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Chinese Medicine Apr 2024As one of the most famous natural products, salvianolic acid A (SAA) is undergoing clinical trials for the treatments of angina pectoris and coronary heart disorders....
BACKGROUND
As one of the most famous natural products, salvianolic acid A (SAA) is undergoing clinical trials for the treatments of angina pectoris and coronary heart disorders. However, the in vivo metabolites of SAA have only been tentatively identified, leading to a barrier for precise therapeutical drug monitoring.
METHODS
Ultra-high performance liquid chromatography coupled with quadrupole time of flight tandem mass spectrometry (UPLC-Qtof-MS/MS) was firstly employed to acquire high-resolution MS and MS spectra for all metabolites. Through paying special attention onto the features of ester bond dissociation, metabolism sites were restricted at certain regions. To further determine the metabolism site, such as the monomethylated products (M23, M25, and M26), post collision-induced dissociation energy-resolved mass spectrometry (post-CID ER-MS) was proposed through programming progressive exciting energies to the second collision chamber of hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS) device.
RESULTS
After SAA oral administration, 29 metabolites (M1-M29), including five, thirteen, and sixteen ones in rat plasma, urine, and feces, respectively, were detected in rats. The metabolism route was initially determined by applying well-defined mass fragmentation pathways to those HR-m/z values of precursor and fragment ions. Metabolism site was limited to SAF- or DSS-unit based on the fragmentation patterns of ester functional group. Through matching the dissociation trajectories of concerned 1-generation fragment ions with expected decomposition product anions using post-CID ER-MS strategy, M23 and M25 were unequivocally assigned as 3'-methyl-SAA and 3''-methyl-SAA, and M26 was identified as 2-methyl-SAA or 3-methyl-SAA. Hydrolysis, methylation, glucuronidation, sulfation, and oxidation were the primary metabolism channels being responsible for the metabolites' generation.
CONCLUSION
Together, the metabolism regions and sites of SAA metabolites were sequentially identified based on the ester bond dissociation features and post-CID ER-MS strategy. Importantly, the present study provided a promising way to elevate the structural identification confidence of natural products and metabolites.
PubMed: 38671484
DOI: 10.1186/s13020-024-00931-z -
Dentistry Journal Apr 2024Panoramic radiography imaging modality is widely used by dentists for diagnosing dental and jaw conditions. It can also detect carotid artery calcification (CAC),...
Carotid Artery Calcification Detected on Panoramic Radiography Is Significantly Related to Cerebrovascular Accident, Coronary Artery Disease, and Poor Oral Health: A Retrospective Cross-Sectional Study.
Panoramic radiography imaging modality is widely used by dentists for diagnosing dental and jaw conditions. It can also detect carotid artery calcification (CAC), indicative of calcified atherosclerotic plaques in the carotid arteries. This cross-sectional retrospective study at the University of Tennessee Health Science Center investigated the link between CAC identified on panoramic radiograph (PR) and cerebrovascular accident (CVA), coronary artery disease (CAD), and poor oral health. Data from 314 CAC patients collected from 2014 to 2023 included age at diagnosis, gender, and clinical histories of hypertension, hyperlipidemia, diabetes mellitus, CVA, CAD, and the decay, missing, and filled permanent teeth (DMFT) index. These patients were age- and gender-matched with non-CAC patients for analysis. The findings revealed high prevalences of hypertension (86.2%), hyperlipidemia (57.6%), diabetes mellitus (30.7%), CVA (15.5%), and CAD (28.7%) amongst CAC patients and the average DMFT index was 26.6. A comparative analysis of 276 matched controls demonstrated significant differences in hypertension (85.9% vs. 57.6%), hyperlipidemia (58.3% vs. 33.7%), diabetes (32.6% vs. 22.1%), CVA history (14.9% vs. 5.1%), CAD (26.1% vs. 9.8%), and DMFT scores (26.3 vs. 23.7), all indicating strong associations between CAC and these health conditions. The adjusted analysis showed that hypertension (aOR: 3.20 [95% CI: 2.06-5.07]), hyperlipidemia (aOR: 1.70 [95% CI: 1.14-2.50]), CVA (aOR: 2.20 [95% CI: 1.13-4.30]), and CAD (aOR: 2.10 [95% CI: 1.28-3.60]) were significantly associated with CAC. Notably, only 41.7% of the patients received a medical consultation after CAC detection on PR. It is crucial for dentists to refer patients for further evaluation.
PubMed: 38668011
DOI: 10.3390/dj12040099 -
Nutrition, Metabolism, and... Jul 2024Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis...
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge.
METHODS AND RESULTS
Between January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed. On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage.
CONCLUSION
Switch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Middle Aged; Dyslipidemias; Biomarkers; Cholesterol, LDL; Risk Assessment; Atherosclerosis; Treatment Outcome; Time Factors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Heart Disease Risk Factors; Patient Discharge; Patient Admission; Risk Reduction Behavior; PCSK9 Inhibitors; Risk Factors; Hypolipidemic Agents; Aged, 80 and over; Practice Patterns, Physicians'; Proprotein Convertase 9
PubMed: 38664125
DOI: 10.1016/j.numecd.2024.03.007 -
Journal of Cardiovascular Computed... Apr 2024Among patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion...
BACKGROUND
Among patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCT) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCT among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion.
METHODS
AI-QCT was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream O-HO-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCT. Absolute stress myocardial blood flow ≤2.3 ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4-8.3] years.
RESULTS
662 of 768 (86%) patients had conclusive AI-QCT result. In patients with normal O-HO-PET perfusion, an abnormal AI-QCT result (n = 147/331) vs. normal AI-QCT result (n = 184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17-5.21, p = 0.018). This did not pertain to patients with abnormal O-HO-PET perfusion (abnormal AI-QCT result (n = 269/331) vs. normal AI-QCT result (n = 62/331); adjusted HR 1.09, 95% CI 0.58-2.02, p = 0.794) (p-interaction = 0.039).
CONCLUSION
Among patients with obstructive CAD on coronary CTA referred for downstream O-HO-PET perfusion imaging, AI-QCT showed incremental prognostic value among patients with preserved perfusion by O-HO-PET imaging, but not among those with reduced perfusion.
PubMed: 38664074
DOI: 10.1016/j.jcct.2024.04.001 -
Anatolian Journal of Cardiology Apr 2024The incidence and mortality of cardiovascular diseases, of which coronary heart disease (CHD) is a significant cardiovascular burden, are on the rise. Pyroptosis as an...
The incidence and mortality of cardiovascular diseases, of which coronary heart disease (CHD) is a significant cardiovascular burden, are on the rise. Pyroptosis as an incipient programmed cell death mediated by inflammasomes can sense cytoplasmic contamination or interference and is typically marked by intracellular swelling, plasma membrane blistering and intense inflammatory cytokine release. As research on pyroptosis continues to progress, there is mounting evidence that pyroptosis is a vital participant in the pathophysiological basis of CHD. Atherosclerosis is the major pathophysiological basis of CHD and involves pyroptosis of endothelial cells, macrophages, vascular smooth muscle cells, and other immune cells, often in association with the release of pro-inflammatory factors. When cardiomyocytes are damaged, it will eventually lead to heart failure. Previous studies have covered that pyroptosis plays a critical role in CHD. In this review, we describe the properties of pyroptosis, summarize its contribution and related targets to diseases involving angina pectoris, myocardial infarction, myocardial ischemia in perfusion injury and heart failure, and highlight potential drugs for different heart diseases.
PubMed: 38661060
DOI: 10.14744/AnatolJCardiol.2024.4001 -
JACC. Asia Apr 2024Depression is a known risk factor for cardiovascular disease (CVD), but the potential sex differences in this association remain unclear.
BACKGROUND
Depression is a known risk factor for cardiovascular disease (CVD), but the potential sex differences in this association remain unclear.
OBJECTIVES
The aim of this study was to investigate the association between depression and subsequent CVD events, and to explore potential sex differences.
METHODS
The authors conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4,125,720 individuals aged 18 to 75 years without a history of cardiovascular disease or renal failure and missing data at baseline. Participants were followed up for a mean of 1,288 days to assess the association between depression and subsequent CVD events, such as myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation.
RESULTS
Our analysis revealed a significant association between depression and subsequent composite CVD events in both men and women, with a stronger association observed in women. The HR for the composite endpoint was 1.64 (95% CI: 1.59-1.70) in women and 1.39 (95% CI: 1.35-1.42) in men after multivariable adjustment ( for interaction <0.001). Furthermore, the individual components of the composite endpoint were also associated with depression in both men and women, each of which was also observed to be more strongly associated in women.
CONCLUSIONS
Our study provides evidence of a significant association between depression and subsequent CVD events in both men and women, with a more pronounced association observed in women. These findings highlight the importance of addressing depression and tailoring prevention and management strategies according to sex-specific factors.
PubMed: 38660110
DOI: 10.1016/j.jacasi.2023.11.015 -
Journal of Cardiology Cases Apr 2024A 34-year-old man with a history of Kawasaki disease had been experiencing chest pain at rest since middle school. Multidetector-row computed tomography showed no...
UNLABELLED
A 34-year-old man with a history of Kawasaki disease had been experiencing chest pain at rest since middle school. Multidetector-row computed tomography showed no aneurysm formation; however, the right coronary artery had an anomalous origin with moderate stenosis. Invasive coronary angiography revealed moderate right coronary artery stenosis with a fractional flow reserve of 0.97. Finally, with a positive acetylcholine provocation test and elevated index of microvascular resistance, the patient was diagnosed with microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries. This is the first reported case of both microvascular and epicardial vasospastic angina after Kawasaki disease. In patients with a history of Kawasaki disease, even those without cardiac sequelae, coronary endothelial and microvascular dysfunctions should be taken into consideration.
LEARNING OBJECTIVE
We report the first case of both microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries after Kawasaki disease.Coronary endothelial and microvascular dysfunctions should be taken into consideration in patients with a history of Kawasaki disease, even those without cardiac sequelae.
PubMed: 38646083
DOI: 10.1016/j.jccase.2023.12.011 -
Cellular and Molecular Gastroenterology... Apr 2024Irritable bowel syndrome (IBS) shows genetic predisposition, and large-scale genome-wide association studies (GWAS) are emerging, based on heterogeneous disease...
BACKGROUND & AIMS
Irritable bowel syndrome (IBS) shows genetic predisposition, and large-scale genome-wide association studies (GWAS) are emerging, based on heterogeneous disease definitions. We investigated the genetic architecture of IBS defined according to gold standard Rome Criteria.
METHODS
We conducted GWAS meta-analyses of Rome III IBS and its subtypes in 24,735 IBS cases and 77,149 asymptomatic control subjects from 2 independent European cohorts (UK Biobank and Lifelines). Single-nucleotide polymorphism (SNP)-based heritability (h) and genetic correlations (r) with other traits were calculated. IBS risk loci were functionally annotated to identify candidate genes. Sensitivity and conditional analyses were conducted to assess impact of confounders. Polygenic risk scores were computed and tested in independent datasets.
RESULTS
Rome III IBS showed significant SNP-heritability (up to 13%) and similar genetic architecture across subtypes, including those with manifestations at the opposite ends of the symptom spectrum (r = 0.48 between IBS-D and IBS-C). Genetic correlations with other traits highlighted commonalities with family history of heart disease and hypertension, coronary artery disease, and angina pectoris (r = 0.20-0.45), among others. Four independent GWAS signals (P < 5×10) were detected, including 2 novel loci for IBS (rs2035380) and IBS-mixed (rs2048419) that had been previously associated with hypertension and coronary artery disease. Functional annotation of GWAS risk loci revealed genes implicated in circadian rhythm (BMAL1), intestinal barrier (CLDN23), immunomodulation (MFHAS1), and the cyclic adenosine monophosphate pathway (ADCY2). Polygenic risk scores allowed the identification of individuals at increased risk of IBS (odds ratio, 1.34; P = 1.1×10).
CONCLUSIONS
Rome III Criteria capture higher SNP-heritability than previously estimated for IBS. The identified link between IBS and cardiovascular traits may contribute to the delineation of alternative therapeutic strategies, warranting further investigation.
PubMed: 38643935
DOI: 10.1016/j.jcmgh.2024.04.002 -
Journal of Cardiothoracic Surgery Apr 2024Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of...
BACKGROUND
Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of SVA is insignificant, while ruptured SVA usually causes severe symptoms including heart failure and myocardial ischemia.
CASE PRESENTATION
We present an unusual case of a 64-year-old female manifesting with exertional dyspnea as well as angina pectoris for three months. Echocardiography and cardiac computed tomographic angiography confirmed unruptured left-coronary and non-coronary SVAs. The left anterior descending artery and left circumflex artery were stretched and compressed by the SVA which causing myocardial ischemia. The patient finally received aortic root replacement (Bentall procedure) and got symptom relieved.
CONCLUSIONS
Giant unruptured SVA originating from left coronary sinus is extremely rare. Our case highlights that giant SVA should be considered in cases with angina pectoris. Echocardiography and coronary computed tomographic angiography are useful and important for diagnosis. Surgery is highly recommended in patients with SVA.
Topics: Female; Humans; Middle Aged; Sinus of Valsalva; Aortic Aneurysm; Echocardiography; Tomography, X-Ray Computed; Angina Pectoris
PubMed: 38643125
DOI: 10.1186/s13019-024-02730-x -
Cureus Mar 2024We describe our first experience with the Triolifter (Fuji Systems, Yokohama, Japan) in cardiac surgery. The Triolifter is a less expensive, novel organ fixation device...
We describe our first experience with the Triolifter (Fuji Systems, Yokohama, Japan) in cardiac surgery. The Triolifter is a less expensive, novel organ fixation device developed as a fixation indenter mainly for traction of the lung under video-assisted surgery and is now available in Japan. An 84-year-old man diagnosed with unstable angina pectoris underwent emergency coronary artery bypass grafting (CABG) under cardiac arrest. Following the declamping of the aorta and the resumption of the beating heart, bleeding from the left anterior descending artery (LAD) anastomosis site was observed. The Triolifter was used as a heart positioner to expose the anastomosis site for hemostasis in the setting of an on-pump beating heart. Hemostasis of the posterior descending artery (PDA) anastomosis site could also be confirmed by traction of the right ventricular anterior wall using the Triolifter. It could be effectively and safely used with neither significant subepicardial hematoma nor epicardial injury. In Japan, the Triolifter might be used as one of the insurance-covered devices in off-pump CABG in the future, but globally, it could also be used in on-pump CABG without hesitation because it is so inexpensive.
PubMed: 38638758
DOI: 10.7759/cureus.56461