bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4406New hypothesis of the insulin resistance development: role of adipose-derived stem cell proliferation and adipogenesis
Authors: Stafeev I , Michurina S , Podkuychenko N , Sklyanik I , Panevina A , Shestakova E , Yah'yaev K , Ratner E , Vorotnikov A , Menshikov M , Yashkov Y , Parfyonova Y E , Shestakova M 
Published: October 2019

Abstract

Background
Obesity, remaining a topical issue of modern medicine, leads to development of latent inflammation and insulin resistance in adipose tissue with subsequent development of type 2 diabetes mellitus (T2DM). Among patients with obesity, patients with obesity and normal glucose tolerance (NGT) are often encountered. In our study we have tested the hypothesis that low proliferative potential of adipose derived stromal cells (ADSC) associates with reduced formation of new fat depots, excess accumulation of fat in the functional adipocytes and their hypertrophy, resulting in fat inflammation and insulin resistance.

Methods
We screened two groups of obese patients with or without T2DM, matched for BMI, age, and duration of obesity to test the hypothesis that hypertrophy and decreased renewal of adipocytes may underlie transition from obesity to T2DM. All patients were matched for carbohydrate metabolism (fasting blood glucose level, glycated hemoglobin, HOMA-IR index and M-index). The subcutaneous and omental fat tissue biopsies were obtained during bariatric surgery from obese individuals with or without T2DM. The morphology and immunophenotype of subcutaneous and omental fat was assessed in frozen tissue sections. ADSC were isolated from both types of fat tissue biopsies and screened for morphology, proliferative potential and inflammatory status.

Results
The non-diabetic patients had normal carbohydratemetabolism andmoderate insulin resistancemeasured byHOMA-IR and hyperinsulinemic clamp (M-index),while T2DM patientswere extremely insulin resistant by both indexes. The average size of diabetic adipocytes was higher than that of non-diabetic in both subcutaneous and omental fat tissues, indicating adipocyte hypertrophy in T2DM. We have shown that ADSC from T2DM patients had significantly higher level of inflammation. According to measurement of p62 expression and LC3 modification we can say that ADSC from T2DM patients have less autophagy level compare with ADSC from NGT patients. Immunohistochemistry have shown that patients with T2DM have much more infiltration of CD68+-cells in subcutaneous and omental adipose tissue and immunophenotype (balance of M1-M2 macrophages) of adipose tissue at this patients shift toward inflammatory state.

Conclusion
These results suggest that decreased proliferation and increased hypertrophy of diabetic ADSC may lead to reduced insulin sensitivity via increased inflammation mediated by M1-macrophages and JNK1/2 pathway.

Acknowledgement/Funding
This work was supported by RSF grant #17-15-01435
P4409Cardiorespiratory fitness is inversely associated with the inflammatory status in the general population
Authors: Lehnert K , Gross S , Baumeister S E , Ewert R , Glaeser S , Nauck M , Felix S B , Doerr M , Bahls M 
Published: October 2019

Abstract

Background/Introduction
Low-grade systemic chronic inflammation is a major risk factor for cardiometabolic diseases. Higher physical activity has athero- and cardioprotective effects, potentially through its anti-inflammatory properties. However, the relation between resting inflammatory status and cardiorespiratory fitness (CRF) in population-based settings remains to be elucidated. While previous research has shown inverse associations between CRF and high-sensitive C-reactive protein (hs-CRP) levels, relations with other inflammatory markers are not yet well examined.

Purpose
We assessed the relation between markers of CRF (i.e. maximal oxygen uptake [VO2peak], oxygen uptake at the anaerobic threshold [VO2@AT], oxygen pulse [O2HRmax] and maximal workload [max. Watt]) and hs-CRP as well as total white blood cell (WBC), monocyte, neutrophil, lymphocyte, eosinophil and basophil counts.

Methods
Data of the population-based cohort Study of Health in Pomerania (SHIP) was used (n=1,481; 51% male; age range 20–81 years). CRF was assessed using standardized cardio-pulmonary exercise testing (CPET) according to a modified Jones protocol. The Dimension Vista 500 analytical system was used to measure hs-CRP concentrations. Fluorescence-activated cell sorting was used to assess total as well as subpopulation WBC count. We excluded subjects with missing data, anti-rheumatic/steroid/anti-inflammatory medication as well as chronic inflammatory and hepatic diseases, gastritis, hepatitis infection, severe renal disease, chronic lung disease, asthma, chronic bronchitis, previous myocardial infarction, left ventricular ejection fraction <40% and previous cancer. Linear regression models, adjusted for age, sex, current smoking and lean-mass, were used to assess the relation between CPET and inflammatory parameters.

Results
A 14 ml/min (95%-confidence interval [CI] −23 to −6, p=0.004) lower VO2peak was associated with a one mg/L higher hs-CRP. A lower VO2peak was also related with a one Gpt/L greater WBC (β: −42. 95% CI: −55 to −27 ml/min, p<0.001) as well as neutrophil (β: −57, 95% CI: −77 to −36 ml/min, p<0.001), lymphocyte (β: −63, 95% CI: −107 to 19 ml/min, p=0.005) and monocyte count (β: −204, 95% CI: −360 to −47 ml/min, p=0.011). No significant associations were found for eosinophil and basophil count. Similar results were found for VO2@AT, O2HRmax and max. Watt.

Conclusion
Results suggest an inverse association between CRF and resting inflammatory status. Our non-significant findings with regards to eosinophils and basophils may be expected since these cell types are generally involved in type 2 immune responses related to allergic skin and airway inflammation as well as immunity against parasites. Overall, our results imply that potential biological mechanisms underlying the athero- and cardioprotective effects of high CRF may be related to lower chronic inflammation in fitter individuals.
P4411Analysis of cardiometabolic traits highlights shared biological pathways
Authors: Timasheva Y , Zudina L , Balkhiyarova Z , Kaakinen M , Munroe P , Prokopenko I 
Published: October 2019

Abstract
Genome-wide association studies (GWAS) have contributed to a major leap forward in the unravelling of the genetic basis of complex disorders, and identified over 900 genetic loci for blood pressure (BP) regulation, 160 for coronary artery disease (CAD) and 140 for type 2 diabetes (T2D). The ubiquitousness of genetic pleiotropy and the fact that cardiovascular diseases, T2D, and other metabolic disorders share a number of risk factors, suggest that these conditions may have common underlying molecular mechanisms. We aimed to dissect shared genetic factors contributing to the comorbidity of these diseases using multi-phenotype approach.
Using summary statistics from published GWAS available in public domain, including those from GWAS consortia DIAGRAM/DIAMANTE (T2D), MAGIC/ENGAGE (glycaemic), ICBP (blood pressure, BP), CARDIOGRAM (cardiovascular), GLGC/ENGAGE (lipids), GIANT (obesity), we analysed 3429 single nucleotide variants (SNVs) associated with 63 cardiometabolic phenotypes (defined as related to T2D, cardiovascular and metabolic disorders).
We identified 301 unique association signals, and found 426 CAD/BP SNVs overlapping with 1194 SNVs reported for other phenotypes and located within 100kb from one another. Further analysis revealed 49 linkage patterns for cardiometabolic phenotypes (D'>0.9, r2>0.8). Specifically, nine SNVs in SH2B3-ATXN2 locus are associated with CAD, systolic and diastolic BP, stroke, ICAM-1 and diabetes; three SNVs in ATP5G1- UBE2Z influence CAD risk, T2D, and anthropometric traits; nine SNVs in TCF7L2 are associated with pulse pressure (PP), body mass index (BMI), glycaemic traits and T2D risk; four SNVs in ADAMTS9 and three in BCL2 are associated with BP traits, T2D, and abdominal obesity; twelve SNVs in IRS1 gene are related to hypertension, T2D risk, glycaemic and lipid traits; ten SNVs in MTNR1B affect PP, T2D susceptibility, and glycaemic traits; six SNVs in KLF14 influence systolic BP, T2D, and high density lipoproteins (HDL) level; nine SNVs in ABO affect CAD, T2D, and stroke susceptibility, as well as lipids and ICAM-1 level; eight SNVs in CDKAL1 are associated with systolic BP, increased T2D risk, and glycaemic traits; two in SLC39A8 affect BP traits, lipid levels, and BMI.
Our results highlight the pathways that influence multiple cardiometabolic phenotypes, including circadian rhythm regulation (MTNR1B), pancreatic islet function and insulin signalling (CDKAL1 and IRS1), appetite control and nutritional regulation (NUCB2 and ATXN2), immune and inflammatory signaling (SH2B3 and SLC39A8), cell cycle regulation and apoptosis (UBE2Z and BCL2), angiogenesis (ADAMTS9), suggesting that similar disease-driving biological processes are implicated in the pathogenesis of these diseases.
P4415Long obstructive sleep apneas as a biomarker of atrial fibrillation
Authors: Allam S , Reddy P , Valladares E , Hammond T , Grbach V , Basrawala H , Patel K , Konecna E , Konecny V , Borok Z , Khoo M , Doshi R , Somers V , Konecny T 
Published: October 2019

Abstract

Background
Even though obstructive sleep apnea (OSA) is strongly associated with atrial fibrillation (AF), the use of traditional OSA scoring by apnea hypopnea index (AHI) did not result in improved arrhythmia outcomes in recent randomized trials. Longer OSA episodes lead to stronger pro-arrhythmic changes, and whether very long OSA episodes are more prevalent in AF patients remains unknown.

Purpose
We hypothesized that AF patients with mild-moderate OSA manifest greater percentage of long (>20s), very long (>30s), and extremely long (>40s) OSA episodes, compared to control OSA patients matched to AHI, age and sex.

Methods
From patients studied with diagnostic polysomnography in our laboratory between 2016 and 2018, we selected 22 patients with mild-moderate untreated OSA of which 11 patients had history of paroxysmal AF and 11 patients did not have any cardiac history. The length, oxygen desaturation, and relationship to neighboring events was manually re-measured in all recorded apnea and hypopnea events.

Results
In the 22 included patients (age 62.5±9.1 years, AHI 12.8±6.1, 40% female) we recorded 1021 apneas: 508 in the AF group and 513 in the control group. AF patients had longer apneas compared to the patients without AF history (mean length 28.7±11.7s vs. 23.3±9.9s; p<0.0001). The proportion of apneas that were long (>20s), very long (>30s), and extremely long (>40s) was greater in the AF group as compared to the control (p=0.0039, p=0.0215, p=0.0104, respectively; see figure). The acute oxygen saturation drops (>2%) during apneas were comparable between the AF group and control groups (p=0.13), but the long (>20s) apneas were prone to greater oxygen desaturations.
Length of Apneas

Conclusions
While traditional scoring of OSA focuses on episodes lasting >10s, our data newly show that longer durations of OSA events are particularly prevalent in AF patients. These results, combined with recent mechanistic studies showing that longer apneas exert greater pro-arrhythmic effect on atrial conduction, suggest that novel scoring of OSA placing more weight on longer apneas should be explored, especially when screening and titrating OSA therapy in patients at risk of AF.
P4450Atherosclerosis in women with systemic lupus erythematosus with and without nephritis
Authors: Panafidina T , Popkova T V , Novikova D S 
Published: October 2019

Abstract

Background
Nephritis in systemic lupus erythematosus (SLE) is a factor contributing to early development of atherosclerosis (AS).

Objectives
The aim of the study is to determine differences in cardiovascular risk factors and AS in SLE pts with and without lupus nephritis (LN).

Methods
The study included 162 females, age 35 [26–43] years (median [interquartile range 25–75%])) with SLE (ACR,1997). We divided SLE pts on two groups, comparable in age: the 1st group is the pts with LN (n=84, 52%), the 2nd - without LN (n=78, 48%). We considered traditional factors of cardiovascular disease (CVD): (smoking, family history of CVD, blood pressure, cholesterol (total, HDL, LDL) and triglyceride (TG) levels, body mass index, diabetes mellitus) and SLE-related factors (age at onset, duration, clinical features, SLE Disease Activity Index (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics damage index (SLICC/DI), treatment with steroids); intima-media thickness (IMT) and the 10-year risk for coronary events. Carotid intima-media wall thickness of common carotid arteries was measured by high resolution B-mode ultrasound. The 10-year risk for coronary events was estimated by the Framingham risk equation.

Results
Median SLE duration was 8,0 [2,3–17,0] years, SLEDAI 2K – 8 [3–16], SLICC/DI score – 2 [0–3], duration of prednisone treatment – 72 [26–141] months. SLE pts from the 1st group had higher prevalence of hypertension (61% vs 36%, p<0,01), systolic blood pressure (130 [110–150] vs 120 [110–130]mm Hg, p<0,01), diastolic blood pressure (80 [70–95] vs 70 [70–80] mm Hg, p<0,05), TG concentration (136 [98–184] vs 100 [61–162] mg/dl, p<0,01), Framingham Risk Score (5 [1–30] vs 1 [1–27]%, p<0,05), SLEDAI-2K (12 [5–19] vs 4 [2–10], p<0,ehz745.08501), SLICC/DI score (2 [0–4] vs 0 [0–2], p<0,01), prednisone therapy duration (95 [26–192] vs 44 [14–98] months, p<0,05), prednisone cumulative dose (34,4 [13,6–82,5] vs 15,7 [6,2–35,2] g, p<0,001), mean IMT (0,73 [0,65–0,83] vs 0,67 [0,61–0,75] mm, p<0,01), than the pts from the 2nd group. There is no difference in CVD frequency in these groups (17% vs 8%, p=0,084).

Conclusions
SLE patients with and without LN had no difference in frequency of clinical manifestations of AS (CVD), but had a greater value of mean IMT, Framingham Risk Score and a higher incidence of both traditional (hypertension, TG concentration) and SLE-related (disease activity, prednisone therapy) risk factors for AS.
P4492Peripheral blood mononuclear cell expression of the stabilizing RNA-binding protein HuR is associated with incidence and extent of human atherosclerotic cardiovascular disease
Authors: Sachse M , Mareti A , Georgiopoulos G , Sopova K , Vlachogiannis N , Tual-Chalot S , Kritsioti C , Laina A , Kontogiannis C , Zaman A , Spyridopoulos I , Gatsiou A , Stamatelopoulos K , Stellos K 
Published: October 2019

Abstract

Background
Human Antigen R (HuR) is a stabilizing RNA-binding protein that regulates the expression of several pro-inflammatory molecules. However, its regulation in human atherosclerotic cardiovascular disease remains unknown.

Purpose
To determine the association of peripheral blood mononuclear cell HuR expression with established markers of increased cardiovascular risk and atherosclerosis burden in patients with subclinical or clinically overt coronary artery disease (CAD).

Methods
HuR mRNA expression was measured in peripheral blood mononuclear cells derived from 289 patients with stable CAD or acute myocardial infarction (AMI) and 373 individuals without clinically overt cardiovascular disease (CVD). Structural and functional vascular measurements including intima-media thickness (IMT) and number of atheromatous plaques by carotid and femoral artery ultrasonophaphy, markers of arterial wave reflections by pulse wave analysis and pulse wave velocity were used as surrogate markers of subclinical CVD. The number of angiographically confirmed diseased coronary arteries (>50% stenosis) was used to assess the extent of CAD.

Results
HuR mRNA expression was significantly increased in patients with CAD (both stable and AMI) compared to controls (p=0.039). Subgroup analysis revealed that STEMI patients (n=107) had increased levels of HuR expression compared to NSTEMI (n=49, p=0.03). Among patients with stable CAD (n=133), high HuR expression was independently associated with the number of diseased coronary arteries (OR=1.35 for 1-SD increase in HuR, 95% CI 1.07–1.72, p=0.012), as well as with reduced ejection fraction (EF<45%, OR=1.32 per 1-SD increase, 95% CI 1.05–1.85, p=0.024). Among individuals without CVD, high HuR was associated with lower HDL levels (adjusted beta=-5.2 mg/dl for highest versus lowest quartile, p=0.03) and higher diastolic blood pressure (adjusted beta=3.6 mmHg, p=0.007), while, after adjustment for traditional cardiovascular risk factors, HuR levels in individuals without CVD were independently associated with increased IMT in the common carotid artery (mean increase 6.2% for highest versus lowest quartile, p=0.019).

Conclusion
HuR expression is associated with early subclinical arterial disease in individuals without clinically overt CVD and with the presence and severity of cardiac and vascular dysfunction in patients with clinically overt CAD. These findings imply a clinical role of the HuR pathway in cardiovascular disease and warrant further investigation.
P4494Renal insufficiency mitigates the protective effects of elevated anti endothelial cell antibodies on survival in patients undergoing coronary angiography
Authors: Teodorovich N , Gandelman G , Jonas M , Shimoni S , George J , Swissa M 
Published: October 2019

Abstract

Background
We previously demonstrated that elevated levels of antiendothelial cell antibodies are associated with improved survival of patients undergoing coronary angiography. However, renal insufficiency, which is associated with decreased survival, leads to increased level of the antiendothelial cell antibodies. The purpose of this study was to evaluate the correlation of the levels of these antibodies with survival in patients with normal versus reduced renal function.

Patients and methods
This was a single center prospective study. Eight hundred thirty eight consecutive patients undergoing coronary angiography with detectable antibody levels were enrolled. The levels of antiendothelial antibodies were determined by ELISA and measured in optical density units. Renal insufficiency was defined as adjusted GFR<60 ml/min. The mean follow up was 30 months.

Results
Of total 838 patients, 481 (57%) had normal and 357 (42.6%) had reduced renal function. Total mortality was 13.6%, being significantly higher in patients with reduced (23.2%) versus normal (6.4%) renal function (p<0.0001). Antiendothelial cell antibody levels were higher in patients with normal versus reduced renal function (4.76±7.05 versus 3.84±6.09 OD units, p=0.042). Antiendothelial cell antibody levels were significantly higher in survived versus deceased patients (4.56±6.82 versus 3.14±5.50 OD units, p=0.014). This association with survival was even more pronounced in patients with normal renal function (4.98±7.19 versus 11.69±3.29 OD units, p<0.0001). In patients with reduced renal function, there was no significant difference between survived and deceased patients (3.89±6.12 versus 3.68±6.05 OD units, p=0.788).

Conclusions
Renal insufficiency leads to mild decrease in the antiendothelial cell antibodies' levels. Higher levels of antiendothelial cell antibodies are associated with improved survival in patients undergoing coronary angiography. This association is significant in patients with normal but not reduced renal function. Thus, the effect of the higher levels of these antibodies on survival cannot be explained by its association with renal dysfunction.
P4510Impact of secondary tricuspid regurgitation on survival in heart failure - insights from COMMIT-HF registry
Authors: Nowak J , Pyka L , Kurdziel M , Siedlecki L , Niedziela J , Krajewski A , Skowron W , Danicic M , Kazik A , Gasior M 
Published: October 2019

Abstract

Background
Functional tricuspid regurgitation (fTR) is common in left sided heart disease, especially in patients with concomitant left-sided valvular diseases and can lead to functional impairment and reduced survival. However, the impact of fTR on survival in chronic heart failure with reduced left ventricular ejection fraction (HFrEF) without severe left valvular diseases (LVD) is not fully established. The aim of the present study was to observe if moderate to severe fTR may influence the survival in patients with HFrEF without severe LVD.

Methods
We have analyzed a large single-center registry (n=2731) of HFrEF patients treated in a large-volume cardiovascular center between 2009–2015. After exclusion of patients with severe aortic and mitral valve disease we have included 2435 patients with HFrEF (left ventricular ejection fraction (LVEF) ≤35%). Functional moderate to severe tricuspid regurgitation without severe left valvular diseases was present in 465 patients. Twelve -month vital status was available for the whole patient population. Univariate and multivariate Cox proportional hazard regression models were performed to evaluate the relationship between moderate to severe fTR and mortality in the study group.

Results
Comparison of clinical data of fTR and non-fTR in HFrEF patients revealed some significant differences (age 63.3±12.9 vs 61.3±12.4, p=0.002; female sex 25.8% vs 17,9%, p<0.001; chronic kidney disease stage III-V 45.3 vs 26.6%, p=0.001; atrial fibrillation 52.4% vs 28.5%, p<0.001). Twelve-month all-cause mortality was over 2-fold higher in the fTR group (21.2% vs 8.1%, p<0.001). There were no significant differences with regard to the medical treatment, implantable defibrillator or cardiac resynchronization therapy. The presence of fTR was identified as an independent echocardiographic factor impaired 12-month all-cause survival (HR 1.59, CI 1.2- 2.09, p<0.001, figure 1)

Conclusion
Apart from the LVEF, the presence of moderate to severe fTR may predict 12-month all-cause mortality in patients with HFrEF.

Acknowledgement/Funding
None
P4520APAP therapy does not improve impaired sleep quality and sympatho-vagal balance: a randomized trial in patients with obstructive sleep apnea and systolic heart failure
Authors: Spiesshoefer J , Aries J A , Giannoni A G , Fox H F , Boentert M B , Bitter T B , Oldenburg O O 
Published: October 2019

Abstract

Introduction and purpose
In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown.

Methods
In this randomized controlled trial, sleep quality and SVB in patients with HFrEF and OSA were monitored noninvasively across different breathing conditions (5-minute segments of OSA or normal breathing [NB]) during stable N2 sleep) at baseline (T0), during APAP initiation (T1) and after 6 months of successful APAP treatment (T2).

Results
75 patients (61 male, 65±12 years, LVEF 31±9%) were enrolled. OSA was associated with a 17% increase in the low frequency/high frequency component ratio of heart rate variability (LF/HF) versus baseline, suggesting an increase in sympathetic drive (SVB) with OSA compared with normal breathing at baseline. Respiratory indices and oxygen saturation all significantly improved at both T1 and T2, but 6 months' APAP had no clinically relevant effect on objective sleep quality versus control. In HFrEF patients -suitable for HRV analysis (n=23)-, there was a trend (p=0.097) towards an increase in LF/HF at T2 in the therapy group (+17%), suggesting increased SVB.

Conclusion
Treatment of OSA in systolic HF patients improves respiratory indices but has no favorable effect on sleep quality. While OSA per se was associated with an increase in sympathetic drive, APAP treatment was not associated with a desired reduction in sympathetic drive. There was even a trend towards additional increases in sympathetic drive during the entire night and N2 sleep in particular.

Acknowledgement/Funding
This research (conductance of the APAP trial) has been supported by Resmed Germany (Martinsried, Germany).