bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carvedilol suppresses coronary artery spasm in A-kinase anchoring protein 150 knockout mouse
Authors: Konno Y , Hanada K , Umezaki H , Hirosawa S , Iwasaki I , Kato K , Soma T , Washima S , Saito K , Shibutani S , Tomita H 
Published: October 2024

Abstract

Backgrounds
A-kinase anchoring proteins (AKAPs) act as scaffold to regulate activation of protein kinases and subsequent downstream signaling. AKAP 150 interacts with protein kinase A and protein kinase C, and has a critical role in regulating L-type calcium channel activity. We previously reported enhanced phospholipase C activity as an important mechanism of coronary spastic angina (CSA), known as Prinzmetal’s angina. Coronary artery spasm was induced by intravenous ergometrine injection in mouse model of vascular smooth muscle cell (VSMC)-specific enhanced phospholipase C activity concomitantly with enhanced intracellular Ca2+ concentration ([Ca2+]i). Then, we hypothesized that coronary artery spasm would be inhibited by AKAP 150 knockout, however, coronary artery spasm was unexpectedly induced in AKAP 150 knockout (AKAP-KO) mice without affecting [Ca2+]i, suggesting that AKAP-KO mouse is an unique model of CSA independent of [Ca2+]i. Previous report showed that AKAP-KO mice have a high Ca2+/calmodulin-dependent protein kinase (CaMK) II activity, and carvedilol, a non-selective beta-adrenergic receptor antagonist, inhibits CaMK II activity.

Aim
We tested the hypothesis that carvedilol could prevent coronary artery spasm via inhibiting CaMK II activity, which is a key molecule to regulate VSMC contraction, in AKAP-KO mice.

Methods and Results
We pretreated 14-18-weeks-old AKAP-KO mice with intraperitoneal injection of carvedilol (2.5mg/kg), propranolol (20mg/kg), or vehicle (control). Coronary artery spasm, evaluated by ST-segment elevation on lead II of body surface electrocardiogram, was induced by intravenous ergometrine injection (30mg/kg) in all controls (5/5, 100%) and all propranolol-treated mice (5/5, 100%), whereas it tended to be inhibited in carvedilol-treated mice (3/6, 50%) (p=0.08 vs control). In isolated VSMCs obtained from the aorta of AKAO-KO mice, the changes in [Ca2+]i from baseline in response to acetylcholine (ACh, 100μM) did not differ among the groups of pretreatment with carvedilol (10μM), propranolol (10μM), or vehicle, indicating that coronary artery spasm in AKAP-KO mice was induced by Ca2+-independent mechanism. In response to ACh, the phosphorylation of CaMK II was tended to be decreased (p=0.07), and the phosphorylation of myosin light chain was decreased (p&lt;0.05) in VSMCs treated with carvedilol compared with control.

Conclusions
Carvedilol may inhibit coronary artery spasm probably via inhibiting CaMK II activity in AKAP-KO mice. Our results may provide a new paradigm into the pathogenesis of CSA as a model of enhanced Ca2+ sensitivity and important clinical implications for the mechanism of calcium channel antagonist-refractory coronary artery spasm.
Association of polymorphism of apolipoprotein e gene with acute myocardial infarction and its short term clinical outcome
Authors: Chaliha M , Baruah Chaliha S , Borah P K 
Published: October 2024

Abstract

Background/Introduction
Myocardial infarction (MI) is a multifactorial disease influenced by environmental and genetic factors. Apolipoprotein E (ApoE) is a protein incorporated into serum lipoproteins directing their catabolism via binding to receptors. It is a structural component of both chylomicrons and very low density lipoprotein (VLDL) remnants. ApoE is thought to play a central role in atherosclerosis by participating in overall plasma cholesterol homeostasis. In addition to other classical risk factors, positive family history of cardiovascular disease (CVD) has been found to be significantly and independently associated with MI in epidemiological studies (1). Besides traditional cardiovascular risk factors it is likely that additional genetic factors like ApoE gene polymorphism may interact with environmental factors to determine overall cardiovascular risk of an individual to develop MI.

Purpose
The purpose of our study was to determine the risk of association of variants of ApoE gene with Acute Myocardial Infarction. Moreover, we also wanted to study the impact of ApoE gene polymorphism in short term major adverse cardiac events (MACE) in patients with MI not willing for coronary intervention.

Methods
In this case control study a total of 200 consecutively admitted AMI patients admitted to the coronary care unit of our hospital were enrolled to the study along with 200 age and gender matched controls admitted during the same time period . ApoE gene polymorphism was detected by DNA extraction, DNA amplification by PCR in a DNA thermal cycler followed by restriction enzyme digestion(2). Chi square test was used to investigate the difference in genotype and allele frequencies in casend controls and also between observed and expected frequencies in the realm of Hardy-Weinberg equilibrium. Odds Ratio (OR) with 95 % confidence interval and p values were calculated while analysing the association of different genotypes of ApoE genetic polymorphism with the disease and MACE. Logistic regression analysis was carried out amongst the groups under consideration to find the unadjusted OR and adjusted OR of the genotypes in relation to the disease.p&lt;0.05 was considered as significant Analysis was done in SPSS software.

Results
Besides the traditional risk factors Apo E4 allele (OR 2.298, CI 1.305-4.044 ) and Apo E3/E4 genotype (OR 2.116, CI 1.008-4.443, p=0.048) showed strong of association with the disease. There was a higher population of Apo E3/E4 genotypes and Apo E2/E3 genotypes with MACE events (25.6% and 28.6%), while the common ApoE3/E3 genotypes had a MACE event of 10.5 %. However, the difference was not significant (p=0.071, Χ 2 =8.63 df =4). Similarly, ApoE4 allele showed a non significantly higher MACE events (p=0.22, Χ 2 =3.01 df =4)

Conclusion
ApoE4 allele and ApoE3/E4 genotype are strongly and independently associated with AMI.RISK FACTORS AND RISK OF MIGenotype and MACE
Baseline shock index-creatinine clearance score and long-term mortality after ACS. Results from 24 years of follow-up of the ABC study on heart disease
Authors: Berton G , Mahmoud H T , Palmieri R , Cavuto F , Cordiano R , Merotto D , Dario M L , Dal Bo A , Bagato F 
Published: October 2024

Abstract

Background
Shock Index-Creatinine Clearance score (SI-C) is an updated version of the shock index that includes renal function. Recent studies reported its potential as a novel and simple risk stratification tool for predicting in-hospital mortality in acute coronary syndrome (ACS) patients.

Purpose
To assess the long-term predictive value of baseline SI-C score in patients after ACS.

Methods
This preliminary prospective analysis included 589 patients with ACS admitted to three Italian hospitals and discharged alive. Baseline clinical and laboratory data were collected within the first 7 hospitalization days and baseline SI-C score was calculated as [(SI×100)-estimated creatinine clearance]. Patients were prospectively followed for 24 years or until death.

Results
Virtually all patients completed the follow-up, representing 7066 person-years. Patients' mean age was 66±12 years, 70% were males, and 482(82%) had died during follow-up. Compared to those who survived, deceased patients were significantly different in many of the baseline clinical characteristics. They also showed a significantly higher SI-C values ( -11± 25 vs. -36±23, p&lt;0.0001). The predictive value of SI-C for 24-year mortality was very good (area under the curve= 0.783, 95% CI: 0.738-0.827, p&lt;0.001). The cumulative risk was significantly higher in the upper SI-C tertile (log-rank = 162.1, p &lt; 0.001). Unadjusted Cox regression survival analysis showed that the SI-C score was significantly associated with long-term all-cause mortality (HR: 2.1, 95%CI 1.8-2.3, p&lt;0.0001). Similar results were obtained with the fully adjusted model.

Conclusion
Baseline SI-C seems to be an effective and independent predictor of long-term all-cause mortality after ACS.
Prognostic impact of the extent of coronary artery disease in patients with acute transmural myocardial infarction undergoing complete percutaneous revascularization
Authors: Canton L , Amicone S , Asta C , Marinelli V , Casuso Alvarez M , Bela' R , Impellizzeri A , Bertolini D , Di Iuorio O , Tattilo F P , Ryabenko K , Foa' A , Armillotta M , Sansonetti A , Pizzi C 
Published: October 2024

Abstract

Background
The management of acute myocardial infarction has been revolutionised by the introduction of early coronary angiography and the reperfusion strategies. Recent studies support the standard of care of complete myocardial revascularization in all patients with ST-elevation myocardial infarction (STEMI) without assessing the prognostic role of the extent of coronary artery disease (CAD).

Purpose
To evaluate whether the extent of CAD in patients with STEMI has a prognostic impact independent of complete myocardial revascularization.

Methods
Observational cohort study of 365 patients with STEMI who underwent complete revascularization. For each patient the extent of CAD has been quantified using Gensini Score (GS), which takes into account both the severity and location of the lesions. The primary endpoint of the study was all-cause mortality, while cardiovascular mortality and a composite of major adverse cardiovascular events (MACE: cardiovascular mortality, recurrent acute myocardial infarction or myocardial revascularization and stroke) were defined as secondary endpoints. To assess the prognostic role of GS in predicting all-cause mortality, the area under the curve (AUC) was calculated. The best cut-off was determined as the one that maximized Youden's index (sensitivity + specificity - 1).

Results
Patients with a GS &gt;80, indicating extensive coronary disease, had significantly higher rates of both cardiovascular [4 (16.7%) vs. 12 (3.5%); p = 0.002] and all-cause mortality [5 (20.8%) vs. 24 (7%); p = 0.016], than those with a GS ≤80. A GS &gt;80 was demonstrated to be an independent predictor of all-cause mortality [hazard ratio = 5; 95% confidence interval: 1.5-16.8; p = 0.01]

Conclusions
The Gensini Score can identify high-risk patients with STEMI who may benefit from more intensive therapies to improve prognosis, although current guidelines do not specify treatment based on the extent of coronary disease.Long-term outcomes according to GSPrognostic value of GS
Clinical characteristics and outcomes of patients with acute coronary syndrome without standard metabolic cardiovascular risk factors
Authors: Komaki S , Matsuura Y , Tanaka H , Moribayashi K , Yamamura Y , Kurogi K , Ideguchi T , Yamamoto N , Tsuruda T , Kaikita K 
Published: October 2024

Abstract

Background/Introduction
Patients with acute coronary syndrome (ACS) commonly present with hypertension, diabetes mellitus (DM), and dyslipidaemia as standard modifiable metabolic risk factors. However, little is known about patients with ACS who do not have these risk factors.

Purpose
This study investigated the clinical characteristics and outcomes of patients with ACS without these risk factors who underwent primary percutaneous coronary intervention (PCI).

Methods
This retrospective, single-centre observational study included 1131 consecutive patients with ACS who were admitted to a hospital between January 2013 and May 2021. After excluding patients who did not undergo revascularization or who underwent emergency coronary artery bypass surgery, 947 patients who underwent primary PCI were included in the analysis. Patients were classified into two groups: those with one or more of the following: hypertension, DM, or dyslipidaemia (risk group) and those without any of these factors (non-risk group). Major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction (MI), stroke, and heart failure requiring rehospitalisation, were assessed at the 1-year follow-up.

Results
This study classified 78 patients (8.2%) in the non-risk group, who exhibited a significantly lower body mass index (BMI) [23.0 (interquartile range: 21.8–24.7) vs. 23.8 (interquartile range: 21.8–26.2) kg/m2, p = 0.016], compared to the risk group. There were no significant differences in smoking history between the two groups (51.2% vs. 48.9%, p = 0.39). Within 1 year after PCI, MACE occurred in 146 (15.4%) patients (88 [9.2%] with all-cause death, 13 [1.3%] with MI, 23 [2.4%] with stroke, and 27 [2.8%] with heart failure requiring rehospitalisation), with a significantly higher incidence in the non-risk group compared to the risk group (24.4% vs. 14.6%, p = 0.027). Multivariate analysis revealed that both being in the non-risk group and having a low BMI (&lt; 21.5) were independent determinants for the incidence of MACE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.01–2.29; p = 0.042 and HR: 3.08; 95% CI: 1.30–7.27; p = 0.010, respectively). Kaplan–Meier survival analysis showed a higher MACE rate in the non-risk group than in the risk group (p = 0.009).

Conclusions
Patients with ACS without hypertension, DM, or dyslipidaemia have a poorer prognosis than those with these risk factors, independent of the presence of a lower BMI, and the underlying pathophysiology in this subset of patients needs to be clarified.figure
Residual cardiovascular risk in patients with acute coronary syndromes: from hs-CRP and LDL-C to JCAD
Authors: Kraler S , Liberale L , Tirandi A , Moriero M , Carbone F , Wenzl F A , Puspitasari Y M , Raeber L , Templin C , Muller O , Roffi M , Camici G G , Gorog D A , Montecucco F , Luescher T F 
Published: October 2024

Abstract

Background
Patients with a recent acute coronary syndrome (ACS) remain at high residual cardiovascular risk to which cholesterol, inflammation, and yet-to-be-identified pathways jointly contribute (1). The novel Junctional Protein Associated with Coronary Artery Disease (JCAD) protein drives incident cardiovascular events via pathways, among them fibrinolysis, that act independently from lipid metabolism and inflammation (2).

Purpose
Whether circulating JCAD provides predictive utility over and above established risk factors among ACS patients at residual lipid risk (RLR), residual inflammatory risk (RIR), or both (RILR), remains unknown.

Methods
Among patients participating in the multicentre SPUM-ACS study, patients at RLR (on-statin LDL-C ≥70.0 mg/dl), RIR (on-statin hs-CRP ≥2.0 mg/l) or both (RILR; on-statin LDL-C ≥70.0 mg/dl and CRP ≥2.0 mg/l),(1,3) and propensity-score matched (PSM) controls were identified, and the contributions of plasma hs-CRP, LDL-C and JCAD toward recurrent major adverse cardiovascular events (MACE; defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) were studied by fitting uni- and multivariable-adjusted Cox proportional hazard regression models.

Results
Patients at RLR, RIR, or both (RILR) were at higher MACE risk compared to controls (hazard ratio [HR] per log2 increase, 1.51; 95% confidence interval (CI), 1.05-2.17; HR, 1.78; 95% CI, 1.23-2.58; and HR 1.75; 95% CI, 1.12-2.74; Figure 1). Among those at RLR, MACE risk increased with increasing levels of hs-CRP and JCAD, respectively, in uni- (HR, 1.17; 95% CI, 1.06–1.30; HR, 1.29; 95% CI, 1.03-1.62) and multivariable-adjusted models (adjusted [a]HR, 1.16; 95% CI, 1.03–1.30; aHR, 1.27; 95% CI, 1.01-1.60), whereas no association of LDL-C and future MACE risk was noted. Similarly, among patients at RIR, MACE risk increased by 1.28-fold per log2 increase in plasma JCAD (HR, 1.28; 95% CI, 1.03–1.59), which prevailed in multivariable-adjusted models accounting for potential confounders (aHR, 1.31; 95% CI, 1.04–1.65). In ACS patients at both residual inflammatory and lipid risk, MACE risk associated almost linearly with increasing JCAD levels (HR, 1.45; 95% CI, 1.09–1.92), independently of potential confounders (aHR, 1.47; 95% CI, 1.11–1.97). Meanwhile, no association of LDL-C or hs-CRP with MACE risk was identified among these high-risk patients (Figure 2).

Conclusions
ACS patients at RIR, RLR, or both are at high ischaemic risk, with JCAD ranking among the top predictors of MACE across the broad spectrum of residual risk. Our data highlight the importance of novel pathways to address residual cardiovascular risk, with JCAD ranking among most promising candidates.
Extent and impact of obesity in patients with diabetes and acute myocardial infarction - experience from a national cohort
Authors: Ritsinger V , Lagerqvist B , Norhammar A 
Published: October 2024

Abstract

Background
Elevated body mass index (BMI) has an adverse effect on cardiovascular riskfactors where diabetes and coronary artery disease increases with obesity. However, less in known about the prevalence and the grades of obesity in a diabetes population with acute myocardial infarction (AMI) and the impact on prognosis. Further, for the moment there is a shortage of access to cardioprotective weight loss medications as Glucagon Like Peptide Receptor Agonists (GLP-1 RA).

Purpose
To explore features and grades of obesity in patients with diabetes and AMI and impact on outcome in a national perspective.

Methods
All patients with diabetes and AMI admitted for coronary angiography in Sweden the years 2010-2021 were included. Information on BMI was collected at the time of angiography and grouped into obesity categories: low BMI (&lt;18.5 kg/m2), normal BMI (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obesity grade 1 (30.0-34.9 kg/m2), obesity grade 2 (35.0-39.9 kg/m2) and obesity grade 3 (≥40.0 kg/m2). Information on baseline characteristics and outcome was collected from national registries. Mortality was followed until March 2022. Restricted cubic spline analysis of association between continuous BMI and age-adjusted mortality was performed where normal BMI served as a reference with Hazard Ratio (HR) 1.0.

Results
Of 19 378 patients with diabetes, 67% were men and 46% suffered a STEMI. Normal BMI was present in 21%, overweight in 41%, obesity grade 1 in 25%, obesity grade 2 in 9% and obesity grade 3 in 3% (Figure 1). Age was decreasing with grade of obesity (72 years in normal BMI vs. 62 years in obesity grade 3, p&lt;0.001). Hypertension and hyperlipidaemia were more common in patients with more severe obesity than in those with normal BMI (67% vs. 80%, p&lt;0.001, and 44% vs. 50%, p&lt;0.001, in normal BMI and obesity grade 3 respectively) while a higher proportion of those with normal BMI had suffered a previous MI (10% vs. 6% in obesity grade 3, p&lt;0.001) and a previous stroke (10% vs. 5% in obesity grade 3, p&lt;0.001). In patients with normal BMI STEMI was more common (51% vs. 39%, p&lt;0.001) than in those with obesity grade 3. In patients with obesity grade 3 GLP-1 RA was used in 14% compared to 4% in those with normal BMI. Figure 2 depicts age-adjusted HR and 95% Confidence Interval for mortality for different BMI levels with a U-shaped pattern illustrating that associated mortality risk is higher when obesity is present especially grade 2 and 3.

Conclusion
Obesity is common affecting around one third of patients with diabetes and AMI and impacts survival. This strengthens that after AMI use of effective weight loss cardioprotective treatment should be prioritised in patients with diabetes and obesity especially if severe.
Myocardial infarction risk across cancer subtypes - nationwide registry study
Authors: Shanmuganathan J , Jacobsen P A J , Schou M S , Torp Pedersen C T P , Poulsen L , Polcwiartek C B P , Godtfredsen S J G , Gislason G G , Koeber L K , Nielsen D N , El-Galaly T E C , Sogaard P S , Mamas M A M , Freeman P F , Kragholm K K 
Published: October 2024

Abstract

Background
Progress in cancer treatments have significantly improved patient outcomes, leading to increased survival rates. However, patients with cancer continue to have higher rates of cardiovascular events an area that has traditionally not received much attention.

Purpose
The aim of this study was to examine the risk of myocardial infarction in patients with different types of cancer compared with age- and sex-matched population controls with benign skin cancer.

Methods
Patients with cancer between 2000-2016 were identified within the Danish National Patient Registry. Cox regression was used accounting for the competing risk of death reporting hazard ratios (HR) for both myocardial infarction and mortality. Models were adjusted for age, sex, hypercholesterolemia, atrial fibrillation, hypertension and anticoagulant therapies of all included subjects. Patients with a previous myocardial infarction were excluded from the analysis.

Results
A total of 503.616 patients were included in the final analysis of whom 355.920 had cancer with different cancer types and 147.696 were controls with benign skin cancer.
The one-year outcome of myocardial infarction (Figure 1) was overall significant higher for all subtypes of cancer especially lymphoma HR 1.66 (interquartile range [IQR]: 1.45-1.89), bladder cancer HR 1.64 (IQR: 1.39-1.94), and gastrointestinal cancer HR 1.53 (IQR: 1.40-1.69). Hepatobiliary and pancreatic cancer, breast cancer and malignant melanoma had reduced but not significantly different HRs of 0.96 (IQR: 0.80-1.15), 0.92 (IQR: 0.79-1.07), and 0.76 (IQR: 0.60-0.96), respectively. The one-year competing risk of death (Figure 2) was overall higher for all subtybes of cancer especially hepatobiliary and pancreatic cancer and lung cancer with HRs of 52.11 (IQR: 50.18-54.11) and 41.62 (IQR: 40.17-43.12).

Conclusion
The one-year risk of myocardial infarction varied across cancer subtypes. Notably, lymphoma, bladder, and gastrointestinal cancers were associated with higher risks, whereas hepatobiliary and pancreatic, breast, and malignant melanoma cancer showed no statistically significant associations. The clinical significance of these differences must be viewed within the context of the significant competing risk of death in this cancer population.Risk Of Myocardial InfarctionCompeting Risk Of Death