Journal: Eur J Prev Cardiol

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Abstract

Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology.

van Buuren F, Gati S, Sharma S, Papadakis M, ... D\'Ascenzi F, Mellwig KP
This article provides an overview of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology on sports participation in individuals with valvular heart disease (VHD). The aim of these recommendations is to encourage regular physical activity including sports participation, with reasonable precaution to ensure a high level of safety for all affected individuals. Valvular heart disease is usually an age-related degenerative process, predominantly affecting individuals in their fifth decade and onwards. However, there is an increasing group of younger individuals with valvular defects. The diagnosis of cardiac disorders during routine cardiac examination often raises questions about on-going participation in competitive sport with a high dynamic or static component and the level of permissible physical effort during recreational exercise. Although the natural history of several valvular diseases has been reported in the general population, little is known about the potential influence of chronic intensive physical activity on valve function, left ventricular remodelling pulmonary artery pressure, and risk of arrhythmia. Due to the sparsity of data on the effects of exercise on VHD, the present document is largely based on clinical experience and expert opinion.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 12 Apr 2021; epub ahead of print
van Buuren F, Gati S, Sharma S, Papadakis M, ... D'Ascenzi F, Mellwig KP
Eur J Prev Cardiol: 12 Apr 2021; epub ahead of print | PMID: 33846742
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Abstract

Functional capacity assessment and Minimal Clinically Important Difference in post-acute cardiac patients: the role of Short Physical Performance Battery.

Rinaldo L, Caligari M, Acquati C, Nicolazzi S, ... Marcassa C, Corrà U
Background
The Short Physical Performance Battery (SPPB) test is a well-established tool to assess physical performance, and to identify frail patients. Assessment of the SPPB in a specific population of elder patients in cardiac rehabilitation phase after a cardiac event is missing.
Aim
The aim of this study was to correlate SPPB and the cardiac rehabilitation outcome in a group of elder patients after a cardiac event and to identify the Minimal Clinically Important Difference (MCID) of the SPPB.
Methods
Consecutive (n = 392) patients aged ≥75 years, in the rehabilitation phase after cardiac surgery (70.1%), congestive heart failure (7.4%), or acute coronary syndrome (22.5%), were enrolled. SPPB was performed twice: on admission and discharge. The MCID was assessed with the \'anchor method\', and the Patient Global Impression of Change was employed as the anchor.
Results
On admission, SPPB classified 56, 117, 116, and 94 patients as severe, moderate, mild, or minimal/no limitations, respectively. Patients with the lower SPPB had the longer length of stay, and the higher complications rate. At receiver operating characteristic analysis, an SPPB improvement >1 was identified as the MCID (area-under-curve 0.77, 95% CI 0.67-0.85). Overall, 285 patients (74.2%) had a \'clinically significant\' improvement in SPPB, with a rate of improvement higher in patients with severe/moderate limitations (83.0%) and lower in those with mild (78.9%) or minimal/no limitations (53.6%).
Conclusion
A lower SPPB score is associated with a higher complications rate in the post-acute phase. An improvement >1 point of SPPB was identified as the MCID; this reference value could serve as the goal for rehabilitation interventions.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 11 Apr 2021; epub ahead of print
Rinaldo L, Caligari M, Acquati C, Nicolazzi S, ... Marcassa C, Corrà U
Eur J Prev Cardiol: 11 Apr 2021; epub ahead of print | PMID: 33846721
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Abstract

No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study.

Miao L, Deng GX, Yin RX, Nie RJ, ... Wang Y, Li H
Background
Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction.
Methods
A two-sample Mendelian randomization study on disease was conducted, i.e. \"coronary heart disease\" (n = 184,305) and \"acute myocardial infarction\" (n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10-8, were used as an instrumental variable.
Results
None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction (p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923-1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932-1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy (p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction.
Conclusions
The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:227-234
Miao L, Deng GX, Yin RX, Nie RJ, ... Wang Y, Li H
Eur J Prev Cardiol: 09 Apr 2021; 28:227-234 | PMID: 33838042
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Abstract

Prognostic value of total testosterone levels in patients with acute coronary syndromes.

Gencer B, Vuilleumier N, Nanchen D, Collet TH, ... Rodondi N, Mach F
Background
Endogenous testosterone levels decrease in men with aging. Controversies persist regarding the screening and treatment of low testosterone levels in patients with acute coronary syndromes (ACS).
Methods and results
Total serum testosterone levels were measured in 1054 men hospitalized for ACS that were part of a Swiss prospective cohort. Total testosterone levels were classified first in tertiles and using the cut-off of 300 ng/dL. Primary endpoint was all-cause mortality at one year. Cox regression models adjusting for the GRACE score (composite of age, heart rate systolic blood pressure, creatinine, cardiac arrest at admission, ST segment deviation, abnormal troponin enzyme and Killip classification), preexisting diabetes and inflammation (high-sensitivity C-reactive protein). A total of 430 men (40.8%) had total testosterone levels ≤300 ng/dL. Low total testosterone levels were correlated with lower high-density lipoprotein cholesterol and higher triglycerides, high-sensitivity C-reactive protein, high-sensitivity troponin T, N-terminal-pro B-type natriuretic peptide and glucose levels (all p < 0.01). Patients in the lowest testosterone tertile had a mortality rate at one-year of 5.4% compared with 2.9% in the highest tertile with an unadjusted hazard ratio of 1.92 (95% confidence interval 0.96-1.90, p = 0.095) and adjusted hazard ratio of 1.26 (95% confidence interval 0.57-2.78, p = 0.565). In an exploratory analysis, the highest mortality rate (10.3%) was observed in men aged >65 years old belonging to the lowest testosterone tertile.
Conclusion
In this large population of men with ACS, we found a prevalence of low total endogenous testosterone levels of almost 40%. However, low testosterone levels were not significantly associated with mortality after adjustment for high-risk confounders.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:235-242
Gencer B, Vuilleumier N, Nanchen D, Collet TH, ... Rodondi N, Mach F
Eur J Prev Cardiol: 09 Apr 2021; 28:235-242 | PMID: 33838041
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Abstract

Modifiable lifestyle risk factors and C-reactive protein in patients with coronary artery disease: Implications for an anti-inflammatory treatment target population.

Blaum C, Brunner FJ, Kröger F, Braetz J, ... Seiffert M, Waldeyer C
Background
Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) are associated with increased inflammation represented by elevated C-reactive protein (CRP) levels. Lifestyle changes may influence the inflammatory burden in patients with CAD, relevantly modifying the target population for emerging anti-inflammatory compounds.
Aims
The aims of this study were to analyse the association of modRF and CRP levels in CAD patients, and to define a potential target population for anti-inflammatory treatment with and without the optimisation of modRF.
Methods
We included all patients with angiographically documented CAD from the observational cohort study INTERCATH. Patients with recent myocardial infarction, malignancy, infectious disease, and pre-existing immunosuppressive medication including a history of solid organ transplantation were excluded. Overweight (body mass index (BMI) ≥ 25 kg/m2), smoking, lack of physical activity (PA; <1.5 h/week), and poor diet (≤12 points of an established Mediterranean diet score (MDS), range 0-28 points) were considered as modRF. CRP was measured by a high-sensitivity assay (hsCRP) at baseline. We performed multivariable linear regressions with log-transformed hsCRP as the dependent variable. Based on these associations, we calculated potential hsCRP levels for each patient, assuming optimisation of the individual modRF.
Results
Of 1014 patients, 737 (73%) were male, the mean age was 69 years, and 483 (48%) had an hsCRP ≥ 2 mg/l. ModRF were significantly overrepresented in patients with hsCRP ≥ 2 mg/l compared to patients with an hsCRP < 2 mg/l (BMI ≥ 25 kg/m2: 76% vs 61%; PA < 1.5 h/week: 69% vs 57%; MDS ≤ 12: 46% vs 37%; smoking: 61% vs 54%; p < 0.05 for all). hsCRP increased with the incremental number of modRF present (median hsCRP values for N = 0, 1, 2, 3, and 4 modRF: 1.1, 1.0, 1.6, 2.4, 2.8 mg/l, p < 0.001). Multivariable linear regression adjusting for age, sex, intake of lipid-lowering medication, and diabetes mellitus revealed independent associations between log-transformed hsCRP and all modRF (BMI ≥ 25 kg/m2: exp(ß) = 1.55, p < 0.001; PA < 1.5 h/week: exp(ß) = 1.33, p < 0.001; MDS ≤ 12: exp(ß) = 1.18, p = 0.018; smoking: exp(ß) = 1.18, p = 0.019). Individual recalculation of hsCRP levels assuming optimisation of modRF identified 183 out of 483 (38%) patients with hsCRP ≥ 2 mg/l who could achieve an hsCRP < 2 mg/l via lifestyle changes.
Conclusion
modRF are strongly and independently associated with CRP levels in patients with CAD. A relevant portion of CAD patients with high inflammatory burden could achieve an hsCRP < 2 mg/l by lifestyle changes alone. This should be considered both in view of the cost and side-effects of pharmacological anti-inflammatory treatment and for the design of future clinical trials in this field.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 09 Apr 2021; 28:152-158
Blaum C, Brunner FJ, Kröger F, Braetz J, ... Seiffert M, Waldeyer C
Eur J Prev Cardiol: 09 Apr 2021; 28:152-158 | PMID: 33838040
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Abstract

Prediction of fatal and non-fatal cardiovascular events in young and middle-aged healthy workers: The IberScore model.

Fernández-Labandera C, Calvo-Bonacho E, Valdivielso P, Quevedo-Aguado L, ... Ruilope LM, Sánchez-Chaparro MA
Aims
Our primary objective was to improve risk assessment for fatal and non-fatal cardiovascular events in a working population, mostly young and healthy.
Methods
We conducted a prospective cohort study to derive a survival model to predict fatal and non-fatal 10-year cardiovascular risk. We recruited 992,523 workers, free of diagnosed cardiovascular disease at entry, over six years, from 2004-2009. We divided the sample into two independent cohorts: a derivation one (626,515 workers; from 2004-2006) and a temporal validation one (366,008 workers; over 2007-2009). Then, we followed both cohorts over 10 years and registered all fatal and non-fatal cardiovascular events. We built a new risk calculator using an estimation of cardiovascular biological age as a predictor and named it IberScore. There were remarkable differences between this new model and Systematic Coronary Risk Evaluation (SCORE) (in both the specification and the equation).
Results
Over the 10-year follow-up, we found 3762 first cardiovascular events (6‰) in the derivation cohort. Most of them (80.3%) were non-fatal ischaemic events. If we had been able to use our model at the beginning of the study, we had classified in the \'high-risk\' or \'very high-risk\' groups 82% of those who suffered a cardiovascular event during the follow-up. All the post-estimation tests showed superior performance (true positive rate: 81.8% vs 11.8%), higher discrimination power and better clinical utility (standardised net benefit: 58% vs 13%) for IberScore when compared to SCORE.
Conclusion
Risk assessment of fatal and non-fatal cardiovascular events in young and healthy workers was improved when compared to the previously used model (SCORE). The latter was not reliable to predict cardiovascular risk in our sample. The new model showed superior clinical utility and provided four useful measures for risk assessment. We gained valuable insight into cardiovascular ageing and its predictors.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:177-186
Fernández-Labandera C, Calvo-Bonacho E, Valdivielso P, Quevedo-Aguado L, ... Ruilope LM, Sánchez-Chaparro MA
Eur J Prev Cardiol: 09 Apr 2021; 28:177-186 | PMID: 33838039
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Abstract

The Timed Up and Go test and the ageing heart: Findings from a national health screening of 1,084,875 community-dwelling older adults.

Chun S, Shin DW, Han K, Jung JH, ... Lee SP, Lee SC
Aim
This study aimed to evaluate the relationship between Timed Up and Go test performance and the incidence of older adult heart diseases and mortality.
Methods
This was a retrospective cohort study of 1,084,875 older adults who participated in a national health screening program between 2009-2014 (all aged 66 years old). Participants free of myocardial infarction, congestive heart failure, and atrial fibrillation at baseline were included and were divided into Group 1 (<10 s), Group 2 (10-20 s) and Group 3 (≥20 s) using the Timed Up and Go test scores. The endpoints were incident myocardial infarction, congestive heart failure, atrial fibrillation, and all-cause mortality.
Results
During mean follow-up of 3.6 years (maximum 8.0 years), 8885 myocardial infarctions, 10,617 congestive heart failures, 15,322 atrial fibrillations, and 22,189 deaths occurred. Compared with participants in Group 1, Group 2 and Group 3 participants had higher incidences of myocardial infarction (Group 3: adjusted hazard ratio = 1.40, 95% confidence interval = 1.11-1.77), congestive heart failure (Group 3: adjusted hazard ratio = 1.59, 95% confidence interval = 1.31-1.94) and total mortality (Group 3: adjusted hazard ratio=1.93, 95% confidence interval = 1.69-2.20). The additional risks remained after adjusting for multiple conventional risk factors. For atrial fibrillation, a linear trend of increased risk was observed with slower Timed Up and Go test speed, but was statistically marginal (Group 3: adjusted hazard ratio=1.17, 95% confidence interval=0.96-1.44).
Conclusion
Slower Timed Up and Go test speed is associated with increased risk of developing myocardial infarction, congestive heart failure, and mortality in older adults.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:213-219
Chun S, Shin DW, Han K, Jung JH, ... Lee SP, Lee SC
Eur J Prev Cardiol: 09 Apr 2021; 28:213-219 | PMID: 33838038
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Abstract

Comparison of non-exercise cardiorespiratory fitness prediction equations in apparently healthy adults.

Peterman JE, Whaley MH, Harber MP, Fleenor BS, ... Arena R, Kaminsky LA
Aims
A recent scientific statement suggests clinicians should routinely assess cardiorespiratory fitness using at least non-exercise prediction equations. However, no study has comprehensively compared the many non-exercise cardiorespiratory fitness prediction equations to directly-measured cardiorespiratory fitness using data from a single cohort. Our purpose was to compare the accuracy of non-exercise prediction equations to directly-measured cardiorespiratory fitness and evaluate their ability to classify an individual\'s cardiorespiratory fitness.
Methods
The sample included 2529 tests from apparently healthy adults (42% female, aged 45.4 ± 13.1 years (mean±standard deviation). Estimated cardiorespiratory fitness from 28 distinct non-exercise prediction equations was compared with directly-measured cardiorespiratory fitness, determined from a cardiopulmonary exercise test. Analysis included the Benjamini-Hochberg procedure to compare estimated cardiorespiratory fitness with directly-measured cardiorespiratory fitness, Pearson product moment correlations, standard error of estimate values, and the percentage of participants correctly placed into three fitness categories.
Results
All of the estimated cardiorespiratory fitness values from the equations were correlated to directly measured cardiorespiratory fitness (p < 0.001) although the R2 values ranged from 0.25-0.70 and the estimated cardiorespiratory fitness values from 27 out of 28 equations were statistically different compared with directly-measured cardiorespiratory fitness. The range of standard error of estimate values was 4.1-6.2 ml·kg-1·min-1. On average, only 52% of participants were correctly classified into the three fitness categories when using estimated cardiorespiratory fitness.
Conclusion
Differences exist between non-exercise prediction equations, which influences the accuracy of estimated cardiorespiratory fitness. The present analysis can assist researchers and clinicians with choosing a non-exercise prediction equation appropriate for epidemiological or population research. However, the error and misclassification associated with estimated cardiorespiratory fitness suggests future research is needed on the clinical utility of estimated cardiorespiratory fitness.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:142-148
Peterman JE, Whaley MH, Harber MP, Fleenor BS, ... Arena R, Kaminsky LA
Eur J Prev Cardiol: 09 Apr 2021; 28:142-148 | PMID: 33838037
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Abstract

Comparison of Swiss and European risk algorithms for cardiovascular prevention in Switzerland.

Beuret H, Hausler N, Nanchen D, Méan M, Marques-Vidal P, Vaucher J
Background
In Switzerland, two distinct algorithms are recommended for cardiovascular prevention: (a) Arbeitsgruppe Lipide und Atherosklerose (AGLA); and (b) European Society of Cardiology (ESC). We validated and determined which algorithm better predicts incident atherosclerotic cardiovascular disease and assessed statin eligibility in Switzerland.
Design
A prospective population-based cohort.
Methods
We employed longitudinal data of the CoLaus study involving 6733 individuals, aged 35-75 years, with a 10-year follow-up. Using discrimination and calibration, we evaluated the predictive performance of the AGLA and ESC algorithms for the prediction of atherosclerotic cardiovascular disease.
Results
From the 6733 initial participants, 5529 were analysed with complete baseline and follow-up data. Mean age (SD) was 52.4 (10.6) years and 54% were women. During an average follow-up (SD) of 10.2 years (1.7), 370 (6.7%) participants developed an incident atherosclerotic cardiovascular disease. The sensitivity of AGLA and ESC algorithms to predict atherosclerotic cardiovascular disease was 51.6% (95% confidence interval (CI) 46.4-56.8) and 58.6% (53.4-63.7), respectively. Discrimination and calibration were similar between the AGLA and ESC algorithms, with area under the receiver operating characteristic curve values of 0.78 (95% CI 0.76-0.80) and 0.79 (0.76-0.81), and Brier scores of 0.059 and 0.041, respectively. Among 370 individuals developing incident atherosclerotic cardiovascular disease, only 278 (75%) were eligible for statin therapy at baseline, including 210 (57%) according to both algorithms, 4 (1%) to AGLA only and 64 (17%) to ESC only.
Conclusion
AGLA and ESC algorithms presented similar accuracy to predict atherosclerotic cardiovascular disease in Switzerland. A quarter of adults developing atherosclerotic cardiovascular disease were not identified by preventive algorithms to be eligible for statin therapy.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:204-210
Beuret H, Hausler N, Nanchen D, Méan M, Marques-Vidal P, Vaucher J
Eur J Prev Cardiol: 09 Apr 2021; 28:204-210 | PMID: 33838036
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Abstract

HDL: Fact, fiction, or function? HDL cholesterol and cardiovascular risk.

Allard-Ratick MP, Kindya BR, Khambhati J, Engels MC, ... Rosenson RS, Sperling LS
The measurement of high-density lipoprotein cholesterol is highly utilized by clinicians to help predict cardiovascular risk, but this measure is not causally associated with atherosclerotic cardiovascular disease events. The use of Mendelian randomization studies has led to a change in investigative attention from the high-density lipoprotein cholesterol concentration to its physiological functions. High-density lipoprotein plays key roles in important pathways related to the development of atherosclerotic disease including reverse cholesterol transport, oxidation and inflammation, and endothelial function as well as in other physiological systems including immune system modulation, cellular apoptosis, and endothelial progenitor cell homeostasis. The identification of dysfunctional high-density lipoprotein may better predict future cardiovascular events compared to numerical high-density lipoprotein cholesterol and aid in enhanced clinical risk stratification. The emergence of discrete physiological measurements of high-density lipoprotein, such as cholesterol efflux capacity and the high-density lipoprotein inflammatory index, may provide an opportunity for clinical application in the future. However, the validity of these measurements and their commercial availability remain barriers to a realistic transition to clinical medicine.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:166-173
Allard-Ratick MP, Kindya BR, Khambhati J, Engels MC, ... Rosenson RS, Sperling LS
Eur J Prev Cardiol: 09 Apr 2021; 28:166-173 | PMID: 33838035
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Abstract

Combined effect of work stress and impaired sleep on coronary and cardiovascular mortality in hypertensive workers: The MONICA/KORA cohort study.

Li J, Atasoy S, Fang X, Angerer P, Ladwig KH
Background
Although work stress and impaired sleep are established risk factors for cardiovascular disease (CVD) among healthy individuals, their impact on hypertensive workers is largely unknown.
Design
Prospective cohort study design.
Methods
Hypertensive workers (N = 1959), derived from the population-based MONICA/KORA study in Southern Germany, who were free of any cardiovascular disease and diabetes were interviewed at baseline for work stress (high demand plus low control) and impaired sleep (difficulties falling asleep and/or maintaining sleep). Hazard ratios and 95% confidence intervals (CIs) were estimated by multivariate Cox proportional hazards models with adjustment for relevant covariates.
Results
During a mean follow-up of 17.8 years covering 34,900 person-years, 134 fatal CVD and 73 coronary heart disease (CHD) events were observed. In comparison to participants with low work stress and non-impaired sleep, participants with work stress (hazard ratio (HR) 1.56, 95% CI 0.81-2.98), or impaired sleep (HR 1.76, 95% CI 0.96-3.22) had an increased risk of CVD, while participants with both work stress and impaired sleep had the highest risk of CVD mortality (HR 2.94, 95% CI 1.18-7.33). Participants with both risk conditions had an absolute CVD mortality risk of 7.13 cases per 1000 person-years in comparison to 3.05 cases per 1000-person years in the reference group. Similar risk patterns were found for CHD mortality.
Conclusions
Our findings add a new piece of evidence that work stress together with impaired sleep increase risk of coronary and cardiovascular mortality in hypertensive workers.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Apr 2021; 28:220-226
Li J, Atasoy S, Fang X, Angerer P, Ladwig KH
Eur J Prev Cardiol: 09 Apr 2021; 28:220-226 | PMID: 33838034
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Abstract

EAPC Core Curriculum for Preventive Cardiology (compare to ESC Core Curriculum for the Cardiologist).

Wilhelm M, Abreu A, Adami PE, Ambrosetti M, ... Dendale P, Halle M
Preventive cardiology encompasses the whole spectrum of cardiovascular disease (CVD) prevention, at individual and population level, through all stages of life. This includes promotion of cardiovascular (CV) health, management of individuals at risk of developing CVD, and management of patients with established CVD, through interdisciplinary care in different settings. Preventive cardiology addresses all aspects of CV health in the context of the social determinants of health, including physical activity, exercise, sports, nutrition, weight management, smoking cessation, psychosocial factors and behavioural change, environmental, genetic and biological risk factors, and CV protective medications. This is the first European Core Curriculum for Preventive Cardiology, which will help to standardize, structure, deliver, and evaluate training in preventive cardiology across Europe. It will be the basis for dedicated fellowship programmes and a European Society of Preventive Cardiology (EAPC) subspecialty certification for cardiologists, with the intention to improve quality and outcome in CVD prevention.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 31 Mar 2021; epub ahead of print
Wilhelm M, Abreu A, Adami PE, Ambrosetti M, ... Dendale P, Halle M
Eur J Prev Cardiol: 31 Mar 2021; epub ahead of print | PMID: 33791783
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Abstract

Association of inflammatory disease and long-term outcomes among young adults with myocardial infarction: the Mass General Brigham YOUNG-MI Registry.

Weber B, Biery DW, Singh A, Divakaran S, ... Di Carli MF, Blankstein R
Aims
Autoimmune systemic inflammatory diseases (SIDs) are associated with an increased risk of cardiovascular (CV) disease, particularly myocardial infarction (MI). However, there are limited data on the prevalence and effects of SID among adults who experience an MI at a young age. We sought to determine the prevalence and prognostic implications of SID among adults who experienced an MI at a young age.
Methods and results
The YOUNG-MI registry is a retrospective cohort study from two large academic centres, which includes patients who experienced a first MI at 50 years of age or younger. SID was ascertained through physician review of the electronic medical record (EMR). Incidence of death was ascertained through the EMR and national databases. The cohort consisted of 2097 individuals, with 53 (2.5%) possessing a diagnosis of SID. Patients with SID were more likely to be female (36% vs. 19%, P = 0.004) and have hypertension (62% vs. 46%, P = 0.025). Over a median follow-up of 11.2 years, patients with SID experienced an higher risk of all-cause mortality compared with either the full cohort of non-SID patients [hazard ratio (HR) = 1.95, 95% confidence interval (CI) (1.07-3.57), P = 0.030], or a matched cohort based on age, gender, and CV risk factors [HR = 2.68, 95% CI (1.18-6.07), P = 0.018].
Conclusions
Among patients who experienced a first MI at a young age, 2.5% had evidence of SID, and these individuals had higher rates of long-term all-cause mortality. Our findings suggest that the presence of SID is associated with worse long-term survival after premature MI.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 29 Mar 2021; epub ahead of print
Weber B, Biery DW, Singh A, Divakaran S, ... Di Carli MF, Blankstein R
Eur J Prev Cardiol: 29 Mar 2021; epub ahead of print | PMID: 33784740
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Abstract

Global, regional, and national burden of aortic aneurysm, 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017.

Tyrovolas S, Tyrovola D, Giné-Vázquez I, Koyanagi A, ... Miranda JJ, Panagiotakos D
Aims
This study aimed at evaluating the age, sex, and country-income patterns in aortic aneurysm disease burden, analysing trends in mortality and years of life lost (YLLs), as well as their causal drivers and risk factors, using the 2017 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2017).
Methods and results
We described the temporal, global, and regional (195 countries) patterns of aortic aneurysm (thoracic and abdominal) mortality, YLLs, their drivers [sociodemographic index (SDI), healthcare access and quality index (HAQ index)] and risk factors using the GBD 1990-2017. Correlation and mixed multilevel modelling between aortic aneurysm mortality, YLLs, HAQ index and other variables were applied. From 1990 to 2017, a global declining trend in age-standardized aortic aneurysm mortality was found [2.88 deaths/100 000 (95% uncertainty intervals, UI 2.79 to 3.03) in 1990 and 2.19 deaths/100 000 (95% UI 2.09 to 2.28) in 2017]. Among high-income countries (HICs) a consistent declining Spearman\'s correlation between age-standardised aortic aneurysm mortality, SDI (HICs; 1990 rho: 0.57, P ≤ 0.001; 2017 rho: 0.41, P = 0.001) and HAQ index was observed (HICs; 1990 rho: 0.50, P <0.001; 2016 rho: 0.35, P = 0.006); in comparison with low- and middle-income countries where correlation trends were weak and mixed. At a global level, higher HAQ index was related with lower aortic aneurysm mortality and YLLs [mortality, coef: -0.05, 95% confidence interval (CI): -0.06, -0.04; YLLs, coef: -0.94, 95% CI: -1.17, -0.71].
Conclusions
Age-standardized aortic aneurysm mortality declined globally between 1990 and 2017. Globally, age-standardized aortic aneurysm mortality and YLLs were related to changes in SDI and HAQ index levels, while country-level income-related variations were also observed.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 29 Mar 2021; epub ahead of print
Tyrovolas S, Tyrovola D, Giné-Vázquez I, Koyanagi A, ... Miranda JJ, Panagiotakos D
Eur J Prev Cardiol: 29 Mar 2021; epub ahead of print | PMID: 33783496
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Abstract

Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients.

Andreis A, Imazio M, Piroli F, Avondo S, ... Paneva E, De Ferrari GM
Aims
The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD.
Methods and results
A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61-0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42-0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30-0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12-0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20-2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I2 = 16%), or other DAEs.
Conclusions
The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 28 Mar 2021; epub ahead of print
Andreis A, Imazio M, Piroli F, Avondo S, ... Paneva E, De Ferrari GM
Eur J Prev Cardiol: 28 Mar 2021; epub ahead of print | PMID: 33779702
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Abstract

Treatment target achievement after myocardial infarction and ischaemic stroke: cardiovascular risk factors, medication use, and lifestyle: the Tromsø Study 2015-16.

Hopstock LA, Morseth B, Cook S, Eggen AE, ... Nilsen A, Njølstad I
Aims
To investigate European guideline treatment target achievement in cardiovascular risk factors, medication use, and lifestyle, after myocardial infarction (MI) or ischaemic stroke, in women and men living in Norway.
Methods and results
In the population-based Tromsø Study 2015-16 (attendance 65%), 904 participants had previous validated MI and/or stroke. Cross-sectionally, we investigated target achievement for blood pressure (<140/90 mmHg, <130/80 mmHg if diabetes), LDL cholesterol (<1.8 mmol/L), HbA1c (<7.0% if diabetes), overweight (body mass index (BMI) <25 kg/m2, waist circumference women <80 cm, men <94 cm), smoking (non-smoking), physical activity (self-reported >sedentary, accelerometer-measured moderate-to-vigorous ≥150 min/week), diet (intake of fruits ≥200 g/day, vegetables ≥200 g/day, fish ≥200 g/week, saturated fat <10E%, fibre ≥30 g/day, alcohol women ≤10 g/day, men ≤20 g/day), and medication use (antihypertensives, lipid-lowering drugs, antithrombotics, and antidiabetics), using regression models. Proportion of target achievement was for blood pressure 55.2%, LDL cholesterol 9.0%, HbA1c 42.5%, BMI 21.1%, waist circumference 15.7%, non-smoking 86.7%, self-reported physical activity 79%, objectively measured physical activity 11.8%, intake of fruit 64.4%, vegetables 40.7%, fish 96.7%, saturated fat 24.3%, fibre 29.9%, and alcohol 78.5%, use of antidiabetics 83.6%, lipid-lowering drugs 81.0%, antihypertensives 75.9%, and antithrombotics 74.6%. Only 0.7% achieved all cardiovascular risk factor targets combined. Largely, there was little difference between the sexes, and in characteristics, medication use, and lifestyle among target achievers compared to non-achievers.
Conclusion 
Secondary prevention of cardiovascular disease was suboptimal. A negligible proportion achieved the treatment target for all risk factors. Improvement in follow-up care and treatment after MI and stroke is needed.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 28 Mar 2021; epub ahead of print
Hopstock LA, Morseth B, Cook S, Eggen AE, ... Nilsen A, Njølstad I
Eur J Prev Cardiol: 28 Mar 2021; epub ahead of print | PMID: 33778888
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Abstract

Impact of diabetes on coronary severity and cardiovascular outcomes in patients with heterozygous familial hypercholesterolaemia.

Liu MM, Peng J, Guo YL, Wu NQ, ... Dong Q, Li JJ
Aims
Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular disease. However, the association between T2DM and coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolaemia (HeFH) has not been thoroughly evaluated. Our study aimed to assess the effect of T2DM on CAD severity and hard cardiovascular endpoints in a HeFH cohort.
Methods and results
A total of 432 patients with HeFH with a molecular and/or clinical Dutch Lipid Clinic Network score ≥6 (definite and probable) were enrolled. Patients were divided into a T2DM group (n = 99) and a non-T2DM group (n = 333). The severity of coronary stenosis was assessed by the number of diseased vessels and Gensini, SYNTAX, and Jeopardy scores. Hard endpoints included a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiac death. Cox regression and Kaplan-Meier analyses were used to evaluate the effect of T2DM on hard cardiovascular endpoints. The prevalence of CAD was higher in patients with T2DM compared with those without (96.0% vs. 77.5%, respectively; P < 0.001). Patients with T2DM demonstrated a greater number of diseased vessels (P = 0.029) and more severe coronary lesions with high Gensini, SYNTAX, and Jeopardy score tertiles (P = 0.031, P = 0.001, and P = 0.024, respectively). During a median of 3.75 years up to a maximum of 9 years of follow-up, hard endpoints occurred in 13 of 99 patients with T2DM and 16 of 333 without T2DM at baseline. Compared with patients without T2DM, patients with T2DM were at a significantly greater risk of hard endpoints [multivariate adjusted hazard ratio (HR) 2.32, 95% confidence interval (CI) 1.02-4.84; P = 0.025]. Additionally, patients with T2DM and good glucose control (HbA1c < 7.0%) were at a lower risk of hard endpoints compared with those with poor glucose control (HbA1c ≥ 7.0%, HR 0.08, 95% CI 0.01-0.56; P = 0.011).
Conclusion
We conclude that T2DM is an independent predictor of CAD severity when assessed by number of diseased vessels, Gensini, SYNTAX, Jeopardy scores, and hard cardiovascular endpoints, suggesting that T2DM could be further used for risk stratification of patients with HeFH.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 28 Mar 2021; epub ahead of print
Liu MM, Peng J, Guo YL, Wu NQ, ... Dong Q, Li JJ
Eur J Prev Cardiol: 28 Mar 2021; epub ahead of print | PMID: 33778872
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Abstract

The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy.

Norrish G, Topriceanu C, Qu C, Field E, ... Omar RZ, Kaski JP
Aims
The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events.
Methods and results
Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484-0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7.
Conclusion
In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 26 Mar 2021; epub ahead of print
Norrish G, Topriceanu C, Qu C, Field E, ... Omar RZ, Kaski JP
Eur J Prev Cardiol: 26 Mar 2021; epub ahead of print | PMID: 33772274
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Abstract

Personalized exercise prescription in the prevention and treatment of arterial hypertension: a Consensus Document from the European Association of Preventive Cardiology (EAPC) and the ESC Council on Hypertension.

Hanssen H, Boardman H, Deiseroth A, Moholdt T, ... Coca A, Leeson P
Treatment of hypertension and its complications remains a major ongoing health care challenge. Around 25% of heart attacks in Europe are already attributed to hypertension and by 2025 up to 60% of the population will have hypertension. Physical inactivity has contributed to the rising prevalence of hypertension, but patients who exercise or engage in physical activity reduce their risk of stroke, myocardial infarction, and cardiovascular mortality. Hence, current international guidelines on cardiovascular disease prevention provide generic advice to increase aerobic activity, but physiological responses differ with blood pressure (BP) level, and greater reductions in BP across a population may be achievable with more personalized advice. We performed a systematic review of meta-analyses to determine whether there was sufficient evidence for a scientific Consensus Document reporting how exercise prescription could be personalized for BP control. The document discusses the findings of 34 meta-analyses on BP-lowering effects of aerobic endurance training, dynamic resistance training as well as isometric resistance training in patients with hypertension, high-normal, and individuals with normal BP. As a main finding, there was sufficient evidence from the meta-review, based on the estimated range of exercise-induced BP reduction, the number of randomized controlled trials, and the quality score, to propose that type of exercise can be prescribed according to initial BP level, although considerable research gaps remain. Therefore, this evidence-based Consensus Document proposes further work to encourage and develop more frequent use of personalized exercise prescription to optimize lifestyle interventions for the prevention and treatment of hypertension.

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Eur J Prev Cardiol: 23 Mar 2021; epub ahead of print
Hanssen H, Boardman H, Deiseroth A, Moholdt T, ... Coca A, Leeson P
Eur J Prev Cardiol: 23 Mar 2021; epub ahead of print | PMID: 33758927
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Abstract

Novel antidiabetic drugs and risk of cardiovascular events in patients without baseline metformin use: a meta-analysis.

Masson W, Lavalle-Cobo A, Lobo M, Masson G, Molinero G
Aims
To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naïve patients with type 2 diabetes (T2D).
Methods and results
A meta-analysis was performed of randomized controlled clinical trials of GLP-1RAs and SGLT-2 inhibitors on T2D populations, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoint, explored in the subgroup of SGLT-2 inhibitors studies, was cardiovascular death or hospitalization for heart failure. A random-effects meta-analysis model was applied. Six eligible trials (three studies of SGLT-2 inhibitors and three trials of GLP-1RAs), including 13 049 patients, were identified and considered eligible for the analyses. The new antidiabetic drugs were associated with a significant reduction in MACE [odds ratio (OR): 0.80, 95% confidence interval: 0.70-0.93; I2: 53%]. The subgroup analysis showed the following findings: GLP-1RAs group, OR: 0.77 (95% confidence interval 0.67-0.88); SGLT-2 inhibitors, OR: 0.85 (95% confidence interval 0.63-1.15). SGLT-2 inhibitors were associated with a significant reduction in hospitalization for heart failure or cardiovascular mortality incidence (OR: 0.67, 95% confidence interval: 0.47-0.95; I2: 78%).
Conclusion
In this meta-analysis, new antidiabetic drugs reduced the incidence of MACE in metformin-naïve T2D patients. The beneficial effect was especially observed in the GLP-1RAs subgroup. The use of SGLT-2 inhibitors was associated with a reduction in cardiovascular death or hospitalization for heart failure. These results support the fact that metformin would not be indispensable to obtain positive cardiovascular effects when new antidiabetic drugs are administered.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 22 Mar 2021; 28:69-75
Masson W, Lavalle-Cobo A, Lobo M, Masson G, Molinero G
Eur J Prev Cardiol: 22 Mar 2021; 28:69-75 | PMID: 33606884
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Abstract

The need for PCSK9 inhibitors and associated treatment costs according to the 2019 ESC dyslipidaemia guidelines vs. the risk-based allocation algorithm of the 2017 ESC consensus statement: a simulation study in a contemporary CAD cohort.

Blaum C, Seiffert M, Goßling A, Kröger F, ... Brunner FJ, Waldeyer C
Background
The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of <55 mg/dL for patients with atherosclerotic cardiovascular disease (ASCVD), with a concomitant Class IA upgrade for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients not reaching their LDL-C goal under conventional lipid-lowering therapy.
Aims
We aim to quantify the need for PCSK9i and the related costs to achieve the revised LDL-C goal in ASCVD patients compared to former ESC recommendations, in particular the risk-based 2017 ESC consensus update.
Methods and results
We included patients with ASCVD from an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating a treatment algorithm adding sequentially a statin, ezetimibe, and a PCSK9i was applied with consideration of partial and total statin intolerance. The need for PCSK9i was calculated for three different ESC recommendations (2019 guidelines, 2016 guidelines, 2017 consensus update). Preventable events and treatment costs due to PCSK9i were calculated for a range of annual event rates from 2% to 8% and annual treatment costs of ca. 6050 €. We included 1780 patients (mean age 69.5 years). Median LDL-C at baseline was 85.0 mg/dL, with 61% of patients taking lipid-lowering medication. The need for PCSK9i was simulated to be 42.0% (ESC 2019), 31.9% (ESC 2016), and 5.0% (ESC 2017). The LDL-C goals were achieved in 97.9%, 99.1%, and 60.9% of patients, respectively. Annual treatment cost for PCSK9i per 1 000 000 ASCVD patients would be 2.54 billion € (ESC 2019) compared to 0.30 billion € (ESC 2017). Costs per prevented event due to PCSK9i initiation differed widely, e.g. 887 000 € for an event rate of 3% and a treatment goal of <55 mg/dL compared to 205 000 € for an event rate of 7% and risk-based use of PCSK9i.
Conclusion
The revised LDL-C treatment goals increase the projected need for PCSK9i with a substantial increase in associated treatment cost. An allocation strategy based on residual LDL-C and clinical or angiographic risk factors leads to a more tailored target population for PCSK9i with a reasonable benefit/cost ratio.

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Eur J Prev Cardiol: 22 Mar 2021; 28:47-56
Blaum C, Seiffert M, Goßling A, Kröger F, ... Brunner FJ, Waldeyer C
Eur J Prev Cardiol: 22 Mar 2021; 28:47-56 | PMID: 33580772
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Abstract

Sinergy between drugs and devices in the fight against sudden cardiac death and heart failure.

Boriani G, De Ponti R, Guerra F, Palmisano P, ... D\'Onofrio A, Ricci RP
The impact of sudden cardiac death (SCD) in heart failure (HF) patients is important and prevention of SCD is a reasonable and clinically justified endpoint if associated with a reduction in all-cause mortality. According to literature, in HF with reduced ejection fraction, only three classes of agents were found effective in reducing SCD and all-cause mortality: beta-blockers, mineralcorticoid receptor antagonists and, more recently, angiotensin-receptor neprilysin-inhibitors. In the PARADIGM trial that tested sacubitril/valsartan vs. enalapril, the 20% relative risk reduction in cardiovascular deaths obtained with sacubitril/valsartan was attributable to reductions in the incidence of both SCD and death due to HF worsening and this effect can be added to the known positive effect of implantable cardioverter-defibrillators in appropriately selected patients. In order to maximize the implementation of all the available treatments, patients with HF should be included in virtuous networks with a dialogue between all the physician involved, with commitment by all these physicians for appropriate decision-making on application of pharmacological and device treatments according to available evidence, as well as commitment for drug titration before and after device implant, taking advantage from remote monitoring, and with the safety of back up device therapy when indicated. There are potential synergistic effects of drug therapy, with all the therapies acting on neuro-hormonal and sympathetic activation, but specifically with sacubitril/valsartan, and device therapy, in particular cardiac resynchronization therapy, with added incremental benefits on positive cardiac remodelling, prevention of HF progression, and prevention of ventricular tachyarrhythmias.

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Eur J Prev Cardiol: 22 Mar 2021; 28:110-123
Boriani G, De Ponti R, Guerra F, Palmisano P, ... D'Onofrio A, Ricci RP
Eur J Prev Cardiol: 22 Mar 2021; 28:110-123 | PMID: 33624080
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Abstract

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

Nalini M, Shakeri R, Poustchi H, Pourshams A, ... Kamangar F, Malekzadeh R
Aims
Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.
Methods and results
In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.
Conclusion
Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 22 Mar 2021; 28:98-106
Nalini M, Shakeri R, Poustchi H, Pourshams A, ... Kamangar F, Malekzadeh R
Eur J Prev Cardiol: 22 Mar 2021; 28:98-106 | PMID: 33624066
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Abstract

Cardiovascular effectiveness of human-based vs. exendin-based glucagon like peptide-1 receptor agonists: a retrospective study in patients with type 2 diabetes.

Longato E, Di Camillo B, Sparacino G, Tramontan L, Avogaro A, Fadini GP
Aims
Glucagon like peptide-1 (GLP-1) receptor agonists (GLP-1RA) are effective to control type 2 diabetes (T2Ds) and can protect from adverse cardiovascular outcomes. GLP-1RA are based on the human GLP-1 or the exendin-4 sequence. We compared cardiovascular outcomes of patients with T2D who received human-based or exendin-based GLP-1RA in routine clinical practice.
Methods and results
We performed a retrospective study on the administrative database of T2D patients from the Veneto Region (North-East Italy). We identified patients who initiated a human-based or exendin-based GLP-1RA from 2011 to 2018. The primary outcome was occurrence of major adverse cardiovascular events (MACE). Secondary outcomes were individual MACE components, revascularization, hospitalization for heart failure, or for cardiovascular causes. From 330 193 patients with diabetes, 6620 were new users of GLP-1RA. After propensity score matching, we analysed 1098 patients in each group, who were on average 61 years old, 59.5% males, 13% with established cardiovascular disease, had an estimated diabetes duration of 8.4 years, and a baseline HbA1c of 7.9%. During a median follow-up of 18 months, patients treated with human-based GLP-1RA as compared to those treated with exendin-based GLP-1RA, showed lower rates of MACE [hazard ratio 0.61; 95% confidence interval (CI) 0.39-0.95], myocardial infarction (0.51; 95% CI 0.28-0.94), and hospitalization for cardiovascular causes (0.66; 95% CI 0.47-0.92).
Conclusion
We observed better cardiovascular outcomes among patients treated with human-based vs. exendin-based GLP-1RA under routine care. In the absence of comparative trials and in view of the limitations of retrospective studies, this finding provides a moderate level of evidence to guide clinical decision.

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Eur J Prev Cardiol: 22 Mar 2021; 28:22-29
Longato E, Di Camillo B, Sparacino G, Tramontan L, Avogaro A, Fadini GP
Eur J Prev Cardiol: 22 Mar 2021; 28:22-29 | PMID: 33624059
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Abstract

The mediating role of effective treatments in the relationship between income level and survival in patients with heart failure: a sex- and cohabitation-stratified study.

Andersen J, Gerds TA, Hlatky MA, Gislason G, ... Madelaire C, Strandberg-Larsen K
Aims 
Patients with heart failure and low income have a high mortality risk. We examined whether lower survival among low-income patients with heart failure could be explained by different use of β -blockers, renin-angiotensin system inhibitors (RASi), and implanted devices compared with high-income patients.
Methods and results 
We linked Danish national registries to identify patients with new-onset heart failure between 2005 and 2016. A total of 18 308 patients was included in the main analysis. We collected information on medical treatment and device therapy after discharge. We investigated the remaining income disparity if everybody had the same probability of treatment as the high-income patients. We used causal mediation analysis to examine to what extent treatment differences mediate the association between income and 1-year mortality in strata defined by sex and cohabitation status. If low-income patients had the same probability of initiating β-blockers and RASi treatment as high-income patients, low-income men who lived alone would increase initiation of treatment by 12.4% (CI: 10.0% to 14.9%) and as a result reduce their absolute 1-year mortality by 1.0% (CI: -1.4% to -0.5%). If low-income patients had the same probability of not having breaks in medical treatment and getting device therapy, as high-income patients, low-income patients would increase the probability of not having breaks in treatment between 1.8% and 5.8% and increase the probability of getting device therapy between 1.0% and 3.8%, across strata of sex and cohabitation status.
Conclusion 
Lower rates of treatment initiation appear to mediate the poorer survival seen among patients with heart failure and low income, but only in males living alone.

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Eur J Prev Cardiol: 22 Mar 2021; 28:78-86
Andersen J, Gerds TA, Hlatky MA, Gislason G, ... Madelaire C, Strandberg-Larsen K
Eur J Prev Cardiol: 22 Mar 2021; 28:78-86 | PMID: 33623976
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Impact:
Abstract

Oxygen and pulmonary arterial hypertension: effects, mechanisms, and therapeutic benefits.

Green S, Stuart D
Oxygen is a pulmonary vasodilator. Although treatment of pulmonary arterial hypertension (PAH) is focused on pulmonary vasodilation, treatment guidelines do not recommend O2 therapy for patients unless they develop hypoxaemia. These guidelines point to a lack of evidence of benefit of O2 therapy from randomized controlled trials (RCTs) and to evidence of lack of benefit in a single RCT involving patients with Eisenmenger syndrome. These guidelines did not identify major limitations with the Eisenmenger study or consider other evidence of therapeutic benefit. Recent advances in mechanistic understanding of O2 effects on pulmonary vascular tone, along with substantial evidence of acute effects of O2 in PAH patients, challenge the view that benefits of O2 arise only through correction of hypoxaemia. Evidence presented in this review shows that O2 acts as a pulmonary vasodilator in patients who are normoxaemic; that this probably involves an alveolar mechanism in addition to a blood-borne (oxyhaemoglobin) mechanism; and that therapeutic benefit of O2 does not depend on arterial O2 levels. This suggests that O2 has potential therapeutic benefit for all patients with PAH. Clinical guidelines and practice related to O2 therapy need to be reassessed, and further research is needed.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 22 Mar 2021; 28:127-136
Green S, Stuart D
Eur J Prev Cardiol: 22 Mar 2021; 28:127-136 | PMID: 33623970
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Impact:
Abstract

Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial.

Diaz R, Li QH, Bhatt DL, Bittner VA, ... Steg PG, ODYSSEY OUTCOMES Committees and Investigators
Aims
Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment.
Methods and results
The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL (P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80-0.96; 0.68, 0.49-0.94; and 0.65, 0.44-0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34-2.16; 3.16%, 0.38-5.94; 7.97%, 0.42-15.51; Pinteraction = 0.106).
Conclusions
PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 22 Mar 2021; 28:33-43
Diaz R, Li QH, Bhatt DL, Bittner VA, ... Steg PG, ODYSSEY OUTCOMES Committees and Investigators
Eur J Prev Cardiol: 22 Mar 2021; 28:33-43 | PMID: 33755145
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Abstract

Effects of linagliptin on left ventricular DYsfunction in patients with type 2 DiAbetes and concentric left ventricular geometry: results of the DYDA 2 trial.

Cioffi G, Giorda CB, Lucci D, Nada E, ... Maggioni AP, DYDA 2 investigators
Aims
To evaluate the effect of linagliptin on left ventricular systolic function beyond glycaemic control in type 2 diabetes mellitus.
Methods and results
A multicentre, randomised, double-blind, placebo controlled, parallel-group study, was performed (the DYDA 2 trial). Individuals with type 2 diabetes mellitus and asymptomatic impaired left ventricular systolic function were randomly allocated in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their diabetes therapy. Eligibility criteria were age 40 years and older, haemoglobin A1c 8.0% or less (≤64 mmol/mol), no history of cardiac disease, concentric left ventricular geometry (relative wall thickness ≥0.42), impaired left ventricular systolic function defined as midwall fractional shortening 15% or less at baseline echocardiography. The primary end point was the modification of midwall fractional shortening over time. The main secondary objectives were changes in diastolic and/or in longitudinal left ventricular systolic function as measured by tissue Doppler echocardiography. One hundred and eighty-eight patients were enrolled, predominantly men with typical insulin-resistance comorbidities. At baseline, mean midwall fractional shortening was 13.3%±2.5. At final evaluation, 88 linagliptin patients and 86 placebo patients were compared: midwall fractional shortening increased from 13.29 to 13.82 (+4.1%) in the linagliptin group, from 13.58 to 13.84 in the placebo group (+1.8%, analysis of covariance P = 0.86), corresponding to a 2.3-fold higher increase in linagliptin than the placebo group, although non-statistically significant. Also, changes in diastolic and longitudinal left ventricular systolic function did not differ between the groups. Serious adverse events or linagliptin/placebo permanent discontinuation occurred in very few cases and in the same percentage between the groups.
Conclusions
In the DYDA 2 patients the addition of linagliptin to stable diabetes therapy was safe and provided a modest non-significant increase in left ventricular systolic function measured as midwall fractional shortening.
Trial registration number
ClinicalTrial.gov (ID NCT02851745).

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 22 Mar 2021; 28:8-17
Cioffi G, Giorda CB, Lucci D, Nada E, ... Maggioni AP, DYDA 2 investigators
Eur J Prev Cardiol: 22 Mar 2021; 28:8-17 | PMID: 33755143
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Abstract

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines.

Koskinas KC, Gencer B, Nanchen D, Branca M, ... Mach F, Windecker S
Aims
The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes.
Methods and results
We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria.
Conclusions
In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 22 Mar 2021; 28:59-65
Koskinas KC, Gencer B, Nanchen D, Branca M, ... Mach F, Windecker S
Eur J Prev Cardiol: 22 Mar 2021; 28:59-65 | PMID: 33755142
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Abstract

Drug-resistant hypertension in primary aldosteronism patients undergoing adrenal vein sampling: the AVIS-2-RH study.

Rossi GP, Rossitto G, Amar L, Azizi M, ... Seccia TM, Lenzini L
Aims
We aimed at determining the rate of drug-resistant arterial hypertension in patients with an unambiguous diagnosis of primary aldosteronism (PA). Moreover, we sought for investigating the diagnostic performance of adrenal vein sampling (AVS), and the effect of adrenalectomy on blood pressure (BP) and prior treatment resistance in PA patients subtyped by AVS in major referral centres.
Methods and results
The Adrenal Vein Sampling International Study-2 (AVIS-2) was a multicentre international study that recruited consecutive PA patients submitted to AVS, according to current guidelines, during 15 years. The patients were over 18 years old with arterial hypertension and had an unambiguous diagnosis of PA. The rate of resistant hypertension was assessed at baseline and after adrenalectomy using the American Heart Association (AHA) 2018 definition. Information on presence or absence of resistant hypertension was available in 89% of the 1625 enrolled PA patients. Based on the AHA 2018 criteria, resistant hypertension was found in 20% of patients, of which about two-thirds (14%) were men and one-third (6%) women (χ2 = 17.1, P < 1*10-4) with a higher rate of RH in men than in women (23% vs. 15% P < 1*10-4). Of the 292 patients with resistant hypertension, 98 (34%) underwent unilateral AVS-guided adrenalectomy, which resolved BP resistance to antihypertensive treatment in all.
Conclusions
(i) Resistant hypertension is a common presentation in patients seeking surgical cure of PA; (ii) AVS is key for the optimal management of patients with PA due to resistant hypertension; and (iii) AVS-guided adrenalectomy allowed resolution of treatment-resistant hypertension.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 19 Mar 2021; epub ahead of print
Rossi GP, Rossitto G, Amar L, Azizi M, ... Seccia TM, Lenzini L
Eur J Prev Cardiol: 19 Mar 2021; epub ahead of print | PMID: 33742213
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Abstract

Circulating microRNA as predictors for exercise response in heart failure with reduced ejection fraction.

Witvrouwen I, Gevaert AB, Possemiers N, Beckers PJ, ... Van Craenenbroeck AH, Van Craenenbroeck EM
Aims
Exercise training is a powerful adjunctive therapy in patients with heart failure with reduced ejection fraction (HFrEF), but ca. 55% of patients fail to improve VO2peak. We hypothesize that circulating microRNAs (miRNAs), as epigenetic determinants of VO2peak, can distinguish exercise responders (ER) from exercise non-responders (ENR).
Methods and results
We analysed 377 miRNAs in 18 male HFrEF patients (9 ER and 9 ENR) prior to 15 weeks of exercise training using a miRNA array. ER and ENR were defined as change in VO2peak of >20% or <6%, respectively. First, unsupervised clustering analysis of the miRNA pattern was performed. Second, differential expression of miRNA in ER and ENR was analysed and related to percent change in VO2peak. Third, a gene set enrichment analysis was conducted to detect targeted genes and pathways. Baseline characteristics and training volume were similar between ER and ENR. Unsupervised clustering analysis of miRNAs distinguished ER from ENR with 83% accuracy. A total of 57 miRNAs were differentially expressed in ENR vs. ER. A panel of seven miRNAs up-regulated in ENR (Let-7b, miR-23a, miR-140, miR-146a, miR-191, miR-210, and miR-339-5p) correlated with %changeVO2peak (all P < 0.05) and predicted ENR with area under the receiver operating characteristic curves ≥0.77. Multiple pathways involved in exercise adaptation processes were identified.
Conclusion
A fingerprint of seven miRNAs involved in exercise adaptation processes is highly correlated with VO2peak trainability in HFrEF, which holds promise for the prediction of training response and patient-targeted exercise prescription.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 19 Mar 2021; epub ahead of print
Witvrouwen I, Gevaert AB, Possemiers N, Beckers PJ, ... Van Craenenbroeck AH, Van Craenenbroeck EM
Eur J Prev Cardiol: 19 Mar 2021; epub ahead of print | PMID: 33742210
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Abstract

Dose-response effects of physical activity on all-cause mortality and major cardiorenal outcomes in chronic kidney disease.

Kuo CP, Tsai MT, Lee KH, Lin YP, ... Tseng WC, Tarng DC
Aims
Physical activity has a protective effect against mortality and cardiovascular events in chronic kidney disease (CKD) patients. Nonetheless, how different levels of physical activity affect the health benefits in CKD remains unclear. This study aimed to investigate the dose-response effects of physical activity on mortality and major cardiorenal events in CKD.
Methods and results
We evaluated a longitudinal cohort of 4508 Taiwanese CKD patients between 2004 and 2017. Physical activity was assessed by the NHANES questionnaire and quantified in metabolic equivalent-hours per week (MET-hour/week). Patients were categorized into highly active (≥7.5 MET-h/week), low-active (0.1 to <7.5 MET-h/week), or inactive (0 MET-h/week) groups. Cox regression and restricted cubic spline models were utilized to explore the association between physical activity and the risks of study outcomes, including all-cause mortality, end-stage renal disease (ESRD), and major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, ischaemic stroke, and hospitalized heart failure). During a median follow-up of 686 days, 739 death, 1059 ESRD, and 521 MACE events occurred. Highly active group had the lowest chance of all study outcomes, followed by low-active and inactive groups (P < 0.001). Multivariable Cox regression showed that only highly active group was independently associated with lower risks for all-cause mortality [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.53-0.74], ESRD (HR 0.83, 95% CI 0.72-0.96), and MACE (HR 0.63, 95% CI 0.51-0.76) compared to the inactive group. The risks of MACE did not further decrease once physical activity surpassed 15 MET-h/week, indicating a U-shaped association. The results were consistent in the subgroup and sensitivity analyses.
Conclusion
Physical activity of 7.5 to <15 MET-h/week is associated with lower risks of adverse cardiorenal outcomes and should be integrated into the care of CKD.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 10 Mar 2021; epub ahead of print
Kuo CP, Tsai MT, Lee KH, Lin YP, ... Tseng WC, Tarng DC
Eur J Prev Cardiol: 10 Mar 2021; epub ahead of print | PMID: 33704426
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Abstract

Utility of the CHA2DS2-VASc score for predicting ischaemic stroke in patients with or without atrial fibrillation: a systematic review and meta-analysis.

Siddiqi TJ, Usman MS, Shahid I, Ahmed J, ... Rihal CS, Alkhouli M
Aims
Anticoagulants are the mainstay treatment for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), and the CHA2DS2-VASc score is widely used to guide anticoagulation therapy in this cohort. However, utility of CHA2DS2-VASc in NVAF patients is debated, primarily because it is a vascular scoring system, which does not incorporate atrial fibrillation related parameters. Therefore, we conducted a meta-analysis to estimate the discrimination ability of CHA2DS2-VASc in predicting ischaemic stroke overall, and in subgroups of patients with or without NVAF.
Methods and results
PubMed and Embase databases were searched till June 2020 for published articles that assessed the discrimination ability of CHA2DS2-VASc, as measured by C-statistics, during mid-term (2-5 years) and long-term (>5 years) follow-up. Summary estimates were reported as random effects C-statistics with 95% confidence intervals (CIs). Seventeen articles were included in the analysis. Nine studies (n = 453 747 patients) reported the discrimination ability of CHA2DS2-VASc in NVAF patients, and 10 studies (n = 138 262 patients) in patients without NVAF. During mid-term follow-up, CHA2DS2-VASc predicted stroke with modest discrimination in the overall cohort [0.67 (0.65-0.69)], with similar discrimination ability in patients with NVAF [0.65 (0.63-0.68)] and in those without NVAF [0.69 (0.68-0.71)] (P-interaction = 0.08). Similarly, at long-term follow-up, CHA2DS2-VASc had modest discrimination [0.66 (0.63-0.69)], which was consistent among patients with NVAF [0.63 (0.54-0.71)] and those without NVAF [0.67 (0.64-0.70)] (P-interaction = 0.39).
Conclusion
This meta-analysis suggests that the discrimination power of the CHA2DS2-VASc score in predicting ischaemic stroke is modest, and is similar in the presence or absence of NVAF. More accurate stroke prediction models are thus needed for the NVAF population.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 08 Mar 2021; epub ahead of print
Siddiqi TJ, Usman MS, Shahid I, Ahmed J, ... Rihal CS, Alkhouli M
Eur J Prev Cardiol: 08 Mar 2021; epub ahead of print | PMID: 33693717
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Abstract

Abdominal and gluteo-femoral markers of adiposity and risk of vascular-metabolic mortality in a prospective study of 150 000 Mexican adults.

Gnatiuc L, Tapia-Conyer R, Wade R, Ramirez-Reyes R, ... Emberson JR, Alegre-Díaz J
Aims
Results of previous studies of abdominal adiposity and risk of vascular-metabolic mortality in Hispanic populations have been conflicting. We report results from a large prospective study of Mexican adults with high levels of abdominal adiposity.
Methods and results
A total of 159 755 adults aged ≥35 years from Mexico City were enrolled in a prospective study and followed for 16 years. Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) associated with three markers of abdominal adiposity (waist circumference, waist-hip ratio, and waist-height ratio) and one marker of gluteo-femoral adiposity (hip circumference) for cause-specific mortality before age 75 years. To reduce reverse causality, deaths in the first 5 years of follow-up and participants with diabetes or other prior chronic disease were excluded. Among 113 163 participants without prior disease and aged 35-74 years at recruitment, all adiposity markers were positively associated with vascular-metabolic mortality. Comparing the top versus bottom tenth of the sex-specific distributions, the vascular-metabolic mortality RRs at ages 40-74 years were 2.32 [95% confidence interval (CI) 1.84-2.94] for waist circumference, 2.22 (1.71-2.88) for the waist-hip ratio, 2.63 (2.06-3.36) for the waist-height ratio, and 1.58 (1.29-1.93) for hip circumference. The RRs corresponding to each standard deviation (SD) higher usual levels of these adiposity markers were 1.34 (95% CI 1.27-1.41), 1.31 (1.23-1.39), 1.38 (1.31-1.45), and 1.18 (1.13-1.24), respectively. For the markers of abdominal adiposity, the RRs did not change much after further adjustment for other adiposity markers, but for hip circumference the association was reversed; given body mass index and waist circumference, the RR for vascular-metabolic mortality for each one SD higher usual hip circumference was 0.80 (0.75-0.86).
Conclusions
In this study of Mexican adults, abdominal adiposity (and in particular the waist-height ratio) was strongly and positively associated with vascular-metabolic mortality. For a given amount of general and abdominal adiposity, however, higher hip circumference was associated with lower vascular-metabolic mortality.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 08 Mar 2021; epub ahead of print
Gnatiuc L, Tapia-Conyer R, Wade R, Ramirez-Reyes R, ... Emberson JR, Alegre-Díaz J
Eur J Prev Cardiol: 08 Mar 2021; epub ahead of print | PMID: 33693634
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Abstract

The role of exercise in the prevention of cancer therapy-related cardiac dysfunction in breast cancer patients undergoing chemotherapy: systematic review.

Murray J, Bennett H, Bezak E, Perry R
Aims
Breast cancer (BC) patients undergoing chemotherapy are at risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD; however, its effectiveness remains unclear. The aim of this systematic review was to establish the effect of exercise on global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) in BC patients undergoing chemotherapy, to determine if exercise can prevent the development of CTRCD.
Methods and results
Four databases (Medline, Scopus, eMbase, SPORTDiscus) were searched. Studies were eligible for inclusion if they measured GLS or LVEF prior to and following an exercise intervention of any length in BC patients undergoing chemotherapy and were published in English from 2000 onwards. Risk of bias was evaluated using the QUADAS-2 tool. Of the 398 studies screened, eight were eligible. Changes were similar in exercising (EX) and non-exercising (CON) groups for GLS (EX: pre: -19.6 ± 0.4, post: -20.1 ± 1.0, CON: pre: -20.0 ± 0.4, post: -20.1 ± 1) and LVEF (EX: pre: 58.5 ± 4.1%, post: 58.6 ± 2%, CON: pre: 56.6 ± 4.2%, post: 55.6 ± 4.6%). Exercise maintained or improved peak oxygen uptake (VO2peak) during chemotherapy, while declines were observed in non-exercising groups. The included studies were limited by methodological deficiencies.
Conclusion
The ability of exercise to prevent CTRCD is unclear. However, exercise positively impacts cardiorespiratory fitness in BC patients undergoing chemotherapy. Future research must address the methodological limitations of current research to understand the true effect of exercise in the prevention of CTRCD.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 08 Mar 2021; epub ahead of print
Murray J, Bennett H, Bezak E, Perry R
Eur J Prev Cardiol: 08 Mar 2021; epub ahead of print | PMID: 33693524
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Abstract

β-blocker use and risk of all-cause mortality in patients with coronary heart disease: effect modification by serum vitamin A.

Dhar I, Svingen GFT, Olsen T, Lysne V, ... Ueland PM, Nygård OK
Aims 
Blockade of β-adrenoceptors reduces sympathetic nervous system activity and improves survival in patients with heart failure with reduced left ventricular ejection fraction (HFrEF); however, any improvement in longevity among patients with coronary heart disease (CHD) but without HFrEF remains uncertain. Vitamin A has been linked to the activation of tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine synthesis pathway. We investigated if vitamin A status modified the association of β-blocker use with the risk of all-cause mortality.
Methods and results 
A total of 4118 patients undergoing elective coronary angiography for suspected stable angina pectoris, of whom the majority had normal left ventricular ejection fraction (LVEF) were studied. Hazard ratios (HRs) of all-cause mortality comparing treatment vs. non-treatment of β-blockers according to the tertiles of serum vitamin A were explored in Cox proportional hazards regression models. During a median follow-up of 10.3 years, 897 patients (21.8%) died. The overall LVEF was 65% and 283 (6.9%) had anamnestic HF. After multivariable adjustments for traditional risk factors, medical history, and drug therapies of cardiovascular disease, β-blocker treatment was inversely associated with the risk of all-cause mortality [HR : 0.84; 95% CI (confidence interval), 0.72-0.97]. However, the inverse association was generally stronger among patients in the upper serum vitamin A tertile (HR :0.66; 95% CI, 0.50-0.86; Pinteraction = 0.012), which remained present after excluding patients with LVEF < 40%.
Conclusion 
In patients with suspected CHD, β-blocker treatment was associated with improved survival primarily among patients with high serum vitamin A levels.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 07 Mar 2021; epub ahead of print
Dhar I, Svingen GFT, Olsen T, Lysne V, ... Ueland PM, Nygård OK
Eur J Prev Cardiol: 07 Mar 2021; epub ahead of print | PMID: 33709106
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Abstract

Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. Registry.

Cittadini A, Salzano A, Iacoviello M, Triggiani V, ... Marra AM, Bossone E
Aims
Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients.
Methods and results
The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37-2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28-3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01).
Conclusion
MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target.
Trial registration
ClinicalTrials.gov identifier: NCT023358017.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 06 Mar 2021; epub ahead of print
Cittadini A, Salzano A, Iacoviello M, Triggiani V, ... Marra AM, Bossone E
Eur J Prev Cardiol: 06 Mar 2021; epub ahead of print | PMID: 33693736
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Impact:
Abstract

Future burden of cardiovascular disease in Australia: impact on health and economic outcomes between 2020 and 2029.

Marquina C, Talic S, Vargas-Torres S, Petrova M, ... Zomer E, Ademi Z
Aims
To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia.
Methods and results
A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion.
Conclusion
Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 03 Mar 2021; epub ahead of print
Marquina C, Talic S, Vargas-Torres S, Petrova M, ... Zomer E, Ademi Z
Eur J Prev Cardiol: 03 Mar 2021; epub ahead of print | PMID: 33686414
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Abstract

Protective effects of SGLT-2 inhibitors across the cardiorenal continuum: two faces of the same coin.

Fontes-Carvalho R, Santos-Ferreira D, Raz I, Marx N, Ruschitzka F, Cosentino F
The cardiovascular and renal systems are closely interconnected in health and disease. Disorders affecting one of these systems frequently involve the other. Both diseases progress through a continuous chain of events, defined as the \'cardiorenal continuum\', which is initiated by risk factors that lead to subclinical disease, clinical events, and ultimately to heart failure and end-stage kidney disease. Previous studies have shown that interventions anywhere along this chain of events can interrupt the pathophysiological cascade and provide cardiovascular and/or kidney \'protection\'. More recently, clinical trials with SGLT-2 inhibitors (SGLT2i) have shown a significant reduction in cardiovascular and kidney outcomes. Evidence from EMPA-REG OUTCOME, CANVAS Program, DECLARE-TIMI 58, VERTIS-CV, CREDENCE, and more recently DAPA-HF, EMPEROR-Reduced, and DAPA-CKD show that the beneficial effects of SGLT2i are observed across all stages of the cardiorenal continuum, ranging from patients with diabetes and multiple risk factors to those with established cardiovascular disease and even independently of diabetes status. This review provides a critical appraisal of the efficacy and safety of SGLT2i, demonstrating that this is a novel way to disrupt the chain of pathological events in the cardiorenal continuum and prevent cardiovascular and kidney disease in patients with and without diabetes.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 27 Feb 2021; epub ahead of print
Fontes-Carvalho R, Santos-Ferreira D, Raz I, Marx N, Ruschitzka F, Cosentino F
Eur J Prev Cardiol: 27 Feb 2021; epub ahead of print | PMID: 33659986
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Abstract

Prognostic role of transferrin saturation in heart failure patients.

Campodonico J, Nicoli F, Motta I, Migone De Amicis M, ... Cappellini M, Agostoni P
Aims
In heart failure (HF) iron deficiency (ID) is frequently observed and represents a major mortality risk factor. Purpose of this study was to evaluate the correlation between mortality and ID in a cohort of 661 consecutive patients hospitalized for HF worsening.
Methods and results
Patients were grouped: (i)according to presence(+)/absence(-) of anaemia (A) and ID defined following World Health Organization (WHO) and European Society of Cardiology (ESC)-American College of Cardiology/American Heart Association/HF society of America (ACC/AHA/HFSA) definitions, respectively: Group A-ID- (n = 123), Group A+ID- (n = 80), Group A+ID+ (n = 247), and Group A-ID+ (n = 211); (ii) according to presence of absolute (serum ferritin < 100μg/L) and functional ID [ferritin between 100 and 300μg/L and transferrin saturation (TSAT) < 20%]; and (iii) according to TSAT <20% and ≥20%. Groups were not different for several clinical features but age, gender, kidney function, and chronic obstructive pulmonary disease. Average follow-up was 1.94 year (±420 days). Overall 5 years mortality rate was 29.5%. Only anaemia and functional ID but not ID as defined by guidelines showed an impact on prognosis. Transferrin saturation <20% (n = 360) patients showed worst prognosis compared to TSAT ≥20% (n = 301) patients. In addition, functional ID patients showed worse prognosis compared patients with ferritin <100μg/L and TSAT <20% or ≥20% likely due to more severe chronic inflammatory status [C-reactive protein, 7.4 (interquartile range 2.7-22.6) and 3.2 (1.4-8.7) mg/L, P < 0.0001 respectively].
Conclusion
We confirmed that in HF anaemia is associated to a poor prognosis. Moreover, we showed that patients with TSAT <20% had worse prognosis compared to those with TSAT ≥20% but the composite of ferritin between 100 and 300 μg/L and TSAT <20% identifies HF patients with the poorest survival rate.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 22 Feb 2021; epub ahead of print
Campodonico J, Nicoli F, Motta I, Migone De Amicis M, ... Cappellini M, Agostoni P
Eur J Prev Cardiol: 22 Feb 2021; epub ahead of print | PMID: 33619543
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Abstract

Visual acuity and risk of overall, injury-related, and cardiovascular mortality: the Kangbuk Samsung Health Study.

Han SY, Chang Y, Shin H, Choi CY, Ryu S
Aims 
The associations of visual impairment (VI) with cardio-metabolic risk factors have been reported but its association with cardiovascular mortality remains uncertain. Therefore, we evaluated the association of visual acuity (VA) with overall, injury-related, and cardiovascular mortality.
Methods and results
A cohort study was performed in 580 746 Korean adults (average age, 39.7 years) who were followed for a median of 8.1 years (maximum, 16 years). Presenting VA was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity in the better vision eye was categorized as normal vision (≥0.8), lowered vision (0.5-0.8), mild visual impairment (VI) (0.3-0.5), or moderate to severe VI (<0.3). Vital status and cause of death were ascertained through linkage to national death records. During 4 632 892.2 person-years of follow-up, 6585 overall deaths, 974 cardiovascular deaths, and 1163 injury-related deaths were identified. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for overall mortality among participants with lowered vision, minimal VI, and moderate to severe VI were 1.21 (1.13-1.29), 1.26 (1.15-1.37), and 1.54 (1.40-1.68), respectively, compared with those with normal vision. The corresponding HRs (95% CIs) for injury-related mortality were 1.12 (0.96-1.32), 0.98 (0.76-1.26), and 1.36 (1.04-1.79), respectively, and the corresponding HRs (95% CIs) for cardiovascular mortality were 1.32 (1.12-1.57), 1.43 (1.15-1.77), and 2.41 (1.94-2.99).
Conclusion 
In this large cohort of young and middle-aged individuals, VI was associated with increased risk of mortality especially due to cardiovascular disease.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 21 Feb 2021; epub ahead of print
Han SY, Chang Y, Shin H, Choi CY, Ryu S
Eur J Prev Cardiol: 21 Feb 2021; epub ahead of print | PMID: 33615358
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Abstract

Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.

Banerjee A, Chen S, Pasea L, Lai AG, ... Lip GYH, Hemingway H
Aims
Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both \'direct\', through infection, and \'indirect\', through changes in healthcare.
Methods and results
We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.
Conclusion
Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 20 Feb 2021; epub ahead of print
Banerjee A, Chen S, Pasea L, Lai AG, ... Lip GYH, Hemingway H
Eur J Prev Cardiol: 20 Feb 2021; epub ahead of print | PMID: 33611594
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Abstract

High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid.

Palatini P, Parati G, Virdis A, Reboldi G, ... Borghi C, from the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)
Aims 
Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR).
Methods and results 
Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P < 0.0001) over a multivariable model. However, the risk of CVM related to high UA (≥5.5 mg/dL, top tertile) was much lower in the subjects with HR <median [71.3 b.p.m., adjusted hazard ratio 1.38, 95% confidence interval (CI) 1.20-1.59] than in those with HR ≥median [2.09 (95% CI 1.75-2.51)]. In the participants stratified by HR tertile, the risk related to hyperuricaemia was 2.38 (95% CI 1.82-3.10) in people with HR ≥76 b.p.m. and was 1.24 (95% CI 0.92-1.67) in those with HR <66 b.p.m. Similar results were obtained in the hypertensive patients, in the participants ≥65 years, and in the subjects not taking beta-blockers.
Conclusion 
This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 13 Feb 2021; epub ahead of print
Palatini P, Parati G, Virdis A, Reboldi G, ... Borghi C, from the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)
Eur J Prev Cardiol: 13 Feb 2021; epub ahead of print | PMID: 33582757
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Abstract

Burden of heart failure and underlying causes in 195 countries and territories from 1990 to 2017.

Bragazzi NL, Zhong W, Shu J, Abu Much A, ... Younis A, Dai H
Aims
To provide the first systematic analysis of the burden and underlying causes of heart failure (HF) in 195 countries and territories from 1990 to 2017.
Methods and results
We collected detailed information on prevalence, years lived with disability (YLDs), and underlying causes of HF from the Global Burden of Disease study 2017. Numbers and age-standardized rates of HF prevalence and YLDs were compared by age, sex, socio-demographic index (SDI), and location. The proportions of HF age-standardized prevalence rates due to 23 underlying causes were also presented. Globally, the age-standardized prevalence and YLD rates of HF in 2017 were 831.0 and 128.2 per 100 000 people, a decrease of -7.2% and -0.9% from 1990, respectively. Nevertheless, the absolute numbers of HF prevalent cases and YLDs have increased by 91.9% and 106.0% from 1990, respectively. There is significant geographic and socio-demographic variation in the levels and trends of HF burden from 1990 to 2017. Among all causes of HF, ischaemic heart disease accounted for the highest proportion (26.5%) of age-standardized prevalence rate of HF in 2017, followed by hypertensive heart disease (26.2%), chronic obstructive pulmonary disease (23.4%).
Conclusion
HF remains a serious public health problem worldwide, with increasing age-standardized prevalence and YLD rates in countries with relatively low SDI. More geo-specific strategies aimed at preventing underlying causes and improving medical care for HF are warranted to reduce the future burden of this condition.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur J Prev Cardiol: 11 Feb 2021; epub ahead of print
Bragazzi NL, Zhong W, Shu J, Abu Much A, ... Younis A, Dai H
Eur J Prev Cardiol: 11 Feb 2021; epub ahead of print | PMID: 33571994
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Abstract

Association of fatal myocardial infarction with past level of physical activity: a pooled analysis of cohort studies.

Hansen KW, Peytz N, Blokstra A, Bojesen SE, ... Verschuren WMM, Prescott E
Aims
To assess the association between past level of physical activity (PA) and risk for death during the acute phase of myocardial infarction (MI) in a pooled analysis of cohort studies.
Methods and results
European cohorts including participants with a baseline assessment of PA, conventional cardiovascular (CV) risk factors, and available follow-up on MI and death were eligible. Patients with an incident MI were included. Leisure-time PA was grouped as sedentary (<7 MET-hours), low (7-16 MET-hours), moderate (16.1-32 MET-hours), or high (>32 MET-hours) based on calculated net weekly energy expenditure. The main outcome measures were instant and 28-day case fatality of MI. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate random-effects models. Adjustments for age, sex, CV risk factors, alcohol consumption, and socioeconomic status were made. From 10 cohorts including a total of 1 495 254 participants, 28 140 patients with an incident MI comprised the study population. A total of 4976 (17.7%) died within 28 days-of these 3101 (62.3%) were classified as instant fatal MI. Compared with sedentary individuals, those with a higher level of PA had lower adjusted odds of instant fatal MI: low PA [OR, 0.79 (95% CI, 0.60-1.04)], moderate PA [0.67 (0.51-0.89)], and high PA [0.55 (0.40-0.76)]. Similar results were found for 28-day fatal MI: low PA [0.85 (0.71-1.03)], moderate PA [0.64 (0.51-0.80)], and high PA [0.72 (0.51-1.00)]. A low-to-moderate degree of heterogeneity was detected in the analysis of instant fatal MI (I2 = 47.3%), but not in that of 28-day fatal MI (I2 = 0.0%).
Conclusion
A moderate-to-high level of PA was associated with a lower risk of instant and 28-day death in relation to a MI.

© The Author(s) 2021. Published on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: [email protected]

Eur J Prev Cardiol: 09 Feb 2021; epub ahead of print
Hansen KW, Peytz N, Blokstra A, Bojesen SE, ... Verschuren WMM, Prescott E
Eur J Prev Cardiol: 09 Feb 2021; epub ahead of print | PMID: 33564885
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Abstract

The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study.

Georgiopoulos G, Ntritsos G, Stamatelopoulos K, Tsioufis C, ... Masi S, Evangelou E
Aims
Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF.
Methods and results
Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012-1.024, P < 0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P < 0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P = 0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded.
Conclusions
The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 08 Feb 2021; epub ahead of print
Georgiopoulos G, Ntritsos G, Stamatelopoulos K, Tsioufis C, ... Masi S, Evangelou E
Eur J Prev Cardiol: 08 Feb 2021; epub ahead of print | PMID: 33556963
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Abstract

Offering, participation and adherence to cardiac rehabilitation programmes in the elderly: a European comparison based on the EU-CaRE multicentre observational study.

González-Salvado V, Peña-Gil C, Lado-Baleato Ó, Cadarso-Suárez C, ... Prins L, González Juanatey JR
Aims 
Cardiac rehabilitation (CR) is strongly recommended but participation of elderly patients has not been well characterized. This study aims to analyse current rates and determinants of CR referral, participation, adherence, and compliance in a contemporary European cohort of elderly patients.
Methods and results 
The EU-CaRE observational study included data from consecutive patients aged ≥ 65 with acute coronary syndrome, revascularization, stable coronary artery disease, or heart valve replacement, recruited in eight European centres. Rates and factors determining offering, participation, and adherence to CR programmes and compliance with training sessions were studied across centres, under consideration of extensive-outpatient vs. intensive-inpatient programmes. Three thousand, four hundred, and seventy-one patients were included in the offering and participation analysis. Cardiac rehabilitation was offered to 80.8% of eligible patients, formal contraindications being the main reason for not offering CR. Mean participation was 68.0%, with perceived lack of usefulness and transport issues being principal barriers. Mean adherence to CR programmes of participants in the EU-CaRE study (n = 1663) was 90.3%, with hospitalization/physical impairment as principal causes of dropout. Mean compliance with training sessions was 86.1%. Older age was related to lower offering and participation, and comorbidity was associated with lower offering, participation, adherence, and compliance. Intensive-inpatient programmes displayed higher adherence (97.1% vs. 85.9%, P < 0.001) and compliance (full compliance: 66.0% vs. 38.8%, P < 0.001) than extensive-outpatient programmes.
Conclusion 
In this European cohort of elderly patients, older age and comorbidity tackled patients\' referral and uptake of CR programmes. Intensive-inpatient CR programmes showed higher completion than extensive-outpatient CR programmes, suggesting this formula could suit some elderly patients.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 08 Feb 2021; epub ahead of print
González-Salvado V, Peña-Gil C, Lado-Baleato Ó, Cadarso-Suárez C, ... Prins L, González Juanatey JR
Eur J Prev Cardiol: 08 Feb 2021; epub ahead of print | PMID: 33558875
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Abstract

Antithrombotic therapy in patients undergoing transcatheter aortic valve replacement: the complexity of the elderly.

Bencivenga L, Sepe I, Palaia ME, Komici K, ... Femminella GD, Rengo G
Along with epidemiologic transitions of the global population, the burden of aortic stenosis (AS) is rapidly increasing and transcatheter aortic valve replacement (TAVR) has quickly spread; indeed, it is nowadays also employed in treating patients with AS at intermediate operative risk. Nonetheless, the less invasive interventional strategy still carries relevant issues concerning post-procedural optimal antithrombotic strategy, given the current indications provided by guidelines are not completely supported by evidence-based data. Geriatric patients suffer from high bleeding and thromboembolic risks, whose balance is particularly subtle due to the presence of concomitant conditions, such as atrial fibrillation and chronic kidney disease, that make the post-TAVR antithrombotic management particularly insidious. This scenario is further complicated by the lack of specific evidence regarding the \'real-life\' complex conditions typical of the geriatric syndromes, thus, the management of such a heterogeneous population, ranging from healthy ageing to frailty, is far from being defined. The aim of the present review is to summarize the critical points and the most updated evidence regarding the post-TAVR antithrombotic approach in the geriatric population, with a specific focus on the most frequent clinical settings.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur J Prev Cardiol: 22 Jan 2021; 28:87-97
Bencivenga L, Sepe I, Palaia ME, Komici K, ... Femminella GD, Rengo G
Eur J Prev Cardiol: 22 Jan 2021; 28:87-97 | PMID: 33624104
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Abstract

Associations between acute and long-term exposure to PM2.5 components and temperature with QT interval length in the VA Normative Aging Study.

Peralta AA, Schwartz J, Gold DR, Coull B, Koutrakis P
Aims
Our study adds to the sparse literature on the effect of multiple fine particulate matter (PM2.5) components on QT interval length, an outcome with high clinical relevance in vulnerable populations. To our knowledge, this is the first study to examine the association between spatiotemporally resolved exposures to PM2.5 components and QT interval length.
Methods and results
Among 578 men living in Eastern Massachusetts between 2000 and 2011, we utilized time-varying linear mixed-effects regressions with a random intercept to examine associations between acute (0-3 days), intermediate (4-28 days), and long-term (1 year) exposure to PM2.5 components, temperature, and heart-rate corrected QT interval (QTc). Each of the PM2.5 components and temperature was geocoded to the participant\'s residential address using validated ensemble and hybrid exposure models and gridMET predictions. We also evaluated whether diabetic status modified the association between PM2.5 components and QTc interval. We found consistent results that higher sulfate levels and colder temperatures were associated with significant longer QTc across all moving averages except the day of exposure. The greatest effect of sulfate and temperature was detected for the 28-day moving average. In the multi-pollutant model, each 1.5 µg/m3 IQR increase in daily sulfate was associated with a 15.1 ms [95% confidence interval (CI): 10.2-20.0] increase in QTc interval and in the single-pollutant models a 15.3 ms (95% CI: 11.6-19.1) increase in QTc interval. Other secondary particles, such as nitrate and organic carbon, also prolonged QT interval, while elemental carbon decreased QT interval. We found that diabetic status did not modify the association between PM2.5 components and QTc interval.
Conclusion
Acute and long-term exposure to PM2.5 components and temperature are associated with changes in ventricular repolarization as measured by QT interval.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur J Prev Cardiol: 19 Jan 2021; epub ahead of print
Peralta AA, Schwartz J, Gold DR, Coull B, Koutrakis P
Eur J Prev Cardiol: 19 Jan 2021; epub ahead of print | PMID: 33580791
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This program is still in alpha version.