bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of global left ventricular systolic function in dipper and newly diagnosed nondipper hypertensive patients
Authors: Cakal S , Cakal B 
Published: October 2021

Abstract

Objective
Nondipper hypertension has been associated with enhanced target organ damage and adverse cardiovascular outcomes. The effect of dipper and non-dipper status on cardiac target organ damage has not been comprehensively investigated by two-dimensional strain echocardiography. We aimed to investigate myocardial deformational strain parameters in dipper and non-dipper untreated hypertensive patients.

Material and methods
We included 42 newly diagnosed hypertensive patients without previous history of cardiovascular disease and coexisting chronic disease. Study population consisted of two groups of patients, 23 dipper patients and 19 non dipper patients. Global longitudinal strain (GLS), radial strain and circumferential strain analysis were measured by two-dimensional (2-D) speckle tracking method.

Results
The study population included 42 patients (15 male) with a mean age of 54.5±9 years. The assessment of LV systolic function by GLS showed decreased values in nondippers compared with dippers (−18.13±2.07 vs. −13.7±1.95; p=0.001). But no significant intergroup differences were observed in circumferential and radial strain. The analysis showed that night-time mean arterial pressure (MAP), night-time systolic and diastolic blood pressures (BP), 24-hr SBP, dipping rate and nocturnal reduction rate of MAP were the parameters that correlated with GLS. Only dipping rate was independently associated with left ventricular GLS.

Conclusion
An isolated non-dipper BP was found to cause impaired LV systolic function detected by myocardial strain.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Effect of physical activity on mortality and hospitalization for lower respiratory tract infection in patients with cardiovascular disease
Authors: Jung M 
Published: October 2021

Abstract

Background
Despite the well-validated benefit of physical activity on various health outcomes, little is known about its effect on lower respiratory tract infection. We explored the dose-response associations between physical activity and lower respiratory tract infection outcomes in patients with cardiovascular disease.

Methods
Using the Korean National Health Insurance data, we identified more than 1 million individuals with cardiovascular diseases who had data on self-reported physical activity (baseline 2009–2012). Participants were followed up until 2018–2019 regarding the risk of death or hospitalization due to lower respiratory tract infection according to their physical activity level.

Results
Age- and sex-adjusted hazard ratios (95% confidence interval) for lower respiratory tract infection mortality were 1.00 (reference), 0.70 (0.67–0.74), 0.63 (0.59–0.66), 0.48 (0.43–0.53), and 0.51 (0.45–0.56) for those engaging in physical activity of 0, &lt;500, 500–999, 1000–1499, and ≥1500 MET min/week, respectively. This was similarly applied to hospitalization due to lower respiratory tract infection. Generally, the association was stronger in the elderly population than in the younger population. Restricted cubic spline curve showed a non-linear association, that is, gradual risk reduction with a steeper slope between 0 and 500 MET min/week, reaching a plateau for 1500–1800 MET/min, and the curve flattened out thereafter.

Conclusions
In patients with cardiovascular disease, engaging in even low level of physical activity was associated decreased risk for lower respiratory tract infection outcomes and incremental risk reduction was shown with an increasing physical activity.

Funding Acknowledgement
Type of funding sources: None.
Impact of diabetes on coronary severity and cardiovascular outcomes in patients with heterozygous familial hypercholesterolemia: an analysis of genotype and phenotype
Authors: Liu M M , Li J J 
Published: October 2021

Abstract

Aims
Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular disease. However, the association between T2DM and coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (HeFH) has not been thoroughly evaluated. Our study aimed to assess the effect of T2DM on CAD severity and hard cardiovascular endpoints in a HeFH cohort.

Methods
A total of 432 patients with HeFH with a molecular and/or clinical Dutch Lipid Clinic Network score ≥6 (definite and probable) were enrolled. Patients were divided into a T2DM group (n=99) and a non-T2DM group (n=333). Hard endpoints included a composite of non-fatal myocardial infarction, stroke, and cardiac death.

Results
No differences were observed regarding genetic mutations in patients with and without T2DM. Patients with T2DM demonstrated a greater number of diseased vessels (p=0.029) and more severe coronary lesions with high Gensini, SYNTAX, and Jeopardy score tertiles. Compared with patients without T2DM, patients with T2DM were at a significantly greater risk of hard endpoints (multivariate adjusted hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.02–4.84, p=0.025). Additionally, patients with T2DM and good glucose control (HbA1c &lt;7.0%) were at a lower risk of hard endpoints compared with those with poor glucose control (HbA1c ≥7.0%, HR 0.08, 95% CI 0.01–0.56, p=0.011).

Conclusions
We conclude that T2DM is an independent predictor of CAD severity when assessed by four different tests and worse cardiovascular outcomes, suggesting that T2DM could be further used for risk stratification of patients with HeFH.

Funding Acknowledgement
Type of funding sources: None. Graphical abstract
Impact of early initiation of SGLT2 inhibitor on cardiovascular outcomes in diabetic patients with known atherosclerotic cardiovascular disease or risk factors: propensity score matched analysis
Authors: Sun W , Yan B 
Published: October 2021

Abstract

Purpose
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular benefits in patients with diabetes and atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the impact of early initiation of SGLT2 inhibitor on cardiovascular outcomes in diabetic patients with known and at risk of ASCVD.

Methods
We retrospectively analyzed 29,309 consecutive patients with type 2 diabetes prescribed empagliflozin (N=18,979, 64.8%) and dapagliflozin (N=10,330, 35.2%) between August 2015 and August 2020 in 16 public hospitals in Hong Kong. Patients with diagnosis of diabetes to first prescription of SGLT2 inhibitors (Dx-to-Rx time) ≤12 months were matched with &gt;12 months using propensity score derived from logistic regression. 3,370 matched patients were divided into 4 groups: (i) patients with known ASCVD involving 1 territory (coronary artery, peripheral artery or cerebrovascular disease); (ii) known ASCVD involving &gt;1 territories; (iii) CV risk factor(s) other than diabetes and (iv) no known ASCVD or additional CV risk factors. Incidence rates of 3-point major adverse cardiovascular events (MACE, including non-fatal stroke, non-fatal myocardial infarction and cardiovascular death) were compared between Dx-to-Rx time ≤12 months and &gt;12 months across 4 subgroups during a median follow-up of 2.8 years (IQR 2.2 to 3.4).

Results
Of 29,309 patients (mean age 54.9±11.6 years, female 41.0%), 22.9% had single territory and 6.1% multi-territories ASCVD, 53.3% with additional CV risk factors and 17.7% neither risk factor nor ASCVD. Overall, 19.0% of patients had Dx-to-Rx time ≤12 month; 19.3%, 15.7%, 17.6% and 30.0% in each group, respectively. Overall, Dx-to-Rx time ≤12 months was associated with lower rates of MACE (hazard ratio (HR) =0.27, 95% CI: 0.17–0.42). Subgroup analysis showed similar results in patients with CV risk factors of or known ASCVD but not in patients with neither risk factor nor ASCVD (P for interaction=0.001, Table 1).

Conclusion
Early initiation of SGLT2 inhibitor was associated with significant lower MACE rates in diabetic patients with known ASCVD or additional CV risk factors. The impact was more marked in patients with additional CV risk factors. Our findings suggested early initiation in diabetic patients with known ASCVD and additional CV risk factors.

Funding Acknowledgement
Type of funding sources: None.
Statin use can attenuate the decline in left ventricular ejection fraction during the cardiotoxic chemotherapy: a systemic review and meta-analysis
Authors: Kim J , Miyazaki K 
Published: October 2021

Abstract

Background
Antineoplastic medications such as anthracyclines and trastuzumab are effective in treating various hematologic and solid organ malignancies, however an increased risk of cardiotoxicity in patients has been reported. A decline in left ventricular ejection fraction (LVEF) is a common finding in chemotherapy-induced cardiomyopathy and is sometimes irreversible and lethal. Several agents such as beta blockers and angiotensin-converting enzyme (ACE) inhibitors have shown to reduce the chemotherapy-induced cardiotoxicity in cancer patients. The use of statins, however, to prevent chemotherapy-related cardiotoxicity is not as well studied as other cardioprotective agents. In this study, we aimed to investigate the difference in the degree of decline in the LVEF in patients who received concurrent statin during the chemotherapy compared to those who received chemotherapy alone.

Methods
A systematic search of MEDLINE and EMBASE databases was performed from inception to March 2021 for studies that reported the mean LVEF before and after chemotherapy in patients who received concurrent statin therapy and those who did not receive statin along with the chemotherapy. A random effects meta-analysis was performed to obtain the pooled WMD of LVEF between the intervention (statin with chemotherapy) and the control group (chemotherapy alone) before and after chemotherapy treatments using STATA 16.

Results
Four studies with a total of 297 patients were included in this meta-analysis. Of the 297 patients, 115 patients were in the intervention group and received statin with chemotherapy, while 182 patients were in the control group and received chemotherapy alone. Baseline mean LVEF had no statistically significant difference between the intervention (statin) and the control (no statin) group, and the WMD was −0.38% (95% CI: −1.27 to 0.51, p=0.342). Upon follow-up, the control group patients showed a significantly greater decline in LVEF, with WMD of −6.08% (95% CI: −8.55 to −3.61, p=0.013), compared to the intervention group.

Conclusion
Patients who did not receive statin during the chemotherapy period had a greater mean decline in LVEF from baseline compared to that of the control group after the chemotherapy treatments.

Funding Acknowledgement
Type of funding sources: None.
Increased CaMKII-dependent pro-arrhythmic activity in a novel mouse model of obstructive sleep apnoea
Authors: Schaner B , Lebek S , Hegner P , Maier L S , Arzt M , Wagner S 
Published: October 2021

Abstract

Background
Obstructive sleep apnoea (OSA) is frequently associated with atrial arrhythmias, but detailed mechanisms remain elusive. Most recently, we found an increased CaMKII-dependent pro-arrhythmic activity in patients with sleep apnoea. Since patients suffer from various confounding comorbidities, we have developed a novel mouse model of OSA by tongue enlargement.

Purpose
We tested if mice with OSA exhibit increased atrial CaMKII-dependent pro-arrhythmic activity.

Methods
Polytetrafluorethylene (PTFE) was injected into the tongue of 12 wild-type (WT) and 10 CaMKII knock-out (CKO) mice. 9 WT and 9 CKO mice were used as control without PTFE injection. Inspiratory flow limitations and apnoeas were monitored during murine sleep phases by whole-body plethysmography (Buxco). After eight weeks, isolated atrial cardiomyocytes were incubated with the Ca-sensitive dye FURA-2 AM for 15 min. Regular Ca transients were elicited by electrical field stimulation (1 Hz, 20 V for 4 ms) using epifluorescence microscopy. Pro-arrhythmic non-stimulated events were defined as deviations from diastolic Ca baseline between two stimulated Ca transients.

Results
Sonographic measurements revealed a significant increase in mean tongue diameter from (in mm) 3.7±0.1 to 5.1±0.1 after PTFE injection (n=23, p&lt;0.0001). There was a significant correlation between magnitude of tongue diameter and frequency of apnoeas in OSA mice (p=0.046, r2=0.19, Fig. 1A). Interestingly, we observed a significantly increased frequency of pro-arrhythmic events of (in s–1) 0.06±0.01 in WT OSA mice compared to 0.02±0.01 in WT control mice (p=0.047, Fig. 1B). Similar results were observed at higher stimulation frequencies (2 and 4 Hz). There was a significant correlation of pro-arrhythmic events with inspiratory flow limitations (p=0.03, r2=0.24, Fig. 1C) and with the frequency of apnoeas by strong trend (p=0.06, r2=0.18). In contrast, no increase in atrial pro-arrhythmic events was observed in CKO mice after PTFE injection (for CKO mice after PTFE vs. CKO mice without PTFE, 0.03±0.01 s–1 vs. 0.03±0.01 s–1, p=0.89, Fig. 1B). Accordingly, the correlations between pro-arrhythmic events and both inspiratory flow limitations (p=0.36, r2=0.05, Fig. 1C) and apnoeas (p=0.82, r2=0.004) were completely abolished in CKO mice.

Conclusion
In a novel mouse model of obstructive sleep apnoea, atrial pro-arrhythmic activity was increased in a CaMKII-dependent fashion, which may have therapeutic implications.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Benedikt Schaner / Mr., this work is supported by a research grant of the German Cardiac Society (DGK); Stefan Wagner / Professor, was funded by DFG grants Figure 1
Mapping the endothelial cell S-Sulfhydrome highlights the crucial role of integrin sulfhydration in vascular function
Authors: Bibli D R , Hu D R , Looso D R , Weigert D R , Wittig D R , Papapetropoulos D R , Sigala D R , Fleming D R ,   IVS
Published: October 2021

Abstract

Background
In vascular endothelial cells, cysteine metabolism by the cystathionine-γ lyase (CSE), generates hydrogen sulfide-related sulfane sulfur compounds (H2Sn), that exert their biological actions via cysteine S-sulfhydration of target proteins. This study set out to map the “S-sulfhydrome” i.e. the spectrum of proteins targeted by H2Sn in human endothelial cells.

Methods
LC-MS/MS was used to identify S-sulfhydrated cysteines in endothelial cell proteins and β3 integrin intra-protein disulfide bond rearrangement. Functional studies included endothelial cell adhesion, shear stress-induced cell alignment, blood pressure measurements and flow-induced vasodilatation in endothelial cell-specific CSE knock out mice and a small collective of patients with endothelial dysfunction.

Results
Three paired sample sets were compared: (1) native human endothelial cells isolated from plaque-free mesenteric arteries (CSE activity high) and plaque-containing carotid arteries (CSE activity low), (2) cultured human endothelial cells kept under static conditions or exposed to fluid shear stress to decrease CSE expression, and (3) cultured endothelial cells exposed to shear stress to decrease CSE expression and treated with solvent or the slow-releasing H2Sn donor, SG1002. The endothelial cell “S-sulfhydrome” consisted of 3446 individual cysteine residues in 1591 proteins. The most altered family of proteins were the integrins and focusing on β3 integrin in detail we found that S-sulfhydration affected intra-protein disulfide bond formation and was required for the maintenance of an extended-open conformation of the β leg. β3 integrin S-sulfhydration was required for endothelial cell mechanotransduction in vitro as well as flow-induced dilatation in murine mesenteric arteries. In cultured cells, the loss of S-sulfhydration impaired interactions between β3 integrin and Gα13, resulting in the constitutive activation of RhoA and impaired flow-induced endothelial cell realignment. In humans with atherosclerosis, endothelial function correlated with low H2Sn generation, impaired flow-induced dilatation and a failure to detect β3 integrin S-sulfhydration, all of which were rescued following the administration of an H2S supplement.

Conclusions
Vascular disease is associated with marked changes in the S-sulfhydration of endothelial cell proteins involved in mediating responses to flow. Short term H2Sn supplementation improved vascular reactivity in humans highlighting the potential of interfering with this pathway to treat vascular disease.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft
Is the TCF21 gene protection or risk for coronary artery disease?
Authors: Santos M , Mendonca M I , Temtem M , Sousa J A , Mendonca F , Monteiro J , Sousa A C , Freitas S , Henriques E , Guerra G , Drumond A , Palma Dos Reis R ,   GENEMACOR study
Published: October 2021

Abstract

Introduction
TCF21 is expressed in cells that migrate into the developing plaque facilitating the repair of the vessel wall. However, the rs12190287 risk allele (C) of TCF21 can lead to reduced TCF21 expression being a risk factor for CAD.

Purpose
Investigate whether the variant rs12190287 G&gt;C of TCF21 gene represents a risk factor for CAD in a Southern European population.

Methods
Case-control with 3139 individuals, 1723 CAD patients and 1416 controls, adjusted for age and gender. Genotyping of TCF21 rs12190287 G&gt;C was performed by TaqMan Real-Time PCR. CAD association of each genetic model was evaluated.
Multivariate logistic regression analysis adjusted for confound variables: smoking status, dyslipidemia, diabetes, physical inactivity, and hypertension, was made.

Results
TCF21 rs12190287 G&gt;C has shown significant genotypic differences between cases and controls: GG 9.5% vs 11.9%; GC 43.2% vs 46.5% and CC 47.3% vs 41.6%. CAD risk was significant in all models: dominant (OR 1.28; 95% CI: 1.02–1.61; p=0.033); recessive (OR 1.26; 95% CI: 1.09–1.45; p=0.001); additive (OR 1.20; 95% CI: 1.08–1.34; p=0.001). After multivariate analysis, TCF21 variant was independently associated with CAD.

Conclusion
TCF21 variant rs12190287 G&gt;C may be a risk factor for CAD. It is plausible that TCF21 loci exert its protective effect by promoting infiltration of fibromyocytes in the coronary wall lesion and fibrous layer and loss of TCF21 expression can result in fewer fibromyocytes to fibrous cap increasing vulnerability of the plaque.

Funding Acknowledgement
Type of funding sources: None. Variables associated with CAD risk
Omega-3 fatty acids differentially alter the expression of detoxification enzymes and nitric oxide bioavailability in endothelial cells during IL-6 exposure
Authors: Sherratt S C R , Libby P , Bhatt D L , Dawoud H , Malinski T , Mason R P 
Published: October 2021

Abstract

Background
Atherosclerotic plaques can elaborate reactive oxygen species (ROS) that reduce nitric oxide (NO) bioavailability. Cellular detoxification enzymes including various peroxiredoxin (PRDX) and superoxide dismutase (SOD) isoforms can inactivate ROS. The omega-3 fatty acid (n3-FA) eicosapentaenoic acid (EPA) reduced cardiovascular (CV) events in high-risk patients (REDUCE-IT), a benefit not observed with mixed n3-FAs containing docosahexaenoic acid (DHA).

Purpose
The purpose of this study was to compare the effects of EPA and DHA on NO bioavailability and expression of detoxification enzymes in the vascular endothelium in vitro.

Methods
Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA or DHA at equimolar levels (10 μM) for 2 h, then challenged with IL-6 at 12 ng/ml for 24 h. Proteomic analysis was performed using LC/MS to measure relative protein expression. Only significant (p&lt;0.05) changes between treatment groups &gt;1-fold were analyzed. Cells were stimulated with calcium ionophore to measure NO and peroxynitrite (ONOO-) release using a porphyrinic nanosensor.

Results
EPA, but not DHA, augmented PRDX-2 and SOD1 expression in HUVECs relative to IL-6 alone (1.2-fold and 1.6-fold, respectively, p=0.03). EPA also significantly lowered other isoforms unlike DHA. Either EPA or DHA increased thioredoxin expression by 1.5-fold (p=0.001) and 1.3-fold (p=0.02), respectively and decreased SOD2 expression by 1.5-fold (p=8.75E-11) and 1.6-fold (p=6.03E-9), respectively. IL-6 alone only increased expression of 6 detoxification enzymes by at least 1.2-fold, relative to vehicle. Unlike DHA, EPA also increased the NO to ONOO- release ratio by 36% (p&lt;0.05) relative to IL-6 alone, without changes in NO synthase (eNOS) expression.

Conclusions
n3-FAs differentially influenced NO bioavailability and expression of ROS detoxification proteins, including peroxiredoxin and SOD isoforms. The net benefits of EPA on eNOS function and ROS detoxification may contribute to reduced atherothrombotic risk compared to DHA.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Amarin Pharma Inc., Elucida Research
Contributions of small dense LDL and oxidized LDL on the formation of neoatherosclerosis in patients under statin treatment
Authors: Sakai R , Sekimoto T , Arai T , Tanaka H , Ogura K , Oishi Y , Nomura K , Sakai K , Arai K , Tsujita H , Kondo S , Tsukamoto S , Mori H , Koba S , Shinke T 
Published: October 2021

Abstract

Aim
In-stent neoatherosclerosis (NA) has emerged as an important contributing factor to late stent failure and cardiovascular events. The aim of this study was to investigate whether lipid markers are associated with NA using optical coherence tomography (OCT) after percutaneous coronary intervention (PCI) in patients with coronary artery disease under well-controlled low density lipoprotein cholesterol (LDL-c) on statin treatment.

Methods
We enrolled consecutive 115 patients under statin treatment who underwent PCI with current-generation drug-eluting stent for acute and chronic coronary syndrome. OCT image and various lipid markers were obtained at 1-year for scheduled research assessment. NA was defined as a lipid laden neointima or calcified neointima. Both small dense LDL-c (sd-LDL-c) and remnant lipoprotein cholesterol (RL-c) were measured using direct homogenous assay.

Results
During an average follow-up of 13 months, NA was observed in 14 (13.6%) patients. Not LDL-c but sd-LDL-c, Malondialdehyde-modified LDL (MDA-LDL) as oxidized LDL and (RL-c) were significantly higher in patients with NA. The optimal threshold values of sd-LDL-c, MDA-LDL and RL-c for predicting NA according to receiver operating characteristics analysis were 32.3 mg/dl, 91.0 U/L, and 3.3 mg/dL, respectively. On multivariate logistic regression analysis, sd-LDL-c (≥32.3 mg/dL) and MDA (≥91.0 U/L) were significantly associated with NA (odds ratio [OR]:13.62, p=0.016, OR: 12.68, p=0.01, respectively).

Conclusions
In statin-treated patients, sd-LDL-c and MDA-LDL but not LDL-c might be useful biomarkers to identify the formation of NA at 1 years after PCI. Aggressive reduction of these atherogenic LDL may have a potential to prevent the formation of NA.

Funding Acknowledgement
Type of funding sources: None.