Journal: Eur J Prev Cardiol

Sorted by: date / impact
Abstract

Pulmonary transit of contrast during exercise is related to improved cardio-pulmonary performance in highly trained endurance athletes.

Sanz-de la Garza M, Vaquer-Seguí A, Durán K, Blanco I, ... Bijnens B, Sitges M
Background
The mechanisms underlying the high interindividual variability demonstrated for right-ventricular (RV) adaptation to exercise have not yet been identified, but different pulmonary vascular adaptations among individuals could be involved. Pulmonary transit of agitated saline (PTAS) during exercise has been demonstrated to be a good estimator of vascular reserve.
Aim
The aim of this study was to evaluate the presence of PTAS among endurance athletes (EAs) of both sexes and its influence on RV adaptation to exercise.
Methods
A total of 100 highly trained EAs performed a maximal cardiopulmonary exercise test. Bi-ventricular functional and structural characteristics as well as PTAS were evaluated at baseline and at peak exercise. Athletes were distributed between two groups based on the amount of PTAS during exercise as high (HTPAS; >12 bubbles) and low (LPTAS; ≤12 bubbles).
Results
Overall, 11 EAs exhibited an intra-cardiac shunt at rest and 1 met the criteria for chronic pulmonary disease and were excluded from the study. Among the remaining 88 EAs (51% women), 47 (53%) athletes were classified as HPTAS and 41 (47%) as LPTAS. HPTAS capability was associated with significantly larger RV contractile reserve, larger pulmonary vascular reserve and an enhanced maximal exercise capacity. On multivariate analysis, females were the only independent correlate of the HPTAS capability.
Conclusion
In highly trained endurance athletes, a HPTAS capability during exercise corresponded to an increase in pulmonary vascular and RV contractile reserves as well as an enhanced maximal exercise capacity. The long-term clinical or performance implications of the absence or presence of pulmonary shunting, and the subsequent RV afterload increase while performing exercise, remains to be determined.



Eur J Prev Cardiol: 30 Aug 2020; 27:1504-1514
Sanz-de la Garza M, Vaquer-Seguí A, Durán K, Blanco I, ... Bijnens B, Sitges M
Eur J Prev Cardiol: 30 Aug 2020; 27:1504-1514 | PMID: 31801048
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease.

Feng M, Darabi M, Tubeuf E, Canicio A, ... Guillas I, Kontush A
Background
Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown. We hypothesised that the capacity of high-density lipoprotein (HDL) to acquire free cholesterol upon triglyceride-rich lipoprotein (TGRL) lipolysis by lipoprotein lipase underlies the non-linear relationship between HDL-C and cardiovascular risk.
Methods
To assess our hypothesis, we developed a novel assay to evaluate the capacity of HDL to acquire free cholesterol (as fluorescent TopFluor® cholesterol) from TGRL upon in vitro lipolysis by lipoprotein lipase.
Results
When the assay was applied to several populations markedly differing in plasma HDL-C levels, transfer of free cholesterol was significantly decreased in low HDL-C patients with acute myocardial infarction (-45%) and type 2 diabetes (-25%), and in subjects with extremely high HDL-C of >2.59 mmol/L (>100 mg/dL) (-20%) versus healthy normolipidaemic controls. When these data were combined and plotted against HDL-C concentrations, an inverse U-shape relationship was observed. Consistent with these findings, animal studies revealed that the capacity of HDL to acquire cholesterol upon lipolysis was reduced in low HDL-C apolipoprotein A-I knock-out mice and was negatively correlated with aortic accumulation of [H]-cholesterol after oral gavage, attesting this functional characteristic as a negative metric of postprandial atherosclerosis.
Conclusions
Free cholesterol transfer to HDL upon TGRL lipolysis may underlie the U-shape relationship between HDL-C and cardiovascular disease, linking HDL-C to triglyceride metabolism and atherosclerosis.



Eur J Prev Cardiol: 29 Sep 2020; 27:1606-1616
Feng M, Darabi M, Tubeuf E, Canicio A, ... Guillas I, Kontush A
Eur J Prev Cardiol: 29 Sep 2020; 27:1606-1616 | PMID: 31840535
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Aortic root remodelling in competitive athletes.

Abulí M, Grazioli G, Sanz de la Garza M, Montserrat S, ... Oxborough D, Sitges M
Background
Controversy remains about the cut-off limits for detecting aortic dilatation in athletes, particularly in large-sized individuals. The allometric scaling model has been used to obtain size-independent measurements in cardiovascular structures in the general population.
Aim
The purpose of this study was to validate the use of allometric scaling in the measurement of the aortic root for competitive athletes and to offer reference values.
Methods
This was a cross-sectional study that analyses the dimensions of aortic root found in the echocardiogram performed as part of pre-participation sports screening in competitive athletes between 2012-2015. Beta exponents were calculated for height and body surface area in the whole cohort. In order to establish whether a common exponent could be used in both genders the following model was assessed  = ab*exp(c*sex). If a common exponent could not be applied then sex-specific beta exponents were calculated.
Results
Two thousand and eighty-three athletes (64% men) were included, from a broad spectrum of 44 different sports disciplines, including basketball, volleyball and handball. The mean age was 18.2 ± 5.1 years (range 12-35 years) and all athletes were Caucasian, with a training load of 12.5 ± 5.4 h per week. Indexed aortic root dimension showed a correlation with ratiometric scaling by body surface area (r: -0.419) and generated size independence values with a very light correlation with height (r: -0.084); and with the allometric scaling by body surface area (r: -0.063) and height (r: -0.070). The absolute value of aortic root was higher in men than in women ( < 0.001). These differences were maintained with allometric scaling.
Conclusion
Size-independent aortic root dimension values are provided using allometric scaling by body surface area and height in a large cohort of competitive athletes. Aortic root values were larger in men than in women, both in absolute values and after allometric scaling. The use of these indexed aortic reference ranges can be useful for the early detection of aortic pathologies.



Eur J Prev Cardiol: 30 Aug 2020; 27:1518-1526
Abulí M, Grazioli G, Sanz de la Garza M, Montserrat S, ... Oxborough D, Sitges M
Eur J Prev Cardiol: 30 Aug 2020; 27:1518-1526 | PMID: 31852302
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Behavioural cardiovascular risk factors and prevalence of diabetes in subjects with familial hypercholesterolaemia.

Perez-Calahorra S, Civeira F, Guallar-Castillón P, Pinto X, ... Rodriguez-Artalejo F, Laclaustra M

A low prevalence of type 2 diabetes mellitus has been reported in familial hypercholesterolaemia. Whether a healthier lifestyle could explain it has not been explored. This cross-sectional study determines the prevalence of lifestyle-related cardiovascular risk factors in heterozygous familial hypercholesterolaemia (HeFH) from the Dyslipidaemia Registry of the Spanish Atherosclerosis Society and in the ENRICA study, a representative sample of the adult Spanish general population, weighted to match the age and sex distribution of the HeFH sample. A total of 2185 HeFH patients and 11,856 individuals from ENRICA were included. HeFH had lower body mass index and fewer of them were smokers than in the reference population. A model adjusted for age, sex and body mass index showed that HeFH more frequently had cardiovascular disease (odds ratio (OR) 23.98; 95% confidence interval (CI) 18.40-31.23) and hypertension (OR 1.20; 95% CI 1.07-1.35), and took anti-hypertensive medication (OR 1.36; 95% CI 1.18-1.56) and anti-diabetic medication (OR 1.25; 95% CI 1.00-1.56), but less frequently were smokers (OR 0.79; 95% CI 0.71-0.89). In a HeFH subsample ( = 513) with complete blood glucose information, those patients without cardiovascular disease showed lower prevalence of smoking and type 2 diabetes mellitus, lower body mass index and glucose, and higher diastolic blood pressure than the Spanish population. The differences in type 2 diabetes mellitus were justified mostly by the difference in body mass index. Body mass index adjustment also showed higher prevalence of hypertension and use of anti-hypertensive drugs in HeFH. In summary, HeFH patients had lower body mass index, which may contribute to explaining the lower prevalence of diabetes, and lower current smoking but higher hypertension.



Eur J Prev Cardiol: 29 Sep 2020; 27:1649-1660
Perez-Calahorra S, Civeira F, Guallar-Castillón P, Pinto X, ... Rodriguez-Artalejo F, Laclaustra M
Eur J Prev Cardiol: 29 Sep 2020; 27:1649-1660 | PMID: 31914797
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

Joshi R, Wannamethee SG, Engmann J, Gaunt T, ... Hingorani AD, Schmidt AF
Aims
Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke.
Methods
Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure.
Results
The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke.
Conclusions
Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.



Eur J Prev Cardiol: 29 Sep 2020; 27:1617-1626
Joshi R, Wannamethee SG, Engmann J, Gaunt T, ... Hingorani AD, Schmidt AF
Eur J Prev Cardiol: 29 Sep 2020; 27:1617-1626 | PMID: 31996015
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

ECG criteria for the detection of high-risk cardiovascular conditions in master athletes.

Panhuyzen-Goedkoop NM, Wellens HJ, Verbeek AL, Jørstad HT, Smeets JR, Peters RJ
Objective
Structured electrocardiography (ECG) analysis is used to screen athletes for high-risk cardiovascular conditions (HRCC) to prevent sudden cardiac death. ECG criteria have been specified and recommended for use in young athletes ≤ 35 years. However, it is unclear whether these ECG criteria can also be applied to master athletes >35 years.
Aim
The purpose of this study was to test whether the existing ECG criteria for detecting HRCC in young athletes can be applied to master athletes.
Methods
We conducted a cross-sectional study among athletes >35 years screened for HRCC between 2006 and 2010. We performed a blinded retrospective analysis of master athletes\' ECGs, separately applying European Society of Cardiology (ESC)-2005, Seattle, and International criteria. HRCC were defined using recommendations from the international cardiac societies American Heart Association and American College of Cardiology, and ESC, based on ECG screening and cardiovascular evaluation (CVE).
Results
We included 2578 master athletes in the study, of whom 494 had initial screening abnormalities mandating CVE. Atrial enlargement (109, 4.1%) and left ventricular hypertrophy (98, 3.8%) were the most common ECG abnormalities found using the ESC-2005 or Seattle criteria. Applying the International criteria, ST-segment deviation (66, 2.6%), and T-wave inversion (58, 2.2%) were most frequent. The ESC-2005 criteria detected more HRCC (46, 1.8%) compared with the Seattle (36, 1.4%) and International criteria (33, 1.3%). The most frequently detected HRCC was coronary artery disease (24, 0.9%).
Conclusion
ECG criteria recommended for use in young athletes can be applied to master athletes\' ECGs to detect HRCC. The ESC-2005 criteria had the highest sensitivity for detecting HRCC among master athletes.



Eur J Prev Cardiol: 30 Aug 2020; 27:1529-1538
Panhuyzen-Goedkoop NM, Wellens HJ, Verbeek AL, Jørstad HT, Smeets JR, Peters RJ
Eur J Prev Cardiol: 30 Aug 2020; 27:1529-1538 | PMID: 31996014
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning.

Pina A, Helgadottir S, Mancina RM, Pavanello C, ... Volpe G, Romeo S
Aims
Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. The gold standard for FH diagnosis is genetic testing, available, however, only in selected university hospitals. Clinical scores - for example, the Dutch Lipid Score - are often employed as alternative, more accessible, albeit less accurate FH diagnostic tools. The aim of this study is to obtain a more reliable approach to FH diagnosis by a \"virtual\" genetic test using machine-learning approaches.
Methods and results
We used three machine-learning algorithms (a classification tree (CT), a gradient boosting machine (GBM), a neural network (NN)) to predict the presence of FH-causative genetic mutations in two independent FH cohorts: the FH Gothenburg cohort (split into training data ( = 174) and internal test ( = 74)) and the FH-CEGP Milan cohort (external test,  = 364). By evaluating their area under the receiver operating characteristic (AUROC) curves, we found that the three machine-learning algorithms performed better (AUROC 0.79 (CT), 0.83 (GBM), and 0.83 (NN) on the Gothenburg cohort, and 0.70 (CT), 0.78 (GBM), and 0.76 (NN) on the Milan cohort) than the clinical Dutch Lipid Score (AUROC 0.68 and 0.64 on the Gothenburg and Milan cohorts, respectively) in predicting carriers of FH-causative mutations.
Conclusion
In the diagnosis of FH-causative genetic mutations, all three machine-learning approaches we have tested outperform the Dutch Lipid Score, which is the clinical standard. We expect these machine-learning algorithms to provide the tools to implement a virtual genetic test of FH. These tools might prove particularly important for lipid clinics without access to genetic testing.



Eur J Prev Cardiol: 29 Sep 2020; 27:1639-1646
Pina A, Helgadottir S, Mancina RM, Pavanello C, ... Volpe G, Romeo S
Eur J Prev Cardiol: 29 Sep 2020; 27:1639-1646 | PMID: 32019371
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Exploring the determinants of the cardiac changes after ultra-long duration exercise: The echocardiographic Spartathlon study.

Christou GA, Pagourelias ED, Anifanti MA, Sotiriou PG, ... Kouidi EJ, Deligiannis AP
Aim
The investigation of the pathophysiological determinants of cardiac changes following ultra-long duration exercise.
Methods
Twenty-seven runners who finished a 246 km running race were examined both before and after the finish of the race. Examinations included echocardiography and measurement of body weight and blood biochemical parameters.
Results
Exercise increased left ventricular end-diastolic interventricular septum thickness (LVIVSd) ( < 0.001) and posterior wall thickness (LVPWTd) ( = 0.001) and right ventricular end-diastolic area ( = 0.005), while reduced tricuspid annular plane systolic excursion (TAPSE) ( = 0.004). A minor decrease in the peak absolute values of both left ventricular (from -20.9 ± 2.3% to -18.8 ± 2.0%,  = 0.009) and right ventricular (from -22.9 ± 3.6% to -21.2 ± 3.0%,  = 0.040) global longitudinal strains occurred. There was decrease in body weight ( < 0.001) and increase in both circulating high-sensitivity troponin I ( = 0.028) and amino-terminal pro-B type natriuretic peptide (NT-proBNP) ( = 0.018). The change in the sum of LVIVSd and LVPWTd correlated negatively with percentage change of body weight ( = -0.416,  = 0.049). The only independent determinant of post-exercise NT-proBNP was pulmonary artery systolic pressure ( = 0.797,  = 0.002). Post-exercise NT-proBNP correlated positively with percentage changes of basal (RVbas) ( = 0.582,  = 0.037) and mid-cavity (RVmid) ( = 0.618,  = 0.043) right ventricular diameters and negatively with percentage change of TAPSE ( = -0.720,  = 0.008). Similar correlations with RVbas, RVmid and TAPSE were found for pulmonary artery systolic pressure. Post-exercise high-sensitivity troponin I correlated negatively with percentage change of body weight ( = -0.601,  = 0.039), but was not associated with any cardiac parameter.
Conclusion
The main cardiac effects of ultra-long duration exercise were the decrease in left ventricular end-diastolic dimensions and increase in left ventricular wall thickness, as well as minimal dilatation and alteration in systolic function of right ventricle, possibly due to the altered exercise-related right ventricular afterload.



Eur J Prev Cardiol: 30 Aug 2020; 27:1467-1477
Christou GA, Pagourelias ED, Anifanti MA, Sotiriou PG, ... Kouidi EJ, Deligiannis AP
Eur J Prev Cardiol: 30 Aug 2020; 27:1467-1477 | PMID: 32013601
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of preventive screening and lifestyle interventions in women with a history of preeclampsia: A micro-simulation study.

Lagerweij GR, Brouwers L, De Wit GA, Moons K, ... van Rijn BB, Koffijberg H
Background
Preeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk-based lifestyle interventions in women with previous preeclampsia are beneficial and cost-effective is unknown.
Methods
A micro-simulation model was developed to assess the life-long impact of preventive cardiovascular screening strategies initiated after women experienced preeclampsia during pregnancy. Screening was started at the age of 30 or 40 years and repeated every five years. Data (initial and follow-up) from women with a history of preeclampsia was used to calculate 10-year cardiovascular disease risk estimates according to Framingham Risk Score. An absolute risk threshold of 2% was evaluated for treatment selection, i.e. lifestyle interventions (e.g. increasing physical activity). Screening benefits were assessed in terms of costs and quality-adjusted-life-years, and incremental cost-effectiveness ratios compared with no screening.
Results
Expected health outcomes for no screening are 27.35 quality-adjusted-life-years and increase to 27.43 quality-adjusted-life-years (screening at 30 years with 2% threshold). The expected costs for no screening are €9426 and around €13,881 for screening at 30 years (for a 2% threshold). Preventive screening at 40 years with a 2% threshold has the most favourable incremental cost-effectiveness ratio, i.e. €34,996/quality-adjusted-life-year, compared with other screening scenarios and no screening.
Conclusions
Early cardiovascular disease risk screening followed by risk-based lifestyle interventions may lead to small long-term health benefits in women with a history of preeclampsia. However, the cost-effectiveness of a lifelong cardiovascular prevention programme starting early after preeclampsia with risk-based lifestyle advice alone is relatively unfavourable. A combination of risk-based lifestyle advice plus medical therapy may be more beneficial.



Eur J Prev Cardiol: 30 Aug 2020; 27:1389-1399
Lagerweij GR, Brouwers L, De Wit GA, Moons K, ... van Rijn BB, Koffijberg H
Eur J Prev Cardiol: 30 Aug 2020; 27:1389-1399 | PMID: 32054298
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Triglyceride concentrations and non-high-density lipoprotein cholesterol goal attainment in the ODYSSEY phase 3 trials with alirocumab.

Vallejo-Vaz AJ, Leiter LA, Del Prato S, Taskinen MR, ... Samuel R, Ray KK
Aims
Guidelines recommend targeting non-high-density lipoprotein cholesterol to reduce cardiovascular risk. We assessed the impact of baseline triglycerides on non-high-density lipoprotein cholesterol goal attainment in 10 phase 3 trials with alirocumab versus control ( = 4983).
Methods
Trials were grouped into four pools based on alirocumab dose (75-150 mg every 2 weeks), control (placebo/ezetimibe) and statin use. Baseline triglyceride quintiles were built within each pool. Non-high-density lipoprotein cholesterol goal attainment (very high risk: <100 mg/dl; moderate/high risk: <130 mg/dl), low-density lipoprotein cholesterol goal attainment (very high risk: <70 mg/dl; moderate/high risk: <100 mg/dl) and changes from baseline in lipid parameters were assessed at Week 24 among baseline triglyceride quintiles.
Results
Higher baseline triglycerides were associated with a worse cardiovascular risk profile. Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol increased with higher triglycerides, but the magnitude in non-high-density lipoprotein cholesterol was three- to four-fold higher compared with the increase in low-density lipoprotein cholesterol. Non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol percentage reductions from baseline with alirocumab were similar regardless of baseline triglycerides. A greater proportion of alirocumab-treated patients attained non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol goals compared with placebo or ezetimibe. Unlike low-density lipoprotein cholesterol goal attainment, non-high-density lipoprotein cholesterol goal attainment significantly declined with increasing baseline triglycerides ( < 0.05 for trend tests). A single standard deviation increase in baseline log(triglycerides) was significantly associated with lower odds ratios of attaining non-high-density lipoprotein cholesterol goals in the different pools and treatment (alirocumab/placebo/ezetimibe) groups, unlike low-density lipoprotein cholesterol goal attainment.
Conclusion
Individuals with increased triglycerides have higher non-high-density lipoprotein cholesterol levels and lower rates of non-high-density lipoprotein cholesterol goal attainment (unlike low-density lipoprotein cholesterol goal attainment). Alirocumab improves non-high-density lipoprotein cholesterol goal attainment in this population. These results highlight the impact of triglycerides on non-high-density lipoprotein cholesterol and the need for novel therapies targeting triglyceride-related pathways.



Eur J Prev Cardiol: 29 Sep 2020; 27:1663-1674
Vallejo-Vaz AJ, Leiter LA, Del Prato S, Taskinen MR, ... Samuel R, Ray KK
Eur J Prev Cardiol: 29 Sep 2020; 27:1663-1674 | PMID: 32089006
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Rivaroxaban plus aspirin for the prevention of ischaemic events in patients with cardiovascular disease: a cost-effectiveness study.

Petersohn S, Pouwels X, Ramaekers B, Ten Cate-Hoek A, Joore M
Background
Dual pathway inhibition with 2.5 mg rivaroxaban twice daily plus 100 mg aspirin once daily may be a promising alternative to 100 mg aspirin antiplatelet therapy for the prevention of cardiovascular events in patients with coronary artery disease and/or peripheral arterial disease. However, treatment costs and bleeding risks are higher, and there is another treatment option for peripheral arterial disease, 75 mg clopidogrel. A comprehensive assessment of benefits, risks and costs of dual pathway inhibition versus standard of care is needed.
Methods
We used a state transition model including cardiovascular, ischaemic limb and bleeding events to compare dual pathway inhibition to aspirin antiplatelet therapy in coronary artery disease, and additionally to clopidogrel antiplatelet therapy in peripheral arterial disease patients. We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a €50,000/quality-adjusted life-year threshold.
Results
Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were €32,109 in coronary artery disease and €26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). Incremental cost-effectiveness ratios were below €20,000 in comorbid peripheral arterial disease patients and coronary artery disease patients younger than 65 years, incremental cost-effectiveness ratios were above €50,000 in carotid artery disease patients and coronary artery disease patients older than 75 years.
Conclusion
Lifelong preventive treatment of coronary artery disease and peripheral arterial disease patients at risk of cardiovascular events with dual pathway inhibition improves health outcomes and seems overall cost-effective relative to aspirin antiplatelet therapy and also to clopidogrel antiplatelet therapy for peripheral arterial disease, particularly in comorbid patients, but not in older patients and in carotid artery disease patients. These findings may warrant a targeted approach.



Eur J Prev Cardiol: 30 Aug 2020; 27:1354-1365
Petersohn S, Pouwels X, Ramaekers B, Ten Cate-Hoek A, Joore M
Eur J Prev Cardiol: 30 Aug 2020; 27:1354-1365 | PMID: 32223323
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Low QRS voltages in Olympic athletes: Prevalence and clinical correlates.

Mango F, Caselli S, Luchetti A, Pelliccia A
Background
Recently, novel interest in low QRS voltages was prompted by the observation that low QRS voltages are present in arrhythmogenic cardiomyopathy patients, even before occurrence of symptoms/events.
Aim
The purpose of this study was to assess prevalence and clinical correlates of low QRS voltages in Olympic athletes, evaluated and followed-up within our cardiovascular screening programme.
Methods
Five hundred and sixteen athletes consecutively examined (2010-2011) were included in this study. A low QRS voltage was defined as amplitude of QRS <0.5 mV in limb and/or <1.0 mV in precordial leads. Cardiovascular evaluation included 12-lead and exercise electrocardiogram, echocardiography and, selectively, additional tests to confirm diagnosis. Athletes were followed-up for 5 ± 2 (1-9) years.
Results
The majority of athletes (493; 96%) showed normal/increased R/S-wave voltages, but 23 (4%) had low QRS voltages. No differences were observed in low QRS voltage athletes compared to normal/increased QRS voltages for QRS duration, QTc and PR intervals, left ventricular cavity size and mass, or gender and sport participated. However, premature ventricular beats, occurred more frequently in low QRS voltages (39% vs 7%;  < 0.001), with patterns suggesting origin from left or right free wall. No diseases or events were registered in low QRS voltage athletes over the follow-up.
Conclusions
In Olympic athletes, the prevalence of low QRS voltages was 4%. Athletes with low QRS voltages did not differ from other athletes according to sport participated in or cardiac dimensions. However, more frequently (39% vs 7%) they showed premature ventricular beats, originating from either the left or right free ventricular wall. Therefore, long-term follow-up with serial clinical evaluations is needed in low QRS voltage athletes, in order to definitely clarify the clinical significance.



Eur J Prev Cardiol: 30 Aug 2020; 27:1542-1548
Mango F, Caselli S, Luchetti A, Pelliccia A
Eur J Prev Cardiol: 30 Aug 2020; 27:1542-1548 | PMID: 32228059
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Exercise in the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) era: A Question and Answer session with the experts Endorsed by the section of Sports Cardiology & Exercise of the European Association of Preventive Cardiology (EAPC).

Bhatia RT, Marwaha S, Malhotra A, Iqbal Z, ... Papadakis M, Sharma S

Regular exercise has multiple benefits for physical and mental health, including the body\'s ability to combat infections. The current COVID-19 pandemic and the social distancing measures employed to curtail the impact of the infection are likely to reduce the amount of usual physical activity being performed by most individuals, including habitual exercisers. The uncertainties relating to the impact of the SARS-CoV-2 virus on the heart may cause increased anxiety, particularly in athletes who need to sustain a vigorous exercise regime in order to maintain their skills and fitness in preparation for return to competition after a short re-training period. The aim of this document is to provide practical answers to pertinent questions being posed by the sporting community, in an attempt to offer reassurance, promote safe participation in exercise during as well as after the COVID-19 pandemic and provide a framework of management for physicians caring for athletes.



Eur J Prev Cardiol: 30 Jul 2020; 27:1242-1251
Bhatia RT, Marwaha S, Malhotra A, Iqbal Z, ... Papadakis M, Sharma S
Eur J Prev Cardiol: 30 Jul 2020; 27:1242-1251 | PMID: 32475157
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

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

Scheffers LE, Berg LEV, Ismailova G, Dulfer K, Takkenberg JJ, 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.



Eur J Prev Cardiol: 26 Jul 2020:2047487320942869; epub ahead of print
Scheffers LE, Berg LEV, Ismailova G, Dulfer K, Takkenberg JJ, Helbing WA
Eur J Prev Cardiol: 26 Jul 2020:2047487320942869; epub ahead of print | PMID: 32718238
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

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

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



Eur J Prev Cardiol: 26 Jul 2020:2047487320941987; epub ahead of print
Diaz R, Li QH, Bhatt DL, Bittner VA, ... Steg PG,
Eur J Prev Cardiol: 26 Jul 2020:2047487320941987; epub ahead of print | PMID: 32718237
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Life-threatening and major cardiac events during long-distance races: updates from the prospective RACE PARIS registry with a systematic review and meta-analysis.

Gerardin B, Guedeney P, Bellemain-Appaix A, Levasseur T, ... Collet JP,
Aims
Limited data exist regarding the incidence and aetiology of life-threatening events such as major cardiac events or exertional heat stroke during long-distance races. We aimed to provide an updated incidence, etiology and prognosis of life-threatening events during long-distance races.
Methods
The prospective RACE PARIS registry recorded all life-threatening events/fatal events occurring during 46 marathons, half-marathons and other long-distance races in the Paris area between 2006 and 2016, comprising 1,073,722 runners. Event characteristics were determined by review of medical records and interviews with survivors.
Results
The incidence of life-threatening events, exertional heat stroke and major cardiac events was 3.35 per 100,000, 1.02 per 100,000 and 2.33 per 100,000, respectively, including 18 sudden cardiac arrests (1.67 per 100,000). The main aetiology of sudden cardiac arrest was myocardial ischaemia (11/18), due to acute coronary thrombosis (6/11), stable atherosclerotic coronary artery disease (2/11), coronary dissection (1/11), anomalous connection (1/11) or myocardial bridging (1/11). A third of participants with ischaemia-related major cardiac events presented with pre-race clinical symptoms. Major cardiac events were more frequent in the case of a high pollution index (6.78 per 100,000 vs. 2.07 per 100,000, odds ratio 3.27, 95% confidence interval 1.12-9.54). Case fatality was low (0.19 per 100,000). Similarly, we report in a meta-analysis of eight long-distance race registries comprising 16,223,866 runners a low incidence of long-distance race-related sudden cardiac arrest (0.82 per 100,000) and fatality (0.39 per 100,000). Death following sudden cardiac arrest was strongly associated with initial asystole or pulseless rhythm.
Conclusion
Long-distance race-related life-threatening events remain rare although serious events. Better information for runners on the risk of pre-race clinical symptoms, outside air pollution and temperature may reduce their incidence.



Eur J Prev Cardiol: 26 Jul 2020:2047487320943001; epub ahead of print
Gerardin B, Guedeney P, Bellemain-Appaix A, Levasseur T, ... Collet JP,
Eur J Prev Cardiol: 26 Jul 2020:2047487320943001; epub ahead of print | PMID: 32718236
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Next-generation sequencing to confirm clinical familial hypercholesterolemia.

Reeskamp LF, Tromp TR, Defesche JC, Grefhorst A, ... Hovingh GK, Zuurbier L
Background
Familial hypercholesterolemia is characterised by high low-density lipoprotein-cholesterol levels and is caused by a pathogenic variant in ,or . We investigated which proportion of suspected familial hypercholesterolemia patients was genetically confirmed, and whether this has changed over the past 20 years in The Netherlands.
Methods
Targeted next-generation sequencing of 27 genes involved in lipid metabolism was performed in patients with low-density lipoprotein-cholesterol levels greater than 5 mmol/L who were referred to our centre between May 2016 and July 2018. The proportion of patients carrying likely pathogenic or pathogenic variants in ,oror the minor familial hypercholesterolemia genesandwere investigated. This was compared with the yield of Sanger sequencing between 1999 and 2016.
Results
A total of 227 out of the 1528 referred patients (14.9%) were heterozygous carriers of a pathogenic variant in(80.2%),(14.5%) or(5.3%). More than 50% of patients with a Dutch Lipid Clinic Network score of \'probable\' or \'definite\' familial hypercholesterolemia were familial hypercholesterolemia mutation-positive; 4.8% of the familial hypercholesterolemia mutation-negative patients carried a variant in one of the minor familial hypercholesterolemia genes. The mutation detection rate has decreased over the past two decades, especially in younger patients in which it dropped from 45% in 1999 to 30% in 2018.
Conclusions
A rare pathogenic variant in ,orwas identified in 14.9% of suspected familial hypercholesterolemia patients and this rate has decreased in the past two decades. Stringent use of clinical criteria algorithms is warranted to increase this yield. Variants in the minor familial hypercholesterolemia genes provide a possible explanation for the familial hypercholesterolemia phenotype in a minority of patients.



Eur J Prev Cardiol: 26 Jul 2020:2047487320942996; epub ahead of print
Reeskamp LF, Tromp TR, Defesche JC, Grefhorst A, ... Hovingh GK, Zuurbier L
Eur J Prev Cardiol: 26 Jul 2020:2047487320942996; epub ahead of print | PMID: 32718233
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Electronic cigarettes and health with special focus on cardiovascular effects: position paper of the European Association of Preventive Cardiology (EAPC).

Kavousi M, Pisinger C, Barthelemy JC, Smedt D, ... Vassiliou VS, Løchen ML
Background
Tobacco use is the single largest preventable risk factor for premature death of non-communicable diseases and the second leading cause of cardiovascular disease. In response to the harmful effects of tobacco smoking, the use of electronic cigarettes (e-cigarettes) has emerged and gained significant popularity over the past 15 years. E-cigarettes are promoted as safe alternatives for traditional tobacco smoking and are often suggested as a way to reduce or quit smoking. However, evidence suggests they are not harmless.
Discussion
The rapid evolution of the e-cigarette market has outpaced the legislator\'s regulatory capacity, leading to mixed regulations. The increasing use of e-cigarettes in adolescents and young individuals is of concern. While the long-term direct cardiovascular effects of e-cigarettes remain largely unknown, the existing evidence suggests that the e-cigarette should not be regarded as a cardiovascular safe product. The contribution of e-cigarette use to reducing conventional cigarette use and smoking cessation is complex, and the impact of e-cigarette use on long-term cessation lacks sufficient evidence.
Conclusion
This position paper describes the evidence regarding the prevalence of e-cigarette smoking, uptake of e-cigarettes in the young, related legislations, cardiovascular effects of e-cigarettes and the impact of e-cigarettes on smoking cessation. Knowledge gaps in the field are also highlighted. The recommendations from the population science and public health section of the European Association of Preventive Cardiology are presented.



Eur J Prev Cardiol: 28 Jul 2020:2047487320941993; epub ahead of print
Kavousi M, Pisinger C, Barthelemy JC, Smedt D, ... Vassiliou VS, Løchen ML
Eur J Prev Cardiol: 28 Jul 2020:2047487320941993; epub ahead of print | PMID: 32726563
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

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

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



Eur J Prev Cardiol: 27 Jul 2020:2047487320939217; epub ahead of print
Cioffi G, Giorda CB, Lucci D, Nada E, ... Maggioni AP,
Eur J Prev Cardiol: 27 Jul 2020:2047487320939217; epub ahead of print | PMID: 32722919
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

How to manage an athlete with mitral valve prolapse.

Cavarretta E, Peruzzi M, Versaci F, Frati G, Sciarra L
Introduction
Under the term degenerative mitral valve prolapse different pathophysiological and clinical entities coexist in a spectrum ranging from Barlow\'s disease to fibroelastic deficiency, and represent the most common cause of mitral regurgitation in the general population and in athletes. Carrying a mitral valve prolapse is usually considered a benign condition for athletes, but recently the scientific literature has focused on the malignant, thus rare, arrhythmic mitral valve prolapse and its dramatic association with sudden cardiac death, so that specific features should be considered a red flag and prompt additional exams before clear for competition.
Discussion
As the athlete\'s heart is morphologically accompanied by remodelling and dilatation of the cardiac chambers induced by exercise, it may be challenging to differentiate the degree of left ventricular and atrial dilation induced by significant mitral regurgitation from physiological remodelling, especially in endurance athletes.
Conclusion
This how-to article provides clinical and useful data to manage athletes with mitral valve prolapse and to distinguish high-risk athletes carrying the features of arrhythmic mitral valve prolapse.



Eur J Prev Cardiol: 29 Jul 2020:2047487320941646; epub ahead of print
Cavarretta E, Peruzzi M, Versaci F, Frati G, Sciarra L
Eur J Prev Cardiol: 29 Jul 2020:2047487320941646; epub ahead of print | PMID: 32731762
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Detecting undiagnosed atrial fibrillation in UK primary care: Validation of a machine learning prediction algorithm in a retrospective cohort study.

Sekelj S, Sandler B, Johnston E, Pollock KG, ... Ng FS, Farooqui U
Aims
To evaluate the ability of a machine learning algorithm to identify patients at high risk of atrial fibrillation in primary care.
Methods
A retrospective cohort study was undertaken using the DISCOVER registry to validate an algorithm developed using a Clinical Practice Research Datalink (CPRD) dataset. The validation dataset included primary care patients in London, England aged ≥30 years from 1 January 2006 to 31 December 2013, without a diagnosis of atrial fibrillation in the prior 5 years. Algorithm performance metrics were sensitivity, specificity, positive predictive value, negative predictive value (NPV) and number needed to screen (NNS). Subgroup analysis of patients aged ≥65 years was also performed.
Results
Of 2,542,732 patients in DISCOVER, the algorithm identified 604,135 patients suitable for risk assessment. Of these, 3.0% (17,880 patients) had a diagnosis of atrial fibrillation recorded before study end. The area under the curve of the receiver operating characteristic was 0.87, compared with 0.83 in algorithm development. The NNS was nine patients, matching the CPRD cohort. In patients aged ≥30 years, the algorithm correctly identified 99.1% of patients who did not have atrial fibrillation (NPV) and 75.0% of true atrial fibrillation cases (sensitivity). Among patients aged ≥65 years ( = 117,965), the NPV was 96.7% with 91.8% sensitivity.
Conclusions
This atrial fibrillation risk prediction algorithm, based on machine learning methods, identified patients at highest risk of atrial fibrillation. It performed comparably in a large, real-world population-based cohort and the developmental registry cohort. If implemented in primary care, the algorithm could be an effective tool for narrowing the population who would benefit from atrial fibrillation screening in the United Kingdom.



Eur J Prev Cardiol: 12 Aug 2020:2047487320942338; epub ahead of print
Sekelj S, Sandler B, Johnston E, Pollock KG, ... Ng FS, Farooqui U
Eur J Prev Cardiol: 12 Aug 2020:2047487320942338; epub ahead of print | PMID: 32787456
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association between change in cardiorespiratory fitness and incident hypertension in Swedish adults.

Holmlund T, Ekblom B, Börjesson M, Andersson G, Wallin P, Ekblom-Bak E
Aims
To explore how change in cardiorespiratory fitness is associated with incident hypertension in adults, and whether the association varies between sex, age, body mass index, cardiorespiratory fitness at baseline and follow-up time. A second aim is to study how change in other lifestyle-related variables affects the results.
Methods
A total of 91,728 participants (48% women), normotensive at baseline, with two examinations from occupational health service screenings between 1982 and 2019 (mean duration 4.3 years) were included. Cardiorespiratory fitness was assessed as estimated maximal oxygen consumption using submaximal cycle testing. Change in cardiorespiratory fitness was expressed as the percentage change per year. Incident hypertension was defined as systolic blood pressure of 140 mmHg or greater or diastolic blood pressure of 90 mmHg or greater, or self-reported physician-diagnosed hypertension, at second examination.
Results
A large increase (≥3% annual change) in cardiorespiratory fitness was associated with a 11% lower risk of incident hypertension compared with maintainers (-1 to +1%), after multi-adjustment including change in smoking, body mass index, diet, stress and exercise habits. On the contrary, a small (-1 to -<3%) and large (≥-3%) decrease in cardiorespiratory fitness associated with a 21% and 25% higher risk compared with maintainers. Longer duration between the examinations was associated with stronger risk associations. Preserving, or changing to, risk level for the other lifestyle variables was associated with a higher risk of incident hypertension. However, a simultaneous maintenance of or increase in cardiorespiratory fitness attenuated the risk associated with smoking, and stress.
Conclusion
Preserving or increasing cardiorespiratory fitness should be part of any long-term strategy to decrease the risk of incident hypertension.



Eur J Prev Cardiol: 18 Aug 2020:2047487320942997; epub ahead of print
Holmlund T, Ekblom B, Börjesson M, Andersson G, Wallin P, Ekblom-Bak E
Eur J Prev Cardiol: 18 Aug 2020:2047487320942997; epub ahead of print | PMID: 32812803
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Trends in cardiovascular diseases burden and vascular risk factors in Italy: The Global Burden of Disease study 1990-2017.

Cortesi PA, Fornari C, Madotto F, Conti S, ... Mantovani LG,
Aims
An exhaustive and updated estimation of cardiovascular disease burden and vascular risk factors is still lacking in European countries. This study aims to fill this gap assessing the global Italian cardiovascular disease burden and its changes from 1990 to 2017 and comparing the Italian situation with European countries.
Methods
All accessible data sources from the 2017 Global Burden of Disease study were used to estimate the cardiovascular disease prevalence, mortality and disability-adjusted life years and cardiovascular disease attributable risk factors burden in Italy from 1990 to 2017. Furthermore, we compared the cardiovascular disease burden within the 28 European Union countries.
Results
Since 1990, we observed a significant decrease of cardiovascular disease burden, particularly in the age-standardised prevalence (-12.7%), mortality rate (-53.8%), and disability-adjusted life years rate (-55.5%). Similar improvements were observed in the majority of European countries. However, we found an increase in all-ages prevalence of cardiovascular diseases from 5.75 m to 7.49 m Italian residents. Cardiovascular diseases still remain the first cause of death (34.8% of total mortality). More than 80% of the cardiovascular disease burden could be attributed to known modifiable risk factors such as high systolic blood pressure, dietary risks, high low density lipoprotein cholesterol, and impaired kidney function.
Conclusions
Our study shows a decline in cardiovascular mortality and disability-adjusted life years, which reflects the success in reducing disability, premature death and early incidence of cardiovascular diseases. However, the burden of cardiovascular diseases is still high. An approach that includes the cooperation and coordination of all stakeholders of the Italian National Health System is required to further reduce this burden.



Eur J Prev Cardiol: 23 Aug 2020:2047487320949414; epub ahead of print
Cortesi PA, Fornari C, Madotto F, Conti S, ... Mantovani LG,
Eur J Prev Cardiol: 23 Aug 2020:2047487320949414; epub ahead of print | PMID: 32838553
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Success factors in high-effect, low-cost eHealth programs for patients with hypertension: a systematic review and meta-analysis.

Blok S, van der Linden EL, Somsen GA, Tulevski II, Winter MM, van den Born BH
Background
eHealth programs can lower blood pressure but also drive healthcare costs. This study aims to review the evidence on the effectiveness and costs of eHealth for hypertension and assess commonalities in programs with high effect and low additional cost.
Results
Overall, the incremental decrease in systolic blood pressure using eHealth, compared to usual care, was 3.87 (95% confidence interval (CI) 2.98-4.77) mmHg at 6 months and 5.68 (95% CI 4.77-6.59) mmHg at 12 months\' follow-up. High intensity interventions were more effective, resulting in a 2.6 (95% CI 0.5-4.7) (at 6 months) and 3.3 (95% CI 1.4-5.1) (at 12 months) lower systolic blood pressure, but were also more costly, resulting in €170 (95% CI 56-284) higher costs at 6 months and €342 (95% CI 128-556) at 12 months. Programs that included a high volume of participants showed €203 (95% CI 99-307) less costs than those with a low volume at 6 months, and €525 (95% CI 299-751) at 12 months without showing a difference in systolic blood pressure. Studies that implemented eHealth as a partial replacement, rather than addition to usual care, were also less costly (€119 (95% CI -38-201 at 6 months) and €346 (95% CI 261-430 at 12 months)) without being less effective. Evidence on eHealth programs for hypertension is ambiguous, heterogeneity on effectiveness and costs is high ( = 56-98%).
Conclusion
Effective eHealth with limited additional costs should focus on high intensity interventions, involve a large number of participants and use eHealth as a partial replacement for usual care.



Eur J Prev Cardiol: 10 Sep 2020:2047487320957170; epub ahead of print
Blok S, van der Linden EL, Somsen GA, Tulevski II, Winter MM, van den Born BH
Eur J Prev Cardiol: 10 Sep 2020:2047487320957170; epub ahead of print | PMID: 32915673
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Predictors of pre-rehabilitation exercise capacity in elderly European cardiac patients - The EU-CaRE study.

Marcin T, Eser P, Prescott E, Mikkelsen N, ... de Kluiver EP, Wilhelm M
Aims
Functional capacity is an important endpoint for therapies oriented to older adults with cardiovascular diseases. The literature on predictors of exercise capacity is sparse in the elderly population. In a longitudinal European study on effectiveness of cardiac rehabilitation of seven European countries in elderly (>65 years) coronary artery disease or valvular heart disease patients, predictors for baseline exercise capacity were determined, and reference ranges for elderly cardiac patients provided.
Methods
Mixed models were performed in 1282 patients (mean age 72.9 ± 5.4 years, 79% male) for peak oxygen consumption relative to weight (peak VO; ml/kg per min) with centre as random factor and patient anthropometric, demographic, social, psychological and nutritional parameters, as well as disease aetiology, procedure, comorbidities and cardiovascular risk factors as fixed factors.
Results
The most important predictors for low peak VO were coronary artery bypass grafting or valve surgery, low resting forced expiratory volume, reduced left ventricular ejection fraction, nephropathy and peripheral arterial disease. Each cumulative comorbidity or cardiovascular risk factors reduced exercise capacity by 1.7 ml/kg per min and 1.1 ml/kg per min, respectively. Males had a higher peak VO per body mass but not per lean mass. Haemoglobin was significantly linked to peak VO in both surgery and non-surgery patients.
Conclusions
Surgical procedures, cumulative comorbidities and cardiovascular risk factors were the factors with the strongest relation to reduced exercise capacity in the elderly. Expression of peak VO per lean mass rather than body mass allows a more appropriate comparison between sexes. Haemoglobin is strongly related to peak VO and should be considered in studies assessing exercise capacity, especially in studies on patients after cardiac surgery.



Eur J Prev Cardiol: 30 Oct 2020; 27:1702-1712
Marcin T, Eser P, Prescott E, Mikkelsen N, ... de Kluiver EP, Wilhelm M
Eur J Prev Cardiol: 30 Oct 2020; 27:1702-1712 | PMID: 31852300
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effectiveness of comprehensive cardiac rehabilitation in coronary artery disease patients treated according to contemporary evidence based medicine: Update of the Cardiac Rehabilitation Outcome Study (CROS-II).

Salzwedel A, Jensen K, Rauch B, Doherty P, ... Schmid JP, Davos CH
Background
Despite numerous studies and meta-analyses the prognostic effect of cardiac rehabilitation is still under debate. This update of the Cardiac Rehabilitation Outcome Study (CROS II) provides a contemporary and practice focused approach including only cardiac rehabilitation interventions based on published standards and core components to evaluate cardiac rehabilitation delivery and effectiveness in improving patient prognosis.
Design
A systematic review and meta-analysis.
Methods
Randomised controlled trials and retrospective and prospective controlled cohort studies evaluating patients after acute coronary syndrome, coronary artery bypass grafting or mixed populations with coronary artery disease published until September 2018 were included.
Results
Based on CROS inclusion criteria out of 7096 abstracts six additional studies including 8671 patients were identified (two randomised controlled trials, two retrospective controlled cohort studies, two prospective controlled cohort studies). In total, 31 studies including 228,337 patients were available for this meta-analysis (three randomised controlled trials, nine prospective controlled cohort studies, 19 retrospective controlled cohort studies; 50,653 patients after acute coronary syndrome 14,583, after coronary artery bypass grafting 163,101, mixed coronary artery disease populations; follow-up periods ranging from 9 months to 14 years). Heterogeneity in design, cardiac rehabilitation delivery, biometrical assessment and potential confounders was considerable. Controlled cohort studies showed a significantly reduced total mortality (primary endpoint) after cardiac rehabilitation participation in patients after acute coronary syndrome (prospective controlled cohort studies: hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.20-0.69; retrospective controlled cohort studies HR 0.64, 95% CI 0.53-0.76; prospective controlled cohort studies odds ratio 0.20, 95% CI 0.08-0.48), but the single randomised controlled trial fulfilling the CROS inclusion criteria showed neutral results. Cardiac rehabilitation participation was also associated with reduced total mortality in patients after coronary artery bypass grafting (retrospective controlled cohort studies HR 0.62, 95% CI 0.54-0.70, one single randomised controlled trial without fatal events), and in mixed coronary artery disease populations (retrospective controlled cohort studies HR 0.52, 95% CI 0.36-0.77; two out of 10 controlled cohort studies with neutral results).
Conclusion
CROS II confirms the effectiveness of cardiac rehabilitation participation after acute coronary syndrome and after coronary artery bypass grafting in actual clinical practice by reducing total mortality under the conditions of current evidence-based coronary artery disease treatment. The data of CROS II, however, underscore the urgent need to define internationally accepted minimal standards for cardiac rehabilitation delivery as well as for scientific evaluation.



Eur J Prev Cardiol: 30 Oct 2020; 27:1756-1774
Salzwedel A, Jensen K, Rauch B, Doherty P, ... Schmid JP, Davos CH
Eur J Prev Cardiol: 30 Oct 2020; 27:1756-1774 | PMID: 32089005
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiac rehabilitation of elderly patients in eight rehabilitation units in western Europe: Outcome data from the EU-CaRE multi-centre observational study.

Prescott E, Eser P, Mikkelsen N, Holdgaard A, ... Van\'t Hof AW, de Kluiver EP
Aims
The European Cardiac Rehabilitation in the Elderly (EU-CaRE) HORIZON 2020 project compares the sustainable effects of cardiac rehabilitation (CR) in elderly patients.
Methods and results
A total of 1633 patients with coronary artery disease (CAD) or heart valve replacement (HVR), with or without revascularization, aged 65 or above, who participated in CR were included. Peak oxygen uptake (VO), smoking, body mass index, diet, physical activity, serum lipids, psychological distress and medication were assessed before and after CR (T0 and T1) and after 12 months (T2). Patients undergoing coronary artery bypass surgery or surgical HVR had lower VO at T0 and a greater increase to T1 and T2 (2.8 and 4.4 ml/kg/min, respectively) than CAD patients undergoing percutaneous or no revascularization (1.6 and 1.4 ml/kg/min, respectively). After multivariable adjustment, earlier CR uptake was associated with greater improvements in VO. The proportion of CAD patients with three or more uncontrolled risk factors declined from 58.4% at T0 to 40.1% at T2 ( < 0.0001). Psychological distress scores all improved and adherence to medication was overall good at all sites. There were significant differences in risk factor burden across sites, but no CR program was superior to others.
Conclusions
The outcomes of VO in CR programs across Europe seemed mainly determined by timing of uptake and were maintained or even further improved at 1-year follow-up. Despite significant improvements, 40.1% of CAD patients still had three or more risk factors not at target after 1 year. Differences across sites could not be ascribed to characteristics of the CR programs offered.



Eur J Prev Cardiol: 30 Oct 2020; 27:1716-1729
Prescott E, Eser P, Mikkelsen N, Holdgaard A, ... Van't Hof AW, de Kluiver EP
Eur J Prev Cardiol: 30 Oct 2020; 27:1716-1729 | PMID: 32102550
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term follow-up with a smartphone application improves exercise capacity post cardiac rehabilitation: A randomized controlled trial.

Lunde P, Bye A, Bergland A, Grimsmo J, Jarstad E, Nilsson BB
Background
Mobile health interventions, especially smartphone applications (apps), have been proposed as promising interventions for supporting adherence to healthy behaviour in patients post cardiac rehabilitation (CR). The overall aim of the study was to examine the effect of individualized follow-up with an app for one year on peak oxygen uptake (VO) in patients completing CR.
Design
The study was designed as a single-blinded multicentre randomized controlled trial.
Methods
The intervention group (IG) received individualized follow-up enabled with an app for one year, while the control group (CG) received usual care. The primary outcome was difference in VO. Secondary outcomes included exercise performance (time to exhaustion, peak incline (%) and peak velocity (km/h)), bodyweight, resting blood pressure, lipid profile, triglycerides, exercise habits, health-related quality of life, health status and self-perceived goal achievement.
Results
In total, 113 patients completing CR (73.4% with coronary artery disease, 16.8% after valve surgery and 9.8% with other heart diseases) were randomly allocated to the IG or CG. Intention to treat analyses showed a statistically significant difference in VO between the groups at follow-up of 2.2 ml/kg/min, 95% confidence interval 0.9-3.5 ( < 0.001). Statistically significant differences were also observed in exercise performance, exercise habits and in self-perceived goal achievement.
Conclusions
Individualized follow-up for one year with an app significantly improved VO, exercise performance and exercise habits, as well as self-perceived goal achievement, compared with a CG in patients post-CR. There were no statistically significant differences between the groups at follow-up in the other outcome measures evaluated.



Eur J Prev Cardiol: 30 Oct 2020; 27:1782-1792
Lunde P, Bye A, Bergland A, Grimsmo J, Jarstad E, Nilsson BB
Eur J Prev Cardiol: 30 Oct 2020; 27:1782-1792 | PMID: 32106713
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Quantifying the impact of delayed delivery of cardiac rehabilitation on patients\' health.

Hinde S, Harrison A, Bojke L, Doherty P
Background
Despite its role as an effective intervention to improve the long-term health of patients with cardiovascular disease and existence of national guidelines on timeliness, many health services still fail to offer cardiac rehabilitation in a timely manner after referral. The impact of this failure on patient health and the additional burden on healthcare providers in an English setting is quantified in this article.
Methods
Two logistic regressions are conducted, using the British Heart Foundation National Audit of Cardiac Rehabilitation dataset, to estimate the impact of delayed cardiac rehabilitation initiation on the level of uptake and completion. The results of these regressions are applied to a decision model to estimate the long-term implications of these factors on patient health and National Health Service expenditure.
Results
We demonstrate that the failure of 43.6% of patients in England to start cardiac rehabilitation within the recommended timeframe results in a 15.3% reduction in uptake, and 7.4% in completion. These combine to cause an average lifetime loss of 0.08 years of life expectancy per person. Scaled up to an annual cohort this implies 10,753 patients not taking up cardiac rehabilitation due to the delay, equating to a loss of 3936 years of life expectancy. We estimate that an additional £12.3 million of National Health Service funding could be invested to alleviate the current delay.
Conclusions
The current delay in many patients starting cardiac rehabilitation is causing quantifiable and avoidable harm to their long-term health; policy and research must now look at both supply and demand solutions in tackling this issue.



Eur J Prev Cardiol: 30 Oct 2020; 27:1775-1781
Hinde S, Harrison A, Bojke L, Doherty P
Eur J Prev Cardiol: 30 Oct 2020; 27:1775-1781 | PMID: 32212842
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Improvements in exercise capacity of older adults during cardiac rehabilitation.

Bierbauer W, Scholz U, Bermudez T, Debeer D, ... Schmid JP, Hermann M
Aims
Cardiac rehabilitation plays a vital role in secondary prevention of cardiovascular patients. Female sex and higher age, however, are associated with non-referral to cardiac rehabilitation. Improving exercise capacity during cardiac rehabilitation is essential to reduce morbidity and mortality risks. The objective of this study was to closely examine the beneficial changes in exercise capacity of older patients of both sexes during cardiac rehabilitation and to identify the most important predictors of the change in exercise capacity.
Method
A sample of 13,612 patients (mean age = 69.10 ± 11.8 years, 63.7% men, 19% > 80 years) was analysed. Data were prospectively assessed from 2012-2018 in six Swiss in-patient cardiovascular rehabilitation clinics. Improvement in exercise capacity measured with the six-minute walking test represents the outcome variable. Univariate and multivariate analyses, as well as the random forest method were used to estimate variable importance.
Results
Mean improvement in the six-minute walking test was 113.5 ± 90.5 m (men = 118.7 ± 110.0; women = 104.4 ± 93.0, Cohen\'s d = 0.16). The presence of heart failure, diabetes mellitus and psychiatric diagnoses was related to reduced but nonetheless clinically relevant six-minute walking test improvement. Random forest analysis suggests that baseline exercise capacity, age, time in rehabilitation and heart failure were the most important predictors for improvement in exercise capacity. Clinically relevant improvements in exercise capacity (>45 m) were also present into old age (85 years) and for both sexes.
Conclusion
As indicated by these results, efforts need to be increased to refer eligible patients to structured rehabilitation programmes, irrespective of patients\' age and sex.



Eur J Prev Cardiol: 30 Oct 2020; 27:1747-1755
Bierbauer W, Scholz U, Bermudez T, Debeer D, ... Schmid JP, Hermann M
Eur J Prev Cardiol: 30 Oct 2020; 27:1747-1755 | PMID: 32321285
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

High-intensity interval training is effective and superior to moderate continuous training in patients with heart failure with preserved ejection fraction: A randomized clinical trial.

Donelli da Silveira A, Beust de Lima J, da Silva Piardi D, Dos Santos Macedo D, ... Laukkanen JA, Stein R
Background
Heart failure with preserved ejection fraction (HFpEF) is a prevalent syndrome, with exercise intolerance being one of its hallmarks, contributing to worse quality of life and mortality. High-intensity interval training is an emerging training option, but its efficacy in HFpEF patients is still unknown.
Design
Single-blinded randomized clinical trial.
Methods
Single-blinded randomized clinical trial with exercise training 3 days per week for 12 weeks. HFpEF patients were randomly assigned to high-intensity interval training or moderate continuous training. At baseline and after 12 week follow-up, patients underwent clinical assessment, echocardiography and cardiopulmonary exercise testing (CPET).
Results
Mean age was 60 ± 9 years and 63% were women. Both groups ( = 19) showed improved peak oxygen consumption (VO), but high-intensity interval training patients ( = 10) had a significantly higher increase, of 22%, compared with 11% in the moderate continuous training ( = 9) individuals (3.5 (3.1 to 4.0) . 1.9 (1.2 to 2.5) mL·kg·min,  < 0.001). Ventilatory efficiency and other CPET measures, as well as quality of life score, increased equally in the two groups. Left ventricular diastolic function also improved with training, reflected by a significant reduction in E/e\' ratio by echocardiography (-2.6 (-4.3 to -1.0) . -2.2 (-3.6 to -0.9) for high-intensity interval training and moderate continuous training, respectively;  < 0.01). There were no exercise-related adverse events.
Conclusions
This randomized clinical trial provided evidence that high-intensity interval training is a potential exercise modality for HFpEF patients, being more effective than moderate continuous training in improving peak VO. However, the two strategies were equally effective in improving ventilatory efficiency and other CPET parameters, quality of life score and diastolic function after 3 months of training.



Eur J Prev Cardiol: 30 Oct 2020; 27:1733-1743
Donelli da Silveira A, Beust de Lima J, da Silva Piardi D, Dos Santos Macedo D, ... Laukkanen JA, Stein R
Eur J Prev Cardiol: 30 Oct 2020; 27:1733-1743 | PMID: 31964186
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.