bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ascending aortic length associates to acute aortic dissection
Authors: Korpela T , Salomaa E , Kauhanen P , Selander T , Hedman M , Husso A 
Published: November 2023

Abstract

Background
Acute Stanford type A aortic dissection is a life-threatening condition that is challenging to predict and prevent. The risk for aortic dissection is known to increase with ascending aortic (AA) dilatation, which sets indication for preventive aortic replacement. Anyhow, most of the dissections occur before aortic diameter reaches the diameter indications of preventive surgery.

Purpose
To investigate whether, alongside with aortic dilatation, AA elongation affects the increased risk for aortic dissection.

Methods
This retrospective study included patients treated for Stanford type A aortic dissection (n=102), patients with AA dilatation (max. diameter &gt; 40 mm) (n=134) and healthy controls (n=191). AA length and dimensions were measured from aortic computed tomography angiography (CTA) images. The AA length was defined as a distance between the aortic annulus to the origin of the brachiocephalic trunk.

Results
AA length was significantly increased in patients with aortic dissection when compared to patients with AA dilatation and to healthy controls (106.2 ± 15.1 mm vs. 96.8 ± 11.2 mm vs. 82.5 ± 8.1 mm; p&lt;0.001).
After adjusting AA length to patient's height, BSA, sex and maximal diameter, adjusted length of AA was 99.8 mm in the dissection group, 94.4 mm in the AA dilatation group and 86.0 mm in healthy controls. Thus, when comparing adjusted AA length between the groups, dissected aortas were 13.8 mm longer than in healthy controls and 5.4 mm longer than in dilated non-dissected aortas (p&lt;0.001). Dilated non-dissected aortas were 8.4 mm longer than in healthy controls (p&lt;0.001).
In the dissection cohort, 25/102 (24.5%) patients had maximal AA diameter &lt;55 mm and 16/102 (12.7%) patients had maximal AA diameter ≥55 mm alongside with AA length &gt; 110 mm (Table). By combining 110 mm AA length and &lt;55 mm diameter, 58% of the dissection patients would have been identified instead of using only AA diameter ≥55 mm as a cut-off criteria, based on which only 33% patients met the indication for elective surgery.

Conclusions
To conclude, AA length seems to be a strong predictor of risk of type A aortic dissection and thus might be used as an additional tool in identifying patients for preventive surgery.Cut off - limits
Association of ventricular-arterial interaction with left ventricular remodelling after acute myocardial infarction: a 2-year follow-up study
Authors: Ikonomidis I , Tsilivarakis D , Pavlidis G , Katogiannis K , Kostelli G , Kountouri A , Korakas E , Pliouta L , Michalopoulou E , Thymis J , Vythoulkas D , Vrettou A R , Frogoudaki A , Parissis J , Filippatos G 
Published: November 2023

Abstract

Background/Introduction
Adverse left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) is associated with heart failure.

Purpose
We aimed to investigated the association of ventricular-arterial interaction with LV remodelling in patients with STEMI.

Methods
In 109 patients within 48 hours of myocardial infarction post-primary percutaneous coronary intervention and after 2 years, we measured: (1) pulse wave velocity (PWV-Complior), (2) LV global longitudinal strain (GLS) and left atrial strain, (3) PWV/GLS ratio as a marker of ventricular-arterial interaction, and (4) LV end-diastolic and end-systolic volumes. A &gt;15% decrease in LV end-systolic volume at 2-years follow-up was considered as a criterion of reverse LV remodelling.

Results
Compared with baseline, all patients had reduced PWV, PWV/GLS, LV end-diastolic and end-systolic volumes, while GLS and reservoir left atrial strain were increased (p&lt;0.05) after 2 years. Both baseline and percentage change of PWV/GLS ratio were associated with LV end-systolic volume percentage change at 2 years (r=0.43, p=0.012 and r=0.35, p=0.038, respectively). Patients with LV end-systolic volume reduction &gt;15% had lower baseline PWV and PWV/GLS and higher GLS and left atrial strain than patients with LV end-systolic volume reduction &lt;15% (p&lt;0.05). Multivariable analysis revealed that PWV and PWV/GLS were independently associated with LV remodelling. A baseline value of PWV of 8.1m/s and PWV/GLS of -0.52m/s% had a sensitivity of 84% and 82% and a specificity of 80% and 77% respectively for prediction of LV remodelling (area under the curve: 0.751, p=0.001 and 0.779, p&lt;0.001).

Conclusion
Ventricular-arterial interaction is an independent predictor of LV remodelling after 2 years of the ischemic event.
Vascular effects and benefits through Helical stent implantation vs. conventional stenting: Methodology and initial Results of The MIMICS FLOW investigator-initiated randomized controlled trial
Authors: Rammos C , Messiha D , Petrikhovich O , Akan B , Fakea S , Sacirovic M , Lortz J , Rassaf T 
Published: November 2023

Abstract

Aims
Endovascular treatment is the primary revascularization strategy for symptomatic peripheral artery disease (PAD), which not only restores tissue perfusion but also affects local lower limb arterial endothelial function. Endothelial dysfunction is the pathophysiologic principle involved in the progression of atherosclerosis and is a prognostically relevant cardiovascular biomarker. A helical stent with a unique 3D helical geometry promotes laminar swirling blood flow elevating wall sheer stress, providing superior hemodynamic advantages and excellent clinical performance as compared to conventional stenting. The potential impact on endothelial homeostasis and the detailed mechanisms following a biomimetic or conventional stent are unknown. To this aim we now determined the effect of the Biomimics or a conventional stent on endothelial and vascular function in symptomatic PAD.

Methods
The MIMICS-FLOW is an investigator-initiated single-blind, randomized controlled trial (NCT05447052). The influence of novel stent-platforms with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance was measured by flow-mediated dilation (FMD) and arterial stiffness indices. Vascular function was determined in 70 PAD patients, Rutherford 2, 3 and 4 randomized to a helical stent and the conventional straight nitinol stent before and after lower limb intervention with a one-month follow-up in the nonstenotic segment of the proximal SFA. Perfusion indices, TLR rate and primary patency were assessed.

Results
The methodology and initial results regarding endothelial function after 1 month will be presented at ESC. In brief, 70 Patients aged 67 years were 1:1 randomized to each group prior to stent implantation in the SFA. Rutherford and PACSS class and target lesion locations were balanced between groups. One patient in the helical and 2 patients in the Straight group required a reintervention. A higher improvement in SFA FMD was observed in the helical group as compared to conventional stenting (p&lt;0.05). Importantly, this effect was mirrored also by a greater increase in brachial FMD in the helical vs. conventional group (p&lt;0.05). No impact was observed between groups regarding arterial or aortic stiffness.

Conclusions
Our RCT data provide evidence for an improved vascular function through swirling flow with superior hemodynamics following a helical stent implantation. These findings support the concept for a better mechanistic understanding to enhance endovascular treatment strategies in PAD.
Gut-microbiota-derived phenylacetylglutamine induces oxidative stress in endothelial cells via a NOX2-dependent pathway
Authors: Allemann M , Saeedi Saravi S S , Lee P , Beer J H 
Published: November 2023

Abstract

Introduction
The gut microbiota-derived metabolite phenylacetylglutamine (PAG) is clinically and mechanistically linked to cardiovascular disease (CVD)(1). Here, we aim to identify the effect of PAG on endothelial cells and elucidate the underlying molecular pathways.

Methods
We treated human aortic endothelial cells (HAEC) at a dose of 100 µM PAG (a concentration which can be observed in vivo) for 72h. As a positive control, cells were treated with H2O2 for 1h. For the determination of reactive oxygen species (ROS) formation, we used the CellROX Green assay with subsequent fluorescence microscopy. For signaling studies, protein expression levels of the NADPH oxidases NOX2 and NOX4 as well as the transcription factor NF-kB were determined by western blot analyses.

Results
Our studies showed that PAG treatment for 72h significantly increased the fluorescence intensity after CellROX Green staining (p&lt;0.0001). Concomitantly, our immunoblotting results revealed that NOX2 (p&lt;0.01) and NF-kB (p&lt;0.001) protein levels were upregulated, whereas NOX4 remained unchanged in response to PAG.

Conclusion
We conclude that PAG-induced oxidative stress in endothelial cells is mediated by a NOX2 and NF-kB but not by a NOX4 dependent pathway. This study is a first step towards better understanding the molecular mechanisms of cellular responses to the gut microbiota-derived metabolite PAG.
Impact of baseline thrombocytopenia on bleeding and mortality after Venous thromboembolism: from the COMMAND VTE Registry-2
Authors: Ito S , Hamaguchi T , Kitano M , Yamaji Y , Fukuda H , Nakane E , Yamashita Y , Morimoto T , Kimura T , Inoko M 
Published: November 2023

Abstract

Background and Aims
The impact of baseline thrombocytopenia on the long-term clinical outcomes has not been clarified in patients with venous thromboembolism (VTE) during the direct oral anti-coagulant (DOAC) era.

Methods
This study sought to evaluate an association of baseline thrombocytopenia with major bleeding, recurrent VTE, and mortality risk in patients with VTE. This study included 5173patients from the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND-VTE) Registry-2. Thrombocytopenia was defined as platelet count of &lt;150×109/L and was classified into moderate/severe (&lt;100×109/L) and mild (≧100-&lt;150×109/L), based on the previous reports.

Results
At 5 years after index admission, the moderate/severe thrombocytopenia group had a significantly higher cumulative major bleeding than the no thrombocytopenia group (log-rank test, p&lt;0.001). Moreover, the moderate/severe thrombocytopenia group had a significantly higher cumulative all-cause mortality rates than the no thrombocytopenia group (log-rank test, p &lt; 0.001).

Conclusions
Baseline platelet level could be a prognostic marker for risk stratification.
Lipoprotein(a) and risk of peripheral arterial disease, abdominal aortic aneurysms, and major adverse limb events
Authors: Thomas P , Vedel-Krogh S , F Nielsen S , Nordestgaard B , Kamstrup P 
Published: November 2023

Abstract

Background
Lipoprotein(a) lowering therapy to reduce atherosclerotic cardiovascular disease is currently under investigation in clinical trials, but lipoprotein(a) may also be implicated in peripheral arterial disease (PAD), abdominal aortic aneurysms (AAA), and major adverse limb events (MALE). Yet, data from general population studies are limited, and large studies are needed to determine risk in individuals with the highest lipoprotein(a).

Purpose
To test whether high lipoprotein(a) levels associate with increased risk of PAD, AAA, and MALE, and to provide genetic evidence of causality using LPA genotypes.

Methods
We included 108,146 individuals from a contemporary prospective cohort study of the general population. During a median follow-up of 8.6 years, 2,450 developed PAD, 1,251 AAA, and 489 MALE. We used a historic prospective cohort study of the general population (N=10,960) to replicate findings for MALE (N=116).

Results
High lipoprotein(a) levels and corresponding LPA risk genotypes were associated with increased risk of PAD and AAA (Figure 1). For individuals with lipoprotein(a) levels in the 100th percentile (≥143mg/dL, ≥307nmol/L), multivariable adjusted hazard ratios were 2.99 (95% confidence interval: 2.09-4.30) for PAD and 2.22 (1.21-4.07) for AAA compared to individuals with levels &lt;50th percentile (≤9mg/dL, ≤17nmol/L). For individuals with peripheral arterial disease, corresponding hazard ratios for MALE were 2.70 (1.67-4.37) in the contemporary cohort, 8.12 (3.56-18.55) in the historic cohort, and 3.31 (2.21-4.95) in the two cohorts combined. The absolute 10-year risk of PAD and/or AAA increased with higher age and lipoprotein(a) level for both men and women and in smokers and non-smokers (Figure 2). The absolute risk increase conferred by high (100th percentile) versus low (&lt;50th percentile) lipoprotein(a) was 2-3-fold in all categories of age, sex, and smoking status. Absolute 10-year risks were 23% and 9% in smoking women aged 70-79 years with lipoprotein(a) in the 100th percentile versus &lt;50th percentile, and equivalent values in men were 38% and 15%. The percentage of events attributable to lipoprotein(a) &gt;50th percentile was 11.6% for PAD and 15.0% for AAA.

Conclusion
High lipoprotein(a) levels increased risk of PAD, AAA, and MALE by 2-3-fold in the general population, opening opportunities for prevention given future lipoprotein(a) lowering therapies.Figure 1Figure 2
Lifetime risk of developing peripheral arterial disease: a nationwide longitudinal study
Authors: Soegaard M , Nielsen P B , Behrendt C A , Lip G Y H , Eldrup N , Skjoeth F 
Published: November 2023

Abstract

Background
Peripheral arterial disease (PAD) presents a substantial clinical and public health burden. It remains one of the most impactful cardiovascular conditions in terms of both number of affected individuals and its impact on the individual’s survival, functional ability, and quality of life. Nonetheless, comprehensive data on the risk of developing PAD in the general population is scant.

Purpose
We aimed to quantify the lifetime risk of physician-diagnosed PAD in an unselected, nationwide population.

Methods
We conducted analyses of the entire Danish population aged 40 years and older from 2000 through 2018 using nationwide health administrative data. All individuals free of PAD were followed for up to 19 years. The cumulative incidence and residual lifetime risk of PAD adjusted for the competing risk of death was estimated by a modified survival analysis technique. Results were stratified by age, sex, and socioeconomic status.

Results
The Danish population aged 40-99 years in 2000-2018 included 4,508,932 individuals, among whom 123,479 individuals were diagnosed with PAD during follow-up. The overall lifetime risk from age 40 years during the remaining lifetime was 19.9% (95% CI 19.8%-20.2%). Lifetime risk was higher in men than in women (22.7% vs. 17.8%) and among individuals living alone (22.4% among unmarried or divorced individuals vs. 19.4% among married individuals). The highest lifetime risks were observed among individuals of lower socioeconomic status, especially individuals receiving social welfare payments for whom the lifetime risk exceeded 26%. The residual risk of developing PAD fell with age; for example, a 50-year-old who had not been diagnosed with PAD would still have a 19.6% residual risk during the remaining lifetime, whereas it was 15.4% among individuals aged 70 years.

Conclusions
About one in five individuals are likely to be diagnosed and receive medical attention for PAD during their lifetime with substantial disparities among individual of lower socioeconomic status. This knowledge may be used in public health awareness campaigns and to promote effective strategies to prevent PAD and limit progression in those with the disease and ensure the highest life quality possible.
Serum proteomic profiling of carotid atherosclerosis: a population outcome study
Authors: Sabovcik F , Verheyen A , Ntalianis E , Brguljan J , Kuznetsova T , Cauwenberghs N 
Published: November 2023

Abstract

Background
Circulating proteins reflecting atherosclerosis may improve cardiovascular (CV) disease prediction. We applied feature selection and unsupervised clustering on proteomic data to identify proteins associated with carotid atherosclerosis and construct a protein-based classification system for prediction of CV events.

Methods
491 community-dwelling participants (mean age, 58±11 years; 51% women) underwent carotid ultrasonography and proteomic profiling (CVD II panel, Olink Proteomics). Subsequently, CV outcome was collected (median follow-up time: 10.2 years). We applied partial least squares (PLS) to identify proteins linked to carotid intima-media thickness (cIMT). Next, we assessed the association between future CV events and protein-based phenogroups derived by unsupervised clustering (Gaussian Mixture modelling) based on proteins influential in PLS.

Results
PLS marked 19 proteins as important, which were all associated with cIMT in multivariable-adjusted linear regression. 8 of the 19 proteins were excluded from the clustering due to high collinearity. Based on the 11 remaining proteins, the clustering algorithm subdivided the cohort into two phenogroups. Compared to the first (n=177), participants in the second phenogroup (n=314) presented: i) a more unfavourable lipid profile with higher total cholesterol and triglycerides and lower HDL cholesterol (P≤0.014); ii) higher cIMT (P=0.0020); and iii) a significantly higher risk for future CV events (multivariable-adjusted hazard ratio (95% CI) versus cluster 1: 2.05 (1.26 to 3.52); P=0.0093). The protein-based phenogrouping supplemented the ACC/AHA 10-year ASCVD risk score for prediction of a first CV event.

Conclusions
Phenogrouping based on a focused set of proteins related to carotid atherosclerosis identified individuals at high risk for future CV events. This approach may complement current CV risk stratification strategies.Summary of workflow and findingsCV event prediction
The impact of duration and control of type 1 diabetes mellitus on microvascular function is strongly modified by the gene for connexin 37
Authors: Pitha J , Pithova P , Cichrova M , Dlouha D , Hubacek J A 
Published: November 2023

Abstract

Introduction
Type 1 diabetes mellitus (T1DM) is almost inevitably accompanied by microvascular dysfunction. This could be responsible for cardiovascular events and is supposed to be caused mainly by long-term exposure to hyperglycemia. Nevertheless, relationship between duration and control of T1DM with microvascular complications can be modified by genetic factors; one of frequently discussed candidate genes is connexin37 (cx37), namely its rs1764391 (C1019&gt;T (Pro319&gt;Ser) polymorphism. We already observed sex specific association between cx37 polymorphism with macrovascular changes but also with retinopathy, neuropathy and diabetic foot. In the recent study, we analyzed if the impact of duration and control of T1DM on directly measured microvascular function is modified by cx37 gene polymorphism.

Methods
In 235 men and 227 women with T1DM (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years) wide spectrum of clinical, laboratory and hemodynamic parameters was measured. Establishment of microvascular function measured by photoplethysmography (detection of blood volume changes in the microvasculature in lower extremities) and calculated as Oliva/Roztocil index (ORI), was analyzed. Cx37 gene polymorphism was measured by PCR-RFLP. The correlation (Pearson’s correlation coefficient) between duration of T1DM and ORI was calculated including analysis of potential modification by control of diabetes (HbA1c) and by cx37 gene polymorphism and standardized for potential confounders (sex, age, smoking, presence of hypertension, central obesity …) by multiple regression. The analysis was conducted separately for duration of T1DM below (n=256) and above (n=206) 20 years as the linear relationship between ORI and T1DM duration tends to change accordingly.

Results
In patients with T1DM, distribution of Cx37 genotypes did not differ from the already described populations (TT/CT/CC: 9.7/44.4/45.9%). In patients with satisfactory control of diabetes (HbA1c&lt;53 mmol/mol; n=105) we detected worsening (increase) of ORI with duration of diabetes only in TT homozygotes and CT heterozygotes for duration of at least 20 years (r=0.6, p=0.006), while in patients with unsatisfactory control (HbA1c&gt;60 mmol/mol;n=270), we detected worsening of ORI with duration of diabetes only in CC homozygotes, both for duration 0-20 years (r=0.35, p=0.03) and for duration of at least 20 years (r=0.47, p=0.03).

Conclusion
Microvascular function in satisfactory controlled T1DM was worsening with diabetes duration only in T allele carriers of Cx37 gene, the worsening was detected only for patients with duration longer than 20 years. However, if T1DM control was insufficient, microcirculation was worsening only in CC homozygotes.
Short-and long-term clinical impact of intravascular ultrasound-guided endovascular treatment for patients with peripheral artery disease
Authors: Kodama T , Higashitani M , Ueshima D , Yamaguchi T , Fujimoto Y , Kuwabara M , Miyazaki R , Anzai H , Suzuki K , Jujo K , Murata N 
Published: November 2023

Abstract

Background
Intravascular ultrasound (IVUS) has become a standard procedure in coronary intervention, but it is unclear whether IVUS usage improves procedural success rate or prognosis in patients with peripheral endovascular therapy (EVT).

Methods
This study analyzed more than 2,000 consecutive patients from the TOkyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry that prospectively enrolled consecutive patients with peripheral arterial disease (PAD) in 34 hospitals in Japan from August 2014 to August 2016. The primary outcome is adverse cardiac and cerebrovascular events (MACCE) and limb events including clinical target lesion revascularization (cTLR) and amputation in the median follow-up period of 10.4 month after the first EVT. The secondary outcomes are procedural success rate and major adverse limb events (MALE) in hospital setting. Every analysis was also conducted with adjusted model after propensity score matching.

Results
In enrolled 2,227 eligible cases, we compared the MACCE and limb events between 784 cases with IVUS usage and 1443 patients without IVUS usage during EVT procedure. There was no significant difference of MACCE and limb events between with and without IVUS usage during EVT procedure over 2 years. However, EVT procedure with IVUS usage contributed significantly higher procedural success rate than that without IVUS usage (98.5% vs 96.7%, p=0.02). Moreover, EVT procedure with IVUS usage contributed less MALE (1.6% vs 4.1%, p=0.02) in hospital setting than that without IVUS usage after propensity score matching. Especially, unscheduled revascularization rate in hospital was less in EVT procedure with IVUS usage than that without IVUS usage (1.5% vs 3.7%, p=0.01).

Conclusion
IVUS usage for EVT did not improve MACCE or limb events over 2-years. However, IVUS usage improved procedural success rate and contributed less MALE when limited to the period of hospitalization. IVUS usage could be recommended for EVT procedures.Table