bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early coronary artery atherosclerosis in humans is associated with attenuated coronary retention of klotho
Authors: Akhiyat N , Ozcan I , Lerman L , Lerman A 
Published: October 2024

Abstract

Background
Vascular aging is a key feature of cardiovascular disease. α-klotho (klotho) is a protein inversely associated with aging and may contribute to vascular repair. Lower levels of systemic klotho have been identified in humans with features of early and advanced coronary atherosclerosis. It remains unknown if circulating klotho is present within human coronary circulation and whether cardiovascular klotho retention correlates with atherosclerosis.

Purpose
The current study aimed to assess the presence of klotho within coronary circulation compared to systemic circulation and hypothesized that net coronary klotho retention is attenuated in patients with early age-related features of coronary artery disease (CAD).

Methods
A total of 42 patients that underwent clinically indicated coronary angiogram for chest pain that had no obstructive CAD underwent intravascular ultrasound (IVUS) assessment were retrospectively examined. Virtual histology assessed coronary plaque characteristics. Blood samples simultaneously collected from the proximal aorta and coronary sinus were used for klotho detection using enzyme-linked immunosorbent assay. The net gradient of klotho across cardiovascular circulation was calculated by multiplying the arteriovenous klotho gradient by basal coronary blood flow. A net positive gradient indicated less cardiovascular klotho retention; a net negative gradient indicated greater cardiovascular klotho retention.

Results
Overall, participants were age 54±10 years old and 76% were female. There were overall higher levels of klotho within the coronary sinus (median 0.49 ng/mL [0.15; 1.69]) compared to systemic circulation (median 0.30 ng/mL [0.16; 1.14]). Participant groups were determined by those with positive (n = 20) or negative (n = 22) cardiovascular retention of klotho. Both groups were similar in age (56 ±2 vs. 51 ±2 years old, p = 0.080), gender (72% vs. 80% female, p = 0.580), and had similar occurrences of traditional cardiovascular comorbidities. Those with less cardiovascular klotho retention in the coronary vascular bed had significantly greater degree of non-obstructive coronary artery plaque (Gensini score 3.5 vs. 0, p &lt; 0.001) and had higher percent plaque burden (46% [35; 53] vs. 34% [28; 46], p = 0.044) than those with greater cardiovascular klotho retention.

Conclusions
Patients with early coronary atherosclerosis may be characterized by attenuated retention of klotho within coronary circulation. Moreover, humans appear to have higher circulating klotho in coronary circulation than in systemic circulation. The current study may support a role for mechanism or potential therapeutic target for klotho in coronary atherosclerosis in humans.
Myocardial Bridging: a bridge to spasm?
Authors: O H-Ici D , Kubik S , Manstein M , Joshi S , Paul C , Baerisch A , Kische S 
Published: October 2024

Abstract

Introduction
Myocardial bridges (MBs) represent a congenital anomaly where a segment of a coronary artery passes through the myocardium, resulting in systolic compression. The role of MBs in causing chest pain has been debated, as coronary blood flow occurs primarily in diastole. MBs are generally considered benign, there is growing evidence implicating them in the pathogenesis of coronary artery spasm (CAS). However, the prevalence of CAS in patients in Europe with MBs, particularly assessed through acetylcholine (ACh) testing, remains poorly defined.

Methods
We conducted a retrospective analysis of consecutive patients with angina with no obstructive CAD (ANOCA), ischemia with no obstructive CAD (INOCA), or myocardial infarction with no obstructive coronary arteries (MINOCA) undergoing ACh testing between 2021 and 2024 at our centre. Patients with documented MBs on coronary angiography were included. The presence of epicardial CAS, defined as &gt;90% reduction in coronary diameter with symptoms and/or ischemic electrocardiographic changes, was assessed during ACh provocation testing. Clinical characteristics, Fractional flow reserve (FFR), resting full-cycle ratio (RFR), coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were also analyzed.

Results
From a total of 299 patients who underwent ACh Testing, 21 patients were identified with MBs, (17 Male, 4 Female). The prevalence of focal CAS in the MB among these patients was 90%. None of these patients had abnormal hyperemic (FFR) or non-hyperemic (RFR) measurements. 9 of the 21 patients with MB had increased IMR, and only 1 had a CFR &lt; 2. 1 Patient had both microvascular CAS in addition to focal epicardial CAS.

Conclusion
This analysis provides valuable insights into the prevalence of CAS in patients with MBs undergoing ACh testing. The findings underscore the importance of considering CAS in the evaluation and management of patients with MBs, particularly during provocative testing. Further prospective studies are warranted to validate these findings and elucidate the clinical implications for risk stratification and treatment strategies in this patient population.
Predictive factors and gender insights into abnormal myocardial flow reserve in non-obstructive coronary artery disease: a CZT-SPECT analysis
Authors: Wang Y J , Li J M , Zhang J K , Wu X , Liu X , Liu T , Chen K Y 
Published: October 2024

Abstract

Background
Dynamic myocardial perfusion imaging (D-MPI) using cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT has emerged as a valuable method for assessing coronary microcirculation, particularly compared to conventional SPECT. Additionally, gender-specific disparities in microvascular dysfunction require further investigation.

Objective
This study aims to identify predictive factors for abnormal myocardial flow reserve (MFR) in non-obstructive coronary artery disease (CAD) using CZT-SPECT, with a focus on gender differences in MFR dysfunction.

Methods
A retrospective analysis was conducted on clinical data from 393 patients presenting with symptoms of "chest pain and/or tightness," all of whom were confirmed to lack obstructive CAD by coronary angiography or CT angiography. MFR was measured using CZT-SPECT, with values ≥2.5 considered normal and values &lt;2.5 considered abnormal.

Results
Of the patients, 49.1% (193/393) demonstrated abnormal MFR, with females representing 56.7% (223/393). Females with abnormal MFR exhibited higher averages in age, total cholesterol, LDL-C, creatinine, left atrial diameter, left ventricular posterior wall (LVPW) thickness in diastole, and E/e’ ratio (P &lt; 0.05). Additionally, MDRD-eGFR and mitral annular septal velocity e’ were lower in the abnormal MFR cohort (P &lt; 0.05). Multivariate logistic regression analysis identified elevated LDL-C levels (OR = 1.513, 95%CI: 1.122–2.041, P = 0.007) and increased LVPW thickness (OR = 1.717, 95%CI: 1.140–2.585, P = 0.010) as independent predictors of abnormal MFR in females. ROC analysis suggested optimal cutoff for LDL-C at 3.68 mmol/L (sensitivity 31%, specificity 84%, AUC = 0.586; 95%CI: 0.511–0.661) and LVPW thickness at 9.5 mm (sensitivity 62%, specificity 52%, AUC = 0.576; 95%CI: 0.501–0.652). A combined ROC analysis of LDL-C and LVPW thickness showed a sensitivity of 50% and specificity of 73% (AUC = 0.632, 95%CI: 0.559–0.705). In males, greater left ventricular end-diastolic diameter (LVEDD) was significantly associated with abnormal MFR (P = 0.014), with LVEDD identified as a predictor (OR = 1.130, 95%CI: 1.016–1.258, P = 0.025) and an optimal cutoff at 44.5 mm (sensitivity 88%, specificity 37%, AUC = 0.609; 95%CI: 0.524–0.694). No significant gender differences were observed in overall left ventricular resting myocardial blood flow (MBF) among patients with abnormal MFR (P = 0.072); however, female patients exhibited higher resting MBF in specific territories supplied by the left circumflex and right coronary arteries, and higher E/e’ ratios (P &lt; 0.05). Furthermore, a negative correlation was found between resting MBF in the territory supplied by the right coronary artery and E/e’ in females (r = -0.210, P = 0.030).

Conclusion
Predictors of abnormal MFR in non-obstructive CAD show gender disparities, implicating an association with left ventricular diastolic function.
Minimal coronary microvascular resistance: agreement between continuous and bolus thermodilution
Authors: Mahendiran T , Keulards D , Pijls N , Viscusi M , Gallinoro E , Bertolone D , Van Royen N , Collet C , Knaapen P , De Bruyne B 
Published: October 2024

Abstract

Background
Continuous thermodilution quantifies absolute microvascular resistance (Rµ, Woods units), the quintessential metric of microvascular function. Rµ is minimal during hyperaemia (Rµ,hyper) with increased Rµ,hyper suggestive of microvascular dysfunction. Bolus thermodilution measures the index of microcirculatory resistance (IMR), a dimensionless surrogate of Rµ,hyper.

Purpose
We compared Rµ,hyper measured by continuous thermodilution (invasive Rµ,hyper) with the gold standard [15O]H2O positron emission tomography (PET Rµ,hyper), and explored the correlation between invasive Rµ,hyper and uncorrected IMR.

Methods
The accuracy of invasive Rµ,hyper was assessed in a cohort of 24 patients in which both invasive and PET Rµ,hyper were measured (cohort 1). For both techniques, Rµ,hyper was assessed in both the left anterior descending artery (LAD) and the circumflex artery (LCX), corresponding to 46 measurement of Rµ,hyper in total (LAD=24, LCX=22). Agreement between invasive Rµ,hyper and IMR was evaluated in a cohort of 250 patients with angina and non-obstructive coronary arteries (ANOCA) evaluated in 3 European centres (cohort 2). All measurements in this cohort were performed in the LAD, with patients randomly assigned in a 1:1 ratio to undergo either bolus or continuous thermodilution first. Both techniques were performed by the same operator during the same procedure with a strict interval of 5 minutes between techniques.

Results
In cohort 1, invasive Rµ,hyper exhibited a strong correlation with PET Rµ,hyper (r=0.86 [95% CI 0.76-0.92], p&lt;0.001), with excellent absolute agreement (ICC 0.82 [95% CI 0.70-0.90], p&lt;0.001) (Figure 1). Furthermore, Passing-Bablok regression analysis found no significant systematic (intercept A: 54.53 [95% CI -18.95 to 120.96]) or proportional (slope B: 0.90 [95% CI 0.71 to 1.15]) bias between invasive Rµ,hyper and PET Rµ,hyper. However, in cohort 2, invasive Rµ,hyper exhibited no significant correlation with IMR (r=0.11 [95% CI -0.01 to 0.23], p=0.08) (Figure 2).

Conclusion
Invasive Rµ,hyper derived from continuous thermodilution exhibited excellent agreement with non-invasive Rµ,hyper measured by [15O]H2O PET, the current standard of reference. However, IMR exhibited no significant correlation with invasive Rµ,hyper in patients with stable coronary syndromes.Figure 1.PET vs invasive Rµ,hyperFigure 2.Invasive Rµ,hyper vs IMR
The correlation between angio-IMR and thermodilution-based IMR in patients with ischemia and non obstructive coronary arteries
Authors: Diachyshyn M , Niewiara L , Szolc P , Kleczynski P , Guzik B , Judzialo P , Zmudka K , Legutko J 
Published: October 2024

Abstract

Background
The diagnostic dilemma of angina with no obstructive coronary lesions (INOCA) poses remarkable challenges in clinical practice, and presents as a significant disease burden affecting up to 4 million people annually. Additionally, standard diagnostic tests such as angiography, do not reveal microvascular dysfunction despite clinical symptoms being present. Since the current Gold Standard of functional assessment is based on guidewire dependent measurements (i.e. CFR, IMR). As an invasive method, it is associated with an increased risk of adverse events such as arterial damage. Therefore new modalities are being introduced to improve patient safety, specifically, an angio-IMR (QMR, calculated based on angiography), shows a substantial promise as a potential diagnostic tool for INOCA patients.

Purpose
The aim of this study is to assess correlation between angio-IMR and thermodilution-based invasively measured IMR in INOCA patients.

Methods
In a group of INOCA patients who had undergone coronary angiography with concomitant thermodilution-based assessment of index of microcirculatory resistance (IMR) an additional angio-based IMR calculation was performed.
The INOCA group consisted of 92 patients ranging in age from 49 to 80 years old, with a median age of 66 years. The majority of the patients were female (59.3%), predominantly with arterial hypertension (87%) and dyslipidemia (100%). Diabetes was present in 27% of cases.
Angio-IMR (QMR) was determined by a qualitative angiography software using information about aortic pressures registered during angiography. Coronary microcirculatory dysfunction (CMD) was diagnosed according to current guidelines when IMR ≥ 25 or CFR &lt; 2.0 were present.

Results
Increased IMR values were detected in 26% of patients. Median calculated value of angio-IMR value was 29 [IQR: 22,46], whereas the invasively measured IMR median value was 17 [IQR: 13,26]. A significant correlation between angio-IMR and invasive-IMR values was observed, Spearman Rho 0.29, p&lt;0.001. Detailed scatterplot with histograms is presented in the figure.

Conclusions
Noninvasive methods, such as the Angio-IMR, represent a shift towards reducing the need for additional invasive procedures while still providing valuable diagnostic insights. Angio-IMR is significantly correlated with invasively measured IMR. When evaluated along with the clinical presentation, noninvasive approaches may therefore help mitigate certain risks and healthcare costs associated with invasive techniques.Figure.Correlation angio-IMR vs MR
Role of Galectin-3 in resident macrophages and effects on atherosclerosis
Authors: Li Y , Duan R D , Blanchet X , Jahantigh M N , Su R , Schulz C , Schober A , Weber C , Von Hundelshausen P 
Published: October 2024

Abstract

Background
Arterial macrophages play an important role in atherosclerosis, exhibiting heterogeneity in their origins as either resident or inflammatory monocyte-derived macrophages. Resident macrophages originate predominantly from the yolk sac, and they are endowed with homeostatic functions and can have anti-inflammatory properties under inflammation [1]. Resident macrophages pre-existing within the tissue differentiate into foamy macrophages before monocytes appear in early atherosclerotic lesions [2]. Galectin-3 (Gal-3) encoded by the gene Lgals3, is a crucial effector molecule that is prominently expressed by macrophages [3]. Studies have provided conflicting evidence regarding the role of Gal-3 in atherosclerosis by affecting macrophage functions and monocyte recruitment [4,5].

Purpose
This study aims to investigate the role of Gal-3 in arterial resident macrophages for atherosclerosis and reveal the underlying mechanisms.

Methods
General Lgals3 knockout (Lgals3-/-) and resident macrophage specific knockout (Lgals3-/-Rank-Cretg) mice on the Apoe-deficient background were generated and atherosclerotic lesion development (8 weeks of western diet) was compared.

Results
Our study revealed that Lgals3-/- mice exhibited increased numbers of monocytes and neutrophils in the blood, which was associated with the development of larger atherosclerotic plaques. Plasma Gal-3 concentration from Lgals3-/-Rank-Cretg mice was decreased by 60%, indicating that the majority of circulating Gal-3 is derived from resident macrophages. Surprisingly, Lgals3-/-Rank-Cretg mice did not show the observed increase in blood monocytes and neutrophils, suggesting that this effect was independent of circulating Gal-3. Consistent with a causal role of monocytosis and leukocytosis in atherogenesis, plaque formation in Lgals3-/-Rank-Cretg was not significantly affected. Additionally, Gal-3 deficiency promoted M1 polarization and reduced efferocytosis, phagocytosis and chemokine receptor expression in BMDMs, and the addition of exogenous Gal-3 restored the effect on phagocytosis and blocked CXCL12 and CCL5-induced leukocyte migration.

Conclusion
This study reveals a prominent protective role of Gal-3, primarily through inflammatory macrophages rather than resident macrophages for the development of atherosclerotic lesions. This protective effect is attributed to its homeostatic effects on monocyte and neutrophil numbers, as well as its influence on macrophage functions.
Antibodies against phosphorylcholine in prediction of cardiovascular disease among women: a population-based prospective cohort study
Authors: Frostegard J , Agneta Akesson A A , Emilie Helte E H , Fredrik Soderlund F S , Jun Su J S , Xiang Hua X H , Susanne Rautiainen S R , Alicja Wolk A W 
Published: October 2024

Abstract

Background and aims
Antibodies against phosphorylcholine (anti-PC) have been reported as associated with protection against atherosclerosis, cardiovascular disease (CVD) and other chronic inflammatory diseases. Underlying potential mechanisms have been demonstrated and include anti-inflammatory, clearance of dead cells and inhibition of oxidized low-density lipoprotein-effects. The aim is to study the role of IgM anti-PC and incident CVD among women, where less is known than among men in the general population.

Methods
In a total of 932 women, 66 ± 6 years old at baseline, from the population-based Swedish Mammography Cohort IgM anti-PC levels of sera were measured using ELISA. Prospective associations with any first CVD, ischemic heart disease (IHD), myocardial infarction (MI) and ischemic stroke were assessed using Cox proportional hazard regression, generating hazard ratios (HR) and 95% confidence intervals (CI). The model was adjusted for potential confounding factors.

Results
Over the course of 16 years (14,900 person-years), we identified 113 cases of composite CVD, - 69 cases of ischemic heart disease (IHD), 44 cases of myocardial infarction (MI) and 50 cases of ischemic stroke. IgM antiPC was statistically significantly inversely associated with risk of CVD, IHD and MI, but not with ischemic stroke. Comparing the highest tertile with lowest, we observed multivariable-adjusted HR of 0.26 (95% CI: 0.10–0.66; p-trend &lt;0.01) for MI.

Conclusions
IgM anti-PC may play an active role in inhibition of CVD development in women, especially MI. Elevating anti-PC concentration through immunization, may be a future development in CVD prevention.
Circulating levels of neutrophil extracellular traps reflects local neutrophil activity but not fibrinolytic activity in coronary thrombi from patients with ST-elevation myocardial infarction
Authors: Kindberg K , Nordeng J , Langseth M , Solheim S , Seljeflot I , Stokke M K , Helseth R 
Published: October 2024

Abstract

Introduction
Neutrophil extracellular traps (NETs) are associated with impaired fibrinolysis in ischemic stroke, while NETs degradation enhances lysis of coronary thrombi in ex vivo experiments. Whether circulating NET markers are associated with local fibrinolytic activity in patients with ST-elevation myocardial infarction (STEMI) has not been reported.

Purpose
We investigated associations between circulating NET markers and gene expression of fibrinolytic markers in aspirated coronary thrombi from patients with STEMI. Furthermore, we explored whether local upregulation of NET formation by peptidylarginine deiminase 4 (PAD4) was reflected in the circulation.

Methods
Coronary thrombi from 35 STEMI patients undergoing primary percutaneous coronary intervention (PCI) were aspirated and promptly snap-frozen to -80°C. Peripheral blood samples were collected simultaneously. Median time from start of symptoms to PCI was 152 min. Thrombus gene expression of tissue Plasminogen Activator (tPA), urinary-type Plasminogen Activator (uPA), plasminogen-activation inhibitor type 1 (PAI-1) and PAD4 were quantified with RT-PCR. Gene expression of PAD4 was also measured in circulating leukocytes. Circulating NET markers were measured by a fluorescent nucleic acid stain using fluorometry (dsDNA), an in-house ELISA technique (MPO-DNA) and commercial ELISA (H3Cit). Correlations were tested using Spearman’s rho.

Results
There were no correlations between any of the circulating NET markers and gene expression of the fibrinolytic markers tPA, uPA and PAI-1 in the thrombus. Of the circulating NET markers, dsDNA correlated with thrombus gene expression of PAD4 (rs=0.491 p=0.006), whereas none of the NET markers correlated with gene expression of PAD4 in circulating leukocytes.

Conclusion
Circulating NET markers were not associated with gene expression of fibrinolytic activity in thrombi from patients with STEMI. Local NET formation in the thrombi, measured as PAD4 expression, was associated with the circulating NET marker dsDNA. These findings suggest that circulating NET markers have limited utility for assessing local fibrinolytic activity, but might reflect PAD4-dependent NET formation in coronary thrombi.
Predictors of 1-year follow-up period MACE in patients with NSTEMI
Authors: Popovici I , Munteanu M , Ivanov V , Popovici I , Ciobanu L , Cobet V , Popovici M 
Published: October 2024

Abstract

Background
Identifying viable predictors of MACE in NSTEMI continues to pose a challenge in the field of cardiology. Unraveling these factors will elucidate crucial mechanisms underlying adverse post-infarction outcomes and identify key strategies for optimizing treatment.

Aim
Evaluation by using the multi-marker panel the biomarkers having a high predictive value regarding the risk of MACE developing in patients with NSTEMI.

Methods
The study embraced 550 patients with NSTEMI treated by angioplasty. A panel of 67 biomarkers was quantitatively determined by ELISA, immune assay and flow cytometry on admission in the blood linked to the most important mechanisms conceptually involved in post-infarction evolution (inflammation, endothelial dysfunction, hemostasis disorders, oxidative stress, NETosis, Ang 1-7/Ang II axis etc.) The rate of MACE (cardiac death, stroke, myocardial reinfarction) was estimated in a follow-up period of 18 months. In order to underline the overt predictors, the hazard ratio CI (95%) was assayed. 60 healthy persona formed control series.

Results
Upon admission, the circulating levels of 62 out of 67 biomarkers in patients with NSTEMI significantly deviated from control values. The MACE rate during 1-st year after revascularization was 28% (154 pts). According to hazard ratio (HR) the maximal predictive power regarding MACE risk of 1-year follow-up period was unraveled for 3 markers: endothelial microparticles (EMs), platelet-derived microvesicles (PMVs) and von Willebrand/ADAMTS13 ratio. For EMs – HR 2.21 CI (1.19-3.84; p&lt;0.01); for PMVs - HR 2.56 CI (1.43-3.96; p&lt;0.01); for von Willebrand/ADAMTS13 ratio - HR 2.94 CI (1.77-4.73; p&lt;0.01). EMs-CD62E exceeded control level by 77,6% (325.6±101.5 vs 183.2±67.7 Ms/µL); PMVs-CD62P by 129% (378.6±87.4 vs 165.5±59.6 MVs/µL) and von Willebrand/ADAMTS13 ratio by 88% (2.52±1.88 vs 1.34±1.11). These predictors have not been adjusted to age, gender and cardiovascular risk factors.

Conclusion
Considering the pathophysiological significance of the highlighted predictors of MACE (EMs, PMPs and the von Willebrand/ADAMTS13 ratio) endothelial dysfunction and an activated prothrombotic state emerge as pivotal mechanism in the adverse progression of NSTEMI. THUS, these predictors should indicate a focus on corrective therspy targets.