bluuebunny/crossref_metadata_2025_split huggingface dataset:
T regulatory cells lose their protective phenotype in patients with coronary artery disease (CAD)
Authors: Burkard A , Marchini T , Hansen S , Olawale Abogunloko T , Wolf D , Westermann D 
Published: November 2023

Abstract

Background
Atherosclerosis is accompanied by an auto-immune response that involves autoreactive T cells recognizing peptides from ApoB-100, the core protein of LDL-cholesterol. It has been suggested by preclinical animal models that regulatory T-cells (Treg) counteract this pathogenic response by secreting anti-inflammatory cytokines and direct contact inhibition at younger ages, but convert into pathogenic T cells, expressing pro-inflammatory cytokines such as IFN-g during aging. It has been proposed that Tregs numbers decrease in patients with coronary artery disease (CAD), but clinical evidence remains sparse. Here, we aimed to systematically characterize Tregs in human CAD.

Methods
Patients with a high cardiovascular risk undergoing coronary angiography were included in the Adaptive Immunity in Atherosclerosis (ANIMATE) exploratory biomarker trial at the University Heart-Centre Freiburg-Bad Krozingen, Germany. Peripheral blood mononuclear cells (PBMCs) were isolated from 359 patients. In a case-control design, we selected 80 patients that were matched according to their clinical parameters and divided into 4 groups: younger ≤ 55-year-old patients without (n=19) or with CAD (n=21), and older ≥ 70-year-old patients without (n=18) or with CAD (n=22). We studied Tregs using flow cytometry by targeting extracellular markers, transcription factors, and cytokine expression.

Results
Younger patients without or with CAD did not show significant changes in the frequency of circulating Tregs defined as CD127-/CD25+/FoxP3+ CD4+ T cells. Surprisingly, the number of Tregs in the older patients with CAD was significantly higher (increased by 2-fold) than in patients without CAD (p=0.0036), raising the question of an age-dependent changes in Tregs function that might affect CAD progression. Accordingly, Treg from older patients with CAD showed a lower baseline expression of atheroprotective IL-10, as well as higher IL-17, TNF-a, and INF-g protein expression as assessed by intracellular flow cytometry. Interestingly, Tregs frequency was significantly increased in patients with arterial hypertension, severe CAD and in patients with previous myocardial infarction. Treg frequencies positively correlated with plasma levels of anti-ApoB IgG autoantibodies. Conversely, Treg fractions negatively correlated with total cholesterol and LDL-C levels.

Conclusion
Here we show that in older patients with CAD, Treg are more frequent and have a more inflammatory phenotype than in controls without CAD. These data support the novel concept of Treg plasticity in CAD and show that protective autoimmunity is lost in the course of disease.
Association between smoking status and subclinical coronary atherosclerosis in asymptomatic men
Authors: Han S , Park G M 
Published: November 2023

Abstract

Background
We sought to evaluate the association between smoking status and subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic men.

Methods
We analyzed 6,017 asymptomatic men (mean age 53.2±8.0 years) with no history of coronary artery disease who voluntarily underwent CCTA. Among the study participants, 1,200 (19.9%), 2,828 (47.0%), and 1,989 (33.1%) were categorized as never, former, and current smokers, respectively. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and a degree of stenosis ≥50% was defined as significant. Logistic regression analysis was used to determine the association between smoking status and subclinical coronary atherosclerosis.

Results
Compared with never smokers, there were no statistically significant differences in the adjusted odds ratios (ORs) of former smokers for significant coronary artery stenosis, any coronary, calcified, and mixed plaque (p&gt;0.05 for all). However, the adjusted ORs for non-calcified plaque (1.383; 95% confidence interval [CI] 1.024–1.866; p=0.034) were significantly higher in the former smokers. For current smokers, the adjusted ORs for signiﬁcant coronary artery stenosis (1.481; 95% CI 1.099–1.996; p=0.010), any coronary plaque (1.354; 95% CI 1.149–1.595; p&lt;0.001), calciﬁed plaque (1.261; 95% CI 1.069–1.488; p=0.006), non-calciﬁed plaque (1.759; 95% CI 1.283–2.412; p&lt;0.001), and mixed plaque (2.100; 95% CI 1.444–3.054; p&lt;0.001) were signiﬁcantly higher than those of never smokers.

Conclusions
Among asymptomatic men, current smokers had a significant association with subclinical coronary atherosclerosis on CCTA. Former smokers were also associated with non-calciﬁed plaque, suggesting an increased cardiovascular risk.
Prognostic impact of percutaneous coronary intervention in chronic dialysis patients with acute myocardial infarction
Authors: Cosentino N , Trombara F , Bonomi A , Della Rocca M , Lucci C , Resta M , Moltrasio M , Agostoni P G , Genovesi S , Marenzi G 
Published: November 2023

Abstract

Background
Patients on chronic dialysis are less likely to receive percutaneous coronary intervention (PCI) for treatment of acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Thus, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue.

Purpose
We analyzed data of patients on chronic dialysis hospitalized with AMI (both ST-elevation myocardial infarction [STEMI] and non-ST-elevation myocardial infarction [NSTEMI]) from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they were treated or not with PCI during hospitalization. The primary outcome was in-hospital mortality while 1-year mortality was the secondary endpoint.

Results
During the study period, 265,048 patients were hospitalized with AMI in Lombardy. Of them, 3,206 (1.2%) were on chronic dialysis (age 71±11; 72% males). Among dialysis patients, 44% were treated with PCI, while 54% underwent PCI among non-dialysis patients (P&lt;0.0001). Dialysis was an independent predictor of conservative treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%. It was significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; P&lt;0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; P&lt;0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients treated with PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. Similar results were found in STEMI and NSTEMI patients considered separately.

Conclusions
Our real-world data showed that in patients with AMI on chronic dialysis, PCI use is associated with a significant in-hospital and 1-year survival benefit.
Impact of volume and intensive cardiac care unit availability on mortality of patients with acute myocardial infarction- related cardiogenic shock treated at revascularization capable centers
Authors: Barrionuevo Sanchez M I , Viana Tejedor A , Ariza Sole A , Del Prado N , Garcia M , Sanchez Salado J C , Lorente V , Alegre Canals O , Llao Ferrando I , Bernal J L , Fernandez Perez C , De La Cuerda F J , Triguero Llonch L , Comin Colet J , Elola F J 
Published: November 2023

Abstract

Background
Cardiogenic shock (CS) is associated with a high mortality. The purpose of this study was to assess the impact of hospital structure-related variables as volume of CS cases and availability of intensive cardiac care unit (ICCU) on hospital mortality in patients with ACS-related CS treated at high complexity revascularization capable centers (RCC) from a large nationwide registry.

Methods
This was a retrospective observational study including consecutive patients with main or secondary diagnosis of CS (ICD-10 code: R57.0) and ST elevation myocardial infarction (STEMI). Patients discharged from Spanish National Healthcare System (SNHS) RCC were included (2016-2020). Transfers between hospitals were assigned to reference hospital. Exclusion criteria were &lt;35 years, voluntary discharges or stays ≤ 1 day. Low- and high-volumen hospitals were classified by k-means clustering with 79 cases as the cut-off point selected.
The association between the volume of CS cases attended by each center, availability of ICCU and heart transplantation (HT) programs and in-hospital mortality was assessed by multilevel logistic regression models.

Results
The study population consisted of 3,065 CS-STEMI episodes, of whom 1,759 (57.4%) occurred in 26 centers with ICCU. Figure 1 shows the profile, management and complications of patients according to ICCU availability. A significantly greater number of circulatory support procedures a higher stroke incidence and a longer hospital stay were observed at hospitals with ICCU. A total of 17/44 hospitals (38.6%) were high-volume centers and 19/44 (43%) centers had HT programs available. Treatment at HT centers was not significantly associated with a lower mortality (p=0.264). Both high volume of cases and ICCU showed a non-significant trend to an association with lower mortality in the adjustment model (OR: 0.86 and 0.88, respectively). The interaction between both variables was significantly protective (OR 0.71; p=0.025). After propensity score matching mortality was lower in high volume hospitals with ICCU [OR = 0.79; p=0.0075] (figure 2).

Conclusions
Most CS STEMI patients from this series were attended at RCC with high volume of cases and ICCU available. The combination of high-volume and ICCU availability showed the lowest adjusted in-hospital mortality. These data should be taken into account when designing regional networks for CS management.Figure 1Figure 2
GDF-15 adds to GRACE 2.0 for long-term risk prediction in ACS but echocardiographic parameters do not: A SWEDEHEART prognostication study
Authors: Lenell J , Lindahl B , Erlinge D , Jernberg T , Spaak J , Baron T 
Published: November 2023

Abstract

Background
The risk stratification score GRACE 2.0 has lately been validated to predict all-cause death up to three years after acute coronary syndrome (ACS). GRACE 2.0 does not take important prognostic biomarkers and imaging measurements that may improve long-term risk prediction in to account. This study set out to evaluate the clinical value of such parameters analyzed on top of GRACE 2.0.

Methods
The study was performed in a subset of 773 patients from the TOTAL-AMI cohort with ACS subjects recruited from three Swedish hospitals between 2008 and 2014. Biomarkers were analyzed with a Proximity Extension Assay panel and the echocardiographic parameters, Left Ventricular Ejection Fraction (LVEF) and Global Longitudinal Strain (GLS), were assessed at a core lab. LVEF, GLS and two high yield biomarkers (NTproBNP and GDF-15) were analyzed with Cox proportional hazards regression by stepwise addition of each variable to a baseline model with GRACE 2.0. The C-index was assessed for each model. All models were adjusted for treatment with betablockers and/or RAAS-inhibitors. Outcome was all-cause death at three years.

Results
Forty-one patients had died at three years follow-up. The mean population age was 64 years and 77% were men. Median LVEF was 55 % (inter quartile range: 47-60). LVEF, GLS and GDF-15 all emerged as independent predictors of three-year death in the multivariable models with GRACE 2.0 and medical treatment. Only GDF-15 rendered substantial improvement in the C-index on top of GRACE 2.0 (0.755 to 0.810). The echocardiographic measurements did not improve prognostication on top of GRACE 2.0 and GDF-15.

Conclusions
GRACE 2.0 emerged as a strong long-term risk-predictor irrespective of the biomarkers and imaging measurements. Although LVEF, GLS and GDF-15 also emerged as independent predictors of three-year death only GDF-15 improved the C-index to an extent that may be considered clinically meaningful.
Normal values for left atrial strain, volume and function derived from three-dimensional echocardiography in the general population
Authors: Yafasov M , Javier Olsen F , Grundtvig Skaarup K , Hoejbjerg Lassen M , Dyrby Johansen N , Boje Jensen G , Schnohr P , Moegelvang R , Biering Soerensen T 
Published: November 2023

Abstract

Background
Three-dimensional echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use.

Methods
The study included 4,466 participants from a prospective longitudinal cohort study in the general population, among these 2,082 participants underwent 3DE of the LA. Exclusion criteria were hypertension, diabetes, ischemic heart disease, history of stroke, atrial fibrillation, heart failure, use of heart medication, chronic kidney disease, use of pacemaker, significant valve regurgitation or valve stenosis. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex on 3DE parameters were also evaluated. Mean volumes per second for included participants was 62.4±5.7.

Results
After excluding participants with comorbidities, the final study population constituted of 979 healthy participants, median age was 44 years (interquartile range 32-56 years), 40% men. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were: LA reservoir strain (LASr) 30.8% (18.4-44.2%), LA conduit strain (LAScd) 19.1% (6.8-32.0%), LA contractile strain (LASct) 11.7% (4.3-22.2%) (Figure 1) total LA emptying fraction (LAEF) 61.4% (47.8-71.0%), passive LAEF 37.7% (17.4-53.9%), active LAEF 37.4% (22.2-52.5%), LA minimum volume index (LAVimin) 10.2 (5.9-18.5) ml/m2, and LA maximum volume index (LAVimax) 26.8 (16.5-40.1) ml/m2 (Figure 2). All parameters changed significantly with increasing age (p value for all &lt;0.001). Significant sex-specific differences were observed for all parameters except for active LAEF. Sex significantly modified the association between age and LASr (p for interaction&lt;0.001), LAScd (p for interaction&lt;0.001), LAVimin (p for interaction=0.037), and total LAEF (p for interaction=0.034).

Conclusion
We present age- and sex specific reference material including limits of normality for LA strain, volume, and function by 3DE.
Health outcomes after myocardial infarction: a population study of 56 million people in England
Authors: Hall M , Smith L , Wu J , Hayward C , Batty J A , Lambert P C , Hemingway H , Gale C P 
Published: November 2023

Abstract

Background
Information about the health outcomes of people with myocardial infarction (MI) is required to determine individual health needs, enable earlier detection and treatment of new onset disease, and inform health service planning. Although estimating 10 year cardiovascular disease risk is an established part of primary prevention, this is not the case for MI where comprehensive evidence for the long term impact of MI on subsequent major health outcomes is lacking. Such information is critical not only for the development of guideline recommendations, but also to underpin shared decision making.

Methods
This nationwide cohort study includes 34,116,257 adults in England, contributing 145,912,852 hospitalisations between 1st January 2008 and 31st January 2017 (final follow-up 27th March 2017). The absolute risk of 11 non-fatal health outcomes following MI (subsequent MI and new hospitalisations of heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes, dementia, depression, cancer) and all-cause mortality was calculated via standardised cumulative incidence functions (CIFs) over nine years of follow-up. CIFs were estimated from flexible parametric survival models adjusted for age, sex, year, deprivation and competing risk of death. Risk-set matching by age, sex, and year of hospitalisation determined the relative risk of incident health outcomes compared with non-MI cases.
Findings: There were 433,361 individuals with MI (mean age 67·4 years (SD 14·4); n=286,728 (65·3%) male). Following MI, all-cause mortality was the most frequent event (CIF 37·8%, 95% CI 37·6─37·9%), followed by heart failure (29·6%; 29·4─29·7%), renal failure (27·2%; 27·0─27·4%), atrial fibrillation (22·3%; 22·2─22·5%), severe bleeding (19·0%; 18·8-19·1%), diabetes (17·0%; 16·9─17·1%), cancer (13·5%; 13·3─13·6%), cerebrovascular disease (12·5%; 12·4─12·7%), depression (8·9%; 8·7─9·0%), dementia (7·8%; 7·7─7·9%), subsequent MI (7·1%; 7·0─7·2%), and peripheral arterial disease (6·5%; 6·4─6·6%). Compared with 2,001,301 matched controls, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (HR 1·01; 0·99─1·02) and cancer (HR 0·56; 0·56─0·57).
Interpretation: Up to a third of patients with MI develop heart failure or renal failure, 7% have another MI and four in ten die within ten years. The incidence of heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes, and depression, but not dementia or cancer, was higher than expected during the normal life course without MI. Improved post-MI preventative strategies, encompassing enhanced surveillance and detection, are required to tackle the high incidences of heart failure, atrial fibrillation, cerebrovascular disease, and renal failure observed in this population.
Long-term outcomes of patients with ischemia and no obstructive coronary artery disease (INOCA) - a systematic review and meta-analysis
Authors: Odanovic N , Schwann A , Zhang Z , Kapadia S , Kunnirickal S , Parise H , Tirziu D , Ilic I , Lansky A , Pietras C , Shah S 
Published: November 2023

Abstract

Background
Myocardial ischemia with no obstructive coronary artery disease (INOCA) is an increasingly recognized syndrome that encompasses coronary vasomotor disorders such as coronary microvascular dysfunction (CMD) and coronary vasospasm. However, the prognosis of patients with INOCA is not well defined.

Purpose
To perform a systematic review and meta-analysis of previous studies evaluating the long-term prognosis of patients with INOCA stratified by the underlying vasomotor disorder.

Methods
We searched Medline, Embase, Web of Science, and Cochrane databases combining terms for INOCA and outcomes to identify observational studies evaluating the prognosis of patients with INOCA published between 1984 and 2021. The primary outcomes were composite of all-cause death and MI, and major adverse cardiovascular events (MACE) at annual intervals for up to 5-year follow-up. Meta-analytic averages with 95% confidence intervals (CI) of the incidence of primary outcomes for INOCA, each INOCA endotype, and by method used to determine the diagnosis were calculated using the random effect models.

Results
We identified a total of 52 studies (19765 patients) meeting eligibility criteria. Of those, 22 included patients with vasospastic angina and 34 with microvascular angina. The rate of all-cause death and MI in the vasospastic angina group was 0.7 (95% CI 0.4-1.0)/100 patient-years [Figure 1] and the rate of MACE was 1.1 (95% CI 0.6-1.9)/100 patient-years [Figure 2]. For patients with microvascular angina the rate of all cause death and MI was 1.2 (95% CI 0.7-1.7)/100 patient-years [Figure 1] and the rate of MACE was 2.8 (95% CI 1.8-4.0)/100 patient-years [Figure 2]. Patients with evidence of microvascular dysfunction by non-invasive (CFR) or invasive (CFR, IMR, TIMI frame count) criteria had 2.7 times higher all-cause death and MI rates than patients whose diagnosis was established solely based on an abnormal exercise or imaging stress test (2.6 (95% CI, 0.8-5.1) vs. 0.7(95% CI, 0.4-1.2)/100 patient-years, p=0.034).

Conclusions
Overall, patients with INOCA have a low rate of MACE events or death, although there is heterogeneity based on the underlying phenotype. Patients with vasospastic angina have a relatively benign long-term prognosis, whereas patients with microvascular angina have a significantly higher rate of MACE at long-term follow-up. Among patients with microvascular angina, those with objective evidence of abnormal microvascular function (such as reduced CFR) had 2.7 times higher rates of all-cause death and MI.Incidence of all cause death and MIIncidence of MACE
Declining trends of mortality from ischemic heart disease in European Union 28 countries from 2011 to 2017
Authors: Venturoli E , Cimaglia P , Matese C , Pangallo G , Campo G , Marco Z 
Published: November 2023

Abstract

Aims
We sought to analyze the mortality trend due to ischemic heart disease (IHD) in Europe between 2011 and 2017.

Methods
We used the free publicly available EUROSTAT death certificate database to examine age-adjusted IHD mortality rates (per 100.000 people) and relative average annual percentage change (AAPC) across all European Union 28 countries (EU28) from 2011 to 2017 using the International Classification of diseases, Tenth Revision (ICD-10) codes I20-I25. Deaths occurring before the age of 65 were defined as premature deaths. To calculate annual trends in IHD-related mortality, we assessed the average annual percent change (AAPC) and relative 95% confidence intervals (CIs) using Joinpoint regression analysis (Joinpoint Regression Program version 4.9.1.0 (National Cancer Institute, Bethesda, USA).

Results
Over the study period, 4,478,563 deaths (2,386,442 males) due to IHD occurred in EU28. Age-adjusted IHD death rates steadily decline over the study period from 139.9 to 118.2 per 100,000 people [AAPC: -3.0 (95% CI: -3.8 to -2.2), p&lt;0.0001]. Such reduction was more pronounced in women (from 186.6 to 161.1 per 100,000 people) [AAPC: -3.6 (95% CI: -4.6 to -2.5), p&lt;0.001] than in men (from 105.4 to 86.4 per 100,000 people) [AAPC: -2.6 (95% CI: -3.2 to -2.0), p&lt;0.001] (Figure 1). Moreover, age-adjusted IHD death rates resulted higher in subjects age ≥65 years old; however, a more pronounced decrease was observed in those &lt;65 years (from 21.3 to 17.8) [AAPC: 3.0-, 95% CI: -3.5 to -2.6), p&lt;0.0001] compared to those age ≥65 years old (from 626.3 to 532.4) [AAPC: -2.7, 955 CI: -3.3 to -2.0), p&lt;0.0001).

Conclusions
In EU28, IHD-related mortality declined from 2011 to 2017, especially in women and in subjects aged &lt;65 years old.