bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

Background
The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of &lt;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 &lt;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

Abstract

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 &lt; 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

Abstract

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 (&lt;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

Abstract

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

Abstract

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

Abstract

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 &gt; 3.4 mmol/L increased the risk of CCVD as compared to MetS or LDL-C &gt; 3.4 mmol/L alone in both men and women.

Conclusions
Metabolic syndrome confers an increased risk of CCVD irrespective of sexes; LDL-C &gt; 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

Abstract

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 (&lt;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

AbstractAimsSarcopenia, 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 resultsWe 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 &lt;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 [&lt;7.0 kg/m2 (men) and &lt;5.7 (women); 22.1% vs. 31.0%, P = 0.003], and more patients with low handgrip strength [&lt;26 kg (men) and &lt;18 (women); 67.8% vs. 55.5%, P &lt; 0.001], and slow gait speed [&lt;0.8 m/s (both sexes); 54.5% vs. 41.1%, P &lt; 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.ConclusionsIn 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

AbstractAims: 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).MethodsWe 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.