Search Results (2,304)

Cardiovascular disease is traditionally interpreted through macrocirculatory parameters such as cardiac output, vascular resistance, and epicardial coronary anatomy. However, clinical outcomes frequently diverge from predictions based solely on these indices, particularly in syndromes such as heart failure with preserved ejection fraction (HFpEF), cardiogenic shock, and sepsis-associated myocardial dysfunction. Increasing evidence suggests that the integrity of the microvascular–immune interface plays a central role in determining tissue perfusion and cardiovascular resilience. This review proposes a staged framework of cardiovascular decompensation centered on progressive failure of this interface. In Stage 1, chronic cardiometabolic and inflammatory stress produces a primed but compensated microvascular state characterized by endothelial activation, glycocalyx vulnerability, pericyte remodeling, platelet sensitization, and reduced lymphatic reserve. Perfusion is preserved at rest, but vasodilatory reserve and microvascular stability are reduced, narrowing the effective perfusion window under physiologic stress. In Stage 2, acute insults such as infection, ischemia, or neurohumoral activation precipitate threshold instability within the microcirculation. Perfusion becomes governed by the arterial pressure–critical closing pressure (Pa − Pcrit) relationship rather than traditional arterial–venous gradients. As this window narrows, segmental capillary derecruitment and heterogeneous flow emerge, producing loss of hemodynamic coherence in which systemic blood pressure and cardiac output may appear preserved despite impaired tissue perfusion. In Stage 3, inflammatory amplification and immunothrombotic processes consolidate microvascular dysfunction. Pericyte contraction, endothelial injury, cytokine escalation, and neutrophil extracellular trap formation promote platelet–fibrin deposition and capillary obstruction, transforming reversible conductance failure into structural microvascular impairment. This framework provides a unifying physiologic lens for diverse cardiovascular syndromes, including Type 2 myocardial infarction, HFpEF decompensation, and cardiogenic shock. It also suggests that therapeutic efficacy may depend less on macrocirculatory normalization alone and more on preserving microvascular integrity before immunothrombotic consolidation occurs. Although this model remains hypothesis-generating, it highlights the microvascular–immune interface as a central determinant of cardiovascular stability and a potential target for future precision hemodynamic and immunomodulatory strategies. Full article

Obstructive sleep apnea (OSA) is a sleep-disordered breathing condition characterized by recurrent upper-airway obstruction, leading to intermittent hypoxemia, sleep fragmentation, and sympathetic activation. OSA is highly prevalent in patients with cardiovascular diseases and is strongly associated with hypertension, atrial fibrillation, coronary artery disease, heart failure, and adverse prognosis. This review summarizes current evidence on the pathophysiology of OSA, its cardiovascular consequences, and available diagnostic and therapeutic strategies, with particular attention to clinical implications in cardiology practice. We discuss established treatments such as lifestyle interventions, continuous positive airway pressure, mandibular advancement devices, and selected surgical options, as well as emerging therapies, including pharmacological approaches targeting weight loss and ventilatory control. While OSA treatment improves symptoms and quality of life, evidence for cardiovascular event reduction remains heterogeneous and appears strongly influenced by patient selection and treatment adherence. Identifying patients most likely to benefit from targeted OSA management remains a key challenge. Full article

Aims: Coronary heart disease (CHD) associated with rheumatoid arthritis (RA) is a primary driver of mortality in RA patients. In this study, we sought to establish a combined rat model of CHD and RA by integrating cardiac ischemia/reperfusion (I/R), high-fat diet (HFD), and intradermal administration of bovine type II collagen emulsified in complete Freund’s adjuvant. The aim of constructing this model is to investigate and analyze the pathogenesis of RA-induced CHD under the modulation of HFD and cardiac I/R exposure. Methods and Results: Sixty-four male Sprague–Dawley rats were randomly categorized into eight groups (n = 8 per group): control, I/R, HFD, collagen-induced arthritis (CIA), I/R + CIA, HFD + CIA, I/R + HFD, and I/R + HFD + CIA groups (n = 8 per group). We applied Synchrotron radiation-based X-ray micro-computed tomography (micro-CT) to observe the structural changes within the model over time. To further elucidate molecular mechanisms, transcriptome RNA-seq analysis was carried out to identify key signaling pathways, with particular emphasis on the homeostasis of Toll-like receptor 4 (TLR4)/Myd88 signaling in the ischemic myocardium. Furthermore, we conducted in vivo shRNA-mediated knockdown of polymerase I and transcription release factor (PTRF) and evaluated the co-localization of PTRF and TLR4 through immunofluorescence experiments. It is worth mentioning that our rat model of RA-induced (CHD) under a high-fat diet effectively manifested the relevant pathological features that align with the Traditional Chinese Medicine (TCM) definition of “bi” syndrome. The results indicate that the combined stimulation of HFD and CIA significantly elevated cardiac injury markers (CK-MB, LDH, CRP, and c-TNT) and was accompanied by a more severe expansion of the infarct area and increased cardiomyocyte apoptosis compared to the I/R group alone. In addition, the histopathological evaluation revealed significantly aggravated myocardial inflammation and fibrosis deposition, accompanied by extensive areas of tissue damage, further indicating a state of heightened inflammation and severe cardiac degenerative changes. Consistently, myocardial tissues from rats in the I/R + CIA + HFD group exhibited robust activation of the TLR4/MyD88 signaling pathway and a pronounced elevation in the p-JNK/JNK ratio. Moreover, pronounced co-localization between PTRF and TLR4 was evident in small vessels surrounding the infarcted myocardium. Importantly, AAV-mediated knockdown of PTRF attenuated the HFD- and CIA-induced exacerbation of myocardial injury in I/R rats. Conclusions: We successfully established a rat model of CHD with rheumatic syndrome using I/R in combination with RA and HFD. The present findings suggest that the PTRF-related TLR4/MyD88-JNK signaling pathway may act as an important regulatory mechanism underlying myocardial injury aggravated by combined HFD and CIA stimulation. Full article

Background/Objectives: Epidemiological studies over the first decades of the 21st century have reported a decrease in cardiovascular disease (CVD) morbidity and mortality. Changes in coronary care for acute myocardial infarction (AMI) over these years, including the COVID-19 pandemic period, have been less studied in Eastern and Central Europe. The study aimed to assess changes in coronary care—the time of medical assistance and treatment—for AMI patients over 2000–2023 in urban Kaunas residents aged 25–64. Methods: The data source was study cases from the Kaunas Ischemic Heart Disease Registry (Registry)—Kaunas city residents aged 25–64 years included in the Registry according to MONICA project protocol evaluation methodologies. Data were analyzed by sex and age group (25–54 and 55–64 years). Descriptive statistics (chi-square and z-score values) were used to evaluate the data; the significance level was p < 0.05. A logistic regression analysis was performed to assess the odds ratios of death within 28 days across six time periods. Results: The proportion of AMI patients hospitalized up to 2 h from the onset of pain accounted for about one-fifth of all hospitalized patients in 2000–2016, while in 2017–2023, it significantly decreased. In 2017–2023, compared with 2000–2004 and 2009–2016, significantly fewer men who developed AMI were hospitalized within the first 2 h of emergency presentation (p < 0.05). Over the whole study period, fewer women with AMI were hospitalized within the first 2 h of pain as compared to men (p < 0.05). There were no significant differences in time from pain onset to hospitalization between the age groups. At the same time, from 2009 to 2012, more young AMI patients were hospitalized within the first 2 h (p < 0.05). Percutaneous coronary angioplasty (PTCA) with stenting (PCI) increased 30 times from 2000–2004 to 2020–2023. PCI has been the most available treatment for men with AMI since 2009 and stayed stable from 2013 (66.0%) until 2023 (72.1%). Women with AMI tended to get less PCI, PTCA, and coronary artery bypass grafting (CABG) than men. The pre-pandemic and COVID-19 periods did not differ in the proportions of reperfusion treatment methods used in both men and women. Thrombolysis was very rare, and since 2017, it has not been used in Kaunas because PCI has become more accessible. PCI (2000–2016) and CABG (2009–2016) were more prevalent among the 25–54-year-old AMI patients (p < 0.05). From 2017 to 2023, there were no differences between age groups in the reperfusion procedures used, nor were there differences in treatment between these groups during the pre-pandemic (2017–2019) and peri-COVID-19 pandemic (2020–2023) periods. Conclusions: In Kaunas, the treatment of patients with AMI has improved significantly over the past 20 years. The use of PCI has increased greatly, and the rate of CABG surgery stayed stable, while only every fifth patient has been admitted to the hospital in a timely manner. Men were more likely to receive PCI, and older patients were more likely to undergo CABG. Compared to the period of 2000–2004, the chance of dying within 28 days after AMI was significantly lower in 2017. Full article

Kawasaki disease (KD) represents the foremost cause of acquired pediatric heart disease, with coronary artery injury being the principal factor contributing to adverse prognoses. A significant clinical challenge is that 20–30% of patients demonstrate resistance to intravenous immunoglobulin (IVIG), which markedly elevates the risk of coronary artery lesions and long-term cardiovascular sequelae. Consequently, there is an urgent need to investigate novel pathogenic mechanisms beyond the conventional cytokine storm theory and to identify effective therapeutic targets. This review systematically summarizes the key role of the autophagy–inflammation axis in KD vasculopathy. Current evidence indicates that defective mitophagy and lysosomal dysfunction induce mitochondrial DNA release, resulting in overactivation of the NLRP3 inflammasome and cGAS-STING pathways, which amplify inflammatory responses and aggravate endothelial damage. The regulation of this axis is dynamic during both the acute and recovery phases and is influenced by metabolic reprogramming and epigenetic modifications, which may partially explain the lack of response to IVIG. Pharmacological agents, such as rapamycin and metformin, as well as natural compounds, such as resveratrol and urolithin A, have demonstrated beneficial anti-inflammatory effects in preclinical studies. Targeting the autophagy–inflammation axis represents a significant research direction with the potential to evolve into a promising therapeutic strategy. Mechanistically, restoring the balance of the autophagy–inflammation axis holds promise for mitigating coronary complications and improving long-term cardiovascular outcomes in children with KD; however, this prospect requires validation through prospective clinical studies. Full article

Background: Coronary computed tomography angiography (cCTA) is now indicated as a non-invasive tool for ruling out obstructive coronary artery disease (O-CAD) in patients who are candidates for transcatheter aortic valve implantation (TAVI) showing low-intermediate pre-test probability of O-CAD. In elderly and comorbid TAVI candidates, the safety and accuracy of cCTA as an alternative to invasive coronary angiography (ICA) for ruling out O-CAD remain to be established. Aim: To assess the feasibility, diagnostic accuracy, and clinical safety of cCTA for ruling out proximal O-CAD in elderly, comorbid, high-risk patients undergoing TAVI. Methods: We conducted a retrospective, single-center study including all consecutive patients with severe symptomatic aortic stenosis who underwent TAVI between January 2019 and December 2020. All patients underwent pre-TAVI cCTA. Patients with positive or non-diagnostic cCTA underwent ICA selectively (ICA group). In patients with no-O-CAD, ICA was omitted and proceeded directly to TAVI (no-ICA group). Accordingly, patients were divided into two groups: no-ICA and ICA group. Clinical follow-up was extended up to 5 years, with assessment of major adverse cardiovascular events (MACEs), mortality, heart failure hospitalizations, and unplanned revascularization. Results: Among 355 patients enrolled, 210 were included in the study. Among them, 140 (66.7%) had negative cCTA for O-CAD, and ICA was safely omitted in 132 patients (62.8%). cCTA was inconclusive in 43 patients (20.5%) and positive in 27 (12.9%). ICA confirmed O-CAD in 53 of 78 patients (67.9%) and PCI was performed in 35 of 53 (66.0%). The accuracy of cCTA for ruling in O-CAD was low (66.28%). During the follow-up period (1513 ± 508 days), the no-ICA group showed comparable outcomes to the ICA group in terms of periprocedural complications and long-term results—at both 1 and 5 years—for MACEs, heart failure hospitalizations, mortality and unplanned revascularization. Outcomes remain comparable between the two groups after performing matched-pair analyses. Conclusions: Our data show that cCTA may provide a reliable, safe, and effective alternative to ICA for ruling out obstructive CAD in elderly patients undergoing TAVI when image quality is diagnostic. A cCTA-based strategy allows deferral of ICA in most cases without compromising procedural safety or long-term clinical outcomes, enabling a personalized and tailored clinical pathway. Whether advanced CT techniques, such as CT-FFR and photon-counting CT, may help refine patient selection for invasive coronary assessment remains to be demonstrated. Full article

Background and Clinical Significance: Bicuspid aortic valve (BAV) is the most common congenital heart defect and may coexist with other cardiovascular anomalies. Among these is a single coronary artery (SCA), a rare congenital condition in which the entire coronary circulation originates from a single coronary ostium. Cardiac computed tomography (CCT) enables simultaneous evaluation of coronary artery anatomy and aortic valve morphology with high spatial resolution, which may influence procedural strategy in patients undergoing valve interventions. Case Presentation: This report represents the first documented case of a 59-year-old male with mixed aortic valve disease in whom preoperative CCT revealed the coexistence of BAV, SCA (Lipton type L-I), and myocardial bridging (MB) involving the mid segment of the left anterior descending artery (LAD). Identification of these findings was crucial for preoperative assessment and contributed to the selection of an appropriate surgical strategy. Conclusions: CCT plays a key role in the preoperative evaluation of valvular heart disease, including in patients with coexisting BAV and SCA. It enables individualized procedural planning and minimizes the risk of perioperative complications. Full article

Objective: The prevalence of coronary heart disease (CHD) continues to rise, and there is a lack of methods for early detection. To identify biomarkers for CHD, we analyzed the CACNA2D1 protein concentration in patients with different degrees of coronary artery stenosis to explore the correlation between plasma CACNA2D1 protein concentration and the severity of coronary artery stenosis. Methods: A total of 267 inpatients from the Department of Cardiology at Dalian Central Hospital who underwent coronary angiography were consecutively enrolled. According to the degree of stenosis, they were divided into four groups: minimal stenosis (70 cases), mild stenosis (68 cases), moderate stenosis (66 cases), and severe stenosis (63 cases). The baseline characteristics, clinical laboratory indicators, and CACNA2D1 protein concentration in blood samples of patients in each group were compared, and the correlations were analyzed. Results: As the degree of coronary artery stenosis worsened, plasma CACNA2D1 protein concentration in patients showed a gradual upward trend. The protein concentration was lowest in the mild stenosis group, at 37.68 ng/mL; it was 45.46 ng/mL in the mild-to-moderate stenosis group; it reached 55.22 ng/mL in the moderate stenosis group; and it was highest in the severe stenosis group, at 79.95 ng/mL. Conclusion: There is a correlation between plasma CACNA2D1 protein concentration and the degree of coronary artery stenosis, demonstrating that it has the potential to serve as a biomarker. Full article

Objective: Atherosclerotic renal artery stenosis (ARAS) is increasingly prevalent among aging populations and in patients with diabetes, hyperlipidemia, aortoiliac obstructive disease, coronary artery disease, and/or hypertension. Patients with severe ARAS are at a substantially elevated risk of cardiovascular disease, recurrent congestive heart failure, stroke, ischemic nephropathy, and chronic kidney disease. Therefore, the ARAS-TR study aims to evaluate the effect of renal artery stenting on the clinical outcomes in patients with severe ARAS and renovascular hypertension. Materials: This study was conducted as a multicenter, prospective study between July 2024 and September 2025. It encompassed 278 patients with angiographically confirmed severe ARAS who underwent renal artery stent implantation. Patients were subsequently monitored for 6 months. A paired-samples t-test was used to compare continuous variables pre- and post-intervention, while categorical variables were analyzed using the Pearson chi-square test and Fisher’s exact test. Results: The mean age of the patients was 63.6 [±13.4] years, and the male gender ratio was 52.5%. After renal artery stenting, systolic and diastolic blood pressures decreased significantly at the 6-month follow-up compared with the pre-procedure levels (SBP 166.99 [21.24] vs. 135.40 [15.69], p < 0.001; DBP 96.28 [13.03] vs. 80.39 [11.03], p < 0.001, respectively). GFR (61.23 [28.33] vs. 63.35 [26.36], p = 0.029) and creatinine (1.40 [0.93] vs. 1.29 [0.66], p = 0.004) levels improved compared to baseline. The mean number of antihypertensive drugs required for patients to remain normotensive decreased significantly (3.19 [1.04] vs. 2.48 [1.13], p < 0.001) during the follow-up period. Conclusions: Percutaneous renal artery intervention appears to be a promising and safe strategy for carefully selected high-risk patients presenting with severe ARAS, renovascular hypertension, and non-atrophic kidneys. In this specific clinical context, restoring renal artery patency through percutaneous stenting was associated with improved renal function and observed reduction in the burden of antihypertensive drugs required to sustain normotension. Full article

Gut microbiome composition influences cardiovascular drug efficacy and safety, yet its integration into heart failure (HF) management remains underexplored. Alterations in intestinal microbial communities have been linked to atherosclerosis, coronary artery disease, heart failure, and hypertension through multiple mechanisms. Dysbiosis disrupts the balance between commensal and pathogenic bacterial species, impairing gut barrier function and activating inflammatory pathways. The altered microbial ecosystem modulates the production of key metabolites—such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acids (BAs)—that directly impact cardiovascular function. This narrative review synthesizes current evidence on bidirectional interaction between heart failure pharmacotherapy and gut microbiome composition. Commonly used drugs in heart failure management show microbiome-dependent pharmacokinetics. Digoxin undergoes bacterial inactivation by Eggerthella lenta, while angiotensin converting enzyme inhibitors and beta-blockers demonstrate enhanced efficacy with specific Firmicutes populations. Conversely, certain probiotic strains attenuate drug-induced gut barrier injury and restore gut homeostasis. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists, and angiotensin receptor–neprilysin inhibitors exhibit beneficial microbiome-modulating effects beyond their primary cardiovascular actions. These findings underscore the potential for microbiome-informed precision medicine in heart failure. However, significant methodological challenges must be addressed, including lack of standardization in microbiome profiling, small sample sizes, and limited longitudinal data. Future research should focus on identifying specific microbial signatures that predict drug response, developing targeted probiotic interventions, and conducting prospective clinical trials to validate pharmacomicrobiomics approaches in heart failure management. Full article

Colchicine has emerged as a prominent anti-inflammatory candidate in cardiovascular medicine, supported by a hierarchy of evidence spanning chronic and acute coronary syndromes, post-myocardial infarction care, revascularization, atrial fibrillation, pericardial disease, heart failure, peripheral arterial disease, and mechanistic translational models. Across this literature, the most mature study architecture and the strongest clinical support are derived from completed randomized trials in chronic coronary disease and secondary prevention, where colchicine has been shown to prevent major cardiovascular events (MACEs) when added to standard of care. The clearest clinical benefits are the reduction in non-fatal ischemic events in atherosclerotic disease, prevention of recurrent pericarditis and postoperative atrial fibrillation, and attenuation of inflammatory and plaque-related markers. By contrast, mixed or lower-tier evidence renders its application less consistent in acute coronary syndromes, ST-elevation MI (STEMI), percutaneous coronary intervention (PCI)-related hard outcomes, and heart failure, while a definitive mortality benefit has not been demonstrated. Overall, colchicine is best understood as a targeted clinical adjunct whose value depends heavily on precise indication, timing, dose, gastrointestinal tolerability, and the maturity of the supporting evidence. Full article

Background: Anticoagulation management in very elderly patients with atrial fibrillation (AF) is particularly challenging due to the coexistence of high thromboembolic and bleeding risks, often compounded by multiple comorbidities. Randomized clinical trials rarely include patients aged ≥85 years, leaving important gaps in our understanding of how anticoagulant therapies are selected in this growing population. Methods: We analyzed data from the CRAFT registry, including 2914 patients hospitalized with AF. Patients were stratified into two age groups: <85 years (n = 2322) and ≥85 years (n = 592). Baseline clinical characteristics, comorbidities, and laboratory parameters were compared between groups. Separate multivariable logistic regression analyses were performed for each age group to identify independent predictors of anticoagulant therapy selection. Results: Patients aged ≥85 years exhibited a distinct clinical profile, characterized by higher thromboembolic risk and a greater prevalence of heart failure, renal dysfunction, anemia, and structural heart disease. Renal function was significantly impaired (median eGFR 47.6 vs. 60.0 mL/min; p < 0.001), while NT-proBNP levels were higher and hemoglobin levels lower in this group. Multivariable analysis revealed clear age-related differences in determinants of treatment selection. In patients < 85 years, anticoagulant choice was influenced by multiple clinical factors, including CHA₂DS₂-VA score, renal function, bleeding risk, coronary artery disease, and prior revascularization. In contrast, in patients ≥ 85 years, only two independent predictors remained significant: thromboembolic risk (CHA₂DS₂-VA score; OR 1.34, 95% CI 1.11–1.64) and renal function (eGFR; OR 0.64, 95% CI 0.47–0.89). Anticoagulation in this group was predominantly based on reduced-dose DOACs, with apixaban used most frequently. Conclusions: Very elderly patients with AF represent a clinically distinct, high-risk population. While anticoagulant selection in younger elderly patients reflects a multifactorial decision process, treatment in those aged ≥85 years appears to rely primarily on thromboembolic risk and renal function, suggesting a more streamlined—and potentially oversimplified—approach. Full article

Heart failure (HF) and myocardial infarction (MI) are interconnected syndromes with overlapping pathogenic pathways, including ischemia, neurohormonal activation, and maladaptive remodeling. Hypoxia-response genes, lipid-handling genes, and extracellular matrix (ECM) genes each influence these processes. Understanding their integrated roles can uncover biomarkers and targets. A systematic literature search was conducted (PubMed, Web of Science, and Scopus; 2000–2026; English-only, following PRISMA guidelines) to identify studies on key genes in hypoxia signaling, lipid metabolism, and ECM remodeling in MI/HF. Acute hypoxia (via HIFs) orchestrates metabolic adaptation and inflammation, but chronic HIF activation drives fibrosis and dysfunction. In parallel, genes controlling triglyceride and cholesterol handling (e.g., LPL, APOC3) influence energy supply and vascular risk. Variants in these genes modulate plasma lipids and MI/HF risk. For example, genetic loss-of-function in APOC3 lowers triglycerides and reduces coronary risk. ECM-related genes (e.g., COL4A1, LRP1) govern fibrosis and vascular integrity. Mutations in COL4A1 cause cardiomyocyte hypertrophy and severe fibrosis, while LRP1 regulates matrix remodeling and is upregulated in ischemic myocardium. Throughout, gene functions span acute repair versus chronic maladaptation. Findings derive from mixed sources: rodent models and cell studies demonstrate mechanistic links, while human genetics and cohorts link gene variants to HF/MI outcomes. Many promising biomarkers (e.g., circulating ITGA1) are preliminary, lacking large prospective validation. Not all cited therapeutic ideas have been tested in the treatment of human cardiac disease. The literature mix of species, models, and patient cohorts introduces heterogeneity. Full article

Background: Necrotizing fasciitis (NF) is a rapidly progressing and life-threatening soft tissue infection. It commonly affects the extremities and is triggered by trauma, surgical wounds or compromised skin integrity. Although there have been advancements in diagnosis and treatment, NF continues to be a complex condition due to comorbidities and the wide range of involved pathogens. The aim of this study was to assess the epidemiology, risk factors, and outcomes of NF in Switzerland, focusing on the distinction between polymicrobial and monomicrobial infections and their associated management. Methods: This monocentric retrospective study analyzed 75 patients treated for intraoperatively confirmed NF from 2010 to 2022. Data collection included demographic and clinical variables, comorbidities, and laboratory results. Univariate and multivariate statistical tests were conducted to assess associations between mortality and different infection types. Results: NF was most commonly localized in the lower extremities (52% of cases). Nearly all patients (99%) had at least one comorbidity, with coronary heart disease, kidney disease, and liver disease being most frequently observed. Advanced age was associated with higher in-hospital mortality (OR (odds ratio) 3.80, p = 0.033, q = 0.500, 16 of 44 patients over 60 died), and the overall in-hospital mortality in the cohort was 27%. Kidney disease and smoking were associated with polymicrobial infections, with an OR of 6.60 (p = 0.016, q = 0.130) and 5.60 (p = 0.009, q = 0.130), respectively. Trauma was associated with monomicrobial streptococcal infections (OR 3.40, p = 0.029, q = 0.500), and showed a significant association with Streptococcus pyogenes infections (OR 8.10, p < 0.001, q = 0.004). Conclusions: This study highlights advanced age, trauma, kidney disease and smoking as factors associated with worse outcomes and specific infection patterns in patients with NF. These findings, derived from a Swiss patient population, underscore the importance of early identification of high-risk individuals to improve clinical outcomes. Recognizing these risk profiles may support clinicians in prioritizing rapid escalation of care for the patients most likely to benefit from early and aggressive intervention. Full article

Background/Objectives: Cardiovascular disease (CVD), particularly coronary artery disease (CAD), is increasingly linked to microvascular inflammation driven by interactions between immune, vascular, and neuroendocrine systems. Mast cells (MCs), strategically positioned near blood vessels, play pivotal roles in this process through the release of inflammatory and vasoactive mediators, contributing to increased vascular permeability, endothelial dysfunction, and tissue inflammation in conditions including ischemia–reperfusion (I/R) and CVD. This comprehensive review examines the cellular and molecular mechanisms underlying MC-mediated microvascular inflammation, with emphasis on neuroimmune regulation through the heart–brain axis, and evaluates the therapeutic potential of flavonoids. Methods: A review of in vitro, animal, and clinical studies was conducted to assess MC-mediated cardiovascular pathology and the pharmacological effects of natural flavonoids on MC activation and microvascular inflammation. Results: Psychological and physical stress activates hypothalamic corticotropin-releasing hormone (CRH) signaling, directly triggering coronary MC degranulation via CRHR-1 and CRHR-2 receptors, while co-released neuropeptides, including neurotensin and urocortin, amplify this neuroimmune cascade. Traumatic brain injury, autonomic dysregulation, and atrial fibrillation further perpetuate this bidirectional heart–brain axis, linking neurological stress to microvascular injury and adverse cardiac remodeling. An autocrine–paracrine CRH amplification loop sustains chronic coronary microvascular inflammation, contributing to heart failure with preserved ejection fraction (HFpEF) and MC activation disease (MCAD)-related cardiovascular manifestations. Natural flavonoids were found to inhibit MC activation, suppress inflammatory mediator synthesis, and protect microvascular integrity through multiple molecular targets, including calcium signaling, transcription factors, oxidative stress pathways, and CRHR-1-mediated neuroimmune signaling. Conclusions: While challenges remain regarding bioavailability and standardization, multi-compound formulations targeting multiple risk factors hold promise for preventing CVD progression. Future research directions for advancing these natural compounds toward clinical implementation are identified. Full article