 for cardiovascular mortality. Mortality risk was modified by SEP. Thus, there was no association in the highest SEP but for all other SEP categories, e.g. highest SEP for all-cause mortality 1.01 (0.7-1.39), P = 0.91 and 0.94 (0.6-1.56), P = 0.80 for cardiovascular mortality; lowest SEP 1.58 (1.16-2.19), P = 0.004 for all-cause mortality and 1.87 (1.20-2.90), P = 0.005 for cardiovascular mortality. Excluding participants dying within 5 years of inclusion (n = 274) did not change estimates, suggesting a minimal influence of reverse causation., Conclusions: Living alone was an independent risk factor for all-cause and cardiovascular mortality with more than three decades of follow-up. Individuals in middle- and lower SEPs were at particular risk. Health policy initiatives should target these high-risk individuals., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Echocardiography is suggested in the diagnostic work-up of patients with Type 2 diabetes (T2D). We investigated which echocardiographic parameters that best predicted cardiovascular disease (CVD) and whether this was persistent in both genders in a large cohort of outpatients with T2D., Methods and Results: We performed comprehensive echocardiography in 933 patients with T2D followed at specialized out-patients clinics in Copenhagen, Denmark. Follow-up was performed using national registries and included admission with future CVD events and non-CVD death as competing risk. Median follow-up was 4.8 years and 138 CVD events occurred. In univariable and multivariable analyses, a wide range of structural, diastolic, and systolic measurements predicted CVD including mean E/e' [hazard ratio (HR) 1.06, 95% confidence interval: (1.03-1.10), P < 0.001, C-statistics 0.74 (0.70-0.78)] and global longitudinal strain (GLS) [1.10 (1.01-1.20), P = 0.03, C-statistics 0.73 (0.69-0.77)]. However, this was modified by gender. In men, mean E/e' remained the strongest predictor in multivariable analyses and performed best measured by highest C-statistics [HR 1.15, 95% confidence interval: (1.08-1.21), P < 0.001, C-statistics 0.75 (0.71-0.80)] whereas in women this was GLS [1.39 (1.14-1.70), P = 0.001, C-statistics 0.79 (0.70-0.87)]. These findings persisted when excluding patients with known heart disease and when regarding all-cause mortality as a competing risk., Conclusion: A range of echocardiographic parameters predicted CVD in patients with Type 2 diabetes, however, in multivariable analyses, mean E/e' was the strongest predictor and had the highest model performance. Importantly, this study identifies a hitherto undescribed gender interaction as mean E/e' performed best in men, whereas in women this was GLS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Repolarization is impaired in patients with type 1 diabetes mellitus (T1DM), and repolarization disturbances are associated with an increased mortality. To study cardiac repolarization, we assessed T-wave morphology in patients with T1DM without known heart disease., Methods: 855 T1DM patients without known heart disease were matched 1:2 with 1710 people from a background population. Rate-corrected T-wave morphology markers were obtained. Patients were stratified by albuminuria. Results are mean ± standard deviation., Results: T-waves were flatter (0.398 ± 0.059 vs. 0.382 ± 0.062, p < 0.001) and more asymmetric (0.082 ± 0.068 vs. 0.071 ± 0.084, p = 0.001) in T1DM. Patients with albuminuria had an increased heart rate (normoalbuminuria: 71 ± 13 bpm, microalbuminuria: 75 ± 12 bpm, p < 0.001, macroalbuminuria: 78 ± 12 bpm, p < 0.001) and more asymmetric T-waves (normoalbuminuria: 0.079 ± 0.060, microalbuminuria: 0.094 ± 0.085, p < 0.01, macroalbuminuria: 0.101 ± 0.080, p < 0.01), but the QTc interval remained unchanged., Conclusions: T1DM is associated with changes in T-wave morphology. T-wave asymmetry but not QTc interval is associated with albuminuria in T1DM and may be used for stratification., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: To investigate the association between resting heart rate (RHR) and markers of chronic low-grade inflammation. Also, to examine whether elevated resting heart rate is independently associated with cardiovascular and all-cause mortality in the general population, or whether elevated RHR is merely a marker of chronic low-grade inflammation., Methods and Results: A group of 6518 healthy subjects from the the Danish general population were followed for 18 years during which 1924 deaths occurred. Subjects underwent assessment of baseline RHR, conventional cardiovascular risk factors, high-sensitivity C-reactive protein (hsCRP), and fibrinogen. RHR was associated with hsCRP and fibrinogen in uni- and multivariate models (p < 0.0001). A 10 beats per minute increase in RHR was associated with increased cardiovascular and all-cause mortality in univariate models - HR (95%CI) (1.21 (1.14-1.29) and 1.15 (1.11-1.19); multivariate models adjusted for conventional risk factors - 1.16 (1.09-1.24) and 1.10 (1.06-1.14); multivariate models including hsCRP - 1.14 (1.07-1.22) and 1.09 (1.05-1.14); fibrinogen - 1.15 (1.07-1.22) and 1.09 (1.05-1.14); and both hsCRP and fibrinogen - 1.14 (1.07-1.22) and 1.09 (1.05-1.14)., Conclusion: RHR was associated with markers of chronic low-grade inflammation. However, RHR remained associated with both cardiovascular and all-cause mortality after adjusting for markers of chronic low-grade inflammation. This suggests that RHR is an independent risk factor for cardiovascular and all-cause mortality, and not merely a marker of chronic low-grade inflammation.

Background: Elevated resting heart rate is associated with mortality in general populations. Smokers may be at particular risk. The association between resting heart rate (RHR), smoking status and cardiovascular and total mortality was investigated in a general population., Methods: Prospective study of 16,516 healthy subjects from the Copenhagen City Heart Study. 8709 deaths, hereof 3821 cardiovascular deaths, occurred during 33 years of follow-up., Results: In multivariate Cox models with time-dependent covariates RHR was significantly associated with both cardiovascular and total mortality. Current and former smokers had, irrespective of tobacco consumption, greater relative risk of elevated RHR compared to never smokers. The relative risk of all-cause mortality per 10 bpm increase in RHR was (95% CI): 1.06 (1.01-1.10) in never smokers, 1.11 (1.07-1.15) in former smokers, 1.13 (1.09-1.16) in moderate smokers, and 1.13 (1.10-1.16) in heavy smokers. There was no gender difference. The risk estimates for cardiovascular and all-cause mortality were essentially similar. In univariate analyses, the difference in survival between a RHR in the highest (> 80 bpm) vs lowest quartile (< 65 bpm) was 4.7 years in men and 3.6 years in women. In multivariate analyses, the difference was about one year in never smokers and about two years in current and former smokers., Conclusions: In a healthy population resting heart rate is associated with total and cardiovascular mortality. Elevated resting heart rate is associated with greater risk in subjects with a history of smoking than in never smokers., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)