bluuebunny/crossref_metadata_2025 huggingface dataset:
Epicardial fat is associated with adverse ventricular remodeling and diastolic dysfunction in women with ischemia but no obstructive coronary artery disease
Authors: Zamani S K , Robuck E , Wei J , Kwan A C , Pepine C J , Handberg E , Cipher D J , Dey D , Bairey Merz C N , Nelson M D
Published: November 2023

Background

Epicardial fat is a metabolically active adipose tissue depot located between the myocardium and visceral pericardium. Increased epicardial fat is associated with the development of atherosclerosis and obstructive coronary artery disease (CAD). However, information regarding relations between epicardial fat—which covers 80% of the heart surface—and cardiac function, is limited.

Purpose

To evaluate relations between epicardial fat and cardiac morphology and function in all four chambers of the heart.

Methods

To accomplish our objective, we studied 113 participants from the Women’s Ischemia Syndrome Evaluation cohort who underwent invasive measurement of left ventricular end-diastolic pressure and coronary reactivity, and comprehensive rest-stress cardiac magnetic resonance imaging (cMRI) per standardized protocols. Epicardial fat area was measured from a single high resolution steady-state free precession cine cMRI in the horizontal long axis plane (Figure 1A). Left ventricular (LV) mass, bi-ventricular volumes, and ejection fractions, were assessed using a stack of short axis cine images covering both ventricles (Figure 1B). LV concentricity was defined as the mass-to-end-diastolic volume ratio. Strain and strain rate were assessed in all four chambers by feature tracking (Figure 1C). Left atrial (LA) volume was assessed using three orthogonal long-axis cines, while right atrial (RA) area was assessed using a single horizontal long axis cine (Figure 1D). Participants were stratified by the median epicardial fat area, defined as "Low" epicardial fat (<13 cm2, n=48) and "High" epicardial fat (≥13 cm2, n=65).

Results

Participant characteristics are reported in Table 1. Notably, the majority (58%) had "High" epicardial fat and body mass index (BMI) was greater in the "High" epicardial fat group. After adjusting for BMI, however, bi-ventricular stroke index remained lower in the "High" epicardial fat group, as did bi-atrial ejection fraction (fractional area change, RA). Moreover, compared to the "Low" epicardial fat group, LV concentricity and LA booster strain were higher in the "High" epicardial fat group (Figure E-F), while LV longitudinal strain and LV early circumferential diastolic strain rate were lower (Figure G-H). No other major differences were observed between groups, including coronary reactivity or myocardial perfusion reserve.

Conclusions

Together, these data suggest that higher BMI is associated with increased epicardial fat that is related to adverse cardiac remodeling, along with systolic and diastolic dysfunction, across multiple cardiac chambers. Further studies would be useful to define specific mechanism contributing to these observations.Figure 1Table 1
The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study
Authors: Brown O , Drozd M , Mcgowan H , Giannoudi M , Conning-Rowland M , Gierula J , Straw S , Wheatcroft S B , Paradine K , Roberts L D , Levelt E , Ajjan R , Griffin K J , Kearney M T , Cubbon R M
Published: November 2023

Background

Obesity and diabetes mellitus (DM) frequently co-exist, yet their individual contributions to cardiovascular risk remain debated.

Purpose

We explored cardiovascular disease biomarkers, events and mortality in a large cohort stratified by body mass index (BMI) and DM. We hypothesised that DM with normal BMI is associated with a cardiovascular phenotype and event rate comparable to obesity without DM.

Methods

451,355 UK Biobank participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and DM status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischaemic stroke and cardiovascular death, with normal weight non-DM as comparator. Correlation matrices of Poisson model’s coefficients were used to assess correlations between covariates.

Results

5% of participants had DM (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-DM). In the non-DM group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p<0.05); these relationships were diminished in the DM group. Within BMI classes, DM was associated with adverse cardiovascular phenotype (p<0.05), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischaemic stroke and cardiovascular mortality all rose across increasing BMI categories in the DM and non-DM groups (p<0.05). However, normal weight DM had higher cardiovascular mortality than obese non-DM (IRR 2.81 [95% confidence interval: 2.24-3.54] vs IRR 1.84 [1.70-1.98]). Pairwise correlation analysis demonstrated the strongest correlates of cardiovascular parameters were markers of adiposity; this was apparent in the DM and non-DM groups, although these remained modest with Pearson’s correlation coefficients of no more than 0.25.

Conclusions

Obesity and DM are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes. Ideal target range for metrics of adiposity may therefore be lower than currently proposed in people with DM.Table 1:Adjusted IRR of CV deathFigure 1:KM Curve for CV death
Lipid core burden in relation to the severity of calcium burden assessed by computed tomographic coronary angiography in patients with chronic coronary syndrome
Authors: Nagamine T , Usui E , Hoshino M , Hada M , Hanyu Y , Ueno H , Nogami K , Matsuda K , Sayama K , Sakamoto T , Yonetsu T , Sasano T , Kakuta T
Published: November 2023

Background

Coronary calcium scores (CACS) obtained by computed tomographic coronary angiography (CTCA) enables a noninvasive assessment of coronary calcium burden both in a single vessel and in whole coronary tree. Although higher CACS in coronary tree is known as an atherosclerotic cardiovascular disease risk marker, coronary calcification is also known as a sign of plaque stabilization. Exploring the relationship between coronary calcification and lipid core burden may help understanding a role of calcium in coronary tree.

Purpose

We aimed to examine the relevance of lipid components assessed by near-infrared spectroscopy (NIRS) in accordance with different degrees of CACS assessed by preprocedural CTCA imaging.

Methods

We investigated consecutive patients who underwent elective percutaneous coronary intervention (PCI) and pre-PCI CTCA imaged within 3 months before PCI. Patients who had stents in target vessels and who required plaque modification before NIRS imaging were excluded. Target vessels were divided into tertiles based on target vessel CACS (CACSv) and total amount of 3-vessel CACS (CACSt), respectively. Lipid components of the target vessel were evaluated by maximum lipid core burden index in 4mm (maxLCBI4mm). MaxLCBI4mm was compared among the tertiles of CACSv and CACSt.

Results

A total of 95 target vessels in 95 patients were evaluated for the final dataset. CACSv categories were defined as follows: 1st tertile (CACSv <66), 2nd tertile (CACSv >66 and <250), and 3rd tertile (CACSv >250). CACSt categories were defined as showing CACSt <190 (1st tertile), CACSt >190 and <700 (2nd tertile), and CACSt >700 (3rd tertile). MaxLCBI4mm increased in proportion to an extent of CACv tertiles (306 [129-463], 280 [125-460], and 444 [345-587], Ptrend <0.01) and an extent of CACt tertiles (265 [99-488], 356 [202-458], and 448 [318-574], Ptrend <0.01).

Conclusions

In patients who underwent elective PCI, higher maxLCBI4mm in the PCI target vessel was associated with both higher CACS in the target vessel and total amount of 3-vessel CACS.
Risk of incident renal cell carcinoma in patients with type 2 diabetes on sodium-glucose co-transporter-2 inhibitor users: a population-based cohort study
Authors: Jong G P , Yang T Y
Published: November 2023

Background and aims

Patients with type 2 diabetes (T2D) are at substantially higher risk for developing renal cell carcinoma (RCC) than the general population. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 inhibitor (SGLT-2I) use on the development of incident RCC in patients with T2D, but the findings are inconsistent. This study aimed to examine the association between SGLT-2I use and incident RCC risk in patients with T2D.

Methods

We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2009–2019). The primary outcome was the risk of incident RCC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Therefore, multiple Cox regression modeling was conducted to analyze the association between SGLT-2I use and incident RCC risk in patients with T2D.

Results

In a cohort of 241,772 patients with T2D using SGLT-2I and 483,544 participants not using SGLT-2Is, 220 and 609 incident RCCs were recorded, respectively. There was a decreased risk of incident RCC for SGLT-2I users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.68, 95% CI 0.58–0.81) compared with non-SGLT-2I users. The sensitivity test for the propensity score 1:1-matched analyses showed similar result (adjusted HR 0.67, 95% CI 0.56–0.81).

Conclusions

SGLT-2I therapy may effectively decrease RCC risk in patients with T2D. More studies are needed to credibly evaluate the effects of SGLT-2I therapy on RCC prevention in patients with T2D.
Fifteen-year follow-up and impact of age and sex on cardiovascular outcomes in diabetes and non-diabetes patients without CAD
Authors: Olesen K K W , Thrane P G , Hansen M K , Gyldenkerne C , Maeng M
Published: November 2023

Background

In the absence of angiographically-detectable coronary artery disease (CAD), patients with diabetes have a risk of myocardial infarction that is comparable to patients without diabetes, while still having higher risks of ischemic stroke and all-cause mortality when followed for up to 10 years. In the current study we extended follow-up to 15 years and, additionally, examined the impact of age and sex on cardiovascular risk in diabetes and non-diabetes patients without CAD.

Purpose

To examine the cardiovascular risk and mortality associated with age and sex in diabetes and non-diabetes patients without CAD.

Methods

We included every patient with no or mild CAD when examined by coronary angiography in Western Denmark from 2003-2021 with and without diabetes. We performed age-stratified (<65 year, 65-74 years, and ≥75 years) and sex-stratified analyses. Patients were followed for up to 15 years. Outcomes were myocardial infarction, ischemic stroke, and all-cause death. We estimated adjusted hazard ratios (aHR) using Cox regression.

Results

We included 60,712 patients without angiographically detectable CAD, of whom 7,690 (12.6%) had diabetes. Median age was 62 years and 51% were men. Median follow-up was 9 years ((inter-quartile range 6-13)). Diabetes was associated with an increased 15-year risk of myocardial infarction (5.8% versus 4.1% aHR 1.30, 95% CI 1.13-1.50), ischemic stroke (8.1% vs 4.0%, aHR 1.87, 95% CI 1.66-2.10), and all-cause death (46.2% vs 33.1%, aHR 1.66, 95% CI 1.58-1.73) compared to patients without diabetes. The relative risk associated with diabetes declined by age (Figure 1), while there was no sex-dependent difference associated with diabetes (Figure 2).

Conclusions

At 15-year follow-up, diabetes patients without angiographically-detectable CAD at baseline had a relatively small increased risk of myocardial infarction but a substantial increased risk of ischemic stroke and all-cause mortality. Furthermore, the relative importance of diabetes decreased with age, while being independent of sex. These results support that aggressive multifactorial cardiovascular risk management, even in the absence of CAD and independently of age and sex, should be initiated when diabetes is diagnosed.Figure 1Figure 2
Impact of glycated hemoglobin A1c on cardiovascular risk in diabetes patients with and without coronary artery disease
Authors: Olesen K K W , Thrane P G , Hansen M K , Gyldenkerne C , Maeng M
Published: November 2023

Background

Guidelines recommend a haemoglobin A1c (HbA1c) target <53 mmol/mol (7%) to achieve microvascular risk reduction. However, the impact of HbA1c target levels on macrovascular complications is less certain. Moreover, we have previously shown that the risk of macrovascular complications is dependent on presence of coronary artery disease (CAD).

Purpose

We tested the hypothesis that HbA1c ≥53 mmol/mol is associated with cardiovascular risk in diabetes patients with and without CAD.

Methods

We conducted a contemporary cohort study including diabetes patients examined by coronary angiography in Western Denmark from 2011-2021. The association between HbA1c and major adverse cardiovascular events (MACE, a composite outcome of myocardial infarction, ischemic stroke, and cardiovascular death) was modeled using restricted cubic splines. Patients were followed for up to 10 years. We estimated adjusted hazards ratios (aHR) using HbA1c of 52 mmol/mol as reference. We also performed stratified analyses by presence of CAD.

Results

We included 15,825 patients with diabetes, of whom 12,200 (77%) had CAD. Median HbA1c was 52 mmol/mol in patients with CAD and 51 mmol/mol in patients without CAD. Using restricted cubic splines, we observed significantly increased MACE rates with HbA1c ≥53 mmol in the entire cohort (Figure 1A). MACE rates plateaued with increasing HbA1c above 65 mmol/mol. When stratifying by presence of CAD, this association between HbA1c and MACE was sustained in patients with CAD (Figure 1B). In contrast, we did not observe any relation between HbA1c and MACE rates in patients without CAD (Figure 1C).

Conclusions

The current study suggest two novel findings. Firstly, a HbA1c <53 mmol/mol target is associated with a reduced risk of macrovascular complications in patients with diabetes. Thus, the impact of glucose control on macrovascular complications corresponds to the HbA1c levels recommended for avoidance of microvascular complications. Secondly, the association between HbA1c and MACE is restricted to diabetes patients with CAD while not observed in those without CAD.Figure 1,A-C
Myocardial performance index improves prediction of major adverse cardiovascular events and heart failure in type 1 and type 2 diabetes without known heart disease: Thousand&1 and Thousand&2 study
Authors: Bahrami H , Jorgensen P G , Hove J D , Dixen U , Rossing P , Jensen M T
Published: November 2023

Background

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite myocardial involvement in diabetes, current risk prediction models do not include parameters of the myocardial function. Myocardial performance index (MPI) reflects left ventricular systolic and diastolic function. The prognostic value of MPI has not been evaluated in larger-scale diabetes populations.

Purpose

To assess the prognostic value of MPI in a larger-scale diabetes population.

Methods

We evaluated two prospective cohort studies: The Thousand&1 Study (1093 individuals with T1D) and The Thousand&2 Study (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We excluded 480 individuals with heart disease. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as the first incident of all-cause death, hospital admission for acute coronary syndrome, heart failure, or stroke.

Results

For included individuals (56% male, 54±15 years, MPI 0.51±0.1, 63% T1D), follow-up was 100% after a median of 5.3 years (interquartile range: 4.8 to 6.3). MPI was significantly associated with MACE (Hazard ratio 1.2, 95% confidence interval 1.0-1.3, p=0.012, per 0.10-unit increase) and heart failure (Hazard ratio 1.3, 95% confidence interval 1.1-1.6, p=0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE better in T1D than in T2D (p=0.031 for interaction). MPI added discriminatory power to the Steno T1D Risk Engine (1,2) in predicting heart failure, but not MACE.

Conclusions

MPI is an independent predictor of MACE and heart failure in T1D and T2D, with the strongest prediction in T1D. Echocardiographic assessment in diabetes may enhance risk prediction.
Machine-learning score using CCTA and stress CMR for prediction of cardiovascular events in patients with obstructive CAD
Authors: Pezel T , Garot P , Toupin S , Hovasse T , Hamzi K , Lefevre T , Unterseeh T , Sanguineti F , Neylon A , Ah-Sing T , Goncalves T , Dillinger J G , Henry P , Bousson V , Garot J
Published: November 2023

Background

In patients with suspected or known coronary artery disease, traditional prognostic risk assessment is based on a limited selection of clinical and imaging findings as coronary computed tomography angiography (CCTA) and stress cardiovascular magnetic resonance (CMR). Machine learning (ML) methods can take into account a greater number and complexity of variables.

Purpose

To investigate the feasibility and accuracy of ML using stress CMR and CCTA data to predict major adverse cardiovascular events (MACE) in patients with suspected or known coronary artery disease, and compared its performance with existing clinical, CMR or CCTA scores.

Methods

Between 2008-2020, consecutive symptomatic patients without known CAD referred for CCTA were screened. Patients with obstructive CAD (at least 1 ≥50% stenosis on CCTA) were further referred for stress CMR. Twenty-three clinical, 7 CCTA, and 11 stress CMR parameters were evaluated. ML involved automated feature selection by LASSO, model building with a XGBoost algorithm. The primary composite outcome was MACE defined by cardiovascular death or nonfatal myocardial infarction. The external validation cohort of the ML score was performed in another center (n=274).

Results

Of 2,210 patients who completed CMR, 2,038 (47% male, mean age 69±12 years) completed follow-up (median 6.8 [IQR 5.9-9.2] years); 281 experienced a MACE (13.8%).

The ML score exhibited a higher area under the curve (AUC) compared with ESC risk score, QRISK3 score, Framingham risk score, and CCTA or stress CMR data alone for prediction of MACE (ML score: 0.85 vs ESC score: 0.66, QRISK3 score: 0.64, Framingham score: 0.63, only CCTA score: 0.76, only CMR: 0.82; all p<0.001). Similar results were obtained with AUC of the Precision-Recall (PR) curves (ML score: 0.59 vs. only CCTA score: 0.39, only CMR: 0.45; all p<0.001). The ML score also exhibited a good area under the curve in the external cohort (AUC ROC: 0.85 and AUC PR curve: 0.57).

Conclusions

The ML score including CCTA and stress CMR data exhibited a higher prognostic value to predict MACE compared with traditional method or traditional scores. In addition, our ML score including CCTA and stress CMR data showed the best performance compared with scores using only CCTA or CMR parameters.ROC et PR curves: ML scorePR curves: ML score
Time to act: the challenge of high incidence of diabetes and prediabetes in patients admitted with different cardiovascular diseases phenotypes
Authors: Medovchshikov V , Yeshniyazov N , Khasanova E , Zholdin B , Kurmanalina G , Kobalava Z
Published: November 2023

Background

Limited studies have focused on diagnosing type 2 diabetes mellitus (T2DM) and prediabetes in hospitalized patients with cardiovascular diseases (CVD) with their different phenotypes. In addition, HbA1c levels in patients admitted for cardiovascular reasons may be lower than in patients with symptoms of hyperglycemia.

Purpose

To assess the incidence of newly and previously diagnosed T2DM and prediabetes among patients hospitalized with CVD, depending on the reasons for admission.

Methods

In the single-center prospective study (registry) we enrolled 773 patients ≥40 years with established CVD and arterial hypertension (HTN) without type 1 diabetes mellitus, except for previously diagnosed T2DM and prediabetes who were admitted to the City Clinical hospital. We also assessed the reasons for admission. From 06.01.2018 to 03.01.2020 275 (35.6%) patients hospitalized with acute coronary syndrome (ACS), 163 (21.1%) with acute decompensated heart failure (ADHF), 157 (20.3%) with HTN, 75 (9.7%) with atrial fibrillation or flutter (AF), 67 (8.7%) with chronic coronary syndrome (CCS) and 36 (4.7%) with newly diagnosed T2DM. All of them screened for T2DM and prediabetes using HbA1c and fasting plasma glucose by ADA Guidelines.

Results

Screening results are shown in Picture 1. The overall incidence of T2DM or prediabetes in hospitalized patients with CVD was 55.9%, and before the screening, only 25.7% were diagnosed with T2DM or prediabetes. The highest incidence of T2DM or prediabetes, including previously diagnosed, was among patients admitted with ADHF – 71.2%, and the lowest, 46.2%, in those hospitalized with ACS.

Picture 2 presents mean levels of HbA1c in patients with newly and previously diagnosed T2DM, depending on the reasons for admission. The highest HbA1c levels were identified in patients with CVD who were hospitalized with symptoms of hyperglycemia and in whom the diagnosis of T2DM was confirmed (р<0,001). However, patients hospitalized with ADHF, AF and CCS had a HbA1c level almost twice lower than in patients hospitalized with newly diagnosed T2DM and lower than in those hospitalized with ACS and HTN (р<0,001). At the same time, HbA1c levels in previously diagnosed T2DM did not differ significantly between groups.

Conclusion

Thus, about 1 out of 2 patients hospitalized with CVD have a T2DM or prediabetes, and more than a third of patients without a T2DM or prediabetes (41%) were previously undiagnosed. In addition, patients admitted with ADHF, AF, and CCS with newly diagnosed T2DM had lower levels of baseline HbA1c than patients with overt symptoms of hyperglycemia, ACS, and HTN. All this has a potential impact on the target groups of screening and initial therapy of T2DM, including new classes of drugs.Picture 1Picture 2
Elevated plasma factor XI is predicts cardiovascular complications in patients with type 2 diabetes mellitus
Authors: Paszek E , Polak M , Bryk-Wiazania A , Konieczynska M , Natorska J , Zabczyk M , Undas A
Published: November 2023

Background

Atherothrombotic complications are common in patients with type 2 diabetes mellitus (T2DM), reflecting a chronic prothrombotic state. Circulating factor XI (FXI) has been associated with a prothrombotic fibrin clot phenotype and predicted myocardial infarction, stroke and cardiovascular (CV) death in a number of diseases, including CAD. Its role in T2DM is largely unknown.

Purpose

The purpose of this study was to assess plasma FXI as a predictor of atherothrombotic events in T2DM patients. We also aimed to establish the determinants of elevated plasma FXI in this group of patients.

Methods

In a cohort of 156 patients aged 43–83 years, 56% male, with T2DM of a median duration time of five years, 64.7% with diagnosed CAD, we measured FXI along with a number of fibrin clot parameters, including turbidity, permeation, compaction, lysability, maximum concentration of D-dimer (D-D max), and rate of D-dimer release during tissue plasminogen activator-induced clot lysis. Patients were followed for a median time of 72 (68-74) months for a composite endpoint of nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular (CV) death.

Results

Follow-up was complete for 133 (85.3%) patients. There were 21 (16%) cases of the composite endpoint, including one nonfatal MI, four nonfatal strokes and 16 cases of CV death. Patients with and without the composite endpoint shared a similar demographic and clinical profile with the exception of age and white blood cell count – patients with the endpoint were older (69.4 [8.4] vs. 65.4 [7.8] years, p=0.03) and had a higher leukocyte count (7.8 [1.9] vs. 7.0 [1.3], p=0.02) as compared with the remainder. FXI was elevated above the upper limit of 120% in 25 (18.8%) patients, including 16 (61.9%) with the composite endpoint vs. 12 (10.7%) without the composite endpoint, p<0.001. Individuals with the composite endpoint had higher baseline FXI concentrations as compared with the remainder (120.1±16.8 vs. 104.9±10.7%. p < 0.001), along with higher D-D max (4.1 [3.8-4.3] vs. 3.8 [3.6-4.1] mg/l, p = 0.006) and slightly longer lysis time (t50% 10.1 [9.8-10.9] vs. 9.8 [8.9-10.4] min, p = 0.03). On multivariable analysis, co-existing CAD, LDL cholesterol, and thrombin activatable fibrinolysis inhibitor activity were independent predictors of elevated FXI in T2DM patients.

Conclusion

Elevated plasma FXI in T2DM patients is associated with CAD, LDL cholesterol and TAFI, and predicts myocardial infarction, stroke, and CV death in long term follow-up. Our finding may have implications for risk stratification and suggests a role for FXI inhibitors in T2DM patients with a high risk of atherothrombotic complications.
Effects of sodium-glucose contrasporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on vascular function and liver steatosis in diabetes
Authors: Ikonomidis I , Michalopoulou E , Pavlidis G , Prentza V , Katogiannis K , Kostelli G , Vythoulkas D , Kountouri A , Korakas E , Pliouta L , Thymis J , Lambadiari V
Published: November 2023

Background/Introduction

Patients with type-2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) present increase risk of cardiovascular disease. Sodium-glucose contrasporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to significantly reduce the risk of cardiovascular complications.

Purpose

The aim of the study was to investigate the effect of treatment with SGLT-2i or GLP-1RA on vascular function and liver steatosis and fibrosis in patients with T2DM and NAFLD.

Methods

Thirty patients with T2DM and NAFLD (mean age: 57±11 years) were randomized to receive SGLT-2i (dapagliflozin; n=15) or GLP-1RA (dulaglutide; n=15). At baseline and at 6 months post-treatment, we measured: (1) Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5-25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. (2) Pulse wave velocity (PWV) and augmentation index (AI) using Complior (ALAM Medical), (3) NAFLD fibrosis score (NFS), and (4) Controlled attenuation parameter (CAP) score to assess steatosis grade and liver stiffness (E) to evaluate fibrosis score using liver elastography (FibroScan, Echosens).

Results

At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of vascular function (p>0.05). Compared with baseline, all patients had reduced PBR, PWV, AI, NFS, CAP and E (p<0.05) after 6-month treatment. In the whole study population, the percentage reduction of markers of steatosis (NFS) correlated with the corresponding decrease in PBR (r=0.34, p=0.040) and PWV (r=0.31, p=0.043) post-treatment. Both treatments with SGLT-2i and GLP-1RA reduced markers of liver steatosis and fibrosis (Table).

Conclusion

Both treatments with SGLT-2i and GLP-1RA improve vascular function and reduce liver steatosis in patients with T2DM and NAFLD after 6-month treatment.Table
ZNF259 rs964184 genetic variant is associated with metabolic syndrome in a Portuguese population
Authors: Sa D , Mendonca M I , Santos M , Temtem M , Sousa F , Freitas S , Borges S , Henriques E , Rodrigues M , Guerra G , Drumond A , Sousa A C , Palma Dos Reis R
Published: November 2023

Background

Zinc finger protein (ZPR1) encoded by the ZNF259 gene has been associated with defects in transcription and cell cycle progression. Additionally, the promoter site of ZPR1 binds to peroxisome proliferator-activated receptor gamma (PPARG), which plays a crucial role in insulin sensitivity and obesity. It's not consensual in its association with Metabolic Syndrom (MetS).

Aim

To estimate the influence of the ZNF259 rs964184 variant in MetS appearance.

Methods

A case-control study was performed with 3134 subjects (mean age 52.8 ± 8.1 years, 76.4% male) recruited from the Research Unit database, a regional quality clinical registry of hospital admissions. 1756 were patients with MetS and 1378 controls without MetS. MetS was diagnosed according to the International Diabetes Federation (IDF) criteria. The ZNF259 rs964184 C>G was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). The bivariate analysis evaluated the genotypic and allelic distribution in the two groups, with and without MetS. Multivariate Logistic Regression assessed the variables independently associated with MetS.

Results

There were significant differences in genotype and allele distributions for the ZNF259 C>G variant between patients with MetS and without MetS. Wild-type genotype CC was increased in the non-MetS group, whereas the risk GG was higher in patients with MetS (P=0.008). Similarly, C allele frequencies were significantly higher in the non-MetS group, while the G allele was highly present MetS population (P=0.002). After multivariate logistic regression, GC genotype (OR=1.23; 95%CI:1.05–1.45; p=0.011) and GG genotype (OR=1.59; 95%CI:1.01–2.50; p=0.047) remained as independent risk factors for Metabolic Syndrome.

Conclusions

This study presents novel data and findings that may have important implications for assessing MetS risk in our population. For the first time in a Portuguese population, we demonstrated that ZNF259 genetic changes are significantly associated with more than 60% increased probability of having Metabolic Syndrome.
Long-term spermidine therapy potentially protects the heart against estrogen deprivation in female rats via suppressing cardiac mitochondrial dysfunction, inflammation, oxidative stress, and apoptosis
Authors: Kaorop W , Maneechote C , Pratchayasakul W , Kumfu S , Arunsak B , Chattipakorn S C , Chattipakorn N
Published: November 2023

Background

Postmenopausal women have been associated with a higher risk of cardiovascular diseases (CVDs). Several pathophysiological mechanisms, including cardiac mitochondrial dysfunction, oxidative stress, inflammation, and cardiomyocyte apoptosis, played a key role in the development of postmenopausal CVDs. Long-term estrogen supplementation is widely used to treat postmenopausal symptoms, but it has been linked to an increased risk of breast cancer and cardiac complications. Spermidine is a natural organic compound which has been shown to exert cardioprotection under several pathological conditions. However, the benefits of spermidine against impaired cardiac function due to estrogen-deprivation are unknown.

Purpose

To investigate the effects of therapeutic intervention with spermidine on cardiac mitochondrial function, oxidative stress, inflammation, and programmed cardiomyocyte death in rats with estrogen deprivation.

Methods

Fifteen female Wistar rats underwent ovariectomy (OVX) to induce estrogen deprivation. After 12 weeks, all OVX-operated rats were randomly divided into three interventional groups as follows: 1) vehicle or OV (n = 5), 2) spermidine or OS (20 mg/kg/day, p.o., n = 5), and 3) estradiol or OE (50 µg/kg/day, s.c., n = 5) for an additional 8 weeks. At the end of the experiment, echocardiography for the heart’s function was performed. Then, all the rats were sacrificed, and their hearts were dissected for mitochondrial and molecular analysis, including the protein expressions of inflammation, oxidative stress, and apoptosis.

Results

Treatment with either spermidine or estrogen provided a similar cardioprotective efficacy against OVX-induced estrogen deprivation in reducing mitochondrial membrane potential depolarization and cardiac inflammation, as shown by increased red to green fluorescence and lowered p-NFkB to NFkB ratios, respectively (Fig. 1A, B). Spermidine and estrogen also exerted anti-oxidative stress via increasing glutathione peroxidase (GPX4) and anti-apoptosis via decreasing the cleaved caspase-3 to procaspase-3 ratio following OVX-induced estrogen deficiency (Fig. 1C, D). All of the beneficial effects of spermidine and estrogen led to an improved left ventricular ejection fraction (89% for OS and OE vs. 76% for OV).

Conclusion

Long-term treatment with spermidine rescued cardiac mitochondrial dysfunction, inflammation, oxidative stress, and apoptosis, resulting in the restoration of left ventricular function with the same efficacy as estrogen treatment. These findings suggest that spermidine could be a novel therapeutic strategy to alleviate the adverse cardiac complications associated with postmenopausal women.
Effect of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on markers of neurohumoral activation and left atrial strain
Authors: Ikonomidis I , Katogiannis K , Pavlidis G , Thymis J , Pliouta L , Kousathana F , Kountouri A , Prentza V , Michalopoulou E , Tsilivarakis D , Kostelli G , Katsanaki E , Maratou E , Lambadiari V
Published: November 2023

Background

We investigated the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on neurohumoral biomarkers, left ventricular and left atrial function in type 2 diabetes mellitus.

Patients and methods

A total of 200 patients (60.3±10.3 years old, 138 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n= 50 served as controls), liraglutide (n=50), empagliflozin (n=50) or their combination (GLP-1RA+SGLT-2i) (n= 50) as add-on. We measured at baseline and 6 months posttreatment: (a) Left atrial reservoir strain (LASr) (b) serum biomarkers of cardiac function as Growth/Differentiation Factor-15 (GDF-15), NTproBNP, Placental Growth Factor (PLGF).

Results

In all patients, increasing GDF-15 levels at baseline were positively related with NTproBNP (r=0.230, p=0.017), PWV (r=0.357, p<0.001), GLS (r=0.425, p=0.005) and negatively related with LASr (r=-0,388, p=0.005).

Increasing NTproBNP concentration at baseline was positively related with GLS (r=0.454, p=0.002) and negatively related with LASr (r=-0,424, p=0.002).

Treatment with SGLT-2i improved GDF-15 and NTproBNP (2032±187 vs 1803±178 pg/mL, p=0.016, 215±67 vs 124±52 pg/mL, p=0.005, respectively), while treatment with GLP-1RA had a neutral effect on these biomarkers (p>0.05). However, the combined treatment of SGLT-2i with GLP-1RA also improved the examined biomarkers (p<0.05).

Compared to baseline, no significant change in GDF-15 and NTproBNP levels was observed in patients treated with insulin (1815±234 vs 1730±192 pg/mL, p=0.235, 245±43 vs 232±32 pg/mL, p=0.583, respectively).

After intervention, all patients treated with GLP1RA, SGLT2i and their combination improved left atrial reservoir strain (GLP1RA: 30.7±9.3 vs 33.9±9.7%, p=0,011, SGLT2i 30±8.3 vs 32.3±7.3%, p=0.04/ GLP1&SGLT2i :29.1±8,7 vs 31.3±8.2, p=0.007) in comparison with insulin (33±8.3% vs 32.8±7,4, p=0.829).

Conclusions

Treatment with GLP-1RA, SGLT-2i and their combination for 6 months showed a greater improvement of markers of neurohumoral activation and left atrial function compared to insulin, suggesting a role in heart failure prevention.
Gender differences in lifestyle and psycho-social aspects of medical students. A cross sectional study
Authors: Winfred Gnanaraj J P , Hariharan R , Sandeep S , Gnanaraj J P , Raghunanthan S , Anusuya M , Shanthi T S , Samuel Dinesh A , Sudharshini S , Ramalakshmi J , Anne Princy S , Penchalliah C , Balamanikandan M , Umadevi T B , Rajendran V
Published: November 2023

Background

Incidence of premature cardiovascular deaths in medical practitioners is on the increase. Lifestyle habits, psychosocial and emotional status of medical students has the potential to initiate the premature onset of cardiovascular disease. Gender differences in diagnosis and management of cardiovascular diseases is well known. However, data on gender differences in heart healthy status of medical students are sparce.

Purpose

To investigate the gender differences heart healthy lifestyle habits among undergraduate medical students of a medical college from low-and-middle income country in south Asia.

Methods

All students pursing MBBS between 2017 and 2018 were included in the cross-sectional study. The study had Institutional ethics committee approval and the participation was voluntary. Anthropometric measurements (weight using digital weighting scale, height, waist and hip circumference using measuring tape), vital signs (pulse and blood pressure using digital manometer) and self-reported lifestyle/psychosocial cum behavioural pattern (using a specially designed proforma) were collected for all the participants. (525)

Results

824 medical students were enrolled in the study of whom 377 (45.8%) were women. Overall 37.1% had abnormal body mass index (BMI) and 27.8% had abnormal waist hip ratio (WHR). Overall 14% and 10.3% students had abnormal systolic (≤ 85 mm of Hg) or diastolic blood pressure(BP) (≤ 135 mm of Hg) readings respectively. 19.4% of students had either systolic or diastolic abnormal BP values.

Gender differences: Abnormal BMI and abnormal WHR (Figure 1A) were found in similar proportion among women and men. However less women has abnormal BP readings compared to men. More men has abnormal diastolic BP and abnormal systolic BP compared to women. Either systolic or diastolic BP values were abnormal in lower proportion of women (7.8% vs 29.4%; P<0.001). Women had less physically active minutes per day compared to men (71.15 ± 68.2 vs 109. 38± 81.7; P < 0.001). A feeling of lack of self-worth (73.5%) was common among medical students, however no significant gender differences were observed (Figure 1B). Significantly more women students have harbored suicidal thoughts than men. Women students were more likely to feel life style counseling is necessary for medical students and were more likely to implement lifestyle changes if advised.

Conclusion

High blood pressure and feeling of lack of self-worth is commonly observed in medical students. Women were more likely to harbor suicidal thoughts, bitterness and anger more likely to implement lifestyle modifications if advised. Interventions warranted at improving heart healthy lifestyle patterns is warranted, and must be optimized by observed gender differences.Figure 1Gender and life style habits
Men with non-obstructive coronary disease have higher risk of exercise-induced myocardial ischemia detected by cardiopulmonary exercise test
Authors: Li S , Zhao L T , Yuan Y F , Zhang P
Published: November 2023

Background

Non-obstructive coronary artery disease (NOCAD) had similar morbidity and mortality as patients with obstructive coronary artery disease but less understood. Limited studies analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD.

Methods

A total of 289 NOCAD patients (mean age 60, 56% women) who had ischemic symptoms and ⫹ 50% coronaries stenoses confirmed by coronary angiography performed the symptom-limited CPET. We used the predicted % peak VO2, O2 pulse trajectory, and exercise ECG test to assess inducible myocardial ischemia.

Results

Compared with women, men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%) and downward pattern of O2 pulse trajectory (2% vs. 0%) (P < 0.0001). Instead, women with NOCAD had higher prevalence of shallow pattern of O2 pulse trajectory (21% vs. 6%, P < 0.0001). Men with NOCAD had higher proportions of increased risk of exercise-induced myocardial ischemia (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, P < 0.0001). After adjustment, men with NOCAD demonstrated significantly lower predicted % peak VO2 (β -27.4, 95% CI -30.74 – -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 – 9.19) and myocardial ischemia risk detected by CPET (OR 3.14, 95% CI 1.78 – 5.54) (P < 0.0001).

Conclusion

Men with NOCAD had higher risk of exercise-induced myocardial ischemia detected by CPET that should be given rigorous management and follow-up to prevent cardiovascular events.
Exercise performance and the risk of incident atrial fibrillation
Authors: Lu C T , Sung S H
Published: November 2023

Background

Atrial fibrillation (AF) is a global health problem that correlates with the increased risks of cardiovascular diseases, quality of life, mortality and global health expenditures. While many of cardiovascular risk factors have been related to the development of AF, a satisfied lifestyle behavior, including regular exercise and a good cardiorespiratory fitness, could be the upstream intervention to modify the risk factors and reduce the AF incidence.

Purpose

We examined the relationship of the exercise performance with risk of incident atrial fibrillation and its subsequent comorbidities.

Methods

From 2003 to 2012, we retrospectively included 19,680 consecutive patients without previous diagnosis of AF, who were referred to exercise treadmill testing for clinical reasons. The baseline characteristics and the exercise parameters during exercise testing were accessed in all enrolled subjects. Multivariable Cox proportional hazard models identified the independent association between exercise performance and risk of new-onset atrial fibrillation, risk of ischemic stroke and major adverse cardiovascular events (MACE). Cubic spline regression model assessed the risk of new-onset AF across fitness level.

Results

Among a total of 15,450 subjects (mean age, 54.9 ± 11 years; 59% male) with a median follow-up duration of 137 months, 515 (3.33%) new-onset AF cases were found. There was an 8% lower risk of AF incidence (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97), a 12% lower risk of ischemic stroke incidence (hazard ratio, 0.88; 95% confidence interval, 0.83-0.94), and a 14% lower risk of MACE (hazard ratio, 0.86; 95% confidence interval, 0.84-0.88) for every 1 peak achieved metabolic equivalents (METs) increase in the exercise treadmill testing after adjusting confounding factors. In the subgroup analysis, the peak achieved METs during exercise treadmill testing was significantly associated with the risk of new-onset AF across various subgroups, including age, gender, body mass index (BMI) and underlying diseases. There were significant interactions in age subgroup (P for interaction 0.0047) and subgroup stratified by the presence of chronotropic incompetence (P for interaction 0.0212).

Conclusions

Exercise capacity is inversely correlated with AF incidence across fitness level. A better exercise performance indicates a lower AF incidence, ischemic stroke incidence and MACE. Regular physical activity may help to reduce inflammation and improve the function of the heart, which may help to prevent the development of AF. Further research is needed to fully understand the underlying mechanisms.Kaplan–Meier curveSubgroup analysis
Agreement between two independent raters in identifying exercise oscillatory ventilation in patients with heart failure
Authors: Silva F M F , Milani M , Silveira A D , Cipriano Junior G , Cipriano G F B
Published: November 2023

Background

Heart failure (HF) leads to several functional and ventilatory limitations, including exercise oscillatory ventilation (EOV), whose presence is associated with an adverse prognosis, with a risk more than 4 times higher for a cardiovascular event. Methods to identify the presence of EOV were created and are being reformulated based on the amplitude and duration in the oscillation of the ventilatory cycles. Despite the documented association between EOV and prognosis in HF, the diversity of methods and subjective interpretation can compromise the diagnosis and adequate risk stratification.

Purpose

To analyze the agreement of the EOV identification between two independent raters and compare the clinical characteristics of the patients with and without EOV.

Methods

A cross-sectional study was carried out using an electronic questionnaire containing graphs of exercise ventilation over time from treadmill cardiopulmonary stress tests (CPET) performed in patients with HF, with preserved or reduced left ventricular ejection fraction (LVEF). The graphs were interpreted by two cardiologists with extensive experience in performing CPET. The research was approved by the institution's ethics and research committee. Agreement was evaluated by Cohen Kappa statistics and the proportion of agreements between raters. Differences among variables according to the presence of EOV (identified by at least one of the raters) were analyzed with Mann-Whitney test. A two-sided p-value < 0.05 was considered significant for all analyses.

Results

The sample consisted of 31 patients (74% men, 56 years ± 10 years) with a LVEF of 44 ± 12%, 61% with reduced LVEF, 80% with NYHA functional classification I/II, and peak oxygen uptake (VO2peak) of 17.6 ± 4.3 mL/kg/min. The EOV identification by the raters revealed a moderate agreement, with Kappa of 0.56. The proportion of agreement was 84% (26 of 31 cases) and the specific agreement (presence of EOV) was 50% (5 of 10 cases) (Figure 1). Regarding the clinical characteristics of patients with and without EOV (Figure 2), the only variable with statistical difference was VO2peak, with lower values in the patients with EOV (14.9 versus 17.9 mL/kg/min; p = 0.019).

Conclusion

The agreement between two experienced raters was only moderate, which demonstrate that the identification of EOV remains challenging. The only clinical characteristics associated with presence of EOV in our sample was VO2peak, suggesting a poor prognosis in patients with HF and EOV.