Journal: Eur J Prev Cardiol

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Abstract

Myocardial infarction and peripheral arterial disease: Treatment patterns and long-term outcome in men and women results from a Swedish nationwide study.

Sigvant B, Hasvold P, Thuresson M, Jernberg T, Janzon M, Nordanstig J
Background
Differences in comorbidity, pharmacotherapy, cardiovascular (CV) outcome, and mortality between myocardial infarction (MI) patients and peripheral arterial disease (PAD) patients are not well documented.
Aim
The aim of this study was to compare comorbidity, treatment patterns, CV outcome, and mortality in MI and PAD patients, focusing on sex differences.
Methods
This observational, population-based study used data retrieved from mandatory Swedish national registries. The risks of MI and death were assessed by Kaplan-Meier analysis. Secondary preventive drug use was characterized. Cox proportional risk hazard modelling was used to determine the risk of specific events.
Results
Overall, 91,808 incident MI patients and 52,408 PAD patients were included. CV mortality for MI patients at 12, 24, and 36 months after index was 12.3%, 19.3%, and 25.4%, and for PAD patients it was 15.5%, 23.4%, and 31.0%. At index, 89% of MI patients and 65% of PAD patients used aspirin and 74% and 53%, respectively, used statins. Unlike MI women, women with PAD had a lower rate of other CV-related comorbidities and a lower risk of CV events (age-adjusted hazard ratio 0.81, 95% confidence interval 0.79‒0.84), CV death (0.78, 0.75‒0.82), and all-cause death (0.78, 0.76‒0.80) than their PAD male counterparts.
Conclusion
PAD patients were less intensively treated and had a higher CV mortality than MI patients. Women with PAD were less likely than men to present with established polyvascular disease, whereas the opposite was true of women with MI. This result indicates that the lower-limb vasculature may more often be the index site for atherosclerosis in women.

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: 24 Oct 2021; 28:1426-1434
Sigvant B, Hasvold P, Thuresson M, Jernberg T, Janzon M, Nordanstig J
Eur J Prev Cardiol: 24 Oct 2021; 28:1426-1434 | PMID: 34695221
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Abstract

Association of short-term exposure to air pollution with myocardial infarction with and without obstructive coronary artery disease.

Ishii M, Seki T, Kaikita K, Sakamoto K, ... Kawakami K, JROAD Investigators
Background
Air pollution including particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) increases the risk of acute myocardial infarction. However, whether short-term exposure to PM2.5 triggers the onset of myocardial infarction with nonobstructive coronary arteries, compared with myocardial infarction with coronary artery disease, has not been elucidated. This study aimed to estimate the association between short-term exposure to PM2.5 and admission for acute myocardial infarction, myocardial infarction with coronary artery disease, and myocardial infarction with nonobstructive coronary arteries.
Design
This was a time-stratified case-crossover study and multicenter validation study.
Methods
This study used a nationwide administrative database in Japan between April 2012-March 2016. Of 137,678 acute myocardial infarction cases, 123,633 myocardial infarction with coronary artery disease and 14,045 myocardial infarction with nonobstructive coronary arteries were identified by a validated algorithm combined with International Classification of Disease (10th revision), diagnostic, and procedure codes. Air pollutants and meteorological data were obtained from the monitoring station nearest to the admitting hospital.
Results
In spring (March-May), the short-term increase of 10 µg/m3 in PM2.5 2 days before admission was significantly associated with admission for acute myocardial infarction, myocardial infarction with nonobstructive coronary arteries, and myocardial infarction with coronary artery disease after adjustment for meteorological variables (odds ratio 1.060, 95% confidence interval 1.038-1.082; odds ratio 1.151, 1.079-1.227; odds ratio 1.049, 1.026-1.073, respectively), while the association was not significant in other variables. These associations were also observed after adjustment for other co-pollutants. The risk for myocardial infarction with nonobstructive coronary arteries (vs myocardial infarction with coronary artery disease) was associated with an even lower concentration of PM2.5 under the current environmental standards.
Conclusions
This study showed the seasonal difference of acute myocardial infarction risk attributable to PM2.5 and the difference in the threshold of triggering the onset of acute myocardial infarction subtype.

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: 24 Oct 2021; 28:1435-1444
Ishii M, Seki T, Kaikita K, Sakamoto K, ... Kawakami K, JROAD Investigators
Eur J Prev Cardiol: 24 Oct 2021; 28:1435-1444 | PMID: 34695220
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Abstract

Extracellular vesicle species differentially affect endothelial cell functions and differentially respond to exercise training in patients with chronic coronary syndromes.

Kränkel N, Strässler E, Uhlemann M, Müller M, ... Möbius-Winkler S, Landmesser U
Background
Extracellular vesicles are released upon cellular activation and mediate inter-cellular communication. Individual species of extracellular vesicles might have divergent roles in vascular homeostasis and may show different responses to therapies such as exercise training.
Aims
We examine endothelial effects of medium-size and small extracellular vesicles from the same individual with or without chronic coronary syndrome, and in chronic coronary syndrome patients participating in a four-week high-intensity interval training intervention.
Methods
Human aortic endothelial cells were exposed to medium-size extracellular vesicles and small extracellular vesicles isolated from plasma samples of study participants. Endothelial cell survival, activation and re-endothelialisation capacity were assessed by respective staining protocols. Extracellular vesicles were quantified by nanoparticle tracking analysis and flow cytometry. Extracellular vesicle microRNA expression was quantified by realtime-quantitative polymerase chain reaction.
Results
In patients with chronic coronary syndrome (n = 25), plasma counts of leukocyte-derived medium-size extracellular vesicles were higher than in age-matched healthy controls (n = 25; p = 0.04) and were reduced by high-intensity interval training (n = 15; p = 0.01 vs baseline). Re-endothelialisation capacity was promoted by medium-size extracellular vesicles from controls, but not by medium-size extracellular vesicles from chronic coronary syndrome patients. High-intensity interval training for 4 weeks enhanced medium-size extracellular vesicle-mediated support of in vitro re-endothelialisation. Small extracellular vesicles from controls or chronic coronary syndrome patients increased endothelial cell death and reduced repair functions and were not affected by high-intensity interval training.
Conclusion
The present study demonstrates that medium-size extracellular vesicles and small extracellular vesicles differentially affect endothelial cell survival and repair responses. This equilibrium is unbalanced in patients with chronic coronary syndrome where leukocyte-derived medium-size extracellular vesicles are increased leading to a loss of medium-size extracellular vesicle-mediated endothelial repair. High-intensity interval training partially restored medium-size extracellular vesicle-mediated endothelial repair, underlining its use in cardiovascular prevention and therapy to improve endothelial function.

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: 24 Oct 2021; 28:1467-1474
Kränkel N, Strässler E, Uhlemann M, Müller M, ... Möbius-Winkler S, Landmesser U
Eur J Prev Cardiol: 24 Oct 2021; 28:1467-1474 | PMID: 34695219
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Abstract

Long-term cumulative blood pressure in young adults and incident heart failure, coronary heart disease, stroke, and cardiovascular disease: The CARDIA study.

Nwabuo CC, Appiah D, Moreira HT, Vasconcellos HD, ... Gidding SS, Lima JAC
Aims
Cumulative blood pressure (BP) is a measure that incorporates the severity and duration of BP exposure. The prognostic significance of cumulative BP in young adults for cardiovascular diseases (CVDs) in comparison to BP severity alone is, however, unclear.
Methods and results
We investigated 3667 Coronary Artery Risk Development in Young Adults participants who attended six visits over 15 years (year-0 (1985-1986), year-2, year-5, year-7, year-l0, and year-15 exams). Cumulative BP was calculated as the area under the curve (mmHg × years) from year 0 through year 15. Cox models assessed the association between cumulative BP (year 0 through year 15), current BP (year 15), and BP change (year 0 and year 15) and CVD outcomes. Mean (standard deviation) age at year 15 was 40.2 (3.6) years, 44.1% were men, and 44.1% were African-American. Over a median follow-up of 16 years, there were 47 heart failure (HF), 103 coronary heart disease (CHD), 71 stroke, and 191 CVD events. Cumulative systolic BP (SBP) was associated with HF (hazard ratio (HR) = 2.14 (1.58-2.90)), CHD (HR = 1.49 (1.19-1.87)), stroke (HR = 1.81 (1.38-2.37)), and CVD (HR = 1.73 (1.47-2.05)). For CVD, the C-statistic for SBP (year 15) was 0.69 (0.65-0.73) and change in C-statistic with the inclusion of SBP change and cumulative SBP was 0.60 (0.56-0.65) and 0.72 (0.69-0.76), respectively. For CVD, using year-15 SBP as a reference, the net reclassification index (NRI) for cumulative SBP was 0.40 (p < 0.0001) and the NRI for SBP change was 0.22 (p = 0.001).
Conclusions
Cumulative BP in young adults was associated with the subsequent risk of HF, CHD, stroke, and CVD. Cumulative BP provided incremental prognostic value and improved risk reclassification for CVD, when compared to single BP assessments or changes in BP.

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: 24 Oct 2021; 28:1445-1451
Nwabuo CC, Appiah D, Moreira HT, Vasconcellos HD, ... Gidding SS, Lima JAC
Eur J Prev Cardiol: 24 Oct 2021; 28:1445-1451 | PMID: 34695218
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Abstract

Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease.

Bouabdallaoui N, Messas N, Greenlaw N, Ferrari R, ... Tardif JC, CLARIFY Investigators
Aims
Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the \'smoker\'s paradox\' suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease.
Methods
The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers.
Results
Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p < 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p < 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p < 0.05).
Conclusion
In contrast to the \'smoker\'s paradox\', current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).

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: 24 Oct 2021; 28:1460-1466
Bouabdallaoui N, Messas N, Greenlaw N, Ferrari R, ... Tardif JC, CLARIFY Investigators
Eur J Prev Cardiol: 24 Oct 2021; 28:1460-1466 | PMID: 34695217
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Abstract

Impact of environmental pollution and weather changes on the incidence of ST-elevation myocardial infarction.

Biondi-Zoccai G, Frati G, Gaspardone A, Mariano E, ... Romeo F, Versaci F
Background
Environmental pollution and weather changes unfavorably impact on cardiovascular disease. However, limited research has focused on ST-elevation myocardial infarction (STEMI), the most severe yet distinctive form of acute coronary syndrome.
Methods and results
We appraised the impact of environmental and weather changes on the incidence of STEMI, analysing the bivariate and multivariable association between several environmental and atmospheric parameters and the daily incidence of STEMI in two large Italian urban areas. Specifically, we appraised: carbon monoxide (CO), nitrogen dioxide (NO2), nitric oxide (NOX), ozone, particulate matter smaller than 10 μm (PM10) and than 2.5 μm (PM2.5), temperature, atmospheric pressure, humidity and rainfall. A total of 4285 days at risk were appraised, with 3473 cases of STEMI. Specifically, no STEMI occurred in 1920 (44.8%) days, whereas one or more occurred in the remaining 2365 (55.2%) days. Multilevel modelling identified several pollution and weather predictors of STEMI. In particular, concentrations of CO (p = 0.024), NOX (p = 0.039), ozone (p = 0.003), PM10 (p = 0.033) and PM2.5 (p = 0.042) predicted STEMI as early as three days before the event, as well as subsequently, and NO predicted STEMI one day before (p = 0.010), as well as on the same day. A similar predictive role was evident for temperature and atmospheric pressure (all p < 0.05).
Conclusions
The risk of STEMI is strongly associated with pollution and weather features. While causation cannot yet be proven, environmental and weather changes could be exploited to predict STEMI risk in the following days.

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: 24 Oct 2021; 28:1501-1507
Biondi-Zoccai G, Frati G, Gaspardone A, Mariano E, ... Romeo F, Versaci F
Eur J Prev Cardiol: 24 Oct 2021; 28:1501-1507 | PMID: 34695216
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Abstract

European Society of Cardiology Quality Indicators for Cardiovascular Disease Prevention: developed by the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with the European Association for Preventive Cardiology of the European Society of Cardiology.

Aktaa S, Gencer B, Arbelo E, Davos CH, ... Visseren FLJ, Gale CP
Aims
To develop a set of quality indicators (QIs) for the evaluation of the care and outcomes for atherosclerotic cardiovascular disease (ASCVD) prevention.
Methods and results
The Quality Indicator Committee of the European Society of Cardiology (ESC) formed the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with Task Force members of the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice and the European Association of Preventive Cardiology (EAPC). We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for ASCVD prevention by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. In total, 17 main and 14 secondary QIs were selected across six domains of care for ASCVD prevention: (i) structural framework, (ii) risk assessment, (iii) care for people at risk for ASCVD, (iv) care for patients with established ASCVD, (v) patient education and experience, and (vi) outcomes.
Conclusion
We present the 2021 ESC QIs for Cardiovascular Disease Prevention, which have been co-constructed with EAPC using the ESC methodology for QI development. These indicators are supported by evidence from the literature, underpinned by expert consensus and aligned with the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice to offer a mechanism for the evaluation of ASCVD prevention care and outcomes.

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 Oct 2021; epub ahead of print
Aktaa S, Gencer B, Arbelo E, Davos CH, ... Visseren FLJ, Gale CP
Eur J Prev Cardiol: 22 Oct 2021; epub ahead of print | PMID: 34687540
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Abstract

Combined assessment of stress cardiovascular magnetic resonance and angiography to predict the effect of revascularization in chronic coronary syndrome patients.

Gavara J, Perez N, Marcos-Garces V, Monmeneu JV, ... Chorro FJ, Bodi V
Aims
The role of revascularization in chronic coronary syndrome (CCS) and the value of ischaemia vs. anatomy to guide decision-making are in constant debate. We explored the potential of a combined assessment of ischaemic burden by vasodilator stress cardiovascular magnetic resonance (CMR) and presence of multivessel disease by angiography to predict the effect of revascularization on all-cause mortality in CCS.
Methods and results
The study group comprised 1066 CCS patients submitted to vasodilator stress CMR pre-cardiac catheterization (mean age 66 ± 11 years, 69% male). Stress CMR-derived ischaemic burden (extensive if >5 ischaemic segments) and presence of multivessel disease in angiography (two- or three-vessel or left main stem disease) were computed. The influence of revascularization on all-cause mortality was explored and adjusted hazard ratios (HRs) with the corresponding 95% confidence intervals were obtained. During a median 7.51-year follow-up, 557 (52%) CMR-related revascularizations and 308 (29%) deaths were documented. Revascularization exerted a neutral effect on all-cause mortality in the whole study group [HR 0.94 (0.74-1.19), P = 0.6], in patients without multivessel disease [n = 598, 56%, HR 1.12 (0.77-1.62), P = 0.6], and in those with multivessel disease without extensive ischaemic burden [n = 181, 17%, HR 1.66 (0.91-3.04), P = 0.1]. However, compared to non-revascularized patients, revascularization significantly reduced all-cause mortality in patients with simultaneous multivessel disease and extensive ischaemic burden (n = 287, 27%): 3.77 vs. 7.37 deaths per 100 person-years, HR 0.60 (0.40-0.90), P = 0.01.
Conclusions
In patients with CCS submitted to catheterization, evidence of simultaneous extensive CMR-related ischaemic burden and multivessel disease identifies the subset in whom revascularization can reduce all-cause mortality.

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 Oct 2021; epub ahead of print
Gavara J, Perez N, Marcos-Garces V, Monmeneu JV, ... Chorro FJ, Bodi V
Eur J Prev Cardiol: 22 Oct 2021; epub ahead of print | PMID: 34686874
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Abstract

Combinations of BMI and cardiorespiratory fitness categories: trends between 1995 and 2020 and associations with CVD incidence and mortality and all-cause mortality in 471 216 adults.

Hemmingsson E, Väisänen D, Andersson G, Wallin P, Ekblom-Bak E
Aims
To describe time trends in combinations of cardiorespiratory fitness (CRF) and body mass index (BMI) status, and to analyse their associations with cardiovascular disease (CVD) incidence and mortality and all-cause mortality.
Methods and results
Prospective cohort study with data from occupational health screenings in Swedish employees, including n = 471 216 (aged 18-74 years) between 1995 and 2020, and n = 169 989 in risk analyses. Cardiorespiratory fitness was estimated from a submaximal cycle test. High CRF was defined as top quartile, and low CRF as bottom quartile. Body mass index was used to define normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥30 kg/m2). Outcome data (CVD incidence and mortality, all-cause mortality) were obtained from national registers. From 1995 to 2020, the combination of obesity + low CRF increased from 2.1% to 5.3% (relative increase 154%) whereas the combination of normal weight + high CRF decreased from 13.2% to 9.3% (-30%) (both P < 0.001). Negative changes were more pronounced in men, younger ages, and non-university educated. At the end of the period, prevalence of obesity + low CRF were higher in men vs. women (3.1% vs. 2.2%), older vs. younger (3.7% vs. 1.7%), and in non-university vs. university educated (5.0% vs. 0.3%), all P-value <0.001. Having a high CRF attenuated the risk of all three outcomes in all BMI categories, especially in individuals with obesity (hazard ratio 3.90 vs. 6.67 for CVD mortality). Both a low BMI and a high CRF prolonged age of onset for all three outcomes.
Conclusions
The combination of obesity with low CRF has increased markedly since the mid-90s, with clear implications for increased CVD morbidity and mortality, and all-cause mortality.

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

Eur J Prev Cardiol: 19 Oct 2021; epub ahead of print
Hemmingsson E, Väisänen D, Andersson G, Wallin P, Ekblom-Bak E
Eur J Prev Cardiol: 19 Oct 2021; epub ahead of print | PMID: 34669922
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Abstract

Maternal hypercholesterolaemia during pregnancy affects severity of myocardial infarction in young adults.

Cacciatore F, Bruzzese G, Abete P, Russo G, Palinski W, Napoli C
Aims
Elevated maternal cholesterol during pregnancy (MCP) enhances atherogenesis in childhood, but its possible impact on acute myocardial infarction (AMI) in adults is unknown.
Methods and results
We retrospectively evaluated 310 patients who were admitted to hospital and whose MCP data were retrievable. Eighty-nine AMI patients with typical chest pain, transmural infarction Q-waves, elevated creatinine kinase, and 221 controls hospitalized for other reasons were identified. The AMI cohort was classified by MI severity (severe = involving three arteries, left ventricle ejection fraction ≤35, CK-peak >1200 mg/dL, or CK-MB >200 mg/dL). The association of MCP with AMI severity was tested by linear and multiple regression analysis that included conventional cardiovascular risk factors, gender, age, and treatment. Associations of MCP with body mass index (BMI) in patients were assessed by linear correlation. In the AMI cohort, MCP correlated with four measures of AMI severity: number of vessels (β = 0.382, P = 0.001), ejection fraction (β = -0.315, P = 0.003), CK (β = 0.260, P = 0.014), and CK-MB (β = 0.334, P = 0.001), as well as survival time (β = -0.252, P = 0.031). In multivariate analysis of patients stratified by AMI severity, MCP predicted AMI severity independently of age, gender, BMI, and CHD risk factors (odds ratio = 1.382, 95% confidence interval 1.046-1.825; P = 0.023). Survival was affected mainly by AMI severity.
Conclusions
Maternal cholesterol during pregnancy is associated with adult BMI, atherosclerosis-related risk, and severity of AMI.

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: 17 Oct 2021; epub ahead of print
Cacciatore F, Bruzzese G, Abete P, Russo G, Palinski W, Napoli C
Eur J Prev Cardiol: 17 Oct 2021; epub ahead of print | PMID: 34662903
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Abstract

Estimation of LDL cholesterol in chronic kidney disease.

Bauer F, Seibert FS, Rohn B, Babel N, Westhoff TH
Aims 
Most of the laboratories make use of the Friedewald formula to assess low-density lipoprotein cholesterol (LDL-C). The accuracy of this approach, however, crucially depends on triglyceride concentrations. Since hypertriglyceridaemia is a characteristic trait of the lipid profile in chronic kidney disease (CKD), the present study examines the accuracy of the Friedewald formula in this population. It aims to derive and validate a more accurate equation for CKD.
Methods 
Cross-sectional study on two cohorts of subjects (overall n = 3.514) with estimated glomerular filtration rate (eGFR) <60 mL/min comparing directly measured LDL-C (LDL-Cmeas) as assessed by an enzymatic assay (Roche, Switzerland) to concentrations estimated by the Friedewald (LDL-CF) and the Martin\'s formula (LDL-CM). Accuracy was analysed by Bland-Altman and linear regression analyses. In the first cohort, a novel formula was derived to assess LDL-C in CKD. The formula was validated in Cohort 2.
Results 
Cohort 1 comprised 1738 subjects, and Cohort 2 comprised 1776 subjects. The mean eGFR was 29.4 ± 14.4 mL/min. In Cohort 1, LDL-CF was highly correlated with LDL-Cmeas (R2 = 0.92) but significantly underestimated LDLmeas by 11 mg/dL. LDL-C = cholesterol - HDL - triglycerides/7.98 was derived as the optimal equation for the calculation of LDL-C in Cohort 1 and was successfully validated in Cohort 2 (bias of 1.6 mg/dL). The novel formula had a higher accuracy than both the Friedewald (bias -12.2 mg/dL) and the Martin\'s formula (bias -4.8 mg/dL).
Conclusion 
The Friedewald formula yields lower LDL-C concentrations in CKD than direct enzymatic measurements, which may lead to undersupply of this cardiovascular high-risk population in a treat-to-target approach.

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: 12 Oct 2021; 28:1402-1408
Bauer F, Seibert FS, Rohn B, Babel N, Westhoff TH
Eur J Prev Cardiol: 12 Oct 2021; 28:1402-1408 | PMID: 33624033
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Abstract

Hospitalizations for cardiovascular diseases attributable to tobacco smoking in France in 2015.

Bonaldi C, Pasquereau A, Hill C, Thomas D, ... Thanh VN, Olié V
Aims
Tobacco smoking is a major risk factor for many cardiovascular diseases. In France, the daily smoking prevalence is among the highest in high-income European countries. This study estimated the number of hospitalizations for cardiovascular diseases attributable to smoking in France in 2015, and the number of stays that could have been avoided if there had been 10% less current smokers or if the prevalence of current smokers had been 20%.
Methods
Age- and sex-specific attributable fractions were calculated by combining relative risks extracted from the literature with the prevalence of smoking estimated in the 2014 Health Barometer, a national representative survey. These fractions were applied to hospitalization stays with a primary diagnosis for a cardiovascular disease whose risk is known to increase with smoking.
Results
In France in 2015, 250,813 hospital stays (95% uncertainty interval=234,869-269,807) related to a cardiovascular condition were estimated as attributable to smoking. This represented 21% of all stays for a cardiovascular condition. Ischemic heart disease accounted for the largest share of smoking-related stays (39%). If the number of current smokers had been 10% lower or if the prevalence of smoking in the population had dropped to below 20%, 5867 stays and 25,911 stays, respectively, would have been prevented.
Conclusions
In France, a large number of hospital stays for cardiovascular disease are attributable to tobacco smoking. A 10% reduction in smoking would avoid nearly 6000 hospital stays per year; more than 25,000 annual hospital stays if only 20% of the French population smoked.

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: 12 Oct 2021; 28:1327-1333
Bonaldi C, Pasquereau A, Hill C, Thomas D, ... Thanh VN, Olié V
Eur J Prev Cardiol: 12 Oct 2021; 28:1327-1333 | PMID: 34647590
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Abstract

Physical activity attenuates cardiovascular risk and mortality in men and women with and without the metabolic syndrome - a 20-year follow-up of a population-based cohort of 60-year-olds.

Ekblom-Bak E, Halldin M, Vikström M, Stenling A, ... Leander K, Hellénius ML
Aims
The purpose of this study was to analyse the association of leisure-time physical activity of different intensities at baseline, and cardiovascular disease incidence, cardiovascular disease mortality and all-cause mortality in a population-based sample of 60-year-old men and women with and without established metabolic syndrome, for more than 20 years of follow-up. A secondary aim was to study which cardiometabolic factors may mediate the association between physical activity and long-term outcomes.
Methods
A total of 3693 participants (53% women) underwent physical examination and laboratory tests, completed an extensive questionnaire at baseline 1997-1999 and were followed until their death or until 31 December 2017. First-time cardiovascular disease events and death from any cause were ascertained through regular examinations of national registers.
Results
Metabolic syndrome prevalence was 23.0%. In metabolic syndrome participants, light physical activity attenuated cardiovascular disease incidence (hazard ratio = 0.71; 95% confidence interval 0.50-1.00) compared to sedentary (reference) after multi-adjustment. Moderate/high physical activity was inversely associated with both cardiovascular disease and all-cause mortality, but became non-significant after multi-adjustment. Sedentary non-metabolic syndrome participants had lower cardiovascular disease incidence (0.47; 0.31-0.72) but not significantly different cardiovascular disease (0.61; 0.31-1.19) and all-cause mortality (0.92; 0.64-1.34) compared to sedentary metabolic syndrome participants. Both light and moderate/high physical activity were inversely associated with cardiovascular disease and all-cause mortality in non-metabolic syndrome participants (p<0.05). There were significant variations in several central cardiometabolic risk factors with physical activity level in non-metabolic syndrome participants. Fibrinogen mediated the protective effects of physical activity in non-metabolic syndrome participants.
Conclusion
Physical activity of different intensities attenuated cardiovascular risk and mortality in 60-year old men and women with metabolic syndrome during a 20-year follow-up.

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

Eur J Prev Cardiol: 12 Oct 2021; 28:1376-1385
Ekblom-Bak E, Halldin M, Vikström M, Stenling A, ... Leander K, Hellénius ML
Eur J Prev Cardiol: 12 Oct 2021; 28:1376-1385 | PMID: 34647588
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Abstract

Heritability of a resting heart rate in a 20-year follow-up family cohort with GWAS data: Insights from the STANISLAS cohort.

Xhaard C, Dandine-Roulland C, Villemereuil P, Floch EL, ... Rossignol P, Girerd N
Background
The association between resting heart rate (HR) and cardiovascular outcomes, especially heart failure, is now well established. However, whether HR is mainly an integrated marker of risk associated with other features, or rather a genetic origin risk marker, is still a matter for debate. Previous studies reported a heritability ranging from 14% to 65%.
Design
We assessed HR heritability in the STANISLAS family-study, based on the data of four visits performed over a 20-year period, and adjusted for most known confounding effects.
Methods
These analyses were conducted using a linear mixed model, adjusted on age, sex, tea or coffee consumption, beta-blocker use, physical activity, tobacco use, and alcohol consumption to estimate the variance captured by additive genetic effects, via average information restricted maximum likelihood analysis, with both self-reported pedigree and genetic relatedness matrix (GRM) calculated from genome-wide association study data.
Results
Based on the data of all visits, the HR heritability (h2) estimate was 23.2% with GRM and 24.5% with pedigree. However, we found a large heterogeneity of HR heritability estimations when restricting the analysis to each of the four visits (h2 from 19% to 39% using pedigree, and from 14% to 32% using GRM). Moreover, only a little part of variance was explained by the common household effect (<5%), and half of the variance remained unexplained.
Conclusion
Using a comprehensive analysis based on a family cohort, including the data of multiple visits and GRM, we found that HR variability is about 25% from genetic origin, 25% from repeated measures and 50% remains unexplained.

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: 12 Oct 2021; 28:1334-1341
Xhaard C, Dandine-Roulland C, Villemereuil P, Floch EL, ... Rossignol P, Girerd N
Eur J Prev Cardiol: 12 Oct 2021; 28:1334-1341 | PMID: 34647585
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Abstract

Age- and gender-specific upper limits and reference equations for workload-indexed systolic blood pressure response during bicycle ergometry.

Hedman K, Lindow T, Elmberg V, Brudin L, Ekström M
Background
Guidelines recommend considering workload in interpretation of the systolic blood pressure (SBP) response to exercise, but reference values are lacking.
Design
This was a retrospective, consecutive cohort study.
Methods
From 12,976 subjects aged 18-85 years who performed a bicycle ergometer exercise test at one centre in Sweden during the years 2005-2016, we excluded those with prevalent cardiovascular disease, comorbidities, cardiac risk factors or medications. We extracted SBP, heart rate and workload (watt) from ≥ 3 time points from each test. The SBP/watt-slope and the SBP/watt-ratio at peak exercise were calculated. Age- and sex-specific mean values, standard deviations and 90th and 95th percentiles were determined. Reference equations for workload-indexed and peak SBP were derived using multiple linear regression analysis, including sex, age, workload, SBP at rest and anthropometric variables as predictors.
Results
A final sample of 3839 healthy subjects (n = 1620 female) were included. While females had lower mean peak SBP than males (188 ± 24 vs 202 ± 22 mmHg, p < 0.001), workload-indexed SBP measures were markedly higher in females; SBP/watt-slope: 0.52 ± 0.21 versus 0.41 ± 0.15 mmHg/watt (p < 0.001); peak SBP/watt-ratio: 1.35 ± 0.34 versus 0.90 ± 0.21 mmHg/watt (p < 0.001). Age, sex, exercise capacity, resting SBP and height were significant predictors of the workload-indexed SBP parameters and were included in the reference equations.
Conclusions
These novel reference values can aid clinicians and exercise physiologists in interpreting the SBP response to exercise and may provide a basis for future research on the prognostic impact of exercise SBP. In females, a markedly higher SBP in relation to workload could imply a greater peripheral vascular resistance during exercise than in males.

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

Eur J Prev Cardiol: 12 Oct 2021; 28:1360-1369
Hedman K, Lindow T, Elmberg V, Brudin L, Ekström M
Eur J Prev Cardiol: 12 Oct 2021; 28:1360-1369 | PMID: 34647584
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Abstract

Obesity, overweight and risk for cardiovascular disease and mortality in young women.

Dikaiou P, Björck L, Adiels M, Lundberg CE, ... Manhem K, Rosengren A
Aims
The aim of this study was to investigate the relation between body mass index (BMI) in young women, using weight early in pregnancy as a proxy for pre-pregnancy weight, and risk for early cardiovascular disease (CVD) and mortality.
Methods and results
In this prospective, registry-based study, we used weight data in early pregnancy from women, registered in the Swedish Medical Birth Registry, and who gave birth between 1982 and 2014 (n = 1,495,499; median age 28.3 years). Of the women, 118,212 (7.9%) were obese (BMI ≥ 30 kg/m2) and 29,630 (2.0%) severely obese (BMI ≥ 35 kg/m2). After a follow-up of median 16.3 years, we identified 3295 and 4375 cases of acute myocardial infarction (AMI) and ischemic stroke (IS) corresponding to 13.4 and 17.8 per 100,000 observation years, respectively, occurring at mean ages of 49.8 and 47.3 years. Compared to women with a BMI 20-<22.5 kg/m2, the hazard ratio (HR) of AMI increased with higher BMI from 1.40 (95% confidence interval (CI) 1.27-1.54) among women with BMI 22.5-<25.0 kg/m2 to 4.71 (95% CI 3.88-5.72) among women with severe obesity, with similar findings for IS and CVD death, after adjustment for age, pregnancy year, parity and comorbidities at baseline. Women with BMI 30-<35.0 and ≥35 kg/m2 had increased all-cause mortality with adjusted HR 1.53 (95% CI 1.43-1.63) and 1.83 (95% CI 1.63-2.05), respectively.
Conclusion
A significant increase in the risk for early AMI, IS and CVD death was noticeable in overweight young women, with a marked increase in obese women.

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

Eur J Prev Cardiol: 12 Oct 2021; 28:1351-1359
Dikaiou P, Björck L, Adiels M, Lundberg CE, ... Manhem K, Rosengren A
Eur J Prev Cardiol: 12 Oct 2021; 28:1351-1359 | PMID: 34647583
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Abstract

Leisure time physical activity is associated with improved HDL functionality in high cardiovascular risk individuals: a cohort study.

Hernáez Á, Soria-Florido MT, Castañer O, Pintó X, ... Fitó M, Lassale C
Aims
Physical activity has consistently been shown to improve cardiovascular health and high-density lipoprotein-cholesterol levels. However, only small and heterogeneous studies have investigated the effect of exercise on high-density lipoprotein functions. Our aim is to evaluate, in the largest observational study to date, the association between leisure time physical activity and a range of high-density lipoprotein functional traits.
Methods
The study sample consisted of 296 Spanish adults at high cardiovascular risk. Usual leisure time physical activity and eight measures of high-density lipoprotein functionality were averaged over two measurements, one year apart. Multivariable linear regression models were used to explore the association between leisure time physical activity (exposure) and each high-density lipoprotein functional trait (outcome), adjusted for cardiovascular risk factors.
Results
Higher levels of leisure time physical activity were positively and linearly associated with average levels over one year of plasma high-density lipoprotein-cholesterol and apolipoprotein A-I, paraoxonase-1 antioxidant activity, high-density lipoprotein capacity to esterify cholesterol and cholesterol efflux capacity in individuals free of type 2 diabetes only. The increased cholesterol esterification index with increasing leisure time physical activity reached a plateau at around 300 metabolic equivalents.min/day. In individuals with diabetes, the relationship with cholesteryl ester transfer protein followed a U-shape, with a decreased cholesteryl ester transfer protein activity from 0 to 300 metabolic equivalents.min/day, but increasing from there onwards. Increasing levels of leisure time physical activity were associated with poorer high-density lipoprotein vasodilatory capacity.
Conclusions
In a high cardiovascular risk population, leisure time physical activity was associated not only with greater circulating levels of high-density lipoprotein-cholesterol, but also with better markers of high-density lipoprotein functionality, namely cholesterol efflux capacity, the capacity of high-density lipoprotein to esterify cholesterol and paraoxonase-1 antioxidant activity in individuals free of diabetes and lower cholesteryl ester transfer protein activity in individuals with type 2 diabetes.

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: 12 Oct 2021; 28:1392-1401
Hernáez Á, Soria-Florido MT, Castañer O, Pintó X, ... Fitó M, Lassale C
Eur J Prev Cardiol: 12 Oct 2021; 28:1392-1401 | PMID: 34647580
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Abstract

Abdominal aortic calcification: from ancient friend to modern foe.

Bartstra JW, Mali WPTM, Spiering W, de Jong PA
Background
Abdominal aortic calcifications were already ubiquitous in ancient populations from all continents. Although nowadays generally considered as an innocent end stage of stabilised atherosclerotic plaques, increasing evidence suggests that arterial calcifications contribute to cardiovascular risk. In this review we address abdominal aortic calcification from an evolutionary perspective and review the literature on histology, prevalence, risk factors, clinical outcomes and pharmacological interventions of abdominal aortic calcification.
Design
The design of this study was based on a literature review.
Methods
Pubmed and Embase were systematically searched for articles on abdominal aortic calcification and its synonyms without language restrictions. Articles with data on histology, prevalence, risk factors clinical outcomes and/or pharmacological interventions were selected.
Results
Abdominal aortic calcification is highly prevalent in the general population and prevalence and extent increase with age. Prevalence and risk factors differ between males and females and different ethnicities. Risk factors include traditional cardiovascular risk factors and decreased bone mineral density. Abdominal aortic calcification is shown to contribute to arterial stiffness and is a strong predictor of cardiovascular events and mortality. Several therapies to inhibit arterial calcification have been developed and investigated in small clinical trials.
Conclusions
Abdominal aortic calcification is from all eras and increasingly acknowledged as an independent contributor to cardiovascular disease. Large studies with long follow-up must be carried out to show whether inhibition of abdominal aortic calcification will further reduce cardiovascular risk.

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

Eur J Prev Cardiol: 12 Oct 2021; 28:1386-1391
Bartstra JW, Mali WPTM, Spiering W, de Jong PA
Eur J Prev Cardiol: 12 Oct 2021; 28:1386-1391 | PMID: 34647579
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Abstract

Finding very high lipoprotein(a): the need for routine assessment.

Nurmohamed NS, Kaiser Y, Schuitema PCE, Ibrahim S, ... Knaapen P, Stroes ESG
Aims
To validate the reported increased atherosclerotic cardiovascular disease (ASCVD) risk associated with very high lipoprotein(a) [Lp(a)] and to investigate the impact of routine Lp(a) assessment on risk reclassification.
Methods and results
We performed a cross-sectional case-control study in the Amsterdam UMC, a tertiary hospital in The Netherlands. All patients in whom a lipid blood test was ordered between October 2018 and October 2019 were included. Individuals with Lp(a) >99th percentile were age and sex matched to individuals with Lp(a) ≤20th percentile. We computed odds ratios (ORs) for myocardial infarction (MI) and ASCVD using multivariable logistic regression adjusted for age, sex, and systolic blood pressure. Furthermore, we assessed the additive value of Lp(a) to established ASCVD risk algorithms. Lipoprotein(a) levels were determined in 12 437 individuals, out of whom 119 cases [Lp(a) >99th percentile; >387.8 nmol/L] and 119 matched controls [Lp(a) ≤20th percentile; ≤7 nmol/L] were included. Mean age was 58 ± 15 years, 56.7% were female, and 30.7% had a history of ASCVD. Individuals with Lp(a) levels >99th percentile had an OR of 2.64 for ASCVD [95% confidence interval (CI) 1.45-4.89] and 3.39 for MI (95% CI 1.56-7.94). Addition of Lp(a) to ASCVD risk algorithms led to 31% and 63% being reclassified into a higher risk category for Systematic Coronary Risk Evaluation (SCORE) and Second Manifestations of ARTerial disease (SMART), respectively.
Conclusion
The prevalence of ASCVD is nearly three-fold higher in adults with Lp(a) >99th percentile compared with matched subjects with Lp(a) ≤20th percentile. In individuals with very high Lp(a), addition of Lp(a) resulted in one-third of patients being reclassified in primary prevention, and over half being reclassified in secondary 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: 10 Oct 2021; epub ahead of print
Nurmohamed NS, Kaiser Y, Schuitema PCE, Ibrahim S, ... Knaapen P, Stroes ESG
Eur J Prev Cardiol: 10 Oct 2021; epub ahead of print | PMID: 34632502
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Abstract

Cardiovascular health, genetic predisposition, and lifetime risk of type 2 diabetes.

Wang K, Kavousi M, Voortman T, Ikram MA, Ghanbari M, Ahmadizar F
Aims
Data on the lifetime risk of type 2 diabetes (T2D) incidence across different cardiovascular health (CVH) categories are scarce. Moreover, it remains unclear whether a genetic predisposition modifies this association.
Methods and results
Using data from the prospective population-based Rotterdam Study, a CVH score (body mass index, blood pressure, total cholesterol, smoking status, diet, and physical activity) was calculated and further categorized at baseline. Genetic predisposition to T2D was assessed and divided into tertiles by creating a genetic risk score (GRS). We estimated the lifetime risk for T2D within different CVH and GRS categories. Among 5993 individuals free of T2D at baseline [mean (standard deviation) age, 69.1 (8.5) years; 58% female], 869 individuals developed T2D during follow-up. At age 55 years, the remaining lifetime risk of T2D was 22.6% (95% CI: 19.4-25.8) for ideal, 28.3% (25.8-30.8) for intermediate, and 32.6% (29.0-36.2) for poor CVH. After further stratification by GRS tertiles, the lifetime risk for T2D was still the lowest for ideal CVH in the lowest GRS tertiles [21.5% (13.7-29.3)], in the second GRS tertile [20.8% (15.9-25.8)], and in the highest tertile [23.5% (18.5-28.6)] when compared with poor and intermediate CVH.
Conclusion
Our results highlight the importance of favourable CVH in preventing T2D among middle-aged individuals regardless of their genetic predisposition.

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

Eur J Prev Cardiol: 27 Sep 2021; epub ahead of print
Wang K, Kavousi M, Voortman T, Ikram MA, Ghanbari M, Ahmadizar F
Eur J Prev Cardiol: 27 Sep 2021; epub ahead of print | PMID: 34583386
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Abstract

Trends in peripheral arterial disease incidence and mortality in EU15+ countries 1990-2017.

Goodall R, Salciccioli JD, Davies AH, Marshall D, Shalhoub J
Aims
The aim was to assess trends in peripheral arterial disease (PAD) incidence and mortality rates in European Union(15+) countries between 1990 and 2017.
Methods and results
This observational study used data obtained from the 2017 Global Burden of Disease study. Age-standardised mortality and incidence rates from PAD were extracted from the Global Health Data Exchange for EU15+ countries for the years 1990-2017. Trends were analysed using Joinpoint regression analysis.Between 1990 and 2017, the incidence of PAD decreased in all 19 EU15+ countries for females, and in 18 of 19 countries for males. Increasing PAD incidence was observed only for males in the United States (+1.4%). In 2017, the highest incidence rates were observed in Denmark and the United States for males (213.6 and 202.3 per 100,000, respectively) and in the United States and Canada for females (194.8 and 171.1 per 100,000, respectively). There was a concomitant overall trend for increasing age-standardised mortality rates in all EU15+ countries for females, and in 16 of 19 EU15+ countries for males between 1990 and 2017. Italy (-25.1%), Portugal (-1.9%) and Sweden (-0.6%) were the only countries with reducing PAD mortality rates in males. The largest increases in mortality rates were observed in the United Kingdom (males +140.4%, females +158.0%) and the United States (males +125.7%, females +131.2%).
Conclusions
We identify shifting burden of PAD in EU15+ countries, with increasing mortality rates despite reducing incidence. Strong evidence supports goal-directed medical therapy in reducing PAD mortality - population-wide strategies to improve compliance to optimal goal-directed medical therapy are warranted.

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 Sep 2021; 28:1201-1213
Goodall R, Salciccioli JD, Davies AH, Marshall D, Shalhoub J
Eur J Prev Cardiol: 19 Sep 2021; 28:1201-1213 | PMID: 34551087
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Abstract

Residential greenness and increased physical activity in patients after coronary artery bypass graft surgery.

Sadeh M, Brauer M, Chudnovsky A, Ziv A, Dankner R
Aims
Physical activity is a fundamental component of rehabilitation following coronary artery bypass (CABG) surgery. Proximity to neighbourhood green spaces may encourage physical activity. We investigated the association between residential greenness and exercise-related physical activity post-CABG surgery.
Methods
Participants in a prospective cohort study of 846 patients (78% men) who underwent CABG surgery at seven cardiothoracic units during the time period 2004-2007 were interviewed regarding their physical activity habits one day before and one year after surgery. Exposure to residential neighbourhood greenness (within a 300 m buffer around their place of residence) was measured using the Normalized Difference Vegetative Index. Participation in exercise-related physical activity (yes/no), weekly duration of exercise-related physical activity and the change in exercise-related physical activity between baseline and follow-up were examined for associations with residential greenness, adjusting for socio-demographic factors, propensity score adjusted participation in cardiac rehabilitation and health-related covariates after multiple imputation for missing variables.
Results
Living in a higher quartile of residential greenness was associated with a 52% greater odds of being physically active (OR 1.52, 95% CI 1.22-1.90). This association persisted only (OR 1.75, 95% CI 1.35-2.27) among patients who did not participate in cardiac rehabilitation following surgery and was stronger in women (OR 2.38, 95% CI 1.40-4.07) than in men (OR 1.37, 95% CI 1.07-1.75). Participants who lived in greener areas were more likely to increase their post-surgical physical activity than those who lived in less green areas (OR 1.59, 95% CI 1.25-2.01).
Conclusions
Residential greenness appears to be beneficial in increasing exercise-related physical activity in cardiac patients, especially those not particpating in cardiac rehabilitation after CABG surgery.

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: 19 Sep 2021; 28:1184-1191
Sadeh M, Brauer M, Chudnovsky A, Ziv A, Dankner R
Eur J Prev Cardiol: 19 Sep 2021; 28:1184-1191 | PMID: 34551086
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Abstract

The effects of transitions in metabolic health and obesity status on incident cardiovascular disease: Insights from a general Chinese population.

Guo X, Li Z, Zhou Y, Yu S, ... Liu Y, Sun Y
Background
Recent studies have investigated the association of transitions in metabolic health and obesity status over time with the risk of cardiovascular disease, focusing on the subgroup demonstrating metabolically healthy obesity. However, these studies have produced inconsistent results. This study evaluates the relation in a general Chinese population.
Methods
We conducted a prospective cohort study in a general population in Northeast China, with examinations of cardiovascular health from 2012-2015 and follow-up for incident cardiovascular disease until 2018. Cox proportional hazards and logistic regression models were used to investigate the association of baseline metabolic health and obesity status and transitions in those statuses with cardiovascular disease risk.
Results
A total of 7472 participants aged ≥35 years who were free of cardiovascular disease at baseline were included in this analysis. Over a median follow-up of 4.66 years, a total of 344 cardiovascular disease events occurred. Among the 3380 participants who were obese at baseline, 37.1% were metabolically healthy. Metabolically healthy obesity was associated with a 48% increased risk of cardiovascular disease (hazard ratio: 1.48; 95% confidence interval: 1.07-2.06) compared with the metabolically healthy non-obese group at baseline. Transition from metabolically healthy obesity to metabolically unhealthy obesity was associated with elevated cardiovascular disease risk with an odds ratio of 1.82 (95% confidence interval: 1.06-3.14) compared with metabolically healthy non-obesity throughout after adjustment. Even maintaining metabolically healthy obesity over time was associated with a higher risk of cardiovascular disease (odds ratio: 1.72; 95% confidence interval: 1.00-2.97).
Conclusions
Weight control and management of existing metabolic disorders should be prioritized in all obese population.

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 Sep 2021; 28:1250-1258
Guo X, Li Z, Zhou Y, Yu S, ... Liu Y, Sun Y
Eur J Prev Cardiol: 19 Sep 2021; 28:1250-1258 | PMID: 34551085
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Abstract

Cardiorespiratory fitness and survival following cancer diagnosis.

Fardman A, Banschick GD, Rabia R, Percik R, ... Grossman E, Maor E
Aims
Data on the association of cardiorespiratory fitness with survival of cancer patients are limited. This study aimed to evaluate the association between midlife cardiorespiratory fitness and survival after a subsequent cancer diagnosis.
Methods
We evaluated 19,134 asymptomatic self-referred adults who were screened in preventive healthcare settings. All subjects were free of cardiovascular disease and cancer at baseline and completed a maximal exercise stress test. Fitness was categorised into age-specific and sex-specific quintiles according to the treadmill time and dichotomised to low (quintiles 1-2) and high fitness groups.
Results
The mean age was 50 ± 8 years and 72% were men. During a median follow-up of 13 years (interquartile range 7-16) 517 (3%) died. Overall, 1455 (7.6%) subjects developed cancer with a median time to cancer diagnosis of 6.4 years (interquartile range 3-10). Death from the time of cancer diagnosis was significantly lower among the high fitness group (Plog rank = 0.03). Time-dependent analysis showed that subjects who developed cancer during follow-up were more likely to die (P < 0.001). The association of cancer with survival was fitness dependent such that in the lower fitness group cancer was associated with a higher risk of death, whereas among the high fitness group the risk of death was lower (hazard ratio 20 vs. 15; Pfor interaction = 0.047). The effect modification persisted after applying a 4-year blanking period between fitness assessment and cancer diagnosis (Pfor interaction = 0.003).
Conclusion
Higher midlife cardiorespiratory fitness is associated with better survival among cancer patients. Our findings support fitness assessment in preventive healthcare 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: 19 Sep 2021; 28:1242-1249
Fardman A, Banschick GD, Rabia R, Percik R, ... Grossman E, Maor E
Eur J Prev Cardiol: 19 Sep 2021; 28:1242-1249 | PMID: 34551084
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Abstract

Early cardiovascular structural and functional abnormalities as a guide to future morbid events.

Duprez DA, Duval S, Hoke L, Florea N, ... Lee J, Cohn JN
Aims
Our aim was to evaluate the predictive value of a battery of 10 non-invasive tests of cardiovascular structural and functional health on the future risk of cardiovascular morbid events.
Methods and results
A total of 1900 asymptomatic adults concerned about their risk for cardiovascular disease underwent non-invasive assessment with 10 tests of vascular and cardiac structure and function. A disease score (DS) was calculated for each individual based on these 10 tests. Follow-up (mean 9.2 years) for cardiovascular morbidity and mortality was available for 1442 individuals (mean age 53.2 years, 48.2% women). Those in the lowest DS tertile (0-2) experienced 0.16 cardiovascular events per 100 patient-years (PY), those in the middle tertile (3-5) experienced 0.86 events per 100 PY, and those in the highest tertile (6+) experienced 1.3 events per 100 PY (p < .001). Sensitivity analysis, assuming a neutral effect of DS on projected events in subjects not followed, did not alter statistical significance. Risk assessment using the Framingham risk score (FRS) also predicted morbid events but the two methods differed in identifying individuals at high risk. The net reclassification index was improved by 0.11 (p = 0.01) when DS was added to FRS.
Conclusions
Assessing the biological disease process in the arteries and heart of asymptomatic adults provides a guide to the risk of a future cardiovascular morbid event. Larger and longer studies are needed to determine whether risk factor algorithms, the severity of the biological process or some combination is the optimal method for identifying individuals in need of intervention to delay morbid events.

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 Sep 2021; 28:1214-1221
Duprez DA, Duval S, Hoke L, Florea N, ... Lee J, Cohn JN
Eur J Prev Cardiol: 19 Sep 2021; 28:1214-1221 | PMID: 34551082
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Abstract

Non-adherence to established dietary guidelines associated with increased mortality: the Copenhagen General Population Study.

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

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

Eur J Prev Cardiol: 19 Sep 2021; 28:1259-1268
Ewers B, Marott JL, Schnohr P, Nordestgaard BG, Marckmann P
Eur J Prev Cardiol: 19 Sep 2021; 28:1259-1268 | PMID: 34551079
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Abstract

Bereavement in the year before a first myocardial infarction: Impact on prognosis.

Wei D, Janszky I, Ljung R, Leander K, ... Li J, László KD
Background
Death of the spouse in middle and old age is associated with an increased risk of cardiovascular and total mortality, particularly during the months after the loss. Knowledge regarding the effect of bereavement on prognosis in acute myocardial infarction (AMI) is limited. We analysed whether bereavement the year before the AMI is associated with prognosis.
Methods
We studied first AMI patients who participated in the Stockholm Heart Epidemiology Program (N = 1732). During or shortly after the hospitalization, patients or their family members completed a questionnaire regarding bereavement, sociodemographic, clinical and lifestyle factors; five months after their first infarction, surviving patients attended a clinical examination. Participants were followed for cardiovascular events and mortality for a median of 14 years.
Results
Overall bereavement, that is, death of a close friend or family member (including spouse/partner), the year before the first AMI was not associated with the combined outcome of non-fatal recurrent AMI and death due to ischaemic heart diseases. However, exposure to the loss of the spouse/partner was associated with an increased risk of the outcome (adjusted hazard ratio and (95% confidence interval): 1.55 (1.06-2.27)). We found no evidence that psychiatric disorders or blood lipids, glucose, coagulation and inflammatory markers mediated this association.
Conclusions
Loss of spouse/partner the year before the first AMI was associated with an increased risk of the combination of non-fatal recurrent AMI and death due to ischaemic heart disease. If confirmed by others, the findings may be informative for tertiary prevention of AMI.

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 Sep 2021; 28:1229-1234
Wei D, Janszky I, Ljung R, Leander K, ... Li J, László KD
Eur J Prev Cardiol: 19 Sep 2021; 28:1229-1234 | PMID: 34551078
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Abstract

Obesity, cardiovascular risk and healthcare resource utilization in the UK.

le Roux CW, Hartvig NV, Haase CL, Nordsborg RB, Olsen AH, Satylganova A
Aims
Obesity and cardiovascular diseases (CVDs) often co-occur, likely increasing the intensity of healthcare resource utilization (HCRU). This retrospective, observational database study examined the joint effect of obesity and cardiovascular risk status on HCRU and compared HCRU between body mass index (BMI) categories and CVD-risk categories in the UK.
Methods
Patient demographics and data on CVD and BMI were obtained from the UK Clinical Practice Research Datalink. Cardiovascular risk status, calculated using the Framingham Risk Equation, was used to categorize people into high-risk and low-risk groups, while a CVD diagnosis was used to define the established CVD group. Patients were split into BMI categories using the standard World Health Organization classifications. For each CVD and BMI category, mean number and costs of general practitioner contacts, hospital admissions and prescriptions were estimated.
Results
The final study population included 1,600,709 patients. Data on CVD status were available on just over one-quarter of the sample (28.6%) and BMI data for just less than half (43.2%). The number of general practitioner contacts and prescriptions increased with increasing BMI category for each of the three CVD-risk groups. The group with established CVD had the greatest utilization of all components of healthcare resource, followed by high CVD risk then low CVD-risk groups.
Conclusion
Increasing BMI category and CVD-risk status both affected several HCRU components. These findings highlight the importance of timely obesity management and treatment of CVD-risk factors as a means of preventing increasing HCRU.

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 Sep 2021; 28:1235-1241
le Roux CW, Hartvig NV, Haase CL, Nordsborg RB, Olsen AH, Satylganova A
Eur J Prev Cardiol: 19 Sep 2021; 28:1235-1241 | PMID: 34551077
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Abstract

Physical exercise training in patients with a Fontan circulation: A systematic review.

Scheffers LE, Berg LEMV, Ismailova G, Dulfer K, Takkenberg JJM, Helbing WA
Background
Patients with a Fontan circulation have a reduced exercise capacity, which is an important prognostic predictor of morbidity and mortality. A way to increase exercise capacity in Fontan patients might be exercise training. This systematic review assesses the effects of exercise training investigated in Fontan patients in order to provide an overview of current insights.
Design and methods
Studies evaluating an exercise training intervention in Fontan patients published up to February 2020 were included in this systematic review.
Results
From 3000 potential studies, 16 studies reported in 22 publications met the inclusion criteria. In total, 264 Fontan patients with mean age range 8.7-31 years, were included. Different training types including inspiratory muscle training, resistance training and aerobic training were investigated. Main outcome measures reported were peak oxygen uptake, cardiac function, lung function, physical activity levels and quality of life. Peak oxygen uptake increased significantly in 56% of the studies after training with an overall mean increase of +1.72 ml/kg/min (+6.3%). None of the studies reported negative outcome measures related to the exercise programme. In four studies an adverse event was reported, most likely unrelated to the training intervention.
Conclusions
Exercise training in Fontan patients is most likely safe and has positive effects on exercise capacity, cardiac function and quality of life. Therefore exercise training in Fontan patients should be encouraged. Further studies are required to assess the optimal training type, intensity, duration and long-term effects.

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 Sep 2021; 28:1269-1278
Scheffers LE, Berg LEMV, Ismailova G, Dulfer K, Takkenberg JJM, Helbing WA
Eur J Prev Cardiol: 19 Sep 2021; 28:1269-1278 | PMID: 34551076
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Abstract

miR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: an analysis of the OptimEx-Clin trial.

Gevaert AB, Witvrouwen I, Van Craenenbroeck AH, Van Laere SJ, ... Van Craenenbroeck EM, OptimEx-Clin Study Group
Aims
In patients with heart failure with preserved ejection fraction (HFpEF), exercise training improves the quality of life and aerobic capacity (peakV·O2). Up to 55% of HF patients, however, show no increase in peakV·O2 despite adequate training. We hypothesized that circulating microRNAs (miRNAs) can distinguish exercise low responders (LR) from exercise high responders (HR) among HFpEF patients.
Methods and results
We selected HFpEF patients from the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx) study which attended ≥70% of training sessions during 3 months (n = 51). Patients were defined as HR with a change in peakV·O2 above median (6.4%), and LR as below median (n = 30 and n = 21, respectively). Clinical, ergospirometric, and echocardiographic characteristics were similar between LR and HR. We performed an miRNA array (n = 377 miRNAs) in 14 age- and sex-matched patients. A total of 10 miRNAs were upregulated in LR, of which 4 correlated with peakV·O2. Validation in the remaining 37 patients indicated that high miR-181c predicted reduced peakV·O2 response (multiple linear regression, β = -2.60, P = 0.011), and LR status (multiple logistic regression, odds ratio = 0.48, P = 0.010), independent of age, sex, body mass index, and resting heart rate. Furthermore, miR-181c decreased in LR after exercise training (P-group = 0.030, P-time = 0.048, P-interaction = 0.037). An in silico pathway analysis identified several downstream targets involved in exercise adaptation.
Conclusions
Circulating miR-181c is a marker of the response to exercise training in HFpEF patients. High miR-181c levels can aid in identifying LR prior to training, providing the possibility for individualized management.

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 Sep 2021; epub ahead of print
Gevaert AB, Witvrouwen I, Van Craenenbroeck AH, Van Laere SJ, ... Van Craenenbroeck EM, OptimEx-Clin Study Group
Eur J Prev Cardiol: 10 Sep 2021; epub ahead of print | PMID: 34508569
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Abstract

Normative cardiopulmonary exercise data for endurance athletes: the Cardiopulmonary Health and Endurance Exercise Registry (CHEER).

Petek BJ, Tso JV, Churchill TW, Guseh JS, ... Wasfy MM, Baggish AL
Aims
Accurate interpretation of cardiopulmonary exercise testing (CPET) relies on age, gender, and exercise modality-specific reference values. To date, clinically applicable CPET reference values derived from a source population of endurance athletes (EAs) have been lacking. The purpose of this study was to generate CPET reference values for use in the clinical assessment of EA.
Methods and results
Prospective data accrued during the clinical care of healthy EA were used to derive CPET reference values and to develop novel equations for V˙O2peak. The performance of these equations was compared to the contemporary standard of care equations and assessed in a discrete EA validation cohort. A total of 272 EA (age = 42 ± 15 years, female = 31%, V˙O2peak = 3.6 ± 0.83 L/min) met inclusion criteria and comprised the derivation cohort. V˙O2peak prediction equations derived from general population cohorts described a modest amount of V˙O2peak variability [R2 = 0.58-0.70, root mean square error (RMSE) = 0.46-0.54 L/min] but were mis-calibrated (calibration-in-the-large = 0.45-1.18 L/min) among EA leading to significant V˙O2peak underestimation. Newly derived, externally validated V˙O2peak prediction equations for EA that included age, sex, and height for both treadmill (R2 = 0.74, RMSE = 0.42 L/min) and cycle ergometer CPET (Cycle: R2 = 0.69, RMSE = 0.42 L/min) demonstrated improved accuracy.
Conclusion
Commonly used V˙O2peak prediction equations derived from general population cohorts perform poorly among competitive EA. Newly derived CPET reference values including novel V˙O2peak prediction equations may improve the clinical utility of CPET in this rapidly growing patient 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: 05 Sep 2021; epub ahead of print
Petek BJ, Tso JV, Churchill TW, Guseh JS, ... Wasfy MM, Baggish AL
Eur J Prev Cardiol: 05 Sep 2021; epub ahead of print | PMID: 34487164
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Abstract

Time trends in ischaemic heart disease incidence and mortality over three decades (1990-2019) in 20 Western European countries: systematic analysis of the Global Burden of Disease Study 2019.

Vancheri F, Tate AR, Henein M, Backlund L, ... Palmieri L, Strender LE
Aims
To investigate and compare changes in the rates of ischaemic heart disease (IHD) incidence and mortality between 1990 and 2019 in 20 high-income Western European countries with similar public health systems and low cardiovascular risk.
Methods and results
The 2020 updated version of the Global Burden of Disease database was searched. Variability and differences in IHD incidence and mortality rates (per 100 000) between countries over time, were calculated. A piecewise linear (join point) regression model was used to identify the slopes of these trends and the points in time at which significant changes in the trends occur. Ischaemic heart disease incidence and mortality rates varied widely between countries but decreased for all between 1990 and 2019. The relative change was greater for mortality than for incidence. Ischaemic heart disease incidence rates declined by approximately 36% between 1990 and 2019, while mortality declined by approximately 60%. Breakpoint analysis showed that the largest decreases in incidence and mortality occurred between 1990 and 2009 (-32%, -52%, respectively), with a much slower decrease after that (-5.9%, -17.6%, respectively), and even a slight increase for some countries in recent years. The decline in both incidence and mortality was lower in the Mediterranean European countries compared to the Nordic and Central European regions.
Conclusions
In the Western European countries studied, the decline in age-standardized IHD incidence over three decades was slower than the decline in age-standardized IHD mortality. Decreasing trends of both IHD incidence and mortality has substantially slowed, and for some countries flattened, in more recent years.

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: 05 Sep 2021; epub ahead of print
Vancheri F, Tate AR, Henein M, Backlund L, ... Palmieri L, Strender LE
Eur J Prev Cardiol: 05 Sep 2021; epub ahead of print | PMID: 34487157
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Impact:
Abstract

Impact of activity trackers on secondary prevention in patients with coronary artery disease: a systematic review and meta-analysis.

Kaihara T, Intan-Goey V, Scherrenberg M, Falter M, Frederix I, Dendale P
Aims
Coronary artery disease (CAD) is related to high rates of morbidity and mortality among cardiovascular diseases (CVDs). Activity trackers have been used in cardiac rehabilitation (CR) in the last years. However, their effectiveness to influence outcomes after CAD is debated. This review summarizes the latest data of impact of activity trackers on CVD risk and outcomes: peak oxygen consumption (VO2), major adverse cardiovascular events (MACE), quality of life (QoL), and low-density lipoprotein-cholesterol (LDL-C).
Methods and results
Articles from 1986 to 2020 in English were searched by electronic databases (PubMed, Cochrane Library, and Embase). Inclusion criteria were: randomized controlled trials of CAD secondary prevention using an activity tracker which include at least peak VO2, MACE, QoL, or LDL-C as outcomes. Meta-analysis was performed. After removing duplicates, 604 articles were included and the screening identified a total of 11 articles. Compared to control groups, intervention groups with activity trackers significantly increased peak VO2 [mean difference 1.54; 95% confidence interval (CI) (0.50-2.57); P = 0.004] and decreased MACE [risk ratio 0.51; 95% CI (0.31-0.86); P = 0.01]. Heterogeneity was low (I2 = 0%) for MACE and high (I2 = 51%) for peak VO2. Intervention with an activity tracker also has positive impact on QoL. There was no between-group difference in LDL-C.
Conclusion
CR using activity trackers has a positive and multi-faceted effect on peak VO2, MACE, and QoL in patients with CAD.

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: 01 Sep 2021; epub ahead of print
Kaihara T, Intan-Goey V, Scherrenberg M, Falter M, Frederix I, Dendale P
Eur J Prev Cardiol: 01 Sep 2021; epub ahead of print | PMID: 34472613
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Abstract

Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials.

Anand SS, Hiatt W, Dyal L, Bauersachs R, ... Eikelboom J, Bonaca MP
Aims
Peripheral artery disease (PAD) patients suffer a high risk of major cardiovascular (CV) events, with athero-thrombo-embolism as the underlying pathophysiologic mechanism. Recently, two large randomized clinical trials evaluated the efficacy and safety of low-dose rivaroxaban twice daily plus aspirin in stable PAD outpatients and those immediately after peripheral revascularization. We sought to determine if the effects of low-dose rivaroxaban and aspirin compared to aspirin alone are consistent across this broad spectrum of PAD patients.
Methods and results
We conducted a random-effects meta-analysis of the COMPASS and VOYAGER randomized trials among 11 560 PAD patients (4996 from COMPASS and 6564 from VOYAGER) in the primary analysis and 9332 (2768 from COMPASS and 6564 from VOYAGER) with lower extremity (LE)-PAD in the secondary analysis. The hazard ratio (HR) for the composite of CV death, myocardial infarction, ischaemic stroke, acute limb ischaemia, or major vascular amputation was 0.79 (95% confidence interval, CI: 0.65-0.95) comparing low-dose rivaroxaban plus aspirin to aspirin alone. While the risk of major bleeding was increased with low-dose rivaroxaban plus aspirin compared to aspirin alone [HR: 1.51 (95% CI: 1.22-1.87)], there was no significant increase in severe bleeding [HR: 1.18 (95% CI: 0.79-1.76)]. Similar effects were observed in the subset with symptomatic LE-PAD.
Conclusions
Among PAD patients, low-dose rivaroxaban plus aspirin is superior to aspirin alone in reducing CV and limb outcomes including acute limb ischaemia and major vascular amputation. This reduction is offset by a relative increase in major bleeding, but not by an excess of fatal or critical organ bleeding. The consistency of findings of these trials supports the use of combination low-dose rivaroxaban plus aspirin in PAD patients across a broad spectrum of disease.

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

Eur J Prev Cardiol: 30 Aug 2021; epub ahead of print
Anand SS, Hiatt W, Dyal L, Bauersachs R, ... Eikelboom J, Bonaca MP
Eur J Prev Cardiol: 30 Aug 2021; epub ahead of print | PMID: 34463737
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Impact:
Abstract

Aspirin for the primary prevention of cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis.

Pallikadavath S, Ashton L, Brunskill NJ, Burton JO, Gray LJ, Major RW
Aims
Cardiovascular disease (CVD) is the major cause of morbidity and mortality in individuals with chronic kidney disease (CKD). This study assessed the risks and benefits of aspirin in the primary prevention of CVD in individuals with CKD.
Methods and results
Ovid MEDLINE was searched from 2015 to 15th of September 2020 to include randomized controlled trials that assessed aspirin versus placebo in adults with non-end stage CKD without a previous diagnosis of CVD. A pre-specified protocol was registered with PROSPERO (identification number CRD42014008860). A random effects model was used to calculate a pooled hazard ratio (HR), pooled risk difference, and the number needed to treat or harm (NNT/NNH). The primary endpoint was CVD. Secondary endpoints included: all-cause mortality; coronary heart disease; stroke; and major and minor bleeding events. Five trials were identified (n = 7852 total, n = 3935 aspirin, n = 3917 placebo). Overall, 434 CVD events occurred. There was no statistically significant reduction in CVD events (HR 0.76, 95% confidence interval (CI) 0.54-1.08; P = 0.13, I2 = 63%), all-cause mortality (HR 0.94, 95% CI 0.74-1.19; P = 0.60, I2 = 21%), coronary heart disease events (HR 0.66, 95% CI 0.27-1.63; P = 0.37, I2 = 64%) or stroke (HR 0.87, 95% CI 0.6-1.27; P = 0.48, I2 = 24%) from aspirin therapy. The risk of major bleeding events were increased by approximately 50% (HR 1.53, 95% CI 1.13-2.05; P = 0.01, I2 = 0%) and minor bleeding events were more than doubled (HR 2.64, 95% CI 1.64-4.23; P < 0.01, I2 = 0%).
Conclusions
Aspirin cannot be routinely recommended for the primary prevention of CVD in individuals with CKD as there is no evidence for its benefit but there is an increased risk of bleeding.

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: 26 Aug 2021; epub ahead of print
Pallikadavath S, Ashton L, Brunskill NJ, Burton JO, Gray LJ, Major RW
Eur J Prev Cardiol: 26 Aug 2021; epub ahead of print | PMID: 34448849
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Abstract

Cardiac structure and function in response to a multi-stage marathon over 4486 km.

Klenk C, Brunner H, Nickel T, Sagmeister F, ... Schütz U, Schmidt-Trucksäss A
Aims
To investigate whether participation in the Trans Europe Foot Race 2009 (TEFR), an ultramarathon race held over 64 consecutive days and 4486 km, led to changes in cardiac structure and function.
Methods
Cardiac magnetic resonance imaging was performed in 20 of 67 participating runners (two women; mean ± SD age 47.8 ± 10.4 years) at three time points (baseline scan at 294 ± 135 km (B), scan two at 1735 ± 86 km (T1) and scan three at 3370 ± 90 km (T2)) during the TEFR. Imaging included an assessment of left ventricular structure (mass) and function (strain). In parallel, cardiac troponin I, NT-pro-BNP, myostatin and GDF11 were determined in venous blood samples. A subsample of ten runners returned for a follow-up scan eight months after the race.
Results
Left ventricular mass increased significantly (B, 158.5 ± 23.8 g; T1, 165.1 ± 23.2 g; T2, 167 ± 24.6 g; p < 0.001) over the course of the race, although no significant change was seen in the remaining structural and functional parameters. Serum concentrations of cardiac troponin I and NT-proBNP significantly increased 1.5 - and 3.5-fold, respectively, during the first measurement interval, with no further increase thereafter (cardiac troponin I, 6.8 ± 3.1 (B), 16.9 ± 10.4 (T1) and 17.1 ± 9.7 (T2); NT-proBNP, 30.3 ± 22.8 (B), 135.9 ± 177.5 (T1) and 111.2 ± 87.3 (T2)), whereas the growth markers myostatin and GDF11 did not change. No association was observed with functional parameters, including the ejection fraction and the volume of both ventricles. The follow-up scans showed a reduction to baseline values (left ventricular mass 157 ± 19.3 g).
Conclusions
High exercise-induced cardiac volume load for >2 months in ultra-endurance runners results in a physiological structural adaptation with no sign of adverse cardiovascular remodelling.

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: 22 Aug 2021; 28:1102-1109
Klenk C, Brunner H, Nickel T, Sagmeister F, ... Schütz U, Schmidt-Trucksäss A
Eur J Prev Cardiol: 22 Aug 2021; 28:1102-1109 | PMID: 34425589
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Impact:
Abstract

Yield and clinical significance of genetic screening in elite and amateur athletes.

Limongelli G, Nunziato M, D\'Argenio V, Esposito MV, ... Frisso G, Salvatore F
Aims
The purpose of this study was to assess the value of genetic testing in addition to a comprehensive clinical evaluation, as part of the diagnostic work-up of elite and/or amateur Italian athletes referred for suspicion of inherited cardiac disease, following a pre-participation screening programme.
Methods
Between January 2009-December 2018, of 5892 consecutive participants, 61 athletes were investigated: 30 elite and 31 amateur athletes. Elite and amateur athletes were selected, on the basis of clinical suspicion for inherited cardiac disease, from two experienced centres for a comprehensive cardiovascular evaluation. Furthermore, the elite and amateur athletes were investigated for variants at DNA level up to 138 genes suspected to bear predisposition for possible cardiac arrest or even sudden cardiac death.
Results
Of these 61 selected subjects, six (10%) had diagnosis made possible by a deeper clinical evaluation, while genetic testing allowed a definite diagnosis in eight (13%). The presence of >3 clinical markers (i.e. family history, electrocardiogram and/or echocardiographic abnormalities, exercise-induced ventricular arrhythmias) was associated with a higher probability of positive genetic diagnosis (75%), compared with the presence of two or one clinical markers (14.2%, 8.1%, respectively, p-value = 0.004).
Conclusion
A combined clinical and genetic evaluation, based on the subtle evidence of clinical markers for inherited disease, was able to identify an inherited cardiac disease in about one-quarter of the examined athletes.

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 Aug 2021; 28:1081-1090
Limongelli G, Nunziato M, D'Argenio V, Esposito MV, ... Frisso G, Salvatore F
Eur J Prev Cardiol: 22 Aug 2021; 28:1081-1090 | PMID: 34425588
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Abstract

The use of cardiac imaging in the evaluation of athletes in the clinical practice: A survey by the Sports Cardiology and Exercise Section of the European Association of Preventive Cardiology and University of Siena, in collaboration with the European Association of Cardiovascular Imaging, the European Heart Rhythm Association and the ESC Working Group on Myocardial and Pericardial Diseases.

D\'Ascenzi F, Anselmi F, Mondillo S, Finocchiaro G, ... Papadakis M, Dendale P
Aims
Pre-participation evaluation (PPE) is recommended to prevent sudden cardiac death in athletes. Although imaging is not advocated as a first-line screening tool, there is a growing interest in the use of echocardiography in PPE of athletes. This survey aimed to map the use of imaging in the setting of PPE and explore physician beliefs and potential barriers that may influence individual practices.
Methods
An international survey of healthcare professionals was performed across ESC Member Countries. Percentages were reported based on the number of respondents per question.
Results
In total, 603 individuals from 97 countries participated in the survey. Two-thirds (65%) of respondents use echocardiography always or often as part of PPE of competitive athletes and this practice is not influenced by the professional or amateur status of the athlete. The majority (81%) of respondents who use echocardiography as a first-line screening tool perform the first echocardiogram during adolescence or at the first clinical evaluation, and 72% repeat it at least once in the athletes\' career, at 1-5 yearly intervals. In contrast, cardiac magnetic resonance is reserved as a second-line investigation of symptomatic athletes. The majority of the respondents did not report any barriers to echocardiography, while several barriers were identified for cardiac magnetic resonance.
Conclusions
Echocardiography is frequently used as a first-line screening tool of athletes. In the absence of scientific evidence, before such practice is recommended, large studies using echocardiography in the PPE setting are necessary.

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 Aug 2021; 28:1071-1077
D'Ascenzi F, Anselmi F, Mondillo S, Finocchiaro G, ... Papadakis M, Dendale P
Eur J Prev Cardiol: 22 Aug 2021; 28:1071-1077 | PMID: 34425587
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Abstract

Comparison of recent ceramide-based coronary risk prediction scores in cardiovascular disease patients.

Leiherer A, Mündlein A, Laaksonen R, Lääperi M, ... Fraunberger P, Drexel H
Aim
Cholesterol-based risk prediction is often insufficient in cardiovascular disease (CVD) patients. Ceramides are a new kind of biomarkers for CVD. The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses only circulating ceramide levels, determined by coupled liquid chromatography-mass spectrometry, to allocate patients into one of four risk categories. This test has recently been modified (CERT2) by additionally including phosphatidylcholine levels.
Methods and results
In this observational cohort study, we have recruited 999 Austrian patients with CVD and followed them for up to 13 years. We found that CERT and CERT2 both predicted cardiovascular events, cardiovascular mortality, and overall mortality. CERT2 had the higher performance compared to CERT and also to the recent cardiovascular risk score of the ESC/EAS guidelines (Systematic COronary Risk Evaluation (SCORE)) for low-risk European countries. Combining CERT2 with the ESC/EAS-SCORE, predictive capacity was further increased leading to a hazard ratio of 3.58 (2.02-6.36; P < 0.001) for cardiovascular events, 11.60 (2.72-49.56; P = 0.001) for cardiovascular mortality, and 9.86 (4.23-22.99; P < 0.001) for overall mortality when patients with very high risk (category 4) were compared to those with low risk (category 1). The use of the combined score instead of the ESC/EAS-SCORE significantly improved the predictive power according to the integrated discrimination improvement index (P = 0.004).
Conclusion
We conclude that CERT and CERT2 are powerful predictors of cardiovascular events, cardiovascular mortality, and overall mortality in CVD patients. Including phosphatidylcholine to a ceramide-based score increases the predictive performance and is best in combination with classical risk factors as used in the ESC/EAS-SCORE.

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: 20 Aug 2021; epub ahead of print
Leiherer A, Mündlein A, Laaksonen R, Lääperi M, ... Fraunberger P, Drexel H
Eur J Prev Cardiol: 20 Aug 2021; epub ahead of print | PMID: 34417607
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Abstract

The role of cardiopulmonary exercise testing in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis.

Wadey CA, Weston ME, Dorobantu DM, Pieles GE, ... Taylor RS, Williams CA
Aims
The role of cardiopulmonary exercise testing (CPET) in predicting major adverse cardiovascular events (MACE) in people with congenital heart disease (ConHD) is unknown. A systematic review with meta-analysis was conducted to report the associations between CPET parameters and MACE in people with ConHD.
Methods and results
Electronic databases were systematically searched on 30 April 2020 for eligible publications. Two authors independently screened publications for inclusion, extracted study data, and performed risk of bias assessment. Primary meta-analysis pooled univariate hazard ratios across studies. A total of 34 studies (18 335 participants; 26.2 ± 10.1 years; 54% ± 16% male) were pooled into a meta-analysis. More than 20 different CPET prognostic factors were reported across 6 ConHD types. Of the 34 studies included in the meta-analysis, 10 (29%), 23 (68%), and 1 (3%) were judged as a low, medium, and high risk of bias, respectively. Primary univariate meta-analysis showed consistent evidence that improved peak and submaximal CPET measures are associated with a reduce risk of MACE. This association was supported by a secondary meta-analysis of multivariate estimates and individual studies that could not be numerically pooled.
Conclusion
Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well-conducted prospective multicentre cohort studies are needed to confirm these findings.

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

Eur J Prev Cardiol: 17 Aug 2021; epub ahead of print
Wadey CA, Weston ME, Dorobantu DM, Pieles GE, ... Taylor RS, Williams CA
Eur J Prev Cardiol: 17 Aug 2021; epub ahead of print | PMID: 34405863
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Abstract

Lipoprotein (a) as a treatment target for cardiovascular disease prevention and related therapeutic strategies: a critical overview.

Parthymos I, Kostapanos MS, Mikhailidis DP, Florentin M
Advances in several fields of cardiovascular (CV) medicine have produced new treatments (e.g. to treat dyslipidaemia) that have proven efficacy in terms of reducing deaths and providing a better quality of life. However, the burden of CV disease (CVD) remains high. Thus, there is a need to search for new treatment targets. Lipoprotein (a) [Lp(a)] has emerged as a potential novel target since there is evidence that it contributes to CVD events. In this narrative review, we present the current evidence of the potential causal relationship between Lp(a) and CVD and discuss the likely magnitude of Lp(a) lowering required to produce a clinical benefit. We also consider current and investigational treatments targeting Lp(a), along with the potential cost of these 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: 13 Aug 2021; epub ahead of print
Parthymos I, Kostapanos MS, Mikhailidis DP, Florentin M
Eur J Prev Cardiol: 13 Aug 2021; epub ahead of print | PMID: 34389859
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Impact:
Abstract

Impact of sarcopenia on prognosis in patients with heart failure with reduced and preserved ejection fraction.

Konishi M, Kagiyama N, Kamiya K, Saito H, ... Momomura SI, Matsue Y
Aims
Sarcopenia, one of the extracardiac factors for reduced functional capacity and poor outcome in heart failure (HF), may act differently between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). We sought to investigate the impact of sarcopenia on mortality in HFpEF and HFrEF.
Methods and results
We performed a post hoc analysis of a multicentre prospective cohort study, including 942 consecutive older (age ≥65 years) hospitalized patients: 475 with HFpEF (ejection fraction ≥45%, age 81 ± 7 years, 48.8% men) and 467 with HFrEF (ejection fraction <45%, age 78 ± 8 years, 68.1% men). Sarcopenia was diagnosed according to the international criteria incorporating muscle strength (handgrip strength), physical performance (gait speed), and skeletal muscle mass (appendicular skeletal mass). The HFpEF group consisted of fewer patients with low appendicular skeletal muscle mass index measured using bioelectrical impedance analysis [<7.0 kg/m2 (men) and <5.7 (women); 22.1% vs. 31.0%, P = 0.003], and more patients with low handgrip strength [<26 kg (men) and <18 (women); 67.8% vs. 55.5%, P < 0.001], and slow gait speed [<0.8 m/s (both sexes); 54.5% vs. 41.1%, P < 0.001] than the HFrEF group, resulting in a similar sarcopenia prevalence in the two groups (18.1% vs. 21.6%, P = 0.191). Sarcopenia was an independent predictor of 1-year mortality in both HFpEF and HFrEF [hazard ratio (95% confidence interval) 2.42 (1.36-4.32), P = 0.003 in HFpEF and 2.02 (1.08-3.75), P = 0.027 in HFrEF; P for interaction = 0.666] after adjustment for other predictors.
Conclusions
In older patients with HF, sarcopenia contributes to mortality similarly in HFpEF and HFrEF.

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: 08 Aug 2021; 28:1022-1029
Konishi M, Kagiyama N, Kamiya K, Saito H, ... Momomura SI, Matsue Y
Eur J Prev Cardiol: 08 Aug 2021; 28:1022-1029 | PMID: 33624112
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Impact:
Abstract

Impact of sex-specific target dose in chronic heart failure patients with reduced ejection fraction.

Veenis JF, Rocca HB, Linssen GCM, Erol-Yilmaz A, ... Brugts JJ, CHECK-HF investigators
Aims
A recent study suggested that women with heart failure and heart failure reduced ejection fraction might hypothetically need lower doses of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers ( = renin-angiotensin-system inhibitors) and β-blockers than men to achieve the best outcome. We assessed the current medical treatment of heart failure reduced ejection fraction in men and women in a large contemporary cohort and address the hypothetical impact of changing treatment levels in women.
Methods
This analysis is part of a large contemporary quality of heart failure care project which includes 5320 (64%) men and 3003 (36%) women with heart failure reduced ejection fraction. Detailed information on heart failure therapy prescription and dosage were collected.
Results
Women less often received renin-angiotensin-system inhibitors (79% vs 83%, p < 0.01), but more often β-blockers (82% vs 79%, p < 0.01) than men. Differences in guideline-recommended target doses between sexes were relatively small. Implementing a hypothetical sex-specific dosing schedule (at 50% of the current recommended dose in the European Society of Cardiology guidelines in women only) would lead to significantly higher levels of women receiving appropriate dosing (β-blocker 87% vs 54%, p < 0.01; renin-angiotensin-system inhibitor 96% vs 75%, p < 0.01). Most interestingly, the total number of women with >100% of the new hypothetical target dose would be 24% for β-blockers and 52% for renin-angiotensin-system inhibitors, which can be considered as relatively overdosed.
Conclusion
In this large contemporary heart failure registry, there were significant but relatively small differences in drug dose between men and women with heart failure reduced ejection fraction. Implementation of the hypothetical sex-specific target dosing schedule would lead to considerably more women adequately treated. In contrast, we identified a group of women who might have been relatively overdosed with increased risk of side-effects and intolerance.

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: 08 Aug 2021; 28:957-965
Veenis JF, Rocca HB, Linssen GCM, Erol-Yilmaz A, ... Brugts JJ, CHECK-HF investigators
Eur J Prev Cardiol: 08 Aug 2021; 28:957-965 | PMID: 34402878
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Abstract

Temporal trends and predictors of inhospital death in patients hospitalised for heart failure in Germany.

Keller K, Hobohm L, Ostad MA, Göbel S, ... Münzel T, Wenzel P
Aims
We investigated trends in incidence, case fatality rate, patient characteristics and adverse inhospital events of patients hospitalised for heart failure in Germany.
Methods and results
The German nationwide inpatient sample (2005-2016) was used for this analysis. Patients hospitalised due to heart failure were selected for analysis. Temporal trends in the incidence of hospitalisations, case fatality rate and treatments were analysed and predictors of inhospital death were identified. The analysis comprised a total number of 4,539,140 hospitalisations (52.0% women, 81.0% aged ≥70 years) due to heart failure. Although hospitalisations increased from 381 (2005) to 539 per 100,000 population (2016) (β estimate 0.06, 95% confidence interval (CI) 0.06 to 0.07, P < 0.001) in parallel with median age and prevalence of comorbidities, the inhospital case fatality rate decreased from 11.1% to 8.1% (β estimate -0.36, 95% CI -0.37 to -0.35, P < 0.001) and the rate of major adverse cardiovascular and cerebrovascular events (β estimate -0.24, 95% CI -0.25 to -0.23, P < 0.001) decreased from 12.7% to 10.3%. Age 70 years and older (odds ratio (OR) 2.60, 95% CI 2.57 to 2.63, P < 0.001) and cancer (OR 1.93, 95% CI 1.91 to 1.96, P < 0.001) were independent predictors of inhospital death.
Conclusion
Hospitalisations for heart failure increased in Germany from 2005 to 2016, whereas the major adverse cardiovascular and cerebrovascular event rate and inhospital case fatality rate decreased during this period despite higher patient age and increasing prevalence of comorbidities.

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: 08 Aug 2021; 28:990-997
Keller K, Hobohm L, Ostad MA, Göbel S, ... Münzel T, Wenzel P
Eur J Prev Cardiol: 08 Aug 2021; 28:990-997 | PMID: 34402877
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Abstract

Rationale, design and baseline characteristics of the MyoVasc study: A prospective cohort study investigating development and progression of heart failure.

Göbel S, Prochaska JH, Tröbs SO, Panova-Noeva M, ... Münzel T, Wild PS
Background
Heart failure (HF) is a poly-aetiological syndrome with large heterogeneity regarding clinical presentation, pathophysiology, clinical outcome and response to therapy. The MyoVasc study (NCT04064450) is an epidemiological cohort study investigating the development and progression of HF.
Methods
The primary objective of the study is (a) to improve the understanding of the pathomechanisms of HF across the full spectrum of clinical presentation, (b) to investigate the current clinical classifications of HF, and (c) to identify and characterize homogeneous subgroups regarding disease development using a systems-oriented approach. Worsening of HF, that is, the composite of transition from asymptomatic to symptomatic HF, hospitalization due to HF, or cardiac death, was defined as the primary endpoint of the study. During a six-year follow-up period, all study participants receive a highly standardized, biannual five-hour examination in a dedicated study centre, including detailed cardiovascular phenotyping and biobanking of various biomaterials. Annual follow-up examinations are conducted by computer-assisted telephone interviews recording comprehensively the participants´ health status, including subsequent validation and adjudication of adverse events.
Results
In total, 3289 study participants (age range: 35 to 84 years; female sex: 36.8%) including the full range of HF stages were enrolled from 2013 to 2018. Approximately half of the subjects (n=1741) presented at baseline with symptomatic HF (i.e. HF stage C/D). Among these, HF with preserved ejection fraction was the most frequent phenotype.
Conclusions
By providing a large-scale, multi-dimensional biodatabase with sequential, comprehensive medical-technical (sub)clinical phenotyping and multi-omics characterization (i.e. genome, transcriptome, proteome, lipidome, metabolome and exposome), the MyoVasc study will help to advance our knowledge about the heterogeneous HF syndrome by a systems-oriented biomedicine approach.
Trial registration
ClinicalTrials.gov; NCT04064450.

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: 08 Aug 2021; 28:1009-1018
Göbel S, Prochaska JH, Tröbs SO, Panova-Noeva M, ... Münzel T, Wild PS
Eur J Prev Cardiol: 08 Aug 2021; 28:1009-1018 | PMID: 34402876
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Abstract

Prevalence and determinants of the precursor stages of heart failure: results from the population-based STAAB cohort study.

Morbach C, Gelbrich G, Tiffe T, Eichner FA, ... Störk S, STAAB consortium
Aims
Prevention of heart failure relies on the early identification and control of risk factors. We aimed to identify the frequency and characteristics of individuals at risk of heart failure in the general population.
Methods and results
We report cross-sectional data from the prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of residents of Würzburg, Germany. Sampling was stratified 1:1 for sex and 10:27:27:27:10 for age groups of 30-39/40-49/50-59/60-69/70-79 years. Heart failure precursor stages were defined according to American College of Cardiology/American Heart Association: stage A (risk factors for heart failure), stage B (asymptomatic cardiac dysfunction). The main results were internally validated in the second half of the participants. The derivation sample comprised 2473 participants (51% women) with a distribution of 10%/28%/25%/27%/10% in respective age groups. Stages A and B were prevalent in 42% and 17% of subjects, respectively. Of stage B subjects, 31% had no risk factor qualifying for stage A (group \'B-not-A\'). Compared to individuals in stage B with A criteria, B-not-A were younger, more often women, and had left ventricular dilation as the predominant B qualifying criterion (all P < 0.001). These results were confirmed in the validation sample (n = 2492).
Conclusion
We identified a hitherto undescribed group of asymptomatic individuals with cardiac dysfunction predisposing to heart failure, who lacked established heart failure risk factors and therefore would have been missed by conventional primary prevention. Further studies need to replicate this finding in independent cohorts and characterise their genetic and -omic profile and the inception of clinically overt heart failure in subjects of group B-not-A.

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

Eur J Prev Cardiol: 08 Aug 2021; 28:924-934
Morbach C, Gelbrich G, Tiffe T, Eichner FA, ... Störk S, STAAB consortium
Eur J Prev Cardiol: 08 Aug 2021; 28:924-934 | PMID: 34402874
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Abstract

Management of complications of cardiac amyloidosis: 10 questions and answers.

Aimo A, Rapezzi C, Vergaro G, Giannoni A, ... Passino C, Emdin M
Amyloidosis is a systemic disorder characterized by extracellular deposition of insoluble fibrils. The most common forms are amyloid light chain and amyloid transthyretin (ATTR) amyloidoses. Cardiac involvement may be found in both these forms, and is an important cause of morbidity and mortality. The clinical presentation of cardiac amyloidosis (CA) may be represented by congestive heart failure (HF), possibly progressing to end-stage HF, as well as atrial fibrillation with possible thromboembolic events, and also conduction disturbances related to amyloid infiltration of conduction fibres. Beyond therapies targeting the blood dyscrasia or the ATTR amyloidogenic cascade, a careful choice of drug therapies, need for device implantation, and possibly treatments for advanced HF is then warranted. In the present review, we try to provide a useful guide to clinicians treating patients with CA by enucleating 10 main questions and answering them based on the evidence available as well as expert opinion and our clinical experience.

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: 08 Aug 2021; 28:1000-1005
Aimo A, Rapezzi C, Vergaro G, Giannoni A, ... Passino C, Emdin M
Eur J Prev Cardiol: 08 Aug 2021; 28:1000-1005 | PMID: 34402873
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Abstract

Cost-effectiveness of dapagliflozin in chronic heart failure: an analysis from the Australian healthcare perspective.

Savira F, Wang BH, Kompa AR, Ademi Z, ... Liew D, Zomer E
Aim
To assess the cost-effectiveness of dapagliflozin in addition to standard care versus standard care alone in patients with chronic heart failure and reduced ejection fraction.
Methods
A Markov model was constructed based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial to assess the clinical outcomes and costs of 1000 hypothetical subjects with established heart failure and reduced ejection fraction. The model consisted of three health states: \'alive and event-free\', \'alive after non-fatal hospitalisation for heart failure\' and \'dead\'. Costs and utilities were estimated from published sources. The main outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. An Australian public healthcare perspective was employed. All outcomes and costs were discounted at a rate of 5% annually.
Results
Over a lifetime horizon, the addition of dapagliflozin to standard care in patients with heart failure and reduced ejection fraction prevented 88 acute heart failure hospitalisations (including readmissions) and yielded an additional 416 years of life and 288 quality-adjusted life-years (discounted) at an additional cost of A$3,692,440 (discounted). This equated to an incremental cost-effectiveness ratio of A$12,482 per quality-adjusted life-year gained, well below the Australian willingness-to-pay threshold of A$50,000 per quality-adjusted life-year gained. Subanalyses in subjects with and without diabetes resulted in similar incremental cost-effectiveness ratios of A$13,234 and A$12,386 per quality-adjusted life-year gained, respectively.
Conclusion
Dapagliflozin is likely to be cost-effective when used as an adjunct therapy to standard care compared with standard care alone for the treatment of chronic heart failure and reduced ejection fraction.

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: 08 Aug 2021; 28:975-982
Savira F, Wang BH, Kompa AR, Ademi Z, ... Liew D, Zomer E
Eur J Prev Cardiol: 08 Aug 2021; 28:975-982 | PMID: 34402872
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Abstract

Integrating natriuretic peptides and diastolic dysfunction to predict adverse events in high-risk asymptomatic subjects.

Gori M, Lam CSP, D\'Elia E, Iorio AM, ... Gavazzi A, Senni M
Background
Natriuretic peptides and diastolic dysfunction have prognostic value in asymptomatic subjects at risk for heart failure. Their integration might further refine the risk stratification process in this setting. Aim of this paper was to explore the possibility to predict heart failure and death combining diastolic dysfunction and natriuretic peptides in an asymptomatic population at risk for heart failure.
Methods
Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for heart failure. Baseline evaluation included electrocardiogram, echocardiogram, and natriuretic peptides collection. Based on diastolic dysfunction and natriuretic peptides, subjects were classified in four groups: control group (no diastolic dysfunction/normal natriuretic peptides, 57%), no diastolic dysfunction/high natriuretic peptides (9%), diastolic dysfunction/normal natriuretic peptides (24%), and diastolic dysfunction/high natriuretic peptides (11%). We applied Cox multivariable and Classification and Regression Tree analyses.
Results
The mean age of the population was 69 ± 7 years, 44% were women, mean left ventricular ejection fraction was 61%, and 35% had diastolic dysfunction. During a median follow-up of 5.7 years, 95 heart failure/death events occurred. Overall, diastolic dysfunction and natriuretic peptides were predictive of adverse events (respectively, hazard ratio 1.91, confidence interval 1.19-3.05, padjusted = 0.007, and hazard ratio 2.25, confidence interval 1.35-3.74, padjusted = 0.002) with Cox analysis. However, considering the four study subgroups, only the group with diastolic dysfunction/high natriuretic peptides had a significantly worse prognosis compared to the control group (hazard ratio 4.48, confidence interval 2.31-8.70, padjusted < 0.001). At Classification and Regression Tree analysis, diastolic dysfunction/high natriuretic peptides was the strongest prognostic factor (risk range 24-58%).
Conclusions
The DAVID-Berg data suggest that we look for the quite common combination of diastolic dysfunction/high natriuretic peptides to correctly identify asymptomatic subjects at greater risk for incident heart failure/death, thus more suitable for preventive interventions.

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: 08 Aug 2021; 28:937-945
Gori M, Lam CSP, D'Elia E, Iorio AM, ... Gavazzi A, Senni M
Eur J Prev Cardiol: 08 Aug 2021; 28:937-945 | PMID: 34402871
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Abstract

Body mass index and outcomes in ischaemic versus non-ischaemic heart failure across the spectrum of ejection fraction.

Gentile F, Sciarrone P, Zamora E, De Antonio M, ... Emdin M, Vergaro G
Aims
Obesity is related to better prognosis in heart failure with either reduced (HFrEF; left ventricular ejection fraction (LVEF) < 40%) or preserved LVEF (HFpEF; LVEF ≥50%). Whether the obesity paradox exists in patients with heart failure and mid-range LVEF (HFmrEF; LVEF 40-49%) and whether it is independent of heart failure aetiology is unknown. Therefore, we aimed to test the prognostic value of body mass index (BMI) in ischaemic and non-ischaemic heart failure patients across the whole spectrum of LVEF.
Methods
Consecutive ambulatory heart failure patients were enrolled in two tertiary centres in Italy and Spain and classified as HFrEF, HFmrEF or HFpEF, of either ischaemic or non-ischaemic aetiology. Patients were stratified into underweight (BMI < 18.5 kg/m2), normal-weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), mild-obese (BMI 30-34.9 kg/m2), moderate-obese (BMI 35-39.9 kg/m2) and severe-obese (BMI ≥40 kg/m2) and followed up for the end-point of five-year all-cause mortality.
Results
We enrolled 5155 patients (age 70 years (60-77); 71% males; LVEF 35% (27-45); 63% HFrEF, 18% HFmrEF, 19% HFpEF). At multivariable analysis, mild obesity was independently associated with a lower risk of all-cause mortality in HFrEF (hazard ratio, 0.78 (95% confidence interval (CI) 0.64-0.95), p = 0.020), HFmrEF (hazard ratio 0.63 (95% CI 0.41-0.96), p = 0.029), and HFpEF (hazard ratio 0.60 (95% CI 0.42-0.88), p = 0.008). Both overweight and mild-to-moderate obesity were associated with better outcome in non-ischaemic heart failure, but not in ischaemic heart failure.
Conclusions
Mild obesity is independently associated with better survival in heart failure across the whole spectrum of LVEF. Prognostic benefit of obesity is maintained only in non-ischaemic heart failure.

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: 08 Aug 2021; 28:948-955
Gentile F, Sciarrone P, Zamora E, De Antonio M, ... Emdin M, Vergaro G
Eur J Prev Cardiol: 08 Aug 2021; 28:948-955 | PMID: 34402870
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Abstract

Sacubitril-valsartan versus enalapril for acute decompensated heart failure: a cost-effectiveness analysis.

Perera K, Ademi Z, Liew D, Zomer E
Background
The Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilised from an Acute Heart Failure Episode (PIONEER-HF) trial demonstrated significant reductions in N-terminal pro-B-type natriuretic peptide. Our study explored the cost-effectiveness of the use of sacubitril-valsartan versus enalapril in acute decompensated heart failure from the Australian healthcare perspective.
Methods
A Markov model was designed using data from the PIONEER-HF trial to model the clinical progress and costs of patients over a lifetime time horizon. The model consisted of three health states: \'alive and event-free\', \'alive after non-fatal hospitalisation for acute decompensated heart failure\' or \'dead\'. Costs and utilities were estimated from published sources. The cost of sacubitril-valsartan (per the Australian pharmaceutical benefits schedule) was AU$7.08/day. Outcomes of interest were the incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year gained and cost per year of life saved. Cost and benefits were discounted at 5.0% per annum.
Results
Compared to enalapril, sacubitril-valsartan was estimated to cost an additional AU$7464 (discounted) per person, but lead to 0.127 years of life saved (discounted) and 0.096 quality-adjusted life years gained (discounted) over a lifetime analysis. These equated to incremental cost-effectiveness ratios of AU$58,629/year of life saved (US$41,795, EU€58,629, GBP£32,001) and AU$77,889/quality-adjusted life year gained (US$55,526, EU€49,202, GBP£42,504). We have assumed a threshold of AU$50,000/quality-adjusted life year gained to suggest cost-effectiveness.
Conclusions
At its current acquisition price, sacubitril-valsartan in comparison to enalapril is not likely to be cost-effective in the management of acute decompensated heart failure in Australia. A price reduction of more than 25% would confer cost-effectiveness.

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: 08 Aug 2021; 28:966-972
Perera K, Ademi Z, Liew D, Zomer E
Eur J Prev Cardiol: 08 Aug 2021; 28:966-972 | PMID: 34402869
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Impact:
Abstract

Adverse events with sacubitril/valsartan in the real world: emerging signals to target preventive strategies from the FDA adverse event reporting system.

Gatti M, Antonazzo IC, Diemberger I, De Ponti F, Raschi E
Aims
The aim of this study was to characterise clinical priority of adverse events with sacubitril/valsartan for targeting preventive measures.
Methods
We used the US Food and Drug Administration adverse event reporting system (worldwide pharmacovigilance database) to compare adverse events recording sacubitril/valsartan as suspect with other cardiovascular drugs. Disproportionality analyses were performed by calculating the reporting odds ratios, deemed significant when the lower limit of the 95% confidence interval was greater than 1. Clinical priority was assigned to adverse events with significant disproportionality by scoring (range 0-10 points) five features (number of events, magnitude of the lower limit of the 95% confidence interval, mortality frequency, important/designated medical event, biological plausibility).
Results
Sacubitril/valsartan was recorded in 20,021 reports, with 178 adverse events associated with significant disproportionality: 71.9%, 25.9% and 2.2% were classified as weak, moderate and strong clinical priorities, respectively. Increased reporting emerged for several cardiovascular adverse events, including \'renal failure\' (N = 388; lower limit of the 95% confidence interval 2.26), \'hyperkalaemia\' (314; 2.42) and \'angioedema\' (309; 1.56). Sudden cardiac death (priority score 9 points) was the only designated medical event with strong clinical priority. Notably, sudden cardiac death occurred early after sacubitril/valsartan administration (average onset 124 days), with concomitant drugs known for pro-arrhythmic potential (e.g. amiodarone, escitalopram, mirtazapine, loop diuretics) in 26.2% of records.
Conclusion
The increased cardiovascular reporting of sacubitril/valsartan in the real world was largely predictable from pre-approval evidence, underlying disease and likely patients\' comorbidities. The unexpected reporting of sudden cardiac death occurred well before the complete development of positive electrical remodelling induced by sacubitril/valsartan, and calls for stringent clinical monitoring (to reduce the pro-arrhythmic burden related to co-medications), and further investigation on appropriate combination with other preventive measures.

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: 08 Aug 2021; 28:983-989
Gatti M, Antonazzo IC, Diemberger I, De Ponti F, Raschi E
Eur J Prev Cardiol: 08 Aug 2021; 28:983-989 | PMID: 34402868
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Impact:
Abstract

Plasma lipoprotein(a) measured in the routine clinical care is associated to atherosclerotic cardiovascular disease during a 14-year follow-up.

Littmann K, Hagström E, Häbel H, Bottai M, ... Parini P, Brinck J
Aims
To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease.
Methods and results
This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003-17. Outcome data were captured in national outcome registries. Levels of Lp(a) expressed in mass or molar units were examined separately. In adjusted Cox regression models, association between deciles of plasma Lp(a) concentrations, mortality, and cardiovascular outcomes were assessed. A total of 23 398 individuals [52% females, mean (standard deviation) age 55.5 (17.2) years, median Lp(a) levels 17 mg/dL or 19.5 nmol/L] were included. Individuals with an Lp(a) level >90th decile (>90 mg/dL or >180 nmol/L) had hazard ratios (95% confidence interval) of 1.25 (1.05-1.50) for major adverse cardiovascular events (P = 0.013), 1.37 (1.14-1.64) for atherosclerotic cardiovascular disease (P = 0.001), and 1.62 (1.28-2.05) for coronary artery disease (P ≤ 0.001), compared to individuals with Lp(a) ≤50th decile. No association between Lp(a) and mortality, peripheral artery disease, or ischaemic stroke was observed.
Conclusion
High Lp(a) levels are associated with adverse cardiovascular disease outcomes also in individuals with Lp(a) measured in routine clinical care. This supports the 2019 ESC/EAS recommendation to measure Lp(a) at least once during lifetime to assess cardiovascular risk and implies the need for intensive preventive therapy in patients with elevated Lp(a).

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: 02 Aug 2021; epub ahead of print
Littmann K, Hagström E, Häbel H, Bottai M, ... Parini P, Brinck J
Eur J Prev Cardiol: 02 Aug 2021; epub ahead of print | PMID: 34343284
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Impact:
Abstract

Biventricular dysfunction and lung congestion in athletes on anabolic androgenic steroids: a speckle tracking and stress lung echocardiography analysis.

D\'Andrea A, Radmilovic J, Russo V, Sperlongano S, ... Bossone E, Picano E
Aims
The real effects of the chronic consumption of anabolic-androgenic steroids (AASs) on cardiovascular structures are subjects of intense debate. The aim of the study was to detect by speckle tracking echocardiography (STE) right ventricular (RV) and left ventricular (LV) dysfunction at rest and during exercise stress echocardiography (ESE) in athletes abusing AAS.
Methods and results
One hundred and fifteen top-level competitive bodybuilders were selected (70 males), including 65 athletes misusing AAS for at least 5 years (users), 50 anabolic-free bodybuilders (non-users), compared to 50 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis, and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Athletes showed increased LV mass index, wall thickness, and RV diameters compared with controls, whereas LV ejection fraction was comparable within the groups. left atrial volume index, LV and RV strain, and LV E/Em were significantly higher in AAS users. Users showed more B-lines during stress (median 4.4 vs. 1.25 in controls and 1.3 in non-users, P < 0.01 vs. users). By multivariable analyses, LV E/Ea (beta coefficient = 0.35, P < 0.01), pulmonary artery systolic pressure (beta = 0.43, P < 0.001) at peak effort and number of weeks of AAS use per year (beta = 0.45, P < 0.001) emerged as the only independent determinants of resting RV lateral wall peak systolic two-dimensional strain. In addition, a close association between resting RV myocardial function and VO2 peak during ESE was evidenced (P < 0.001), with a powerful incremental value with respect to clinical and standard echocardiographic data.
Conclusions
In athletes abusing steroids, STE analysis showed an impaired RV systolic deformation, closely associated with reduced functional capacity during physical effort, and-during exercise-more pulmonary congestion.

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: 01 Aug 2021; epub ahead of print
D'Andrea A, Radmilovic J, Russo V, Sperlongano S, ... Bossone E, Picano E
Eur J Prev Cardiol: 01 Aug 2021; epub ahead of print | PMID: 34339497
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Impact:
Abstract

Cardiac rehabilitation and all-cause mortality in patients with heart failure: a retrospective cohort study.

Buckley BJR, Harrison SL, Fazio-Eynullayeva E, Underhill P, ... Thijssen DHJ, Lip GYH
Aims 
Despite the benefits of exercise training in the secondary prevention of cardiovascular disease, there are conflicting findings for the impact of exercise-based cardiac rehabilitation (CR) on mortality for patients with heart failure (HF). The aim of this study was therefore to investigate the association of exercise-based CR with all-cause mortality, hospitalisation, stroke, and atrial fibrillation in patients with heart failure.
Methods and results
A retrospective cohort study was conducted which utilized a global federated health research network, primarily in the USA. Patients with a diagnosis of HF were compared between those with and without an electronic medical record of CR and/or exercise programmes within 6 months of an HF diagnosis. Patients with HF undergoing exercise-based CR were propensity score matched to HF patients without exercise-based CR by age, sex, race, comorbidities, medications, and procedures (controls). We ascertained 2-year incidence of all-cause mortality, hospitalization, stroke, and atrial fibrillation. Following propensity score matching, a total of 40 364 patients with HF were identified. Exercise-based CR was associated with 42% lower odds of all-cause mortality [odds ratio 0.58, 95% confidence interval (CI): 0.54-0.62], 26% lower odds of hospitalization (0.74, 95% CI 0.71-0.77), 37% lower odds of incident stroke (0.63, 95% CI 0.51-0.79), and 53% lower odds of incident atrial fibrillation (0.47, 95% CI 0.4-0.55) compared to controls, after propensity score matching. The beneficial association of CR and exercise on all-cause mortality was consistent across all subgroups, including patients with HFrEF (0.52, 95% CI 0.48-0.56) and HFpEF (0.65, 95% CI 0.60-0.71).
Conclusion 
Exercise-based CR was associated with lower odds of all-cause mortality, hospitalizations, incident stroke, and incident atrial fibrillation at 2-year follow-up for patients with HF (including patients with HFrEF and HFpEF).

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: 31 Jul 2021; epub ahead of print
Buckley BJR, Harrison SL, Fazio-Eynullayeva E, Underhill P, ... Thijssen DHJ, Lip GYH
Eur J Prev Cardiol: 31 Jul 2021; epub ahead of print | PMID: 34333607
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Impact:
Abstract

Validation and comparison of 28 risk prediction models for coronary artery disease.

Lenselink C, Ties D, Pleijhuis R, van der Harst P
Aims
Risk prediction models (RPMs) for coronary artery disease (CAD), using variables to calculate CAD risk, are potentially valuable tools in prevention strategies. However, their use in the clinical practice is limited by a lack of poor model description, external validation, and head-to-head comparisons.
Methods and results
CAD RPMs were identified through Tufts PACE CPM Registry and a systematic PubMed search. Every RPM was externally validated in the three cohorts (the UK Biobank, LifeLines, and PREVEND studies) for the primary endpoint myocardial infarction (MI) and secondary endpoint CAD, consisting of MI, percutaneous coronary intervention, and coronary artery bypass grafting. Model discrimination (C-index), calibration (intercept and regression slope), and accuracy (Brier score) were assessed and compared head-to-head between RPMs. Linear regression analysis was performed to evaluate predictive factors to estimate calibration ability of an RPM. Eleven articles containing 28 CAD RPMs were included. No single best-performing RPM could be identified across all cohorts and outcomes. Most RPMs yielded fair discrimination ability: mean C-index of RPMs was 0.706 ± 0.049, 0.778 ± 0.097, and 0.729 ± 0.074 (P < 0.01) for prediction of MI in UK Biobank, LifeLines, and PREVEND, respectively. Endpoint incidence in the original development cohorts was identified as a significant predictor for external validation performance.
Conclusion
Performance of CAD RPMs was comparable upon validation in three large cohorts, based on which no specific RPM can be recommended for predicting CAD risk.

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

Eur J Prev Cardiol: 29 Jul 2021; epub ahead of print
Lenselink C, Ties D, Pleijhuis R, van der Harst P
Eur J Prev Cardiol: 29 Jul 2021; epub ahead of print | PMID: 34329420
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This program is still in alpha version.