Cardiology and cardiovascular medicine最新文献

Atherosclerosis is a chronic inflammatory disease that leads to acute embolism via the formation of atherosclerotic plaques. Plaque formation is first induced by fatty deposition along the arterial intima. Inflammation, bacterial infection, and the released endotoxins can lead to dysfunction and phenotypic changes of vascular smooth muscle cells (VSMCs), advancing the plaque from stable to unstable form and prone to rupture. Stable plaques are characterized by increased VSMCs and less inflammation while vulnerable plaques develop due to chronic inflammation and less VSMCs. Oncostatin M (OSM), an inflammatory cytokine, plays a role in endothelial cells and VSMC proliferation. This effect of OSM could be modulated by p27^KIP1, a cyclin-dependent kinase (CDK) inhibitor. However, the role of OSM in plaque vulnerability has not been investigated. To better understand the role of OSM and its downstream signaling including p27^KIP1 in plaque vulnerability, we characterized the previously collected carotid arteries from hyperlipidemic Yucatan microswine using hematoxylin and eosin stain, Movat Pentachrome stain, and gene and protein expression of OSM and p27^KIP1 using immunostaining and real-time polymerase chain reaction. OSM and p27^KIP1 expression in carotid arteries with angioplasty and treatment with either scrambled peptide or LR12, an inhibitor of triggering receptor expressed on myeloid cell (TREM)-1, were compared between the experimental groups and with contralateral carotid artery. The results of this study elucidated the presence of OSM and p27^KIP1 in carotid arteries with plaque and their association with arterial plaque and vulnerability. The findings suggest that targeting OSM and p27^KIP1 axis regulating VSMC proliferation may have therapeutic significance to stabilize plaque.

Per- and polyfluoroalkyl substances (PFAS) are pervasive environmental pollutants frequently detected in drinking water worldwide. Reports linking PFAS exposure to cardiovascular disease have increased significantly in recent years. Furthermore, women appear to be more susceptible to the adverse effects of PFAS. However, the potential role of ovaries in the increased vulnerability of females to PFAS-related health effects remains unknown. In this study, we investigated the impact of perfluorooctane sulfonate (PFOS), a prominent PFAS, on the cardiovascular function in female rats with intact ovaries and ovariectomized (OVX) females. Bilateral OVX or sham surgeries were performed in 8-week-old female SD rats. Following recovery from surgeries, the rats were given drinking water containing 50 μg/mL of PFOS for 3 weeks. Control groups received PFOS-free water. PFOS exposure significantly reduced body weight but increased blood pressure similarly in both intact and OVX rats. Echocardiography analysis revealed that PFOS exposure decreased cardiac output, end-systolic volume, and end-diastolic volume in intact but not OVX rats. Vascular function studies demonstrated that PFOS equally reduced endothelium-dependent and -independent relaxation responses in intact and OVX rats. The endothelium-independent contractile responses were more pronounced in both intact and OVX rats. eNOS protein levels were similarly decreased in both intact and OVX rats. In conclusion, PFOS affects cardiac function through hormone-dependent mechanisms, while vascular function is impaired independent of ovarian status, indicating an intricate interplay between PFOS exposure, ovarian status, and cardiovascular function.

Importance: Improved pre-operative risk stratification methods are needed for targeted risk mitigation and optimization of care pathways for cardiac patients. This is the first report demonstrating pre-operative, aging-related biomarkers of cellular senescence and immune system function can predict risk of common and serious cardiac surgery-related adverse events.

Design: Multi-center 331-patient cohort study that enrolled patients undergoing coronary artery bypass grafing (CABG) surgery with 30-day follow-up. Included a quaternary care center and two community-based hospitals. Primary outcome was KDIGO-defined acute kidney injury (AKI). Secondary outcomes: decline in eGFR ≥25% at 30d and a composite of major adverse cardiac and kidney events at 30d (MACKE30). Biomarkers were assessed in blood samples collected prior to surgery.

Results: A multivariate regression model of six senescence biomarkers (p16, p14, LAG3, CD244, CD28 and suPAR) identified patients at risk for AKI (NPV 86.6%, accuracy 78.6%), decline in eGFR (NPV 93.5%, accuracy 85.2%), and MACKE30 (NPV 91.4%, accuracy 79.9%). Patients in the top risk tertile had 7.8 (3.3-18.4) higher odds of developing AKI, 4.5 (1.6-12.6) higher odds of developing renal decline at 30d follow-up, and 5.7 (2.1-15.6) higher odds of developing MACKE30 versus patients in the bottom tertile. All models remained significant when adjusted for clinical variables.

Conclusions: A network of senescence biomarkers, a fundamental mechanism of aging, can identify patients at risk for adverse kidney and cardiac events when measured pre-operatively. These findings lay the foundation to improve pre-surgical risk assessment with measures that capture heterogeneity of aging, thereby improving clinical outcomes and resource utilization in cardiac surgery.

Cardiovascular diseases are the leading cause of mortality worldwide, with a disproportionately high burden in low- and middle-income countries. Biomarkers play a crucial role in the early detection, diagnosis, and treatment of cardiovascular diseases by providing valuable insights into the normal and abnormal conditions of the heart and vascular system. The biomarkers derived from the cells and tissues can be identified and quantified in the blood and other body fluids and in tissues. Changes in their expression level under a pathological condition provide clinical information on the underlying pathophysiology that could have predictive, diagnostic, and prognostic value in the treatment of a disease process, and therefore incorporated in clinical guidelines. This enhances the effectiveness of biomarkers in risk stratification and therapeutic decisions in personalized medicine and improvement in patient outcomes. Biomarkers could be protein, carbohydrate, or genome-based and may also be derived from lipids and nucleic acids. Computational biology has emerged as a powerful discipline in biomarker discovery, leveraging computational techniques to identify and validate biological markers for disease diagnosis, prognosis, and drug response prediction. The convergence of advanced technologies, such as artificial intelligence, multi-omics profiling, liquid biopsies, and imaging, has led to a significant shift in the discovery and development of biomarkers, enabling the integration of data from multiple biological scales and providing a more comprehensive understanding of the complex signaling and transcriptional networks underlying disease pathogenesis. In this article, we reviewed the role of computational biology integrated with genomics, proteomics, and metabolomics, together with machine learning techniques and predictive modeling and data integration in the discovery of biomarkers in cardiovascular diseases. We discussed specific biomarkers, including epigenetic, metabolic, and emerging biomarkers, such as extracellular vesicles, miRNAs, and circular RNAs, and their role in the pathophysiology of the heart and vascular diseases.

Background: Timely detection of atrial fibrillation (AF) is critical for stroke prevention. Smartwatches are FDA-approved devices that can now aide in this detection.

Objective: Investigate how socioeconomic status is associated with self-reported psychosocial outcomes, including anxiety, patient activation, and health-related quality of life in stroke survivors using smartwatch for AF detection.

Methods: We analyzed data from the Pulsewatch study, a randomized controlled trial (NCT03761394). Participants in the intervention group wore a cardiac patch monitor in addition to a smartwatch for AF detection, whereas the control group wore only the cardiac patch monitor. Generalized anxiety disorder-7 scale, Consumer Health Activation Index and short-form health survey were completed to assess anxiety, patient activation, physical and mental health status at baseline, 14, and 44 days. We used a longitudinal linear regression model to examine changes in psychosocial outcomes in low (<$50K) vs. high (>$50K) income groups.

Results: A total of 95 participants (average age 64.9± 9.1 years; 57.9% male; 89.5% non-Hispanic white) were included. History of renal disease (p-value 0.029), statin use (p-value 0.034), depression (p-value 0.004), and anxiety (p-value <0.001), were different between the income groups. In the adjusted model, the low-income group was associated with increased anxiety (β 2.75, p-value 0.0003), and decreased physical health status (β -5.07, p-value 0.02). There was no change identified in self-reported patient engagement and mental health status score.

Conclusion: Our findings demonstrate that low SES is associated with worse self-reporting of physical health status, and this may influence psychosocial outcomes in smartwatch users.

Universally, stroke presents as neurological deficits due to the obstruction of blood supply to specific regions of the brain. Among the three main categories of stroke, acute ischemic stroke is the leading cause of death and disability worldwide. As of today, there are two effective treatment methods: thrombolysis and endovascular therapy. Intravenous thrombolysis treatment via tissue plasminogen activator is typically administered within 4.5 hours from the onset of symptoms. Mechanical thrombectomy, a type of endovascular therapy, is indicated for acute ischemic stroke due to a large vessel occlusion occurring within 24 hours since the patient was last seen asymptomatic. Due to the disadvantages of intravenous thrombolysis treatment, such as a limited time window and numerous contraindications, studies have proven the efficacy of mechanical thrombectomy as the standard of care for acute ischemic stroke due to large vessel occlusion in the anterior circulation. Endovascular therapy was associated with higher rates of independent clinical outcome and successful reperfusion rates compared to intravenous thrombolysis treatment. Currently, stent retrievers and aspiration devices are the two most common endovascular therapy techniques. Two prominent studies compared the reperfusion rates between these two techniques, but neither was found to be more beneficial than the other. The decision to use either a stent retriever or direct aspiration depends on the patient and the thrombus involved. This comprehensive article critically discusses the findings on the efficacy of mechanical thrombectomy therapy for acute ischemic stroke and its associated outcomes and complications.

Both ischemic and hemorrhagic strokes are critical health issues and the incidence is on the rise. The rapid neurological degeneration that can occur with either type of stroke warrants prompt medical attention. In the article, we critically reviewed the literature examining their incidence, pathophysiology, and present treatment strategies. Clinical trials show conflicting findings, with ischemic strokes accounting for 87% of all strokes. Brain injury following an ischemic stroke results in cell death and necrosis, immune cells being the primary actors in the process of neuroinflammation. In order to develop neuroprotective drugs against ischemic stroke, detailed investigation of glutamate production and metabolism as well as downstream pathways controlled by glutamate receptors provides significant information on the underlying mechanisms. The permeability of the blood-brain barrier and the degradation of glutamine synthase are two potential mechanisms by which peritoneal dialysis accelerates brain-to-blood glutamate clearance and thus reduces glutamate levels in the brain after a stroke. Oxidative stress in an ischemic stroke disturbs the oxidant-antioxidant balance, which is particularly problematic for brain cells that are high in polyunsaturated fatty acids. Because of demographic factors like age, sex, race/ethnicity, and socioeconomic status, the incidence and prevalence of stroke differ across people and regions. For rapid diagnosis and treatment decisions, diagnostic imaging tools such as vascular imaging, CT, and MRI are essential. To aid in the recovery and lessen neurological impairments following a stroke, novel avenues of research are under investigation on neuroprotective medications that target inflammation, oxidative stress, and neuronal death.

Hypercholesterolemia is a major risk factor for atherosclerosis as oxidized-low-density lipoproteins (ox-LDL) contribute to the formation of foam cells and inflammation. Increased immune cell infiltration and oxidative stress induce instability of a plaque. Rupture of the unstable plaque precipitates adverse ischemic events. Since reactive oxygen species (ROS) play a critical role in plaque formation and vulnerability, regulating ROS generation may have therapeutic potential. Sirtuins, specifically sirtuin-3 (SIRT3), are antigenic molecules that can reduce oxidative stress by reducing mitochondrial ROS production through epigenetic modulation. Lack of SIRT3 expression is associated with dysregulation of ROS and endothelial function following high-fat high-cholesterol diet. SIRT3 deacetylates FOXO3a (Forkhead transcription factor O subfamily member 3a) and protects mitochondria against oxidative stress which can lead to even further protective anti-oxidizing properties. This study was designed to investigate the association between hyperlipidemia, intimal injury, chronic inflammation, and the expression of NAD-dependent deacetylase SIRT-3, FOXO3, antioxidant genes, and oxidative stress in carotid arteries of hypercholesterolemic Yucatan microswine. We found that intimal injury in hypercholesterolemic state led to increased expression of oxidative stress, inflammation, neointimal hyperplasia, and plaque size and vulnerability, while decreasing anti-oxidative regulatory genes and mediators. The findings suggest that targeting the SIRT3-FOXO3a-oxidative stress pathway will have therapeutic significance.

Background: Patients with PR intervals >240ms have atrio-ventricular (AV) dyssynchrony, which can increase risk of atrial fibrillation and all-cause mortality. When requiring pacing, long AV delays (AVDs) have been programmed to avoid ventricular dyssychrony. His bundle pacing (HBP) may provide improved AV synchrony in patients with prolonged PR.

Methods: 10 patients with sinus node dysfunction and prolonged PR who received HBP were studied. Real-time echocardiographic was performed with 3 pacemaker modes (RV septal, non-selective HBP, and selective HBP) using the following pacemaker settings: control (no ventricular pacing), pacing with AVD of 180ms, 150ms, 120ms, 100ms, and 70ms. Echocardiographic Doppler measurements: EA/RR, >40% = AV synchrony; E/e', <8 = normal left atrial pressure; pulmonic-to-aortic pre-ejection time difference, <40ms = interventricular synchrony; septal-to-lateral wall activation time difference, <56ms = intraventricular synchrony; and LVOT VTI. Unpaired T test was used to evaluate for significance. Exclusion criteria: persistent atrial fibrillation, second-degree AV block.

Results: Compared to control programming, HBP showed a 31.5% increase in EA/RR time, a decrease in E/e' of 26.9%, and an increase in the LVOT VTI of 21.3%. Compared to RV septal pacing, there was a similar increase in LVOT VTI. These findings met statistical significance and were considered optimal based on Doppler echocardiography findings primarily at AVDs of 150ms and 120ms. Comparisons between selective and non-selective pacing were not significantly different.

Conclusion: Compared to controls and RV septal pacing, physiologic His bundle pacing was shown to increase markers of AV synchrony and LV stroke volume while maintaining ventricular synchrony.