bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel antidiabetic drugs and risk of cardiovascular events in patients without baseline metformin use: a meta-analysis
Authors: Masson Walter , Lavalle-Cobo Augusto , Lobo Martín , Masson Gerardo , Molinero Graciela
Published: January 2021

Aims

To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naïve patients with type 2 diabetes (T2D).

Methods and results

A meta-analysis was performed of randomized controlled clinical trials of GLP-1RAs and SGLT-2 inhibitors on T2D populations, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoint, explored in the subgroup of SGLT-2 inhibitors studies, was cardiovascular death or hospitalization for heart failure. A random-effects meta-analysis model was applied. Six eligible trials (three studies of SGLT-2 inhibitors and three trials of GLP-1RAs), including 13 049 patients, were identified and considered eligible for the analyses. The new antidiabetic drugs were associated with a significant reduction in MACE [odds ratio (OR): 0.80, 95% confidence interval: 0.70–0.93; I2: 53%]. The subgroup analysis showed the following findings: GLP-1RAs group, OR: 0.77 (95% confidence interval 0.67–0.88); SGLT-2 inhibitors, OR: 0.85 (95% confidence interval 0.63–1.15). SGLT-2 inhibitors were associated with a significant reduction in hospitalization for heart failure or cardiovascular mortality incidence (OR: 0.67, 95% confidence interval: 0.47–0.95; I2: 78%).

Conclusion

In this meta-analysis, new antidiabetic drugs reduced the incidence of MACE in metformin-naïve T2D patients. The beneficial effect was especially observed in the GLP-1RAs subgroup. The use of SGLT-2 inhibitors was associated with a reduction in cardiovascular death or hospitalization for heart failure. These results support the fact that metformin would not be indispensable to obtain positive cardiovascular effects when new antidiabetic drugs are administered.
Delphi consensus recommendations on how to provide cardiovascular rehabilitation in the COVID-19 era
Authors: Ambrosetti Marco , Abreu Ana , Cornelissen Veronique , Hansen Dominique , Iliou Marie Christine , Kemps Hareld , Pedretti Roberto Franco Enrico , Voller Heinz , Wilhelm Mathias , Piepoli Massimo Francesco , Beccaluva Chiara Giuseppina , Beckers Paul , Berger Thomas , Davos Costantinos H , Dendale Paul , Doehner Wolfram , Frederix Ines , Gaita Dan , Gevaert Andreas , Kouidi Evangelia , Kraenkel Nicolle , Laukkanen Jari , Maranta Francesco , Mazza Antonio , Mendes Miguel , Neunhaeuserer Daniel , Niebauer Josef , Pavy Bruno , Gil Carlos Peña , Rauch Bernhard , Sarzi Braga Simona , Simonenko Maria , Cohen-Solal Alain , Sommaruga Marinella , Venturini Elio , Vigorito Carlo
Published: January 2021

This Delphi consensus by 28 experts from the European Association of Preventive Cardiology (EAPC) provides initial recommendations on how cardiovascular rehabilitation (CR) facilities should modulate their activities in view of the ongoing coronavirus disease 2019 (COVID-19) pandemic. A total number of 150 statements were selected and graded by Likert scale [from −5 (strongly disagree) to +5 (strongly agree)], starting from six open-ended questions on (i) referral criteria, (ii) optimal timing and setting, (iii) core components, (iv) structure-based metrics, (v) process-based metrics, and (vi) quality indicators. Consensus was reached on 58 (39%) statements, 48 ‘for’ and 10 ‘against’ respectively, mainly in the field of referral, core components, and structure of CR activities, in a comprehensive way suitable for managing cardiac COVID-19 patients. Panelists oriented consensus towards maintaining usual activities on traditional patient groups referred to CR, without significant downgrading of intervention in case of COVID-19 as a comorbidity. Moreover, it has been suggested to consider COVID-19 patients as a referral group to CR per se when the viral disease is complicated by acute cardiovascular (CV) events; in these patients, the potential development of COVID-related CV sequelae, as well as of pulmonary arterial hypertension, needs to be focused. This framework might be used to orient organization and operational of CR programmes during the COVID-19 crisis.
Cardiovascular effectiveness of human-based vs. exendin-based glucagon like peptide-1 receptor agonists: a retrospective study in patients with type 2 diabetes
Authors: Longato Enrico , Di Camillo Barbara , Sparacino Giovanni , Tramontan Lara , Avogaro Angelo , Fadini Gian Paolo
Published: January 2021

Aims

Glucagon like peptide-1 (GLP-1) receptor agonists (GLP-1RA) are effective to control type 2 diabetes (T2Ds) and can protect from adverse cardiovascular outcomes. GLP-1RA are based on the human GLP-1 or the exendin-4 sequence. We compared cardiovascular outcomes of patients with T2D who received human-based or exendin-based GLP-1RA in routine clinical practice.

Methods and results

We performed a retrospective study on the administrative database of T2D patients from the Veneto Region (North-East Italy). We identified patients who initiated a human-based or exendin-based GLP-1RA from 2011 to 2018. The primary outcome was occurrence of major adverse cardiovascular events (MACE). Secondary outcomes were individual MACE components, revascularization, hospitalization for heart failure, or for cardiovascular causes. From 330 193 patients with diabetes, 6620 were new users of GLP-1RA. After propensity score matching, we analysed 1098 patients in each group, who were on average 61 years old, 59.5% males, 13% with established cardiovascular disease, had an estimated diabetes duration of 8.4 years, and a baseline HbA1c of 7.9%. During a median follow-up of 18 months, patients treated with human-based GLP-1RA as compared to those treated with exendin-based GLP-1RA, showed lower rates of MACE [hazard ratio 0.61; 95% confidence interval (CI) 0.39–0.95], myocardial infarction (0.51; 95% CI 0.28–0.94), and hospitalization for cardiovascular causes (0.66; 95% CI 0.47–0.92).

Conclusion

We observed better cardiovascular outcomes among patients treated with human-based vs. exendin-based GLP-1RA under routine care. In the absence of comparative trials and in view of the limitations of retrospective studies, this finding provides a moderate level of evidence to guide clinical decision.
Utility of risk prediction models to detect atrial fibrillation in screened participants
Authors: Poorthuis Michiel H F , Jones Nicholas R , Sherliker Paul , Clack Rachel , de Borst Gert J , Clarke Robert , Lewington Sarah , Halliday Alison , Bulbulia Richard
Published: January 2021

Aims

Atrial fibrillation (AF) is associated with higher risk of stroke. While the prevalence of AF is low in the general population, risk prediction models might identify individuals for selective screening of AF. We aimed to systematically identify and compare the utility of established models to predict prevalent AF.

Methods and results

Systematic search of PubMed and EMBASE for risk prediction models for AF. We adapted established risk prediction models and assessed their predictive performance using data from 2.5M individuals who attended vascular screening clinics in the USA and the UK and in the subset of 1.2M individuals with CHA2DS2-VASc ≥2. We assessed discrimination using area under the receiver operating characteristic (AUROC) curves and agreement between observed and predicted cases using calibration plots. After screening 6959 studies, 14 risk prediction models were identified. In our cohort, 10 464 (0.41%) participants had AF. For discrimination, six prediction model had AUROC curves of 0.70 or above in all individuals and those with CHA2DS2-VASc ≥2. In these models, calibration plots showed very good concordance between predicted and observed risks of AF. The two models with the highest observed prevalence in the highest decile of predicted risk, CHARGE-AF and MHS, showed an observed prevalence of AF of 1.6% with a number needed to screen of 63. Selective screening of the 10% highest risk identified 39% of cases with AF.

Conclusion

Prediction models can reliably identify individuals at high risk of AF. The best performing models showed an almost fourfold higher prevalence of AF by selective screening of individuals in the highest decile of risk compared with systematic screening of all cases.

Registration

This systematic review was registered (PROSPERO CRD42019123847).
The need for PCSK9 inhibitors and associated treatment costs according to the 2019 ESC dyslipidaemia guidelines vs. the risk-based allocation algorithm of the 2017 ESC consensus statement: a simulation study in a contemporary CAD cohort
Authors: Blaum Christopher , Seiffert Moritz , Goßling Alina , Kröger Friederike , Bay Benjamin , Lorenz Thiess , Braetz Julian , Graef Annika , Zeller Tanja , Schnabel Renate , Clemmensen Peter , Westermann Dirk , Blankenberg Stefan , Brunner Fabian J , Waldeyer Christoph
Published: January 2021

Background

The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of <55 mg/dL for patients with atherosclerotic cardiovascular disease (ASCVD), with a concomitant Class IA upgrade for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients not reaching their LDL-C goal under conventional lipid-lowering therapy.

Aims

We aim to quantify the need for PCSK9i and the related costs to achieve the revised LDL-C goal in ASCVD patients compared to former ESC recommendations, in particular the risk-based 2017 ESC consensus update.

Methods and results

We included patients with ASCVD from an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating a treatment algorithm adding sequentially a statin, ezetimibe, and a PCSK9i was applied with consideration of partial and total statin intolerance. The need for PCSK9i was calculated for three different ESC recommendations (2019 guidelines, 2016 guidelines, 2017 consensus update). Preventable events and treatment costs due to PCSK9i were calculated for a range of annual event rates from 2% to 8% and annual treatment costs of ca. 6050 €. We included 1780 patients (mean age 69.5 years). Median LDL-C at baseline was 85.0 mg/dL, with 61% of patients taking lipid-lowering medication. The need for PCSK9i was simulated to be 42.0% (ESC 2019), 31.9% (ESC 2016), and 5.0% (ESC 2017). The LDL-C goals were achieved in 97.9%, 99.1%, and 60.9% of patients, respectively. Annual treatment cost for PCSK9i per 1 000 000 ASCVD patients would be 2.54 billion € (ESC 2019) compared to 0.30 billion € (ESC 2017). Costs per prevented event due to PCSK9i initiation differed widely, e.g. 887 000 € for an event rate of 3% and a treatment goal of <55 mg/dL compared to 205 000 € for an event rate of 7% and risk-based use of PCSK9i.

Conclusion

The revised LDL-C treatment goals increase the projected need for PCSK9i with a substantial increase in associated treatment cost. An allocation strategy based on residual LDL-C and clinical or angiographic risk factors leads to a more tailored target population for PCSK9i with a reasonable benefit/cost ratio.
Ten-year all-cause mortality according to smoking status in patients with severe coronary artery disease undergoing surgical or percutaneous revascularization
Authors: Takahashi Kuniaki , Thuijs Daniel J F M , Gao Chao , Ono Masafumi , Holmes David R , Mack Michael J , Morice Marie-Claude , Mohr Friedrich-Wilhelm , Curzen Nick , Davierwala Piroze M , Milojevic Milan , Dawkins Keith D , Wykrzykowska Joanna J , de Winter Robbert J , McEvoy John William , Onuma Yoshinobu , Head Stuart J , Kappetein Arie Pieter , Serruys Patrick W ,   the SYNTAX Extended Survival Study Investigators
Published: January 2021

Aims

To evaluate the impact of various smoking status on 10-year all-cause mortality and to examine a relative treatment benefit of coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) according to smoking habits.

Methods and results

The SYNTAX Extended Survival study evaluated vital status up to 10 years in 1800 patients with de novo three-vessel disease and/or left main coronary artery disease randomized to CABG or PCI in the SYNTAX trial. In the present analysis, patients were divided into three groups (current, former, or never smokers), and the primary endpoint of 10-year all-cause mortality was assessed according to smoking status. Smoking status was available in 1793 (99.6%) patients at the time of randomization, of whom 363 were current smokers, 798 were former smokers, and 632 were never smokers. The crude rates of 10-year all-cause mortality were 29.7% in current smokers, 25.3% in former smokers, and 25.9% in never smokers (Log-rank P = 0.343). After adjustment for imbalances in baseline characteristics, current smokers had a significantly higher risk of 10-year all-cause mortality than never smokers [adjusted hazard ratio (aHR): 2.29; 95% confidence interval (CI): 1.60–3.27; P < 0.001], whereas former smokers did not. PCI was associated with a higher risk of all-cause mortality than CABG among current smokers (HR: 1.60; 95% CI: 1.09–2.35; P = 0.017), but it failed to show a significant interaction between revascularization strategies and smoking status (Pinteraction = 0.910).

Conclusion

Current smokers had a higher adjusted risk of 10-year all-cause mortality, whereas former smokers did not. The treatment effect of CABG vs. PCI did not differ significantly according to smoking status.

Clinical trial registration

SYNTAX: ClinicalTrials.gov reference: NCT00114972; SYNTAX Extended Survival. ClinicalTrials.gov reference: NCT03417050.
Efficacy and safety for the achievement of guideline-recommended lower low-density lipoprotein cholesterol levels: a systematic review and meta-analysis
Authors: Khan Safi U , Khan Muhammad U , Virani Salim S , Khan Muhammad Shahzeb , Khan Muhammad Zia , Rashid Muhammad , Kalra Ankur , Alkhouli Mohamad , Blaha Michael J , Blumenthal Roger S , Michos Erin D
Published: January 2021

Aim

The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors).

Methods and results

Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD −1.56; RR 0.94 (0.89–1.00)], cardiovascular mortality [ARD −1.49; RR 0.90 (0.81–1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy.

Conclusion

This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.
Safety and efficacy of alirocumab in a real-life setting: the ODYSSEY APPRISE study
Authors: Gaudet Daniel , López-Sendón José Luis , Averna Maurizio , Bigot Grégory , Banach Maciej , Letierce Alexia , Loy Megan , Samuel Rita , Manvelian Garen , Batsu Isabela , Henry Patrick ,   the ODYSSEY APPRISE Study investigators
Published: January 2021

Aims

To obtain safety and efficacy data of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting in high cardiovascular (CV) risk patients with heterozygous familial hypercholesterolaemia (HeFH) or very-high low-density lipoprotein cholesterol (LDL-C) levels despite maximally tolerated dose of statin ± other lipid-lowering therapies (MTD ± LLTs). ODYSSEY APPRISE was a prospective, single-arm, Phase 3b open-label (≥12 weeks to ≤ 30 months) European/Canadian study with alirocumab.

Methods and results

Patients received alirocumab 75 or 150 mg every 2 weeks, with dose adjustment based on physician’s judgment. In total, 994 patients were enrolled and treated. The mean [standard deviation (SD)] duration of alirocumab exposure was 72.4 (42.5) weeks. Patients with HeFH were younger [mean (SD) age of 53.8 (11.6) vs. 61.6 (10.1) years], more likely to be female (41.7% vs. 29.1%) and had higher baseline LDL-C compared with non-familial hypercholesterolaemia (non-FH) patients [mean (SD) of 5.1 (1.7) vs. 4.1 (1.1) mmol/L]. The overall incidence of treatment-emergent adverse events (TEAEs) was 71.6%; common TEAEs included nasopharyngitis (7.8%), myalgia (7.1%), and headache (6.2%). At Week 12, mean (SD) LDL-C was reduced by 54.8 (20.1)% from baseline [2.6 (1.2) mmol/L], maintained for the trial duration. LDL-C was reduced below 1.8 mmol/L and/or by ≥50% reduction from baseline in 69.1% of patients overall, and for 64.7 and 77.4% of the HeFH and non-FH subgroups, respectively.

Conclusion

In a real-life setting in patients with hypercholesterolaemia and high CV risk, alirocumab was generally well tolerated and resulted in clinically significant LDL-C reductions.
Predicting cardiovascular disease risk across the atherosclerotic disease continuum
Authors: Poppe Katrina K , Wells Sue , Jackson Rod , Doughty Robert N , Kerr Andrew J
Published: January 2021

Aims

Cardiovascular disease (CVD) guidelines dichotomize populations into primary and secondary prevention. We sought to develop a risk equation for secondary prevention of CVD that complements existing equations for primary prevention of CVD, and to describe the distributions of CVD risk across the population.

Methods and results

Adults aged 30–79 years who had routine CVD risk assessment in 2007–16 were identified from a large primary care cohort (PREDICT) with linkage to national and regional datasets. The 5-year risk of developing CVD among people without atherosclerotic CVD (ASCVD) was calculated using published equations (PREDICT-1°). A new risk equation (PREDICT-2°) was developed from Cox regression models to estimate the 5-year risk of CVD event recurrence among patients with known ASCVD. The outcome for both equations was hospitalization for a CVD event or cardiovascular death. Of the 475 161 patients, 12% (57 061) had ASCVD. For those without ASCVD, median (interquartile range) 5-year risks with the PREDICT-1° score were women 2.2% (1.2–4.2%), men 3.5% (2.0–6.6%), and whole group 2.9% (1.6–5.5%). For those with ASCVD, the 5-year risks with the new PREDICT-2° equation were women 21% (15–33%), men 23% (16–35%), and whole group 22% (16–34%).

Conclusion

We developed CVD risk scores for people with ASCVD (PREDICT-2°) to complement the PREDICT-1° scores. Median CVD risk is eight-fold higher among those with ASCVD than those without; however, there was overlap and the widest distribution of CVD risk was among people with ASCVD. This study describes a CVD risk continuum and the limitations of a ‘one size fits all’ approach to assessing risk in people with ASCVD.
Differential association of metabolic syndrome and low-density lipoprotein cholesterol with incident cardiovascular disease according to sex among Koreans: a national population-based study
Authors: Kim Su Yong , Go Tae-Hwa , Lee Jun Hyeok , Moon Jin Sil , Kang Dae Ryong , Bae Se Jin , Kim Se-Eun , Lee Sang Jun , Cho Dong-Hyuk , Park Young Jun , Youn Young Jin , Kim Jang Young , Ahn Sung Gyun
Published: January 2021

Aims

To investigate sex differences in the association of metabolic syndrome (MetS) and/or low-density lipoprotein cholesterol (LDL-C) with the incidence of cardiovascular and cerebrovascular disease (CCVD).

Methods and results

A total of 4 702 458 individuals, aged between 40 and 70, without a previous diagnosis of CCVD, underwent at least two health screenings between 2009 and 2011. Of them, 4 193 878 individuals (48.6% women) fulfilled the study requirements. The main outcome measured was the incidence of CCVD. By the end of 2017, 68 921 CCVD events occurred. Men in high LDL-C only, MetS only, and both MetS and high LDL-C groups had higher risks of CCVD. Women in MetS only and both MetS and high LDL-C groups, but not those in high LDL-C only group, had higher risks of CCVD than those in the reference group. The effect of the interaction between the presence of MetS and high LDL-C levels on the primary outcome was found among women (P for interaction 0.016) but not among men (P for interaction 0.897). A combination of MetS and LDL-C > 3.4 mmol/L increased the risk of CCVD as compared to MetS or LDL-C > 3.4 mmol/L alone in both men and women.

Conclusions

Metabolic syndrome confers an increased risk of CCVD irrespective of sexes; LDL-C > 3.4 mmol/L alone has a greater influence on CCVD occurrence in men than in women. Metabolic syndrome and high LDL-C beget a synergistically detrimental impact on the incidence of CCVD in both men and women. Treatment of dyslipidaemia and metabolic syndrome should be tailored according to patient characteristics.
Genetically determined hypercholesterolaemia results into premature leucocyte telomere length shortening and reduced haematopoietic precursors
Authors: Baragetti Andrea , Bonacina Fabrizia , Da Dalt Lorenzo , Moregola Annalisa , Zampoleri Veronica , Pellegatta Fabio , Grigore Liliana , Pirillo Angela , Spina Rossella , Cefalù Angelo Baldassarre , Averna Maurizio , Norata Giuseppe D , Catapano Alberico L
Published: January 2021

Aims

Leucocyte telomere length (LTL) shortening is a marker of cellular senescence and associates with increased risk of cardiovascular disease (CVD). A number of cardiovascular risk factors affect LTL, but the correlation between elevated LDL cholesterol (LDL-C) and shorter LTL is debated: in small cohorts including subjects with a clinical diagnosis of familial hypercholesterolaemia (FH). We assessed the relationship between LDL-C and LTL in subjects with genetic familial hypercholesterolaemia (HeFH) compared to those with clinically diagnosed, but not genetically confirmed FH (CD-FH), and normocholesterolaemic subjects.

Methods and results

LTL was measured in mononuclear cells-derived genomic DNA from 206 hypercholesterolaemic subjects (135 HeFH and 71 CD-FH) and 272 controls. HeFH presented shorter LTL vs. controls (1.27 ± 0.07 vs. 1.59 ± 0.04, P = 0.045). In particular, we found shorter LTL in young HeFH as compared to young controls (<35 y) (1.34 ± 0.08 vs. 1.64 ± 0.08, P = 0.019); moreover, LTL was shorter in statin-naïve HeFH subjects as compared to controls (1.23 ± 0.08 vs. 1.58 ± 0.04, P = 0.001). HeFH subjects presented shorter LTL compared to LDL-C matched CD-FH (1.33 ± 0.05 vs. 1.55 ± 0.08, P = 0.029). Shorter LTL was confirmed in leucocytes of LDLR-KO vs. wild-type mice and associated with lower abundance of long-term haematopoietic stem and progenitor cells (LT-HSPCs) in the bone marrow. Accordingly, HeFH subjects presented lower circulating haematopoietic precursors (CD34 + CD45dim cells) vs. CD-FH and controls.

Conclusions

We found (i) shorter LTL in genetically determined hypercholesterolaemia, (ii) lower circulating haematopoietic precursors in HeFH subjects, and reduced bone marrow resident LT-HSPCs in LDLR-KO mice. We support early cellular senescence and haematopoietic alterations in subjects with FH.
Impact of sarcopenia on prognosis in patients with heart failure with reduced and preserved ejection fraction
Authors: Konishi Masaaki , Kagiyama Nobuyuki , Kamiya Kentaro , Saito Hiroshi , Saito Kazuya , Ogasahara Yuki , Maekawa Emi , Misumi Toshihiro , Kitai Takeshi , Iwata Kentaro , Jujo Kentaro , Wada Hiroshi , Kasai Takatoshi , Nagamatsu Hirofumi , Ozawa Tetsuya , Izawa Katsuya , Yamamoto Shuhei , Aizawa Naoki , Makino Akihiro , Oka Kazuhiro , Momomura Shin-Ichi , Matsue Yuya
Published: January 2021

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.
QTc-interval prolongation and increased risk of sudden cardiac death associated with hydroxychloroquine
Authors: Ahmadizar Fariba , Soroush Negin , Ikram M Arfan , Kors Jan A , Kavousi Maryam , Stricker Bruno H
Published: January 2021

Aims: 

Hydroxychloroquine and chloroquine ([hydroxy]chloroquine) are drugs used to treat malaria and rheumatological disorders and were recently suggested as beneficial for prevention and treatment of patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. However, longitudinal studies to assess the electrocardiographic and cardiotoxic effects of these drugs are limited. In this study, we aimed to investigate the effect of these drugs on QTc-interval and incidence of sudden cardiac death (SCD).

Methods

We designed a longitudinal follow-up study of individuals within the prospective population-based Rotterdam Study. Eligible individuals had available data on medication and repeated ECG measurements. The study period was between 1 January 1991 and 1 January 2014. We studied on current and past use of [hydroxy]chloroquine as a time-varying exposure; high versus low daily dose of [hydroxy]chloroquine. QTc-interval duration, and the occurrence of SCD were the main outcomes. SCD was defined as an unexpected and sudden death due to cardiac arrhythmia within one hour of the onset of acute symptoms, and in patients without cardiac symptoms within 24 hours before death.

Results 

Among the study population of 14 594 individuals (58.8% women) with an average age of 65 years, 346 patients used [hydroxy]chloroquine at any time during follow-up. The total number of SCD cases was 609. In a multiple linear mixed model analysis, the current use of [hydroxy]chloroquine was associated with a significantly increased duration of the QTc-interval of 8.1 ms (95% CI: 3.6; 12.6) compared with non-users. The association was stronger among current-high daily dosage [15.3 (95%CI: 7.0; 23.6)] compared with current-low daily dosage [5.5 (95%CI: 0.4; 10.7)] users. In a Cox proportional hazard regression analysis, the risk of SCD was significantly higher in participants who were current users of [hydroxy]chloroquine than in non-users [adjusted hazard ratio; 3.7 (95%CI: 1.1; 12.6)].

Conclusions 

In this longitudinal study, persons who received [hydroxy]chloroquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.
Comprehensive multicomponent cardiac rehabilitation in cardiac implantable electronic devices recipients: a consensus document from the European Association of Preventive Cardiology (EAPC; Secondary prevention and rehabilitation section) and European Heart Rhythm Association (EHRA)
Authors: Pedretti Roberto F E , Iliou Marie-Christine , Israel Carsten W , Abreu Ana , Miljoen Hielko , Corrà Ugo , Stellbrink Christoph , Gevaert Andreas B , Theuns Dominic A , Piepoli Massimo F , Reibis Rona , Schmid Jean Paul , Wilhelm Matthias , Heidbuchel Hein , Völler Heinz ,   Document reviewers:, Ambrosetti Marco , Deneke Thomas , Cornelissen Veronique , R. Heinzel Frank , Davos Constantinos H , Kudaiberdieva Gulmira , Frederix Ines , Svendsen Jesper Hastrup , Hansen Dominique
Published: January 2021

Cardiac rehabilitation (CR) is a multidisciplinary intervention including patient assessment and medical actions to promote stabilization, management of cardiovascular risk factors, vocational support, psychosocial management, physical activity counselling, and prescription of exercise training. Millions of people with cardiac implantable electronic devices live in Europe and their numbers are progressively increasing, therefore, large subsets of patients admitted in CR facilities have a cardiac implantable electronic device. Patients who are cardiac implantable electronic devices recipients are considered eligible for a CR programme. This is not only related to the underlying heart disease but also to specific issues, such as psychological adaptation to living with an implanted device and, in implantable cardioverter-defibrillator patients, the risk of arrhythmia, syncope, and sudden cardiac death. Therefore, these patients should receive special attention, as their needs may differ from other patients participating in CR. As evidence from studies of CR in patients with cardiac implantable electronic devices is sparse, detailed clinical practice guidelines are lacking. Here, we aim to provide practical recommendations for CR in cardiac implantable electronic devices recipients in order to increase CR implementation, efficacy, and safety in this subset of patients.
A metabolomic approach to identify the link between sports activity and atheroprotection
Authors: Beutner Frank , Ritter Christian , Scholz Markus , Teren Andrej , Holdt Lesca Miriam , Teupser Daniel , Becker Susen , Thiele Holger , Gielen Stephan , Thiery Joachim , Ceglarek Uta
Published: January 2021

Aims

Physical activity (PA) is a mainstay of cardiovascular prevention. This study aimed to identify metabolic mediators of PA that protect against the development of atherosclerosis.

Methods and results

A total of 2160 participants in the LIFE heart study were analysed with data on PA and vascular phenotyping. In a targeted metabolomic approach, 61 metabolites (amino acids and acylcarnitines) were measured using liquid chromatography–tandem mass spectrometry. We investigated the interactions between PA, metabolites and markers of atherosclerosis in order to uncover possible mediation effects. Intended sports activity, but no daily PA, was associated with a lower degree of atherosclerosis, odds ratio (OR) for total atherosclerotic burden of 0.76 (95% confidence interval 0.62–0.94), carotid artery plaque OR 0.79 (0.66–0.96), and peripheral artery disease OR 0.74 (0.56–0.98). Twelve amino acids, free carnitine, five acylcarnitines were associated with sports activity. Of these, eight metabolites were also associated with the degree of atherosclerosis. In the mediation analyses, a cluster of amino acids (arginine, glutamine, pipecolic acid, taurine) were considered as possible mediators of atheroprotection. In contrast, a group of members of the carnitine metabolism (free carnitine, acetyl carnitine, octadecenoyl carnitine) were associated with inactivity and higher atherosclerotic burden.

Conclusion

Our metabolomic approach, which is integrated into a mediation model, provides transformative insights into the complex metabolic processes involved in atheroprotection. Metabolites with antioxidant and endothelial active properties are believed to be possible mediators of atheroprotection. The metabolomic mediation approach can support the understanding of complex diseases in order to identify targets for prevention and therapy.
Statin treatment reduces the risk of death among elderly frail patients: evidence from a large population-based cohort
Authors: Rea Federico , Mancia Giuseppe , Corrao Giovanni
Published: January 2021

Aims

To assess the protective effect of statins in a large and unselected cohort of frail elderly subjects.

Methods and results

The 460 460 Lombardy residents (Italy), aged ≥65 years, who received ≥3 consecutive prescriptions of a statin during 2011–2012 were identified. A case–control study was performed, the cases being the cohort members who died during 2011–2018. Logistic regression was used to model the outcome risk associated with statin adherence. Adherence to drug therapy was measured by the proportion of the follow-up covered by prescriptions. The analysis was stratified according to four clinical categories (good, medium, poor, and very poor clinical status), based on different life expectancies, as assessed by a prognostic score which had been found to sensitively predict the risk of death. The 7-year death probability increased from 11% (good) to 52% (very poor clinical status). In each clinical status, there was a significant reduction of all-cause mortality as adherence to statin treatment increased. The reduction in the adjusted risk of mortality from the lowest to the highest adherence level was greatest among patients with a good clinical status (−56%) and progressively less among other cohort members, i.e. −48%, −44% and −47% in medium, poor, and very poor groups, respectively. Similar findings were obtained for the risk of cardiovascular mortality.

Conclusion

In a real-life setting, adherence to statin treatment reduced the death risk also in frail elderly patients. However, in these patients, the benefit of statin treatment may be lower than in those in good clinical conditions.
Prediction of recurrent event in patients with coronary heart disease: the EUROASPIRE Risk Model
Authors: De Bacquer Dirk , Ueda Peter , Reiner Željko , De Sutter Johan , De Smedt Delphine , Lovic Dragan , Gotcheva Nina , Fras Zlatko , Pogosova Nana , Mirrakhimov Erkin , Lehto Seppo , Jernberg Tomas , Kotseva Kornelia , Rydén Lars , Wood David , De Backer Guy ,   the EUROASPIRE IV and V National Coordinators
Published: January 2021

Aims

Most patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years.

Methods and results

Prospective data were available for 12 484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and the incidence of the primary endpoint was investigated. This model was then validated in the remaining 4484 patients. The final multivariate model revealed a higher risk for the primary endpoint with increasing age, a previous hospitalization for stroke, heart failure or PCI, a previous diagnosis of peripheral artery disease, self-reported diabetes and its glycaemic control, higher non-high-density lipoprotein cholesterol, reduced renal function, symptoms of depression and anxiety and living in a higher risk country. The model demonstrated excellent internal validity and proved very adequate in the validation cohort. Regarding external validity, the model demonstrated good discriminative ability in 20 148 MI patients participating in the SWEDEHEART register. Finally, we developed a risk calculator to estimate risks at 1 and 2 years for patients with stable CHD.

Conclusion

In patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.
Predicting the transition to and progression of heart failure with preserved ejection fraction: a weighted risk score using bio-humoural, cardiopulmonary, and echocardiographic stress testing
Authors: Pugliese Nicola Riccardo , De Biase Nicolò , Gargani Luna , Mazzola Matteo , Conte Lorenzo , Fabiani Iacopo , Natali Andrea , Dini Frank L , Frumento Paolo , Rosada Javier , Taddei Stefano , Borlaug Barry A , Masi Stefano
Published: January 2021

Aims 

Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B).

Background 

Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment.

Design 

We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B).

Methods and results 

We performed a resting clinical/bio-humoural evaluation and a symptom-limited CPET-ESE in 274 patients (45 Stage A, 68 Stage B, and 161 Stage C-HFpEF) and 30 age- and sex-matched healthy controls. During a median follow-up of 18.5 months, we reported 71 HF hospitalizations and 10 cardiovascular deaths. Cox proportional-hazards regression identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: stress-rest ΔB-lines >10 (3 points), peak oxygen consumption <16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) >900 pg/mL (1 point). The event-free survival probability for low risk (<3 points), intermediate risk (3–6 points), and high risk (>6 points) were 93%, 52%, and 20%, respectively. The area under the curve (AUC) for the scoring system to predict events was 0.92 (95% CI 0.88–0.96), with an accuracy significantly higher than the individual components of the score (all P < 0.01 vs. individual AUCs).

Conclusion 

A weighted risk score including NT-proBNP, markers of cardiopulmonary dysfunction and indices of exercise-induced pulmonary congestion identifies HFpEF patients at increased risk for adverse events and Stage A and B subjects more likely to progress towards more advanced HF stages.
Safety and feasibility of upper limb cardiopulmonary exercise test in Friedreich ataxia
Authors: Pane Chiara , Salzano Andrea , Trinchillo Assunta , Del Prete Claudia , Casali Carlo , Marcotulli Christian , Defazio Giovanni , Guardasole Vincenzo , Vastarella Rossella , Giallauria Francesco , Puorro Giorgia , Marsili Angela , De Michele Giovanna , Filla Alessandro , Cittadini Antonio , Saccà Francesco
Published: January 2021

Aims

To explore the feasibility of upper limbs cardiopulmonary exercise test (CPET) in Friedreich ataxia (FRDA) patients and to compare the results with sex, age, and body mass index (BMI) matched cohort of healthy controls (HC).

Methods and results

Cardiopulmonary exercise test was performed using an upper limbs cycle ergometer on fasting subjects. Peak oxygen uptake (peak VO2) was recorded as the mean value of VO2 during a 20 s period at the maximal effort of the test at an appropriate respiratory exchange rate. The ventilatory anaerobic threshold (AT) was detected by the use of the V-slope method. We performed echocardiography with an ultrasound system equipped with a 2.5 MHz multifrequency transducer for complete M-mode, two-dimensional, Doppler, and Tissue Doppler Imaging analyses. We studied 55 FRDA and 54 healthy matched controls (HC). Peak VO2 showed a significant 31% reduction in FRDA patients compared to HC (15.2 ± 5.7 vs. 22.0 ± 6.1 mL/kg/min; P < 0.001). Peak workload was reduced by 41% in FRDA (42.9 ± 12.5 vs. 73.1 ± 21.2 W; P < 0.001). In FRDA patients, peak VO2 is inversely correlated with the Scale for Assessment and Rating of Ataxia score, disease duration, and 9HPT performance, and directly correlated with activities of daily living. The AT occurred at 48% of peak workload time in FRDA patients and at 85% in HC (P < 0.001).

Conclusions

Upper limb CPET is useful in the assessment of exercise tolerance and a possible tool to determine the functional severity of the mitochondrial oxidative defect in patients with FRDA. The cardiopulmonary exercise test is an ideal functional endpoint for Phases II and III trials through a simple, non-invasive, and safe exercise test.
Dapagliflozin vs. sacubitril-valsartan for prevention of heart failure events in non-diabetic patients with reduced ejection fraction: a cost per outcome analysis
Authors: Arbel Ronen , Aboalhasan Enis , Hammerman Ariel , Azuri Joseph
Published: January 2021

Aims

The Angiotensin Receptor-Neprilysin Inhibitor sacubitril-valsartan (ARNI) and dapagliflozin, a sodium-glucose transport protein 2 inhibitor, reduce the risk of heart failure hospitalization (hHF) and cardiovascular (CV) mortality in patients with reduced ejection fraction (HFrEF). Their comparative value for money is undetermined. Therefore, our aim was to compare the cost per outcome implications of utilizing dapagliflozin vs. ARNI for preventing heart failure (HF) events of non-diabetic patients with HFrEF.

Methods and results

We calculated the cost needed to treat (CNT) to prevent one HF event. The cost needed to treat was estimated by multiplying the annualized number needed to treat (NNT) to prevent one event by each therapy’s annual cost. Efficacy estimates were extracted from published secondary analyses of non-diabetic patients in DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75% of the 2020 US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the trial’s populations and drug costs in various countries.

The annualized NNT to prevent one HF event for dapagliflozin was 31 (95% CI 21–71) vs. 33 (95% CI 24–62) for ARNI. The CNT of dapagliflozin in the US is $141 112 (95% CI $95 592–$323 192) compared to $158 169 (95% CI $115 032–$297 166) for sacubitril-valsartan. The CNT results were sensitive to drug costs in various countries.

Conclusion

Dapagliflozin and ARNI provide comparable value for money for preventing HF events in non-diabetic patients with HFrEF. In healthcare settings where dapagliflozin’s price is significantly lower than ARNI, it provides superior value for money.
Personalized exercise prescription in the prevention and treatment of arterial hypertension: a Consensus Document from the European Association of Preventive Cardiology (EAPC) and the ESC Council on Hypertension
Authors: Hanssen Henner , Boardman Henry , Deiseroth Arne , Moholdt Trine , Simonenko Maria , Kränkel Nicolle , Niebauer Josef , Tiberi Monica , Abreu Ana , Solberg Erik Ekker , Pescatello Linda , Brguljan Jana , Coca Antonio , Leeson Paul
Published: January 2021

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