bluuebunny/crossref_metadata_2025_split huggingface dataset:
What potential risk reduction could be achieved with evolocumab treatment? A simulation based on observational data from a cohort of users in 10 European countries
Authors: Ray K.K , Bridges I , Bruckert E , Van Hout B , Sibartie M , Villa G 
Published: November 2020

Abstract

Background/Introduction
The FOURIER trial enrolled very high-risk patients with a mean LDL-C of 2.5 mmol/L, and demonstrated that evolocumab reduced major cardiovascular events by 1.5% in absolute terms over 2.2 years. Further research may be conducted to understand the potential benefits of evolocumab in the real world.

Purpose
Predict/simulate baseline CV risk and assess potential risk reduction among a large European cohort of evolocumab users.

Methods
We used interim data from an observational study of patients initiating evolocumab across 10 European countries from August 2015 with follow-up through October 2019. Demographic and clinical characteristics, lipid-lowering therapy (LLT) and lipid values were collected from routine medical records (6 months prior to evolocumab initiation through 30 months post initiation). For each patient, we 1) predicted/simulated their 10-year CV risk using three different approaches: i) a prediction using REACH score, ii) a simulation based on FOURIER trial patients, iii) a simulation based on real-world FOURIER-like patients from a published obervational study; 2) calculated their absolute LDL-C reduction on evolocumab treatment; 3) simulated their relative risk reduction (RRR) by randomly sampling from the probability distribution of the rate ratio per 1 mmol/L from the key secondary endpoint in the FOURIER trial landmark analysis; 4) calculated their absolute risk reduction (ARR).

Results
Our analysis included 779 patients initiating evolocumab in clinical practice per local reimbursement criteria, with up to 18 months follow-up. Mean (SD) age was 62.7 (9.6) years and mean (SD) baseline LDL-C was 3.85 (1.39) mmol/L. Mean (SD) absolute LDL-C reduction on evolocumab was 2.1 (1.2) mmol/L. Predicted/simulated 10-year CV risk, RRR and ARR are presented in Table 1. Simulated probability distributions (based on FOURIER) for 10-year CV risk before and after evolocumab treatment are shown in Figure 1.

Conclusion(s)
This cohort of evolocumab users in clinical practice had an almost 2-fold higher baseline LDL-C than patients enrolled in FOURIER trial, which translated to higher baseline CV risk. For that reason, the estimated 10-year absolute benefit in this cohort was larger than expected based on FOURIER trial results.
Figure 1

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Amgen
Effects of smoking cessation on endothelial function assessed by flow-mediated dilation and reactive hyperemia peripheral artery tonometry
Authors: Fukumoto K , Takemoto Y , Norioka N , Takahashi K , Namikawa H , Tochino Y , Shintani A , Yoshiyama M , Shuto T 
Published: November 2020

Abstract

Background
Smoking predisposes individuals to endothelial dysfunction. Both flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, there are differences in the physiology of vascular beds being tested and in the response of conduit and resistive vessels to RH. Therefore, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and by RH-PAT remains unclear.

Purpose
We aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT.

Methods
Thirty-eight consecutive current smokers (mean±standard deviation; age, 65±10 years) who visited our smoking cessation outpatient department and succeeded in smoking cessation with varenicline were enrolled. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. Fifteen current smokers who failed in smoking cessation were enrolled as age- and sex-matched controls. The Spearman's rank correlation coefficient and intraclass correlation coefficient (ICC) for a two-way mixed effects model were performed to assess the agreement of changes in FMD and Ln-RHI. Multivariate logistic regression analysis was performed to examine the associations between the presence of increase in FMD or Ln-RHI and clinical variables.

Results
FMD significantly improved after smoking cessation (3.42%±1.96% to 4.45%±2.28%; p=0.019), whereas Ln-RHI did not (0.53±0.25 to 0.59±0.21; p=0.223). The Spearman's rank correlation coefficient between changes in FMD and Ln-RHI was −0.013, and the ICC was −0.002 (p=0.506). In the multivariate logistic regression analysis, an increase in FMD or Ln-RHI was predicted based on the baseline FMD (odds ratio = 0.54, p=0.013) or Ln-RHI (odds ratio = 0.36, p=0.012), respectively, after adjusting for age and sex.

Conclusions
There was significant improvement in the endothelial function assessed by FMD, but not by Ln-RHI, after smoking cessation. In addition, there was disagreement between changes in FMD and those in Ln-RHI. Smoking cessation may have varying effects on the endothelial function of the conduit and digital vessels.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-aid for scientific research from the ministry of education, science and culture of Japan
Prevalence and pathophysiology of subclinical cardiac dysfunction in obesity patients detected by multimodality diagnostics
Authors: Snelder S , De Groot-De Laat L.E , Biter L.U , Castro Cabezas M , Pouw N , Birnie E , Boxma-De Klerk B , Klaassen R.A , Zijlstra F , Van Dalen B.M 
Published: November 2020

Abstract

Background
Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification.

Purpose
The aim of the study was first to identify the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology by comparing obesity patients with and without cardiac dysfunction.

Methods
The CARDIOBESE-study is a cross-sectional multicentre study of 100 obesity patients (BMI ≥35 kg/m2) without known cardiovascular disease, and 50 age- and gender-matched non-obese controls (BMI ≤30 kg/m2). Echocardiography was performed, blood samples were collected and a Holter monitor was affixed. Cardiac dysfunction was defined as either reduced LV ejection fraction, decreased global longitudinal strain (GLS), diastolic dysfunction, sustained supraventricular or (non)sustained ventricular arrhythmia or an increased BNP.

Results
Figure 1a shows the characteristics of the obesity patients and the non-obese controls. 59 obesity patients (48 [42–50] years, 70% female) showed subclinical cardiac dysfunction: 57 patients had decreased GLS, 2 patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide. Only 1 non-obese control had diastolic dysfunction, none had another sign of cardiac dysfunction. Figure 1b shows the characteristics of obesity patients with and without cardiac dysfunction. Multivariable logistic analysis identified male gender and SDNN-index, which is a heart rate variability parameter and thereby a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients.

Conclusions
There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, inflammation, increased cardiac filling pressure, cardiomyocyte damage or increased left ventricular mass.
Figure 1

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Stichting BeterKeter
Exploring functional and structural vascular changes in obesity: are metabolically healthy obese individuals really healthy?
Authors: Ioakeimidis N , Angelis A , Terentes-Printzios D , Emmanouil E , Dima I , Georgakopoulos C , Solomou E , Rokkas K , Tousoulis D , Vlachopoulos C 
Published: November 2020

Abstract

Purpose
Aim of the study is to compare vascular function and structure parameters among middle-aged men with differences in body mass index (BMI) and metabolic status and to investigate whether obese individuals with a normal metabolic profile have a unhealthy vascular profile.

Methods
We measured carotid-femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT) and brachial flow-mediated dilation (bFMD) in 141 obese (BMI≥30 kg/m2) and in 176 aged-matched men with normal BMI (&lt;25 kg/m2) individuals. All participants had no clinical manifestations or a history of atherosclerotic disease. High sensitivity C-reactive protein (hsCRP) and total testosterone (TT) were measured in all patients.

Results
The two BMI groups were subdivided into subgroups according to presence/absence of abnormal metabolic profile (presence of major cardiovascular risk factors): Metabolically unhealthy obese (MeUO, n=114), metabolically healthy obese (MeHO, n=27), metabolically unhealthy with normal BMI (MeUN, n=122) and metabolically healthy with normal BMI individuals (MeHN, n=54). The four subgroups had similar age. Figure 1 shows the mean cIMT (left plot), cfPWV (middle plot) and bFMD (right plot) of the four subgroups. Carotid IMT and cfPWV is higher and bFMD is lower in metabolically unhealthy compared to individuals with a normal metabolic profile in both patients with obesity and subjects with normal BMI. Interestingly, the MeNO patients had significantly lower cIMT (P&lt;0.05) and cfPWV (P&lt;0.01) and higher bFMD (P&lt;0.01) level compared to MeUN individuals. However, as figure shows all measured vascular parameters were significantly impaired in MeNO patients compared to those of MeHN individuals. MeHO patients had comparable hsCRP and TT levels to those of MeUO and MeUN individuals denoting increased inflammatory activation and endogenous androgen deficiency.

Conclusions
MeHO which is a obesity phenotype that has created lot of debate is associated with a better vascular profile compared to MeUN status, however patients with MeHO have more impaired vascular function and structure parameters than MeHN individuals. This finding implies that even in the absence of overt metabolic aberrations, the MeHO profile may be associated with endothelial dysfunction, increased aortic stiffness and thickness of the carotid arterial wall.
Figure 1. BMI, metabolic status and vascular changes

Funding Acknowledgement
Type of funding source: None
The synthetic glucagon-like peptide-1 receptor agonist liraglutide affects the kinetics of pro-inflammatory kinases and improves insulin sensitivity of 3T3-L1 adipocytes
Authors: Mamontova E , Michurina S , Podkuychenko N , Sorkina E , Stafeev I , Menshikov M , Shestakova M , Parfyonova Y.E 
Published: November 2020

Abstract

Background
Obesity is the main risk factor of latent inflammation, which leads to insulin resistance (IR) which can transform to type 2 diabetes mellitus (T2DM). Today several groups of drugs are used to correct T2DM and its complications. The most perspective treatment is the use of glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide, that affect the insulin exocytosis in pancreatic β-cells. The metabolic pathways in these cells are well studied, but liraglutide's effects on other insulin-sensitive tissues, such as adipose tissue, remain unclear.

Purpose
We wanted to investigate the effect of the synthetic analogue of GLP-1 liraglutide on insulin sensitivity and on inflammatory and mitogenic signaling pathways in 3T3-L1 adipocytes.

Methods
We studied the effects of liraglutide on the kinetics of inflammatory and mitogenic pathways and insulin sensitivity in 3T3-L1 adipocytes, which were differentiated according to standard protocol with insulin, IBMX and dexamethasone. IR was induced by treatment with 1mM free fatty acids for 24 hours. Activities of insulin, mitogenic and inflammatory signaling pathways were analyzed by Western blotting with phospho-specific antibodies. Insulin sensitivity was also assessed by insulin-stimulated [3H]-deoxyglucose uptake analysis.

Results
We have showed that liraglutide promotes the decrease in expression of kinases JNK and ERK. So, under these results, we had a hypothesis that liraglutide changes cAMP-dependent regulation of transcription. In order to check it we have used the inhibitor of adenylyl cyclase (SQ22536) to see whether there will be any effects of liraglutide. As we suspected there was no effect, so our hypothesis of the liraglutide-stimulated activation of cAMP-dependent pathway was confirmed. In the model of IR adipocytes liraglutide promotes the increase of total amount of IRS and Akt and increased phosphorylation of pAkt-T308. When SQ22536 was added there was no effect of liraglutide on insulin sensitivity.

Conclusion
These results suggest the action of liraglutide in 3T3-L1 adipocytes via transcriptional regulation and insulin sensitivity control. According to our hypothesis, GLP-1 analogue liraglutide can influence systemic insulin sensitivity via regulation of adipose tissue metabolism.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Russian Science Foundation
The degree of retinopathy correlates with the presence of silent myocardial ischemia in diabetic patients
Authors: El-Hefny E , Tag El-Din A , Sadek A , Abbas E 
Published: November 2020

Abstract

Background
Silent myocardial is a major component of the total ischemic burden for patients with ischemic heart disease. The disease is more prevalent in diabetic patients than their peers, and early detection of the high-risk group would play an integral role in the prevention of sudden cardiovascular accidents that are common in these patients.

Methods
A prospective cohort study including asymptomatic 53 diabetic patients with diabetic retinopathy who suffer no ischemic cardiac symptoms was conducted. The presence and degree of diabetic retinopathy were evidenced using fundus examination and optical coherence tomography. All the enrolled patients underwent stress-resting 99mTc SestaMIBI myocardial perfusion scintigraphy to detect the ischemic burden. The relation between diabetic retinopathy and silent myocardial ischemia was stratified using statistical analysis.

Results
A total of 13 diabetic patients (24.5%) have silent myocardial ischemia in the form of regional myocardial perfusion abnormalities. The strongest predictors of abnormal tests were the presence of moderate to severe retinopathy, comorbid hypertension and diabetic duration for more than 10 years.

Conclusion
Silent myocardial ischemia affects one in four asymptomatic diabetic patients suffering from diabetic retinopathy. The presence of comorbid risk factors such as high-grade retinopathy, hypertension and/or long diabetic duration surge the incidence and considered additional predictors of the disease.

Funding Acknowledgement
Type of funding source: None
Post-load glucose spike is a determinant of post-MI prognosis in patients without known or newly diagnosed diabetes
Authors: Chattopadhyay S , George A , John J , Sathyapalan T 
Published: November 2020

Abstract

Background
Post-prandial plasma glucose spikes contribute to the progression of atherosclerosis. Glycaemic variability may predict post-ACS prognosis. A third to two-thirds of these patients had diabetes mellitus (DM). Post-ACS prognosis is worse in DM than in those without. This has not been tested in patients without DM.

Purpose
To test whether post-load spike in plasma glucose in patients without known or newly diagnosed DM adversely affects prognosis.

Methods
Retrospective cohort analysis of 847 MI survivors without known or newly diagnosed DM who were followed up for MACE (death and non-fatal MI). The median post-glucose spike (PGS, defined as the difference between the 2h-PG and FPG) was 2.4 mmol/l for the whole cohort and 1.5 mmol/l for the patients with normal glucose tolerance (NGT). Group 1: PGS ≤2.4 mmol/l and Group 2: PGS &gt;2.4 mmom/l were compared using Mann-Whitney test for continuous variables and chi-squared test for categorical variables. Event free survival in the two groups was estimated from the Kaplan–Meier curves and compared using log-rank test. Cox proportional hazard regression identified predictors of MACE. Continuous net reclassification improvement (NRI&gt;0) and integrated discrimination improvement (IDI) and c-statistics determined the added predictive value of glycaemic matrices

Results
MACE was higher in group 2 (OR 1.99, 95% CI 1.36 to 2.91, p=0.0004) compared to group 1. In patients with NGT, MACE was higher in patients with PGS ≥1.5 mmol/l vs those below (OR 2.37, 95% CI 1.31 to 4.26, p=0.0041). Event free survival was worse in pre-diabetes than in the NGT groups (HR 1.57, 95% CI 1.17 to 2.12, p=0.003). and in group 2 than 1 (HR 2.01, 95% CI 1.49 to 2.71, p&lt;0.001). Amongst the patients with NGT, event free survival was worse in patients with PGS ≥1.5 mmol/l (HR 2.09, 95% CI 1.35 to 3.25, p&lt;0.001). PGS independently predicted MACE in the whole cohort (HR 1.16, 95% CI 1.06 to 1.26, p=0.002) and NGT group (HR 2.06, 95% 1.51 to 2.79, p&lt;0.000). Group 2 independently predicted MACE in the whole cohort (HR 1.75, 95% CI 1.26 to 2.42, p&lt;0.001). In the NGT group, PGS &gt;median, independently predicted of MACE (HR 2.67, 95% CI 1.54 to 4.61, p&lt;0.001). The c-statistic a model containing GRS only increased on addition of PGS (δAUC 0.0134, p=0.046) but not on addition of FPG. Within the whole cohort, PGS improved the net reclassification by 28% when added to the model containing GRS only. NGT cohort had higher net improvement at 46.6%. Addition of PGS to the model containing GRS and FPG resulted in NRI&gt;0 of 25.5% in the whole cohort and 56.3% in the NGT cohort. Similar changes were seen in the IDI.

Conclusion(s)
PGS predicts post MI prognosis in patients without known or newly diagnosed DM including in patients with NGT. This suggests that PGS is a more powerful indicator of post-MI prognosis than FPG

Funding Acknowledgement
Type of funding source: None
The prognostic value of socioeconomic status in the open male population and in patients with coronary artery disease
Authors: Pushkarev G , Kuznetsov V , Leznyakova A 
Published: November 2020

Abstract

Background
It has been established that low socioeconomic status associated with a poor prognosis in coronary artery disease (CAD). However the data about psychosocial risk factors in patients with CAD after percutaneous coronary intervention (PCI) are insufficient. Also socioeconomic factors and marital status of individuals are associated with risk of cardiovascular mortality in developed societies but in our country this association has not been studied sufficiently.

Purpose
To assess the relationship between socioeconomic factors, marital status and risk of cardiovascular mortality in working-age male population of Western Siberia and in patients with CAD after PCI.

Methods
A representative sample of 795 men aged 25–64 years living in our city in Russia, was examined with standard epidemiological methods in 1996. Cardiovascular death rate was studied during 12-year prospective follow-up (from 1996 till 2008). The clinical study included 977 consecutive patients with CAD (741 men and 236 women, mean age 58.6±9.4 years) who underwent PCI for the period 2012–2013 in our cardiology research center. Mean duration of follow-up was 12.0±1.8 months.
The relationship between cardiovascular mortality and education, occupation, total income and marital status was evaluated using Cox proportional hazards model. Hazard ratio (HR) was calculated after adjustment for the following confounders: age, systolic and diastolic blood pressure, body mass index, smoking status, total cholesterol, triglycerides, high-density-lipoprotein cholesterol, history of coronary artery disease, and social risk factors.

Results
Over 12 years of prospective cohort study in the male cohort 85 deaths (10.69%) from cardiovascular disease were recorded. After adjusting for all mortality risk factors HR was significantly higher in manual workers – 2.72 (95% CI 1.42–5.23) compared to professionals. Compared to men with higher education, HR was higher for men with low education level – 1.92 (95% confidence interval (CI) 1.14–3.22). Compared to married men, HR was higher in single – 4.08 (95% CI 2.12–7.83), widowed – 3.19 (95% CI 1.22–8.34) and divorced men – 3.18 (95% CI 1.90–5.34). During the prospective clinical study 21 (2.1%) patients with CAD died from cardiovascular disease. After adjustment for the following confounders risk of cardiovascular mortality was significantly higher only in patients with low total income – HR: 5.14, 95% CI 1.73–15.29).

Conclusions
Our results showed that socioeconomic position (low education level and manual occupation) and marital status (widowed, divorced or single) were significant predictors of cardiovascular mortality in open male population. However, low income was significant and independent predictor of cardiovascular mortality in CAD patients after PCI.

Funding Acknowledgement
Type of funding source: None
The effects of different preventive counseling programs on stress level in patients with paroxysmal atrial fibrillation after catheter ablation
Authors: Pogosova N , Yufereva Y.M , Ovchinnikova A.I , Sokolova O.Y , Davtyan K.V 
Published: November 2020

Abstract

Background
Stressful life events may trigger paroxysmal atrial fibrillation (AF) and chronic stress is known to negatively affect long-term outcomes in cardiovascular diseases.

Purpose
To assess the impact of different preventive counseling programs on stress level in patients (pts) after catheter ablation (CA) performed for paroxysmal AF.

Methods
This is a prospective randomized controlled study with 3 parallel groups of pts with paroxysmal AF after CA (radiofrequency or cryoablation). Pts were randomized into 3 groups in 1:1:1 ratio. During hospitalization for CA pts from all groups received single-session preventive counseling with focus on their individual cardiovascular risk factors profile. After discharge pts from Group 1 received remote preventive counseling by phone and pts from Group 2 by email every two weeks for the first 3 months after enrollment (a total of 6 sessions). Group 3 received usual care. All pts underwent stress assessment using a 10-point visual analogue scale (VAS) at baseline and at 12 months after CA.

Results
A total of 135 pts aged 35 to 80 years were enrolled (mean age 57.3±9.1 years, 51.8% men). The groups were well balanced according to demographic and clinical features. At 1 year of follow-up there was a significant reduction of average stress level in both intervention groups vs. control (Table).

Conclusions
Preventive counseling followed by 3 months of remote support via phone and email reduced the stress level in AF pts after CA.

Funding Acknowledgement
Type of funding source: None