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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: Studies indicate that physical activity during leisure and work have opposite associations with cardiovascular disease (CVD) risk factors, referred to as the physical activity health paradox. We investigated how sedentary behaviour and physical activity types during leisure and work are associated with systolic blood pressure (SBP), waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) in an adult general population sample using compositional data analysis., Methods: Participants wore accelerometers for 7 days (right thigh and iliac crest; 24 h/day) and had their SBP, WC, and LDL-C measured. Accelerometer data was analysed using the software Acti4 to derive daily time spent in sedentary behaviour and physical activity types. The measure of association was quantified by reallocating time between sedentary behaviour and 1) walking, and 2) high-intensity physical activity (HIPA; sum of climbing stairs, running, cycling, and rowing), during both domains., Results: In total, 652 participants were included in the analyses (median wear time: 6 days, 23.8 h/day). During leisure, the results indicated that less sedentary behaviour and more walking or more HIPA was associated with lower SBP, while during work, the findings indicated an association with higher SBP. During both domains, the findings indicated that less sedentary behaviour and more HIPA was associated with a smaller WC and lower LDL-C. However, the findings indicated less sedentary behaviour and more walking to be associated with a larger WC and higher LDL-C, regardless of domain., Conclusions: During leisure, less sedentary behaviour and more walking or HIPA seems to be associated with a lower SBP, but, during work, it seems to be associated with a higher SBP. No consistent differences between domains were observed for WC and LDL-C. These findings highlight the importance of considering the physical activity health paradox, at least for some risk factors for CVD., Competing Interests: The authors have declared that no competing interests exist.

Aims: The relevance of adherence to established dietary guidelines is repeatedly challenged. We hypothesised that non-adherence to established dietary guidelines is associated with an excess risk of cardiovascular, non-cardiovascular and all-cause mortality., Methods: We studied 100,191 white adult Danes aged 20-100 years recruited in 2003-2015 and followed up until December 2018. During follow-up equalling 865,600 person-years, 9273 individuals died. Participants' diets were assessed at baseline by a food frequency questionnaire focusing on key foods defining a healthy diet according to Danish dietary guidelines. Individuals were divided into five categories ranging from very high to very low adherence to dietary guidelines and studied with Cox and Fine-Gray regression models. At study inclusion, we collected demographic and lifestyle characteristics by questionnaire, made a physical examination and took a blood sample., Results: Cardiovascular, non-cardiovascular and all-cause mortality increased gradually with increasing non-adherence to dietary guidelines. Cardiovascular mortality was 30% higher (95% confidence interval 7-57%), non-cardiovascular mortality 54% higher (32-79%) and all-cause mortality 43% higher (29-59%) in individuals with very low adherence to dietary guidelines compared with those with very high adherence after adjustments for age, sex, education, income, smoking, leisure time physical activity and alcohol intake. Mortality risk estimates were similar in all strata of adjusted variables., Conclusion: Non-adherence to Danish food-based dietary guidelines is associated with up to 43% increased all-cause mortality in a dose-response manner. The mortality excess was seen for both cardiovascular and non-cardiovascular causes. The public has good reasons to have confidence in and to adhere to established dietary guidelines., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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.)

Background: A high cardiorespiratory fitness (CRF) level is recommended to promote healthy aging. However, the association between CRF and very-long-term prognosis is unclear, and reverse causation may bias results in studies with shorter follow-up., Objectives: This study investigated the association between CRF and mortality in middle-aged, employed men free of cardiovascular disease (CVD)., Methods: Participants from the Copenhagen Male Study, established in 1970 to 1971, were included and stratified into 4 age-adjusted maximal oxygen consumption (Vo 2 max) categories: below the lower limit of normal (lowest 5%); low normal (45%); high normal (45%); and above the upper limit of normal (top 5%). Vo 2 max was estimated by using a bicycle ergometer. Multivariable restricted mean survival time models were performed for all-cause and cardiovascular mortality using Danish national registers., Results: A total of 5,107 men with a mean age of 48.8 ± 5.4 years were included in the study. During the 46 years of follow-up, 4,700 (92%) men died; 2,149 (42.1%) of the men died of CVD. Compared with below the lower limit of normal CRF, low normal CRF was associated with 2.1 years (95% confidence interval [CI]: 0.7 to 3.4; p = 0.002), high normal with 2.9 years (95% CI: 1.5 to 4.2; p < 0.001), and above upper limit of normal with 4.9 years (95% CI: 3.1 to 6.7; p < 0.001) longer mean life expectancy. Each unit increase in Vo 2 max was associated with a 45-day (95% CI: 30 to 61; p < 0.001) increase in longevity. Estimates for cardiovascular mortality were similar to all-cause mortality. Results were essentially unchanged when excluding individuals who died within the first 10 years of follow-up, suggesting a minimal role of reverse causation., Conclusions: CRF was significantly related to longevity over the course of 4 decades in middle-aged, employed men free of CVD. The benefits of higher midlife CRF extend well into the later part of life., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Risk prediction in elderly patients is increasingly relevant due to longer life expectancy., Objectives: This study sought to examine whether electrocardiographic (ECG) changes provide prognostic information incremental to current risk models and to the conventional risk factors., Methods: In all, 6,991 participants from the Copenhagen Heart Study attending an examination at age ≥65 years were included. ECG changes were defined as Q waves, ST-segment depression, T-wave changes, ventricular conduction defects, and left ventricular hypertrophy based on the Minnesota code. The primary endpoint was fatal cardiovascular disease (CVD) event and the secondary was fatal or nonfatal CVD event. In our study, 2,236 fatal CVD and 3,849 fatal or nonfatal CVD events occurred during a median of 11.9 and 9.8 years of follow-up., Results: ECG changes were frequently present (30.6%) and associated with conventional risk factors. All ECG changes except 1 univariably predicted both endpoints. Event rates of ECG changes versus no ECG changes were respectively 41.4% versus 27.8% and 64.6% versus 50.8%. When added to existing risk scores, ECG changes independently increased the risk of both endpoints. Fatal CVD events: hazard ratio (HR): 1.33 (95% confidence interval [CI]: 1.29 to 1.36; p < 0.001) and fatal or nonfatal CVD events: HR: 1.21 (95% CI: 1.19 to 1.24; p < 0.001). When added to conventional risk factors, continuous net reclassification improvement was 42.3% (95% CI: 42.0 to 42.4; p < 0.001) for fatal and 29.2% (95% CI: 28.4 to 29.2; p < 0.001) for fatal or nonfatal events. Categorical net reclassification was 7.1% (95% CI: 6.7 to 9.0; p < 0.001) for fatal and 4.2% (95% CI: 3.5 to 5.6; p < 0.001) for fatal or nonfatal events., Conclusions: Simple assessment of the existence of ECG changes improves risk prediction in the general population of persons age ≥65 years., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined., Methods: From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality., Results: During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08-2.81, p=0.027) and men a 2.09-fold (95% CI: 1.37-3.18, p<0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36-7.99, p<0.01) increase for women and a 3.53-fold (1.78-7.02, p<0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10-20% based on FRS, to low (<10%) or high (>20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p=0.034) and borderline significant for women (p=0.054), while the integrated discrimination improvement was highly significant (P≤0.001) for both genders., Conclusions: suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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.)

Background. Elevated resting heart rate (RHR) is associated with cardiovascular mortality and morbidity. Assessment of heart rate (HR) from Holter recording may afford a more precise estimate of the effect of RHR on cardiovascular risk, as compared to casual RHR. Comparative analysis was carried out in an age-stratified subsample of 131 subjects in the Copenhagen City Heart Study (CCHS). Methods. Casual RHR was assessed from electrocardiograms recorded during clinical assessment. Hourly daytime HRs were mapped by Holter recording. Holter RHR was defined as the average of the lowest 3 hourly HRs recorded and mean HR calculated from all daytime HRs. Follow-up was recorded from public registers. Outcome measure was hazard rate for the combined endpoint of cardiovascular mortality, non-fatal heart failure and non-fatal acute myocardial infarction. Comparison of casual RHR, Holter RHR and mean HR by Multivariate Cox regression was performed. Results. A total of 57 composite endpoints occurred during 17.1 years of follow-up. Regression analysis suggests correlation between Casual RHR and Holter RHR. Multivariate Cox regression analysis adjusted for gender and age demonstrated hazard rates of 1.02 ( p = 0.079) for casual RHR, 1.04 ( p = 0.036*) for Holter RHR, and 1.03 ( p = 0.093) for mean HR for each 10 beat increment in HR. Conclusions. In a comparative analysis on the correlation and significance of differing RHR measurement modalities RHR measured by 24-hour Holter recording was found to be marginally superior as a predictor of cardiovascular morbidity and mortality. The results presented here do not however warrant the abandonment of a tested epidemiological variable. [ABSTRACT FROM AUTHOR]

BackgroundLow-grade chronic inflammation has been proposed to play a major role in the pathogenesis of hypertension. Low-grade chronic inflammation is also closely associated with obesity, an established causative factor in the development of hypertension. The purpose of this study was to investigate the relationship between two markers of inflammation, C-reactive protein (CRP) and fibrinogen, and blood pressure (BP) and other hemodynamic variables in obese subjects.MethodsFrom a large cardiovascular study based in the general population, we selected subjects with a body mass index (BMI) ≥30 kg/m2, free of major cardiovascular diseases, not taking BP-lowering or lipid-lowering drugs (n = 487; women = 51.1%; median (5th to 95th percentile) age = 62 years (36–80)). The cardiovascular study included measurements of traditional and new risk factors, including ankle brachial BP index, a measure of subclinical atherosclerosis. CRP was determined by a high-sensitive assay.ResultsIn partial Spearman rank correlation analysis, adjusted for age and sex, we found no significant relationships between either CRP or fibrinogen and systolic BP, diastolic BP, pulse pressure, or ankle brachial index (ρ: −0.057 to 0.068; P > 0.13). However, fibrinogen and CRP were found to be significantly related to heart rate (ρ: 0.127–0.169; P < 0.01).ConclusionsIn this study of generally healthy obese subjects from the general population, we found no significant relationships between markers of inflammation and systolic BP or diastolic BP, showing that obese subjects with higher levels of inflammatory markers do not have higher BP levels than their obese counterparts with lower levels of inflammatory markers.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.1American Journal of Hypertension (2009); 22, 4, 451–456. doi:10.1038/ajh.2009.1 [ABSTRACT FROM AUTHOR]

Abstract: Background: Low-grade inflammation is a marker for cardiovascular disease (CVD). The inflammatory biomarkers C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR) independently predict CVD. We tested the hypothesis that these biomarkers reflect different aspects of the inflammation associated with CVD. Methods: We studied 2273 subjects without CVD. Log-transformed CRP and suPAR were included in general linear and logistic regression models to compare associations with measures of anthropometry and subclinical organ damage (SOD). Owing to interactions on body mass index (BMI) (P<0.0001), the population was stratified by gender and smoking concerning anthropometry. Results: In both genders, independent of smoking, log-CRP was positively associated with BMI (β: 0.28 to 0.40, P<0.001) and waist circumference (WC) (β: 0.27 to 0.42, P<0.001). In contrast, in smoking women and men, log-suPAR was negatively associated with BMI and WC (β: −0.09 to −0.19, P<0.05). In non-smoking women, log-suPAR was positively associated with BMI and WC (β: 0.14 and 0.16, P<0.001), whereas no associations were found in non-smoking men. No interactions were found on SOD. Adjusted for age, sex, smoking, and physical activity, log-suPAR was associated with an increased urine albumin/creatinine ratio (standardized odds ratio (95% confidence interval (CI)) for highest vs. lower quartiles: 1.36 (1.21–1.52), whereas log-CRP was not (1.10 (0.99–1.22))), and extent of atherosclerosis (standardized proportional odds ratio (95% CI) for carotid plaques 0, 1≤ to ≤3, >3: 1.31 (1.16–1.47), whereas log-CRP was not (1.00 (0.89–1.11))). Conclusions: CRP is positively associated with anthropometric measures, whereas suPAR is linked to endothelial dysfunction and atherosclerosis. [Copyright &y& Elsevier]