bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke and myocardial infarction prevention with GLP1 analogues in high or very-high cardiovascular risk diabetic patients
Authors: Cazorla-Morallon D , Cordero A , Pomares Varo A , Torroba Balmori G , Moreno Garcia M.J , Martinez Rey-Ranal E , Bertomeu-Gonzalez V , Zuazola P
Published: November 2020

Background

Patients with established cardiovascular disease have an increased risk of stroke, even in the absence of atrial fibrillation. Several trials have analysed the effect of glucagon-like peptide-1 receptor (GLP1) analogues on cardiovascular events in patients with high cardiovascular disease.

Methods

We performed a metanalysis with all randomized clinical trial that compared a GLP1 analogue vs. placebo. Primary endpoint was stroke incidence, including ischemic and haemorrhagic aetiology, assessed by fixed-effect model.

Results

We identified 7 trials that compared a GLP analogue (albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide). A total of 56,004 patients were included in the analysis, 27977 treated with a GLP1 analogue. Mean age of the patients was 63.9 (2.1) years, 25,398 (45.4%) patients had cardiovascular disease.

A total of 1,568 strokes were reported, 711 in patients receiving a GLP analogue and 857 in control arm; treatment with a GLP1 analogue reduced the incidence of stroke by 147% (RR: 0.83, 95% CI 0.75–0.92; p<0.001). No heterogeneity between trials was observed (p=0.835). Globally, treatment with GPL1 analogues reduced the incidence of stroke or myocardial infarction by 11% (RR: 0.89, 95% CI 0.84–0.94; p<0.01)

A total of 3,192 cases of myocardial infarction were reported: 1,524 in patients treated with GLP1 analogues and 1,668 with placebo. Treatment with GLP1 analogues reduce the incidence of myocardial infarction by 8% (RR: 0.92, 95% CI 0.86–0.98; p=0.010)

Conclusions

Treatment with a GLP1 analogue reduced the incidence of stroke by 17% and myocardial infarction by 8%, in different trials involving high or very-high risk patients with diabetes.

Forest plot: stroke and MI

Funding Acknowledgement

Type of funding source: None
Lp (a) >50 mg/dl predicts atherosclerotic cardiovascular events in patients with heterozygous familial hypercholesterolemia who achieved LDL-C <2.6 mmol/l
Authors: Funabashi S , Kataoka Y , Hori M , Ogura M , Matsuki K , Doi T , Noguchi T , Harada-Shiba M
Published: November 2020

Introduction

Lipoprotein (a) [Lp (a)] is a plasma lipoprotein which exhibits atherogenic properties. Lp(a) ≥50 mg/dl has been recently shown to associate with a risk of atherosclerotic cardiovascular diseases (ASCVD) in patients with heterozygous familial hypercholesterolemia (HeFH). While current guideline recommends lowering LDL-C as a first-line therapeutic approach in HeFH subjects, it remains to be fully determined whether an elevated level of Lp(a) confers additional ASCVD risks in HeFH patients who achieved a lower LDL-C level.

Purpose

To investigate cardiovascular outcomes in HeFH subjects with a lower LDL-C but an elevated Lp(a) levels.

Methods

182 HeFH patients with on-treatment LDL-C <2.6 mmol/l under lipid-lowering therapies were analyzed. Clinical characteristics and MACE (= a composite of all-cause death, ACS, stroke, PAD and coronary revascularization) were compared in HeFH subjects with Lp(a) ≥ vs. <50 mg/dl.

Results

The averaged LDL-C and Lp (a) levels were 1.9 mmol/l and 26.8 mg/dl, respectively. 19.2% of study subjects exhibited Lp(a)≥50 mg/dl. HeFH patients with Lp(a) ≥50 mg/dl were more likely to be older and have a history of hypertension, but these comparisons did not meet statistical significance. There was no significant difference in on-treatment LDL-C, HDL-C and Triglyceride level (Table). However, during the observational period (median=4.7 years), there was a 2.7-fold (95% CI, 1.41–5.02; p=0.004) greater likelihood of experiencing MACE in subjects with Lp(a) ≥50 mg/dl (picture). Even after adjusting clinical demographics, Lp(a) ≥50 mg/dl remained an independent predictor for the occurrence of MACE (hazard ratio=2.53, 95% CI: 1.29–4.82, p<0.001).

Conclusions

Despite achieving on-treatment LDL-C <2.6 mmol/l, an elevated risk of MACE was observed in HeFH patients with Lp(a) ≥50 mg/dl. Our findings suggest an increased level of Lp(a) as a risk stratification marker and a potential therapeutic target in patients with HeFH.

Clinical outcome

Funding Acknowledgement

Type of funding source: None
Effect of bempedoic acid on uric acid and gout in 3621 patients with hypercholesterolemia: pooled analyses from phase 3 trials
Authors: Ray K.K , Bakris G.L , Banach M , Catapano A , Duell P.B , Mancini G.B.J , Bloedon L , Feng A , Gotto Jr A.M
Published: November 2020

Background

Bempedoic acid (BA), an oral ATP-citrate lyase inhibitor, significantly lowers low-density lipoprotein cholesterol levels in patients with hypercholesterolemia. In clinical trials of BA, small mean increases in uric acid have been reported. BA weakly inhibits organic anion transporter 2 (OAT2) in vitro, which may account for small elevations in serum uric acid.

Purpose

To assess uric acid levels and incidence of gout with BA treatment.

Methods

Data were pooled from 4 randomized (2:1), double-blind studies of BA (180 mg daily) vs placebo for 12 weeks to 52 weeks in patients with hypercholesterolemia on stable background lipid-lowering therapy. Safety assessments included adverse events of special interest (elevation in uric acid levels, gout) and laboratory assessments.

Results

A total of 2424 patients treated with BA and 1197 patients on placebo were included in this analysis. Mean (SD) baseline uric acid levels were 6.0 (1.4) mg/dL for both groups. History of gout was reported by 5.2% (127/2424) and 5.8% (69/1197) in the BA and placebo groups, respectively. At week 12, mean (SD) serum uric acid levels (% change from baseline) increased from baseline with BA treatment by 0.82 (0.97) mg/dL (14.8%) vs –0.02 (0.82) mg/dL (0.67%) for placebo. Elevations in serum uric acid levels typically occurred within the first 4 weeks of treatment, remained stable during treatment, and returned to baseline after treatment discontinuation. Gout was reported in 1.4% (BA) and 0.4% (placebo) of patients, and hyperuricemia was reported in 1.7% (BA) and 0.6% (placebo) of patients. Other potential clinical consequences of elevated uric acid levels (eg, events associated with nephrolithiasis), were similar between groups (0.7% vs 0.8%). In both groups, patients who reported gout during the studies were more likely to have a medical history of gout or elevated baseline uric acid levels (Table). Few patients discontinued treatment due to gout (n=1, <0.1% [BA]) or uric acid increases (n=2, <0.1% [BA]).

Conclusion

Mean increases in uric acid levels were small, remained stable while patients continued to receive treatment, were infrequently associated with AEs, and were reversible on discontinuation of BA

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Esperion Therapeutics funded the research for this study and provided writing support for this abstract. Medical writing assistance was provided by Agnella Izzo Matic, PhD, CMPP, and Kelly M Cameron, PhD, CMPP, of JB Ashtin.
The association between statin pre-treatment and LDL Levels on the rate of STEMI presentation: data from the ACS Israeli Survey (ACSIS) 2008–2018
Authors: Dadon Z , Moriel M , Samuel T.Y , Steinmetz Y , Asher E , Iakobishvili Z , Glikson M , Gottlieb S
Published: November 2020

Background

ST-elevation myocardial infarction (STEMI) mostly occurs as a result of vulnerable coronary artery plaque rupture. Constituting hypolipidemic and pleiotropic effects, statins stabilize coronary artery plaque and may prevent STEMI events.

Purpose

To determine the association between statin pre-treatment and its intensity, low-density-lipoprotein cholesterol (LDL-C) levels and presentation of patients with an ACS (STEMI vs. NSTEMI/unstable angina [UAP]).

Methods

Data was drawn from the Acute Coronary Syndrome Israeli Survey (ACSIS), a biennial prospective survey of ACS patients hospitalized in all CCU/Cardiology departments during 2008–2018. The rate of STEMI vs NSTEMI/UAP at the time of presentation was calculated by LDL-C levels on admission, stratified to 5 subgroups (<50, 50–69, 70–100, 101–130 and >130 mg/dl) and the use of statins, including statin intensity prior to the index ACS event.

Results

Among 5,103 patients, 875 (17%) were pre-treated with high intensity statin (HIST), 1,389 (27%) with low intensity statin (LIST), and 2,839 (56%) were statin naive patients. Statin-pre-treated patients were older, more likely to suffer from co-morbidities and cardiovascular diseases and were more often pre-treated with anti-platelets.

The proportion of patients presenting with STEMI vs. NSTEMI/UAP was significantly lower among HIST vs. LIST vs. statin naive patients (31.0%, 37.8%, 54.0%, respectively, p for trend <0.001). At each LDL-C level, the proportion of STEMI was significantly lower among HIST vs. LIST vs. statin naive patients. Multivariate analysis adjusting for pertinent variables including propensity score for statin use, revealed that HIST was independently associated with lower STEMI presentation, but LDL-C<70 and LIST were not.

Conclusions

Among patients admitted with ACS, pre-treatment with high intensity statin but not LDL-C level, was independently associated with a lower probability of presenting with STEMI.

Funding Acknowledgement

Type of funding source: None
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

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

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

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

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 (<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<0.05) and cfPWV (P<0.01) and higher bFMD (P<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

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

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

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 >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>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<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<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<0.000). Group 2 independently predicted MACE in the whole cohort (HR 1.75, 95% CI 1.26 to 2.42, p<0.001). In the NGT group, PGS >median, independently predicted of MACE (HR 2.67, 95% CI 1.54 to 4.61, p<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>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

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

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
Postoperative course of coronary artery bypass grafting in patients with physical exercise prehabilitation
Authors: Argunova Y , Moskin E , Pomeshkina S , Barbarash O
Published: November 2020

Purpose

To evaluate the clinical effects of high-intensity physical exercise prehabilitation for elective coronary artery bypass grafting on the optimization of the postoperative course in patients with stable coronary artery disease.

Methods

60 male patients with stable coronary artery disease (CAD) were randomized into two groups before elective on-pump CABG. Group 1 patients (n=30, aged of 61.5 [56; 63] years) underwent a 7-day course of treadmill training at 80% of VO2 max. Group 2 patients (n=30, aged of 62.0 [56; 64] years) underwent routine preoperative management. The length of stay in the ICU and the length of stay in the hospital were assessed in all patients. In addition, the postoperative rate of myocardial infarction, stroke, heart rhythm disturbances (including atrial fibrillation), heart failure requiring inotropic support, hydrothorax and hydropericardium requiring puncture, wound infections, sternum diastasis, MODS, and the composite endpoint (total number of complications) were assessed. Statistical analysis was performed using the commercially available software package Statistica 10.0 (Statsoft, USA).

Results

Both groups were comparable in the main clinical and demographic data, and the intraoperative parameters. There were no cases of complications, heart and coronary insufficiency, episodes of heart rhythm disturbance and conduction disorders in patients undergoing preoperative physical training. All patients had good exercise tolerance. The trend towards reduced length of stay in the ICU and the length of stay in the hospital had been found in patients who underwent exercise prehabilitation compared with patients without training (20.0 [19.0; 22.0] vs. 21.0 [20.0; 23, 0] hours, respectively, p>0.05 and 11.0 [9.5; 12.0] vs. 12.0 [10.0; 12.0] days, respectively; p>0.05). There were no cases of intraoperative MI and postoperative stroke in Group 1 patients, whereas one case of MI and one case of stroke were registered in Group 2. The rate of the composite endpoint was lower in Group 1 patients than in Group 2 patients (p=0.02). In addition, the incidence of AF (6.6 and 10%, respectively), heart failure (6.6 and 20%, respectively), hydrothorax (0 and 6.6%, respectively) and pneumonia (0 and 6, 6%, respectively) was lower in Group 1 patients than in Group 2 patients.

Conclusion

The positive effects of high-intensity physical exercise prehabilitation for CABG on the optimization of postoperative course has been confirmed.

Funding Acknowledgement

Type of funding source: None
Do socioeconomic status and ethnicity predict CR outcomes in coronary heart disease patients in Denmark?
Authors: Kjesbu I , Sibilitz K.L , Prescott E
Published: November 2020

Background

Cardiac patients with low socioeconomic status and other ethnic background have worse prognosis and outcomes. Cardiac rehabilitation (CR) has the potential to diminish this socioeconomic and ethnical disparity, but evidence is lacking.

Purpose

To describe if socioeconomic status and ethnicity predicts CR outcomes in coronary heart disease (CHD) patients in Denmark.

Methods

The study is based “The Danish Cardiac rehabilitation database” (DHRD) which monitors quality of CR in Denmark. The study population are all patients with CHD (myocardial infarction or stable coronary artery disease with revascularization or medical treatment) participating in CR reported to the database from Aug 2015 to Mar 2018. The quality indicators (QI) were >80% participation in exercise sessions, >10% increase in VO2peak, smoking cessation, LDL <1.8mmol/L (or 50% reduction of baseline LDL), blood pressure <140/90, dietary consulting, screening for diabetes, screening for depression and medical treatment with acetylsalicylic acid, statins and beta-blockers at completion of CR. Educational level as a marker for socioeconomic status was divided into no-, basic-, medium- and high education, and ethnicity into Danish, Western and non-western origin. We compared QI across educational level and ethnicity using descriptive statistics.

Results

Analyses are based on 9000 patients. Age and gender differed significantly in the groups (all p<0.001). Medical treatment and achievement of LDL- and blood pressure control was overall good with no difference across socioeconomic strata or ethnicity. Despite similar participation rate, higher education was associated with greater improvements in VO2peak. Patients of non-western ethnicity were less often screened for depression and less often received dietary consulting.

Conclusion

In this nationwide quality database for CR, medical treatment and achievement of traditional risk factor goals was good across socioeconomic and ethnic strata. However, outcome in VO2peak and implementation of screening for depression and diabetes showed disparity across socioeconomic and ethnic groups. The effect on long-term outcomes remains to be addressed.

Funding Acknowledgement

Type of funding source: None
Is there an exercise duration threshold for exercise-induced troponin elevation in healthy recreational athletes? The NEEDED 2014 advanced heart rate monitor substudy
Authors: Bjorkavoll-Bergseth M , Auestad B , Kleiven O , Skadberg O , Eftestol T , Melberg T , Moberg Aakre K , Orn S
Published: November 2020

Background/Introduction

Following prolonged strenuous exercise there is an exercise-induced troponin (cTn) elevation in healthy individuals. The precise mechanisms and clinical consequence of this cTn elevation remain to be determined. It has recently been demonstrated that exercise intensity, exceeding a heart rate (HR) of 150 bpm, is correlated with exercise-induced cTn elevation.

Purpose

The present work aims to determine if there is a threshold for exercise duration with a HR exceeding 150 bpm associated with an excessive exercise-induced cTn elevation.

Methods

A total of 177 healthy subjects were included in the present analysis of HR data obtained from sport watches used during a 91-km recreational mountain bike cycle race. Clinical status, cTnI, ECGs, blood pressure and demographics were obtained 24 h prior to- and at 3 h and 24 h after the race. Results are reported as median and 25th and 75th percentile. We used Tree regression to determine the association between elevated cTnI and exercise duration exceeding a HR of 150 bpm.

Results

Subjects were 82% (n=146) males, 44 (39–51) years, with a race time of 3.5 (3.1–3.9) h. Baseline cTnI was 1.9 (1.6–3.3) ng/L. There was a cTnI elevation in all study participants at 3 h, cTnI: 60.0 (36.0–99.3) ng/L, with a significant (p<0.001) reduction at 24 hours following exercise, cTnI: 10.9 (6.1–22.4) ng/L. Tree regression identified 168 min of exercise, with a HR exceeding 150 bpm, to be associated with an excessive increase in cTnI both at 3 h, and at 24 h following the race (figure). The median cTn values above and below the threshold are presented in the Table.

Conclusion

The present analysis suggests that exceeding a specific duration of high intensity exercise may be associated with excessive cTn elevation in susceptible individuals.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Western Norway Health authoritites.
The influence of vigorous training on the structure and cardiorespiratory fitness in adolescent athletes
Authors: Szabo L , Sydo N , Kiss O , Csulak E , Dohy Z , Czimbalmos C , Juhasz V , Horvath V , Suhai F.I , Merkely B , Vago H
Published: November 2020

Introduction

The functional and morphological adaptation of the cardiovascular system to vigorous exercise in adolescents is less understood compared to adult athletes. Therefore, the differential diagnosis of normal cardiovascular adaptation from the possible pathological alterations is challenging. Cardiovascular magnetic resonance is an important method for assessing ventricular function and morphology. Maximal oxygen uptake (VO2 max) has been established as a reliable measure of the maximal ability to produce metabolic power aerobically.

Aims

The aim of this study was to examine left (LV) and right (RV) ventricular morphologic and functional remodeling in elite adolescent athletes using cardiac magnetic resonance imaging (CMR) and cardiopulmonary exercise test (CPET).

Methods

Between 2017 and 2019 116 asymptomatic adolescent (14–20 years) athletes (>6 training hour/week) underwent CMR and CPET as part of a detailed sports cardiology screening. Cine movie images were performed for the quantification of the LV and RV volumes, masses and ejection fraction, and advanced post processing included feature-tracking strain analysis. CPET was performed on a dedicated athlete protocol.

Results

All athletes participated in sports with a high dynamic component. Male athletes (n=74, 16±1 years) demonstrated higher LV and RV end –diastolic volume index (EDVi), stroke volume index (SVi) and mass index (Mi) compared with female athletes (p<0.001). We found significant difference regarding the global circumferential strain (GCS) and mechanical dispersion (MD) of male and female athletes (GCS −34±4 vs. −31±5%; MD 4±2 vs. 7±4% p<0.05). VO2 showed positive correlation with the LV and RV volumetric parameters (EDVi, SVi) and Mi (p<0.001) and the absolute value of GCS (p<0.05), and negative correlation with the MD (p<0.001). In 36 athletes the VO2 max exceeded the age-adjusted expected VO2 max by 130%, which was categorized as excellent. Besides gender, age, and body surface area CMR based LVEDVi and LVMi were independent predictors of VO2 max.

Conclusion

The functional and morphological adaptation of the adolescent cardiovascular system shows noteworthy differences between male and female athletes. VO2 max correlates with several CMR based values including LV and RV volumetric parameters, masses and strain parameters such as GCS and MD.

Strain analysis of an adolescent athlete

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the NVKP_16 funding scheme. ÚNKP-19-3-I New National Excellence Program of the Ministry for Innovation and Technology.
Electrocardiographic (ECG) predictors of major adverse cardiac events in women with ischemia and no obstructive coronary artery disease (INOCA)
Authors: Taha Y.K , Xu K , Mahmoud A.A , Smith S.M , Handberg E.M , Bairey Merz C.N , Pepine C.J
Published: November 2020

Introduction

The Women's Ischemia Syndrome Evaluation (WISE) studies observed that majority of women undergoing coronary angiography for symptoms/signs of ischemia have no obstructive coronary artery disease (INOCA) but have an increased risk of major adverse cardiac events (MACE) exceeding 2.5% yearly by 5 years. Identifying modifiable and non-modifiable factors that help predict or contribute to adverse outcomes in this population is important.

Purpose

Identifying electrocardiographic predictors of MACE in women with INOCA.

Methods

In a cohort of women referred for coronary angiography between 1996–2001 for symptoms and/or signs of ischemia, 944 underwent a resting 12-lead ECG at baseline read at core lab. No obstructive CAD was found in 567/944 (60%), (mean age 55.6±11 years). Complete follow up information for MACE as (first occurrence of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization for heart failure) or angina was available in 425 women.

Results

At follow up (median 5.9 years) MACE had occurred in 17.6% with angina hospitalization in 22.8% of these women. Women who experienced MACE were older (mean age 59±11 vs 55±10 years, P=0.02) and had longer corrected QT interval (mean QTc 437±29.7 vs 425±26.7 ms, P=0.001) vs. women without MACE. Diabetes, hypertension and history of smoking did not differ between MACE groups. Predictors of MACE by univariate analysis were: age at presentation (P=0.013), baseline heart rate (P=0.03), and QTc (P=0.0005). Baseline ST-T wave changes, QTc and waist circumference predicted angina hospitalization (P=0.003, 0.003 and 0.013 respectively). After adjusting for other risk factors in the multivariate analysis (see Figure) QTc, peripheral arterial disease (PAD) and current smoking were found to be independent predictors for MACE. ST-T wave changes and QTc independently predicted angina hospitalizations.

Conclusion

Among ECG findings in women with INOCA, QTc was a significant predictor of MACE and this was driven by hospitalization with angina. Ongoing ischemia likely contributes to these baseline ECG signals which could prove useful to better select subgroups for more intense anti-ischemic management.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI)