bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syk activates the protective mechanism of aorta in the mouse model of aortic dissection
Authors: Hashimoto Y , Aoki H , Majima R , Nakao E , Ito S , Furusho A , Nishida N , Hirakata S , Hayashi M , Fukumoto Y 
Published: November 2020

Abstract

Background
Aortic dissection (AD) is a serious clinical condition that frequently results in fatal outcome. Although recent studies indicate the critical role of inflammation in AD, the molecular pathogenesis of AD is still unclear. Syk is a tyrosine kinase that regulates multiple types of inflammatory cells. Syk is also reported to regulate the function of smooth muscle cells (SMCs), the major component of aortic walls. It is unknown whether and how Syk is involved in AD pathogenesis.

Objective
In the current study, we investigated the role of Syk in AD.

Methods and results
A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII) that caused progressive development of AD from day 7, reaching approximately 80% of AD incidence at day 14. Western blot analysis for activated (phosphorylated) Syk (pSyk) revealed Syk activation at day 3 of BAPN+AngII infusion, followed by transient suppression at day 7, and reactivation at day 14. Double immunofluorescence staining for pSyk and smooth muscle alpha actin showed that Syk was active not only in the infiltrating inflammatory cells, but also in SMCs in AD. Treatment of mice with fostamatinib, a specific Syk inhibitor, resulted in more severe AD compared to the vehicle treatment. The AD lesion length was 3.80±0.86 mm in the vehicle group and 8.87±1.69 mm in the fostamatinib group (P&lt;0.05). Fostamatinib worsened the mortality of mice due to the aortic rupture from 0% in the vehicle group and 42% in the fostamatinib group (P&lt;0.05). Transcriptome analysis revealed that fostamatinib suppressed both positive and negative regulators of inflammatory and defense responses. BAPN+AngII infusion caused activation of Stat3, a critical regulator of inflammatory response, which was suppressed by fostamatinib. As we previously reported that Stat3 activation in SMCs is protective against AD, we examined the relationship between Syk and Stat3 in SMCs in culture. BAPN+AngII challenge caused activations of Syk and Stat3, both of which were suppressed by fostamatinib, indicating that Stat3 was under the control of Syk in the AD model and in SMCs.

Conclusions
These findings uncovered the previously unrecognized role of Syk for protecting the aortic tissue in AD pathogenesis, possibly by activating the protective mechanism of aortic walls including Stat3 in SMCs.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant from Japan Society for the Promotion of Science
Endothelial function indicators in patients with critical limb ischemia compared to patients with limb claudication – one-year follow-up period after endovascular revascularisation
Authors: Kaczmarczyk P , Maga P , Januszek R , Frolow M , Belowski A , Nizankowski R , Chlopicki S , Gregorczyk-Maga I 
Published: November 2020

Abstract

Background
Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease. Limb revascularization is considered the first line of treatment.

Purpose
The aim of the study was to compare endothelial function and clinical outcomes in CLI and non-CLI patients during a 12-month follow-up period after endovascular treatment (PTA).

Methods
The study was conducted as a prospective, single-centre, follow-up evaluation. The authors recruited 30 CLI and 40 non-CLI patients. The following markers of endothelial dysfunction were evaluated: flow-mediated dilatation (FMD), reactive-hyperaemia index (RHI), arterial pulse-waveform analysis (aPWA) indices and clinical markers such as ankle-brachial index, toe-brachial index and Rutherford scale.

Results
Better clinical improvement may be observed in patients with CLI - the mean Rutherford grade significantly decreased in the CLI group (p&lt;0.001). These patients also have better endothelial response to revascularization – CLI patients continue to have improved RHI up to 6 months after PTA, where in non-CLI patients, improvement was only noted during the first month. The mean FMD value did not change significantly during the follow-up in either of the groups. When comparing selected intervals, the FMD values in the CLI and non-CLI groups improved during the first month of observation and then decreased between the 1st and 6th month of follow-up. Finally, in CLI patients, baseline intima-media thickness predicts the number of reinterventions and major adverse events.

Conclusions
Patients with CLI differ significantly from patients with claudication based on clinical response and endothelial changes after revascularization.
Figure 1. A) Kaplan-Meier survival curves according to CLI and non-CLI status for all study endpoints. B) Kaplan-Meier survival curves according to CLI and non-CLI status for reinterventions.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Collegium Medicum of Jagiellonian University - internal grant
Risk of aortic disease in long-distance cross-country skiers; a study of 209,226 patients
Authors: Larsson J , Sundstrom J , Hallmarker U , James S , Andersen K 
Published: November 2020

Abstract

Background/Introduction
Aneurysmal dilatation and dissection of the aorta are two facets of aortic disease that can lead to major disability and death. Some risk factors for aortic disease are also risk factors for atherosclerotic disease, but the overall causes of aortic disease are diverse and largely unknown. Persons with aortic aneurysms are advised to limit their physical activity, but associations of physical activity with subsequent incidence of aortic disease are little known. Earlier studies have shown strong association of performance in Vasaloppet with incidence of hypertension, a major risk factor for aortic disease.

Aim
To investigate associations of high levels of physical activity with incidence of aortic disease.

Methods
We studied 209,226 participants in a 30–90 km cross-country skiing event (Vasaloppet) and 536,038 persons from the general population, matched to the skiers on age, sex and residence. The number of completed races during the study period and the fastest relative finishing time in a race was recorded. The main outcomes were: 1) aortic disease (defined as thoracic and abdominal aortic aneurysm and/or aortic dissection); and 2) aortic dissection.

Results
During a median time at risk of 8.8 years, 1,442 aortic disease events and 265 aortic dissections occurred. Skiers had lower incidence of aortic disease than non-skiers (Cox proportional hazards ratio [HR] 0.42; 95% confidence interval [CI] 0.36–0.50). An association of better finishing time with aortic disease was observed, with a dose-response gradient from the fastest third (HR 0.25; 95% CI 0.18–0.35), via the slowest third (HR 0.64; 95% CI 0.49–0.82) to the non-skiers (reference group). Among skiers the number of completed races was not associated with incidence of aortic disease. Skiers also had lower incidence of acute aortic dissection (HR 0.61; 95% CI 0.44–0.85) than non-skiers. Low event rate among skiers made conclusions in subgroups unreasonable. All results are adjusted for age, sex, education and income. Results were similar in models accounting for use of antihypertensive and cholesterol-lowering medicines and genetic syndromes associated with aortic disease.

Conclusion
Participation in a long-distance skiing event was associated with lower risk of aortic disease and aortic dissection. Faster completion of the race was strongly associated with lower incidence of aortic disease. If causal, this study suggests that high physical activity and exercise may be protective against aortic disease.
Kaplan-Meier Aorta disease

Funding Acknowledgement
Type of funding source: None
Peripheral artery disease impairs myocardial perfusion through increasing pulse wave reflection: the Northern Shanghai study
Authors: Yu S , Teliewubai J , Fan X , Chi C , Ji H , Blacher J , Zhang Y , Xu Y 
Published: November 2020

Abstract

Background
Peripheral artery disease (PAD) is prevalent and substantially contributes to cardiovascular mortality particularly in the elderly, although the pathophysiological impact of PAD on heart itself still needs further investigation. In theory, PAD can increase pulse wave reflection which is an important determinant of subendocardial viability ratio (SEVR), a valuable estimate of myocardial perfusion as indicated by previous invasive studies. Thus, we hypothesize that PAD impairs myocardial perfusion through increasing pulse wave reflection. In this study, we aim to test this hypothesis in a large cohort from the Northern Shanghai Study.

Methods
A total of 2947 community-dwelling elderly Chinese (43.6% male, mean age: 71.3±5.9 years) were recruited. Ankle-brachial index were measured with the VP1000 device and used to diagnose PAD. Pulse wave reflection was estimated as aortic augmentation pressure (AP). Aortic BP, AP and SEVR were assessed by radial applanation tonometry. Multiple linear regression with SEVR and AP as dependent variable and PAD as independent variable, meanwhile adjusted for other covariates, were performed, respectively.

Results
375 (12.7%) participants presented PAD. Compared to subjects without PAD, those with PAD showed significantly lower SEVR (126 vs. 132, P&lt;0.001) but higher AP (19 vs. 17 mmHg, P&lt;0.001). Multiple regression analysis revealed that both SEVR (regression coefficient [B] = −1.69, P=0.04, R2=0.61) and AP (B=1.19, P=0.04, R2=0.56) significantly associated with PAD, respectively. However, the association between SEVR and PAD was abolished when further adjusted for AP (B=−0.49, P=0.52). Similar results were obtained when inter-leg systolic BP difference was used to diagnose PAD.

Conclusions
PAD significantly and independently associates with myocardial perfusion; moreover, this association is mediated by increased pulse wave reflection. These findings provide a new dimension for understanding the pathophysiological mechanisms of cardiac damage of PAD.

Funding Acknowledgement
Type of funding source: None
Arterial stiffness could reflect increased cardiac load and reduced pulmonary function in the general population
Authors: Murai S , Sugiura T , Dohi Y , Takase H , Mizoguchi T , Yamashita S , Seo Y , Fujii S , Ohte N 
Published: November 2020

Abstract

Background
Pulmonary function is known to decrease with age and reduced pulmonary function has been reported to be associated with all-cause mortality and cardiovascular death. The association between pulmonary impairment and atherosclerosis was reported previously but has not been investigated sufficiently in the general population.

Purpose
We hypothesized that arterial stiffness could reflect increase of cardiac load and reduced pulmonary function. The present study aimed to investigate whether increased cardiac load and reduced pulmonary function could affect arterial stiffness in the general population.

Methods
Subjects undergoing their health check-up were enrolled. Plasma B-type natriuretic peptide (BNP) levels and serum high-sensitivity cardiac troponin I (hs-cTnI) levels were measured to evaluate cardiac load and myocardial damage. Radial augmentation index (rAI) was measured to investigate arterial stiffness using HEM-9000AI device. Subjects with an ST-T segment abnormality on the electrocardiogram, renal insufficiency, cancer, active inflammatory disease, or a history of cardiovascular events and pulmonary disease were excluded. Pulmonary function was assessed using spirometry by calculating forced vital capacity (FVC) as a percentage of predicted value (FVC%-predicted), forced expiratory volume in 1 second (FEV1) as a percentage of predicted value (FEV1%-predicted), and the ratio of FEV1 to FVC (FEV1/FVC).

Results
A total of 1100 subjects aged 57 years were enrolled and their median values of BNP and hs-cTnI were 15.5 and 2.3 pg/ml. The levels of rAI were significantly associated with the levels of BNP after adjustment for possible confounders in multivariate regression analysis, but were not with the levels of hs-TnI. While the parameters of pulmonary function were inversely associated with the levels of rAI and hs-cTnI after adjustment for possible confounders in the multivariate regression analysis, but not with the levels of BNP. The other multivariate regression analyses where BNP, hs-cTnI, parameters of pulmonary function, and the other possible factors were simultaneously included as independent variables revealed that the BNP levels and the FVC%-predicted or FEV1%-predicted, besides age, gender, smoking status, body mass index, blood pressure, heart rate, creatinine, fasting plasma glucose, and triglyceride, were significantly associated with the levels of rAI.

Conclusions
The significant associations of rAI with BNP and pulmonary function were revealed in the general population. These findings support that arterial stiffness could reflect increased cardiac load and reduced pulmonary function, in apparently healthy individuals.

Funding Acknowledgement
Type of funding source: None
Impact of lipoprotein(a) levels on angiographic severity of femoropopliteal lesions
Authors: Yanaka K , Akahori H , Imanaka T , Miki K , Yoshihara N , Kimura T , Tanaka T , Asakura M , Ishihara M 
Published: November 2020

Abstract

Background
High lipoprotein(a) [Lp(a)] levels are a risk factor for peripheral artery disease (PAD). However, the association between Lp(a) levels and angiographic severity of PAD has not been systematically studied.

Purpose
The aim of this study was to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD.

Methods
We retrospectively analyzed a single-center database including 108 patients (74±8 years, 69% male) who underwent endovascular therapy for de novo femoropopliteal lesions and measured Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [LP(a) &lt;30 mg/dL; 77 patients] and high Lp(a) [LP(a) ≥30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to peripheral arterial calcium scoring system (PACSS) classification] and lesion length were compared between the groups.

Results
Median Lp(a) was 16 (7–31) mg/dL.The prevalence of TASC II class D (13% vs 38%, P&lt;0.01) and severe calcification (PACSS 4) (6% vs 23%, P=0.02) was significantly higher and lesion length was longer (123±88 mm vs 175±102 mm, P&lt;0.01) in the high Lp(a) group than in the low Lp(a) group.(Table and Figure) In multivariate analysis, Lp(a)≥30 was an independent predictor for TASC II class D (HR=3.67, P=0.02) and PACSS 4 (HR=4.97, P=0.02) prevalence.

Conclusion
Lp(a) was associated with angiographic severity of femoropopliteal lesions in patients with PAD.
Comparison of angiographic severity

Funding Acknowledgement
Type of funding source: None
Serum Lipoprotein(a) levels on clinical outcomes after endovascular therapy
Authors: Tomoi Y , Soga Y , Hiramori S , Ando K 
Published: November 2020

Abstract

Background
While lipoprotein (a) (Lp(a)) is an independent predictor of atherosclerotic diseases involving the coronary and cerebrovascular arteries, its prognostic value in patients with peripheral artery disease (PAD) remains still unclear.

Objective
The aim of study is to determine the role of Lp(a) levels after endovascular therapy (EVT).

Methods
This study was prospective observational study. From September 2016 to April 2019, 676 the patients (873 limbs) who underwent EVT for de-novo PAD were enrolled. We divided into Lp(a) levels ≥40 mg/dl (high Lp(a) group; n=129) and &lt;40 mg/dl (low Lp(a) group; n=547). Outcome measures were major adverse cardiovascular events (MACE; all-cause death, myocardial infarction and stroke), and major adverse limb events (MALE; repeat revascularization for limb and major amputation) at 1 year. Major amputation defined as above forefoot amputation due to vascular cause.

Results
The mean follow-up period was 14.3±8.9 months. Serum Lp(a) levels before EVT were 27.2 (10.0–36.0 mg/dl). High Lp (a) group was significantly older, higher prevalence of history of stroke, chronic kidney disease, and multi-vessel lesions. Cumulative incidence of MACE at 1 year was not significantly between two groups (p=0.53, log-rank test), whereas cumulative incidence of MALE at 1 year was significantly higher in high Lp (a) group (p=0.04, log-rank test). However, after adjusting for prespecified risk factors, high Lp (a) group was not independent predictor in MALE at 1 year.

Conclusion
High Lp (a) might not be associated with cardiovascular events and limb prognosis after EVT for PAD in early phase.

Funding Acknowledgement
Type of funding source: None
Use of dual layered stents in endovascular treatment of extracranial stenosis of the internal carotid artery: one year results of a patient-based meta-analysis of 4 clinical studies
Authors: Stabile E , De Donato G , Musialek P , Deloose K , Nerla R , Sirignano P , Mazurek A , Mansour W , Fioretti V , Esposito F , Chianese S , Bosiers M , Speziale F , Micari A , Esposito G 
Published: November 2020

Abstract

Background
Small sized clinical studies evaluating one year outcomes of CAS performed with two available DLS, Roadsaver® (RS) and CGuard® (CG), have been published.

Purpose
To evaluate one year safety and efficacy of dual layered mesh covered carotid stent systems (DLS) for carotid artery stenting (CAS).

Methods
We performed an individual patient-level meta-analysis including studies enrolling more than 100 CAS with DLS. Primary endpoint was the death and stroke rate; secondary endpoints were restenosis and in-stent thrombosis rates at one year.

Results
Patients were divided in two groups according to DLS (RS N=250; CG N=306). At one year, 11 patients died (1.97%), 7 patients in the group RS (2.8%) and 4 patients in the CG one (1.31%), 10 strokes occurred, 4 in the group RS (1.6%) and 6 in the CG one (1.96%). Overall death and stroke rate was 3.77% (N=21), 11 events in the group RS (4.4%) and 10 in the CG group (3.27%). Symptomatic status was the only predictor of death and or stroke.
At one year restenosis occurred in 12 patients (2.1%), 10 in the group RS (4%) and 2 in the CG one (0.65%) (p=0.007). In stent thrombosis occurred in 1 patient (0.18%) of the group CG (0.32%). RS use was the only independent restenosis predictor.

Conclusions
This study suggests that DLS use for CAS is associated to a low one year death and stroke rate and specific DLS stent use could affect restenosis rate.

Funding Acknowledgement
Type of funding source: None
Height and risk of ischaemic stroke subtypes: a Mendelian randomisation study
Authors: Linden A , Clarke R , Hopewell J.C , Whiteley W.N , Walters R.G , Li L , Chen Z , Parish S 
Published: November 2020

Abstract

Background
Taller adult height is associated with lower risks of ischaemic heart disease in both conventional and Mendelian randomisation studies, providing support for a causal association, but the associations of height with ischaemic stroke and ischaemic stroke subtypes are uncertain.

Purpose
To examine the causal relevance of height for ischaemic stroke and ischaemic stroke subtypes.

Methods
Two-sample Mendelian randomisation analyses were used to examine the associations of height with: (i) ischaemic stroke and ischaemic stroke subtypes in MEGASTROKE (using summary data from 34 217 ischaemic stroke cases), and with (ii) established cardiovascular and other risk factors using individual data from 336 433 participants in UK Biobank and 57 785 in the China Kadoorie Biobank. Instruments for Mendelian randomisation were constructed from up to 3280 height-associated genetic variants, previously identified as having genome-wide significant effects on height.

Results
Genetically-determined taller height was inversely associated with ischaemic stroke (3% [95% CI: 1–6] lower risk per 1 standard deviation taller height) in MEGASTROKE but this masked much stronger opposing associations on risks of different ischaemic stroke subtypes: 15% (95% CI: 9–21) higher risk of cardioembolic stroke, 10% (4–15) lower risk of large-artery atherosclerotic stroke, and 15% (10–20) lower risk of small-vessel stroke (Figure). Genetically-determined taller height was strongly associated with atrial fibrillation and higher lean body mass and lung function but more weakly associated with lower levels of LDL cholesterol and blood pressure.

Conclusions
The findings support a causal association between taller adult height and risk of atrial fibrillation and cardioembolic stroke. The opposing associations of height with other ischaemic stroke subtypes provide further support for considering ischaemic stroke subtypes as distinct diseases in both research and clinical practice.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Medical Research Council, British Heart Foundation
Simultaneous cardio-cerebral embolization. A prospective study
Authors: Mione V , Leclercq T , Bejot Y , Lenfant M , Maza M , Zeller M , Cochet A , Cottin Y 
Published: November 2020

Abstract

Background
Atrial Fibrillation (AF) is a common cause of ischemic stroke but also the most common cause of Coronary Artery Embolism (CE). Many previous case of coexistence of coronary and cerebral embolism have been reported in the literature but in specific situations were clinical signs of stroke but also indisputable clinical and/or electrocardiographic (ECG) signs leaded to the realization of coronarography in emergency.

Objectives
The aim of the study was to determine the existence of simultaneous cardio-cerebral embolization associated in patients with ischemic embolic stroke on de novo AF, in the absence of clinical and/or ECG signs evocative of myocardial infarction (MI).

Methods
We prospectively included patients hospitalized in our institution for ischemic embolic stroke on de novo AF. Patients with history of ischemic disease were excluded. All patients had: 1/ troponin assay; 2/ Cardiac Magnetic Resonance (CMR) imaging with Late-Gadolinium Enhancement (LGE) in order to detect myocardial infarction; 3/ coronary exploration by cardiac CT scan or coronarography to exclude patients with significant coronary lesion.

Results
Between January and December 2019, 32 patients were included. Of them, 15 had subendocardial or transmural LGE on CMR, evocative of MI. Among these 15 MIs we classified acute MIs according to the level of troponin at the admission in stroke unit, the coronarography and T2 hypersignal on cardiac MRI. Median delay of cardiac MRI was 6 days for acute MIs.
CE was clearly identified by coronarography for 4 patients with acute simultaneous cardio-cerebral infarction (56%). The MRI abnormalities showed that lesions of all MIs were transmural, relatively small (average 1.3±0.44 segments) and in most cases in the inferior cardiac wall (47%) and these abnormalities were comparable in sequelae and acute MI. Moreover, the left appendage morphology was a “cactus” in 62.7% of simultaneous acute cardio-cerebral infarction and only 33% in patients without MI or sequelae MI. Strokes were mainly localized in the superficial territory of the middle cerebral artery, and were similar in patients with or without MI. In addition, the rate of sequelae strokes was higher in isolated stroke group than “cardiocerebral infarction” (29.5% versus 13.3%).

Conclusion
Simultaneous acute cardio-cerebral infarction is not uncommon, diagnosed in 22% of our prospective cohort of embolic stroke. Cardiac MRI may help us to diagnose a concomitant cardiac embolization and evaluate the prognosis. Unfortunately optimal therapeutic strategy of these patients is still unknown.
Flow Chart

Funding Acknowledgement
Type of funding source: None