bluuebunny/crossref_metadata_2025_split huggingface dataset:
208Effect of hypertension duration and systolic blood pressure on dementia in patients with atrial fibrillation
Authors: Kim D , Yang P S , Jang E , Yu H T , Kim T H , Uhm J S , Kim J Y , Sung J H , Pak H N , Lee M H , Lip G Y H , Joung B 
Published: October 2019

Abstract

Background
Atrial fibrillation (AF) is associated with a higher risk for cognitive impairment and dementia, with or without a history of clinical stroke. There are a paucity of data on the associations of hypertension duration and blood pressure (BP) level with risk of dementia in patients with AF.

Purpose
We examined associations of duration of hypertension and secondly, systolic blood pressure (SBP) levels with incidence of dementia among patients with AF.

Methods
We enrolled a total 196,388 patients aged ≥50 years who were newly diagnosed as AF and undergoing hypertension treatment from the Korean National Health Insurance Service database (2005–2016). Starting from AF diagnosis, participants were followed up until the date of dementia, death, or December 31, 2016. To incorporate the effect of BP level and hypertension duration changes over time on dementia incidence, we constructed time-updated multivariable Cox models in which BP levels and hypertension duration were updated at each participants' regular national health examination visits (at 0–7 years of follow-up). Similarly, age, BP medications, and health-related behaviors were included as time-varying covariates in these models.

Results
During 1,016,744 person-years of follow-up, there were 32,692 dementia events. A cubic spline curve using continuous hypertension duration measures suggested a linear association between increase of hypertension duration and dementia risk. One-year increase of hypertension duration increased the adjusted risk of dementia with a hazard ratio (HR) of 1.17 [95% confidence interval (CI) 1.13–1.22]. In patients with hypertension duration <6 years, SBP of ≥140 mmHg was significantly associated with higher dementia risk, compared to SBP of <130 mmHg (in patients with hypertension duration <3 years: adjusted HR 1.08, 95% CI 1.01–1.16; and in those with 3 ≤ hypertension duration <6 years: adjusted HR 1.13, 95% CI 1.07–1.20), whereas no significant association between SBP and dementia risk in those with hypertension duration ≥6 years.
SBP and dementia in different duration

Conclusion
In patients with AF, the increase of hypertension duration was strongly associated with increased risk of dementia. Uncontrolled SBP was also associated with higher dementia risk. But, this effect of SBP might be attenuated in patients with longer hypertension duration. These findings suggest more emphasis needed on BP control in AF patients with earlier phase of hypertension (duration <6 years).

Acknowledgement/Funding
The Korean Ministry of Education, Science and Technology (NRF-2017R1A2B3003303) and the Korean Ministry of Health & Welfare (HI16C0058, HI15C1200)
218Different impact of muscle, fat, and bone mass in heart failure with reduced and preserved ejection fraction
Authors: Konishi M , Akiyama E , Matsuzawa Y , Sato R , Kikuchi S , Nakahashi H , Maejima N , Iwahashi N , Hibi K , Kosuge M , Tamura K , Kimura K 
Published: October 2019

Abstract

Background
Low muscle mass with or without fat mass is a main component of cachexia in heart failure (HF) and associated with poor prognosis. There is a paucity of data, however, regarding prognostic impact of each component of body composition (i.e., muscle, fat, and bone mass).

Purpose
We hypothesized that muscle, fat, and bone mass have different impact on prognosis in HF.

Methods
We retrospectively analyzed 418 patients admitted with a diagnosis of HF (71±13 years, 59% male, 46 and 54% with preserved/mid-range (left ventricular ejection fraction (LVEF) ≥40%) and reduced (<40%) LVEF), respectively). Dual-energy X-ray absorptiometry was performed at stable state after decongestion therapy.

Results
Mean appendicular skeletal mass index (ASMI) was 6.9±1.2 kg/m2 in men and 5.6±0.9 in women, so that 55% of patients had low muscle mass categorized by the Asian Working Group of Sarcopenia. During median follow-up of 502 days, 163 (39.0%) patients experienced primary outcome defined as death or heart failure hospitalization. Using optimal cut-off of each body component chosen on the basis of a receiver operating characteristic curve and the Youden method, we demonstrated that lower ASMI defined by the cut-off of 6.5 kg/m2 in male and 5.2 in female (adjusted hazard ratio (HR): 1.768, 95% CI: 1.210–2.581, p=0.003) and bone mass (adjusted HR: 1.498, 95% CI: 1.051–2.152, p=0.025), but not lower fat mass (p=0.34), were associated with elevated risk of primary outcome after multivariate adjustment. Kaplan-Meier curves with p value by Log-rank test were shown in figure. In subgroup analysis, negative impact of lower ASMI was significant regardless of sex and LVEF category, whereas negative impact of low bone mass was significant only in 78 female patients with reduced LVEF.
Figure 1

Conclusions
Indices about muscle and bone mass rather than fat mass had prognostic impact in HF. The impact of each body component may different according to sex and LVEF.
248Real-world Outcome of the ESC 0/1-hour Algorithm when Routinely Applied in Early Presenters
Authors: Twerenbold R , Costabel J P , Campos R , Arbucci R , Nestelberger T , Boeddinghaus J , Rubini M , Wussler D , Lambardi F , Resi S , Trivi M , Mueller C 
Published: October 2019

Abstract

Background
The European Society of Cardiology (ESC) recommends the use of a 0/1h-algorithm for rapid triage of patients with suspected non-ST-elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn). Concerns were articulated about its efficacy and particularly safety when applied in patients presenting early (≤3 hours) after chest pain onset, as hs-cTn concentrations might still be very low or even undetectable in these high-risk patients.

Purpose
We aimed to assess the real-world effectiveness, efficacy, and ultimately safety of the ESC 0/1h-algorithm when routinely applied in early presenters.

Methods
In a prospective international multicenter study enrolling unselected patients presenting with suspected NSTEMI to the ED, patients were assessed according to the ESC 0/1h-algorithm using high-sensitivity cardiac troponin T embedded in routine clinical care. Patients with ST-segment elevation myocardial infarctions were excluded. Safety was quantified by the 30-day incidence of major adverse cardiac events (MACE, defined as the composite of cardiovascular death and myocardial infarction including the index event) in the rule-out group and in outpatients.

Results
Among 2296 patients, 819 (36%) were early presenters. NSTEMI prevalence in early presenters was 11%. Effectiveness was very high as 97% of patients triaged towards rule-out by the ESC 0/1h-algorithm did not require additional cardiac investigations including hs-cTnT measurements at later time points (e.g. 3–12h) or coronary CT-angiography in the ED. Median time to discharge or transfer from the ED was 150 minutes [q1130, q3215]. Efficacy of the ESC 0/1h-algorithm was very high: 67% of patients were triaged towards rule-out and 14% towards rule-in of NSTEMI. Overall, 75% of early presenters underwent outpatient management. Safety of rule-out and outpatient management were excellent in early presenters with a 30-day MACE incidence of both 0% and comparable with 0.3% and 0.1% in late presenters, respectively (p=ns).

Conclusions
These real-world data document for the first time the excellent effectiveness, efficacy and particularly safety of the ESC 0/1h-algorithm when routinely applied in early presenters. No differences in safety could be observed when compared with late presenters.
260Identification of differential roles of microRNA-33a and -33b during atherosclerosis progression with genetically modified mice
Authors: Horie T , Koyama S , Kimura T , Ono K 
Published: October 2019

Abstract

Background
MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33a located within the intron of sterol regulatory element-binding factor (SREBF) 2 targets cholesterol transporter ATP-binding cassette protein A1 (ABCA1) or other anti-atherogenic targets and contributes to atherogenesis. Its inhibition or deletion is known to result in the amelioration of atherosclerosis. However, mice lack the other member of miR-33 family, miR-33b, which exists in humans. Precise evaluation and comparison of the responsibilities of these two miRs during the progression of atherosclerosis are essential and need to be investigated.

Methods and results
The difference between miR-33a and miR-33b in vitro and in vivo were analyzed from multiple directions using genetically modified miR-33a knock-out (KO) and miR-33b knock-in (KI) humanized mice. At first, we performed transcriptomic analysis of primary cultured hepatocytes transfected with synthetic miR-33a, miR-33b, and a control miR and found similar potential target repression and targeting motif of miR-33a and miR-33b in vitro. However, we noticed distinct expression patterns of miR-33a and miR-33b in several organs. By crossing miR-33a KO and miR-33b KI mice, we established four strains with or without miR-33a and miR-33b. Comparison of these strains showed distinct distribution and regulation of miR-33 family. In particular, comparison between mice with only miR-33a (wild-type mice) and mice with only miR-33b (miR-33a−/− miR-33b+/+) revealed 4-fold predominant expression of miR-33b in the liver. Such differential expression resulted in a reduced expression of target genes such as ABCA1 and worsened serum cholesterol profile in mice with only miR-33b. On the contrary, in macrophages the expression levels of miR-33 family genes were similar and their effects on target genes and cholesterol efflux capacity to ApoA-I or HDL cholesterol (HDL-C) were almost comparable. To evaluate the whole body atherogenic potency, we developed ApoE−/− miR-33a+/+ miR-33b−/− mice and ApoE−/− miR-33a−/− miR-33b+/+ mice. ApoE−/− miR-33a−/− miR-33b+/+ mice developed increased atherosclerotic plaque compared with ApoE−/− miR-33a+/+ miR-33b−/− mice, in line with the predominant expression of miR-33b in the liver and decreased serum HDL-C levels whose lower cholesterol efflux capacity were confirmed in 3H-labeled macrophages. On the contrary, a bone marrow transplantation study showed no significant difference in atherosclerosis and serum cholesterol profile, and this was consistent with the relevant expression levels of miR-33a and miR-33b in bone marrow cells.

Conclusions
miR-33 family exhibited differences in distribution and regulation, and particularly in the progression of atherosclerosis, miR-33b would be more potent than miR-33a.
443Natural history of arterial morbidity in vascular ehlers-danlos syndrome
Authors: Frank M , Adham S , Pitoccho F , Denarie N , Mousseaux E , Jeunemaitre X 
Published: October 2019

Abstract

Background
Vascular Ehlers-Danlos syndrome (vascular EDS) is a rare inherited connective tissue disorder, responsible of exceptional organ fragility. The disease is caused by pathogenic COL3A1 variants with a dominant negative effect, except for variants leading to haploinsufficiency. The course of the disease is characterized by the occurrence of recurrent spontaneous arterial accidents (dissections, aneurysm formation, spontaneous ruptures), typically of medium size arteries.

Purpose
To describe the natural history of arterial accidents in a molecularly characterized population of patients with vascular EDS, that benefited from repeated standardized vascular monitoring in a tertiary referral centre.

Methods
All patients from the French natural reference centre for vascular EDS were included in a retrospective cohort study. Standardized monitoring of arterial beds was performed at molecular diagnosis (baseline) and every 15 months thereafter in clinically silent patients, by CT-angiogram or MRA, and by vascular Doppler Ultrasound. In case of symptomatic arterial accidents, diagnostic imaging was also reviewed for arterial defects. Arterial lesions were sorted by date of diagnosis and staged by anatomical location and by type of defect.

Results
Between January 2000 and March 2017, n=144 patients (n=91 index, Sex Ratio 0.68) were diagnosed with vascular EDS at a mean age of 34.0 [25.0; 41.0] years, and regularly followed-up in our centre for a median 5.80 [3.45; 8.80] years. Types of COLA3A1 variants were glycine substitutions (68%), splice-site (31.8%) and those leading to haplosufficiency (8.3%). During follow-up a median 1.57 [0.9; 3.0] arterial accidents per 5 years occurred and n=17 (11.8%) patients died. At first referral, a majority of patients (68.8%) had already presented a disease-related event, predominantly arterial ones, totalling 232 arterial defects (dissections, 72%; aneurysms, 11.2%; ruptures, 9%; carotid cavernous fistula, 4.3% and arteriovenous fistula, 0.9%). Vascular assessment at baseline identified another 255 arterial defects in the same patients that had not been reported previously. At each further vascular monitoring, one third (36%) of patients presented with new arterial defects, a majority of which (66%) were clinically silent. Moreover, 15% of patients at each vascular assessment had evolved on previously diagnosed arterial lesions (healing or aggravation). Notably, neither symptomatic arterial event nor silent evolutivity occurred in haploinsufficient patients.

Conclusion
This study gives an extensive insight into distribution, nature and timeline of arterial defects in patients with vascular EDS in a large patient cohort. Besides known and expected arterial morbidity and mortality, a consistent proportion of clinically silent patients developed new arterial lesions, suggesting that progression of arterial pathology in vascular EDS is not limited to symptomatic arterial events.
454Potential real-world benefits of low-dose rivaroxaban in Chinese stable cardiovascular patients
Authors: Yan B P Y , Chan C K Y , Lai W H S , To O T L 
Published: October 2019

Abstract

Background
Low dose rivaroxaban-plus-aspirin has been shown to reduce cardiovascular (CV) events in patients with stable atherosclerotic vascular disease compared to aspirin alone in the COMPASS trial.

Purpose
We aimed to estimate the potential benefit of low dose rivaroxaban plus aspirin in reduction of major adverse cardiovascular event (MACE, the composite of cardiovascular death, stroke, or myocardial infraction [MI]) among COMPASS-like patients in a Chinese population.

Methods
We retrospectively analyzed 18,693 patients with stable coronary artery disease (CAD) and/or peripheral artery disease (PAD) from 3 hospitals in Hong Kong between 2013 and 2017 for a median follow-up of 36 (IQR 19–52) months. 4,594 (24.6%) COMPASS-like patients were identified based on COMPASS trial inclusion and exclusion criteria. We estimated the absolute risk reduction (ARR) in MACE and number needed to treat (NNT) in COMPASS-like patients based on results from the COMPASS trial (NCT01776424).

Results
Of 4,594 COMPASS-like patients (58.1% males, mean age 75.0±13.0 years), 92.5% patients were diagnosed with CAD, 5.6% PAD, and 1.9% combined CAD/PAD. Overall, 3-year MACE rate was 7.9%; 7.8% in patients with CAD, 6.6% in PAD and 18.4% in combined CAD/PAD (log-rank p<0.01). 3-year CV mortality rate was 3.7% (3.6%, 3.5%, 11.5% in CAD, PAD and combined CAD/PAD respectively, log-rank p<0.01); 3-year stroke rate was 3.2% (3.0%, 4.6%, 6.9% in CAD, PAD and combined CAD/PAD respectively, log-rank p=0.03); and 3-year MI rate was 2.2% (2.3%, 0%, 6.9% in CAD, PAD and combined CAD/PAD respectively, log-rank p<0.01). Among COMPASS-like patients, estimated ARR in MACE with the use of rivaroxaban-plus-aspirin was 1.9% (NNT=53); 0.8% ARR (NNT=123) for CV death, 1.3% ARR (NNT=74) for stroke and 0.3% ARR (NNT=325) for MI.

Conclusion
Our results demonstrated that a significant proportion of “real world” Chinese patients with stable cardiovascular diseases were COMPASS-like patients. Potential clinical benefit of the addition of low dose rivaroxaban to aspirin therapy may be greater in our population than that observed in the trial, with lower number needed to treat.
463Temporal trends in latecomer ST-segment elevation myocardial infarction patients: Insights from the AMIS Plus Registry 1997–2017
Authors: Roberto M , Radovanovic D , Biasco L , Quagliana A , Erne P , Rickli H , Pedrazzini G , Moccetti M 
Published: October 2019

Abstract

Introduction
A relevant proportion of patients experiencing ST-segment elevation myocardial infarction (STEMI) has a late presentation after symptoms onset. Temporal trends deriving from a large real-word scenario for this subgroup of patients are lacking.

Purpose
The aim of the present study was to provide a comprehensive analysis of temporal trends in latecomer STEMI patients, with particular regard to implementation of evidence-based treatments in this population and major in-hospital outcomes.

Methods
All STEMI patients included in the AMIS Plus Registry from January 1997 to December 2017 were included and patient-related delay was assessed: 27 231 patients were available for the final analysis. STEMI patients were classified as early or latecomers according to patient-related delay (≤ or >12 hours, respectively).

Results
22 928 patients were earlycomers (84%) and 4303 patients were classified as latecomers (16%). Across the study period we observed a significant decrease in prevalence of late presentation from 22% to 12.3% (p<0.001, Figure 1). In latecomer STEMI patients there was a gradual uptake of evidence-based pharmacological treatments with an increase in discharge prescription of P2Y12 inhibitors from 6% to 90.7% (p<0.001). Similarly, a marked increase in percutaneous coronary intervention (PCI) rate was observed (12.1–86.6%; p<0.001). Across this 20-year period, in-hospital mortality was reduced to a third (to an absolute rate of 4.5%, p<0.001) and a significant reduction in prevalence of both cardiogenic shock (14.6–4.3%) and re-infarction (5.4–0.2%) during the index hospitalisation was observed (p<0.001 for both variables). Length of hospitalisation in acute care facilities significantly decreased from 10 (6,14) days to 4 (1,7) days (p<0.001). At multivariate analysis, PCI had a strong independent protective effect toward in-hospital mortality (odds ratio 0.3, 95% confidence interval 0.187 to 0.480).
Figure 1

Conclusion
The present study provides a comprehensive picture of temporal trends in late presentation in STEMI over the last 20 years in Switzerland. During the study period in latecomer STEMI population there was a gradual uptake of evidence-based pharmacological treatments and a marked increase in PCI rate. In-hospital mortality was reduced to a third (to an absolute rate of 4.5%) and this reduction seems to be mainly associated with the increasing implementation of PCI.
479Preoperative global longitudinal strain is the best predictor of mortality following transcatheter aortic valve replacement
Authors: Povlsen J A , Rasmussen V G , Vase H , Jensen K T , Terkelsen C J , Christiansen E H , Mathiassen O N , Poulsen S H 
Published: October 2019

Abstract

Background
Prognosis after transcatheter aortic valve replacement (TAVR) is variable. This might depend on preoperative evaluation of myocardial performance by other measurements than ejection fraction (EF).

Purpose
The aim of this study was to investigate the predictive value of preoperative global longitudinal strain (GLS) and the guidelines specified subtypes of aortic stenosis (AS) on mortality following TAVR.

Methods
We included 511 patients with severe AS who underwent TAVR in the period July 2012–June 2017.
Patients were divided into guidelines-specified subgroups based on EF (EF: ≥50 (NEF) or <50% (LEF)), peak gradient (PG: ≥4 (HG) or <4 m/s (LG)) and flow status (stroke volume index (SVI): ≥35 (NF) or <35 ml/min/kg (LF)): (1) HG-NEF (n=228), (2) HG-LEF (n=91), (3) LG-LF-NEF (n=71) and (4) LG-LF-LEF (n=121). We also investigated the effect of replacing EF by GLS in the guideline specified subgroups (GLS ≤−14 (HGLS) and GLS >−14% (LGLS)).

Results
Mean follow up time was 1033 days. Mean age was 80.2±7.1 years. Median overall survival was 5.3±0.3 years. Comorbidity burden was higher in patients with LF – and LEF status in terms of a higher median plasma creatinine (103 [85; 135], p<0.001) and EurologII score (6.1 [3.4; 9.6], p<0.001).
LG-LF-LEF AS was associated with a significantly worse outcome compared with all other groups (p<0.005, Fig. 1A). High gradient status, irrespective of EF (p=0.88), was associated with the best prognosis with a median survival of 5.0±0.5 and 5.5±0.1 years for NEF and LEF, respectively.
Overall and in patients with HG-NEF, impaired GLS (>−14%) was associated with poor outcome (Fig. 1B–D). There was a trend towards a poorer prognosis with GLS >−14% in LG-LF-NEF AS (p=0.10).
In an univariate analysis impaired GLS >−14% (HR 2.04, p<0.005), LG-LF-LEF status (HR 1.82, p=0.001), PG <4m/s (HR 1.74, p=0.001) and tricuspid regurgitation gradient >30 mmHg (HR 1.63, p<0.001) were significant predictors of mortality in contrast to EF, SVI, age, gender and plasma creatinine.
GLS >−14% emerged as the only significant outcome predictor in a multivariate analysis (HR 1.93, p<0.05).
Figure 1

Conclusion
Impaired global longitudinal strain >−14% was the best individual echocardiographic predictor of overall survival in symptomatic severe AS and could identify a subgroup of patients with HG-NEF AS with a worse prognosis.
P303Prognostic value of diastolic wall strain in patients with asymptomatic severe aortic stenosis
Authors: Suwa Y , Miyasaka Y , Taniguchi N , Harada S , Shiojima I 
Published: October 2019

Abstract

Background
Diastolic wall strain (DWS) has been reported to be associated with left ventricular (LV) stiffness and worse clinical outcomes. We sought to assess the utility of this new index for prediction of prognosis in asymptomatic patients with severe aortic stenosis (AS).

Methods
Asymptomatic severe AS patients [peak flow velocity (PFV) ≥4.0m/s, mean pressure gradient (mPG) ≥40mmHg, aortic valve area (AVA) ≤1.0cm2, or indexed AVA ≤0.6cm2/m2)] diagnosed between July 2007 and April 2016 were included in this study. Patients with significant mitral valve disease, posterior wall motion abnormality, prior cardiac surgery, hypertrophic cardiomyopathy, and LV ejection fraction <50% were excluded. DWS was calculated with a validated formula [DWS = (posterior wall thickness at end-systole − posterior wall thickness at end-diastole)/posterior wall thickness at end-systole]. All study patients were prospectively followed up to last visit or death until November 2017, and predictive value of all-cause death was assessed using Cox-proportional hazards modeling. Patients who underwent aortic valve replacement (AVR) during the study period were censored on the date of surgery.

Results
A total of 184 asymptomatic severe AS, 138 (age 76±9year-old, men 41%, PFV 3.9±1.0m/s, mPG 38±19mmHg, AVA 0.83±0.18cm2, indexed AVA 0.56±0.13cm2/m2) met all study criteria. Of whom, 43 (31%) underwent AVR and 28 (20%) died during a mean follow-up of 25±28months. In a multivariable model after adjusting for clinical and echocardiographic variables, advancing age (per10yrs; HR=2.19, 95% CI=1.19–4.03, P<0.05), history of hemodialysis (HR=4.31, 95% CI=1.30–14.35, P<0.05), and low-DWS (DWS <0.30) (HR=2.83, 95% CI=1.25–6.40, P<0.05) were independent predictors of all-cause death. In the Kaplan-Meier estimates of cumulative survival stratified by DWS status were shown (Figure).
The Kaplan-Meier estimates of survival

Conclusion
Low-DWS provides prognostic information in patients with asymptomatic severe AS.