Search Results (6,749)

Heart failure (HF), particularly of an ischemic etiology, is steadily increasing worldwide. Non-anemic iron deficiency (ID) is highly prevalent among HF patients, and it has been related to worse outcomes. Growth differentiation factor 15 (GDF15) has been related to atherosclerotic cardiovascular (CV) disease, HF and iron pathophysiology. Nevertheless, the specific potential role of GDF15 in HF patients with ID has not been fully explored. In this cross-sectional study we determined serum GDF15 levels in 60 HF patients with ID from the IRON-PATH II study. The discriminative capacity of GDF15 in logistic regression models for classifying these patients according to ischemic etiology was defined as the primary endpoint. Additionally, relationships between GDF15 levels and impaired right ventricle function, impaired functional capacity and HF were included as secondary endpoints. GDF15 was inversely related to tricuspid annular plane systolic excursion (TAPSE) and the six-minute walking test (6MWT), and positively related to hallmarks of HF [i.e., N-terminal prohormone of brain natriuretic peptide (NT-proBNP)] and other molecules influenced by HF progression [i.e., creatinine and ferritin]. Moreover, GDF15 was inversely related to hemoglobin, suggesting a potential link to iron homeostasis. Furthermore, GDF15 showed good classification capacity and improved the accuracy of a logistic regression model for ischemic HF classification in patients with ID. Overall, the findings of this study propose serum GDF15 levels as a potential tool for the classification of HF patients with ID according to the ischemic etiology. Full article

Voltage-gated sodium channels (VGSCs) play pivotal roles in cellular function, particularly in the regulation of electrical signaling. Structural defects in these channels cause deleterious effects in a myriad of cell types, leading to various diseases, like epilepsy, cardiac arrythmias, kidney disease, and certain cancers. Over the past decade, significant efforts have been geared toward developing drugs that target the pore domains of these channels, called pore-blocking agents. This approach has seen several setbacks, commonly due to the lack of isoform-specific binding. Alternative targeting strategies are being used to reduce or eliminate the side effects of pore-blocking agents. Transgenic mouse models have proven useful in such studies, and subtype-selective inhibitors were developed. The zebrafish model system was also used to explore neurological, cardiovascular, and metabolic diseases caused by voltage-gated sodium channel dysfunction. Here, we delve into the growing literature on the structure and function of voltage-gated sodium channels, their role in epilepsy and its comorbidities, and the advancement in the use of zebrafish as a model system to explore these channels as therapeutic targets. Full article

Background/Objectives: In the last decade, several studies revealed individual response variability to different antiplatelet agents, and patients who have no response to these drugs are considered poor responders. Some studies explored platelet function during antiplatelet treatment to identify those patients with “high on-treatment platelet reactivity” (HPR), which exposes them to increased risk of major adverse cardiovascular events (MACE). Methods: We conducted a study with patients with ST-elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, including long-term follow-up after 5 years. We used thromboelastography, the total thrombus formation analysis system, and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) to analyze HPR with different methods; selected laboratory parameters were measured during hospitalization to check significant correlations. Results: We identified STEMI patients treated with DAPT with HPR as a risk group for MACE in a 5-year follow-up. Additionally, we have shown that HPR is associated with atherosclerosis by analyzing lipid profile parameters. Conclusions: High on-treatment platelet reactivity (HPR) increases the risk of major adverse cardiovascular events in the long term, especially with elevated C-reactive protein or an atherogenic lipid profile. Standardizing HPR assessment is crucial for optimizing individualized antiplatelet therapy and improving patient outcomes post-STEMI. Full article

Coronary microvascular dysfunction (CMD) is presently recognized as a condition characterized by a reduction in coronary blood flow. CMD is associated with poor cardiac outcomes, and mounting evidence suggests that coronary microcirculation may be impaired in various cardiology pathologies. Non-invasive assessment of CMD remains challenging, and several imaging modalities—positron emission tomography (PET), computed tomography (CT), cardiac magnetic resonance (CMR), myocardial contrast echocardiography (MCE), and transthoracic Doppler echocardiography (TTE)—are proven to quantify coronary flow reserve (CFR) and myocardial blood flow (MBF), both valuable markers of CMD. However, each modality is limited by availability, standardization, and diagnostic utility. Furthermore, a growing number of studies have attempted to correlate CMD indices with systolic myocardial function markers, such as left ventricular ejection fraction, global longitudinal strain, and myocardial work indices. This review refers to the current evidence on CMD imaging and examines the association between CMD indices and systolic function in cardiovascular diseases. Understanding the impact of CMD on myocardial function is essential, as it highlights the coronary microcirculation impairment pathway as a potential target for therapeutic strategies. Full article

Hypertension in adolescence causes early vascular injury manifesting as endothelial dysfunction (ED), which signifies elevated cardiovascular risk. This review synthesizes recent insights (2020–2025) into ED’s mechanisms and detection in hypertensive youth. We highlight how reduced nitric oxide bioavailability, oxidative stress, inflammation, and hormonal changes in puberty contribute to ED and consequent vascular remodeling. Non-invasive diagnostic tools (e.g., flow-mediated dilation, peripheral arterial tonometry) reveal that even asymptomatic hypertensive adolescents have measurable ED linked to arterial stiffness and cardiac changes. Encouragingly, ED in youth appears reversible: exercise and dietary interventions improve endothelial function, and pharmacotherapy (ACE inhibitors, ARBs) can restore endothelial health beyond blood pressure control. Early identification of ED in hypertensive adolescents is therefore critical—it not only refines risk stratification (e.g., unmasking high-risk “white-coat” hypertension) but also presents an opportunity to initiate lifestyle modifications and therapy to preserve vascular function. Full article

Excessive stress disrupts cardiac homeostasis via complex and multifactorial mechanisms, resulting in cardiac dysfunction, cardiovascular disease, or even sudden cardiac death, yet the underlying molecular mechanisms remain poorly understood. Accordingly, we aimed to elucidate how stress induces calcium dysregulation and contributes to cardiac dysfunction and injury through the nuclear receptor subfamily 3 group c member 1 (NR3C1)/Glomulin (GLMN)/FK506-binding protein 12.6 (FKBP12.6) signaling pathway. Using mouse models of acute and chronic restraint stress, we observed that stress-exposed mice exhibited reduced left ventricular ejection fraction, ventricular wall thickening, elevated serum and myocardial cTnI levels, along with pathological features of myocardial ischemia and hypoxia, through morphological, functional, and hormonal assessments. Using transmission electron microscopy and Western blotting, we found that stress disrupted mitochondrial quality control in cardiomyocytes, evidenced by progressive mitochondrial swelling, cristae rupture, decreased expression of fusion proteins (MFN1/OPA1) and biogenesis regulator PGC-1α, along with aberrant accumulation of fission protein (FIS1) and autophagy marker LC3. At the cellular level, ChIP-qPCR and siRNA knockdown confirmed that stress activates the glucocorticoid receptor NR3C1 to repress its downstream target GLMN, thereby preventing FKBP12.6 ubiquitination and degradation, resulting in calcium leakage and overload, which ultimately impairs mitochondrial quality control and damages cardiomyocytes. In conclusion, our findings reveal that stress induces myocardial damage through NR3C1/GLMN-mediated FKBP12.6 ubiquitination, disrupting calcium homeostasis and mitochondrial quality control, and lay a theoretical foundation for dissecting the intricate molecular network of stress-induced cardiomyopathy. Full article

Background/Objectives: Somatotropinomas rank as the second most prevalent functional pituitary neuroendocrine tumors (PitNETs), responsible for acromegaly in adults and gigantism in children. Early diagnosis and treatment would help prevent irreversible physical changes and other associated comorbidities. The aim of this review is to characterize the symptomatic presentation of growth hormone (GH)-secreting PitNET at the time of diagnosis. Methods: A search was conducted in PubMed, Scopus, Cochrane, and the Virtual Health Library (VHL). Primary descriptive and analytical studies were selected if they were written in Spanish or English and addressed the symptoms of acromegaly and/or gigantism due to somatotropinomas. Results: Out of 8470 articles, 93 fulfilled the inclusion criteria, covering 1745 patients (55.4% women). The most frequent diagnostic signs/symptoms were enlarged extremities (12.4%) and facial changes (13.1%). Endocrine–metabolic (42.82%) and cardiovascular (31.45%) were the most prevalent comorbidities. The average diagnostic delay was 6.7 years, with the number of reports of the disease significantly increasing in recent decades, most likely due to ongoing advances in imaging and standardized hormonal tests. Conclusions: Timely recognition of a somatotropinoma’s symptoms and comorbidities is crucial for early diagnosis and referral to specialized care and the prevention of permanent physical and/or physiological changes. Full article

Background and Objectives: Type 2 diabetes (T2DM) substantially increases cardiovascular risk; beyond the well-recognized left-ventricular involvement in diabetic cardiomyopathy, emerging data indicate subclinical right-ventricular (RV) dysfunction may also be present. This study aimed to evaluate whether speckle-tracking echocardiography identifies subclinical right-ventricular systolic dysfunction in type 2 diabetes, despite normal conventional indices and preserved global systolic function. Materials and Methods: We conducted a cross-sectional, single-center study in accordance with STROBE recommendations, enrolling 77 participants, 36 adults with T2DM, and 41 non-diabetic controls, between December 2024 and July 2025. All participants underwent comprehensive transthoracic echocardiography, including conventional parameters (tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TV S’), right ventricular fractional area change (RVFAC)) and deformation imaging (right ventricular global longitudinal strain (RV GLS), right ventricular free wall longitudinal strain (RVFWS)) using speckle-tracking echocardiography. Biochemical and clinical data, including glycosylated hemoglobin (HbA1c), were recorded. Correlation and ROC curve analyses were performed to explore associations and predictive value. Results: The mean age was comparable between the two groups (62.08 ± 9.54 years vs. 60.22 ± 13.39 years; p = 0.480). While conventional RV parameters did not differ significantly between groups, diabetic patients had significantly lower RV GLS (−13.86 ± 6.07% vs. −18.59 ± 2.27%, p < 0.001) and RVFWS (−15.64 ± 4.30% vs. −19.03 ± 3.53%, p < 0.001). HbA1c levels correlated positively with RV strain impairment (RVFWS r = 0.41, p < 0.001). Both RV GLS and RVFWS were independent predictors of RV dysfunction in logistic regression analysis. ROC analysis showed good diagnostic performance for RV GLS, AUC = 0.84 with an optimal cut-off −17.2% (sensitivity 86.1% and specificity 80.5%) and RVFWS, AUC = 0.76 with cut-off −17.6% (sensitivity 77.8; specificity 80.5%) in identifying early myocardial involvement. Conclusions: RV systolic dysfunction may occur early in T2DM, even when traditional echocardiographic indices remain within normal limits. Speckle-tracking echocardiography, particularly RV GLS and RVFWS, offers sensitive detection of subclinical myocardial impairment, reinforcing its value in early cardiovascular risk stratification among diabetic patients. Full article

Background: Mandibular advancement devices (MADs) are considered an effective therapeutic option for managing obstructive sleep apnea syndrome (OSAS) in adults. Obstructive sleep apnea (OSA) is associated with a range of comorbidities, notably cardiovascular disease. The aim of the present retrospective study is to evaluate respiratory and cardiovascular parameters in OSA patients treated with a MAD. Methods: A total of 64 adults with OSA from moderate-to-severe OSAS underwent split-night polysomnography (SN-PSG) at baseline (T0) and after three months of treatment with a MAD (T1) and were subsequently analyzed using statistical methods for a comparative evaluation. Results: After 3 months of treatment, patients showed a significant decrease in mean heart rate (p < 0.05), maximum heart rate (p < 0.01) and in both the AHI and ODI (p < 0.01), along with a significant increase in minimum heart rate (p < 0.05).Conclusions: These findings indicate that MAD therapy may contribute to improvements in both respiratory efficiency and cardiovascular function in individuals with OSAS, offering a valuable integrated treatment strategy for patients with coexisting cardiovascular conditions. Full article

Objectives: Sex-based disparities in COVID-19 outcomes are well-documented, with men experiencing greater acute severity and women showing increased vulnerability to post-viral syndromes. However, longitudinal immunometabolic trajectories in vaccinated individuals remain underexplored. In this study, sex-based differences in long-term metabolic, endocrine, renal, cardiovascular, and inflammatory responses were investigated among vaccinated individuals recovering from SARS-CoV-2 infection. Methods: This retrospective single-center cohort study included 426 adults (199 females, 227 males) with PCR-confirmed symptomatic COVID-19 and at least two vaccine doses. Serial assessments were conducted at baseline, 18-, 24-, and 30-month post-infection. Parameters included fasting glucose, HbA1c, lipid profile, thyroid function, renal markers, CRP, D-dimer, fibrinogen, troponin, and hematologic indices. Statistical analyses assessed longitudinal changes and sex-stratified correlations. Results: Fasting glucose and HbA1c levels significantly declined over time, more prominently in males. Glucose correlated with age and BMI only in females. Lipid levels remained largely unchanged, although males had higher baseline triglycerides. Females showed rising TSH levels and persistently lower free T3; males exhibited higher creatinine, urea, and troponin levels throughout. Inflammatory markers declined significantly in both sexes, with males displaying higher CRP and troponin, and females showing sustained fibrinogen elevation and a temporary lymphocyte surge. D-dimer was elevated in females at the 30-month point. Conclusions: Sex-specific physiological recovery patterns were evident among vaccinated COVID-19 survivors. Males exhibited earlier metabolic and cardiac alterations, while females had more persistent endocrine and inflammatory shifts. These findings underscore the need for sex-tailored long-term monitoring strategies prioritizing early metabolic and cardiac screening in men and prolonged immunoendocrine surveillance in women. Full article

Low-calorie sweeteners (LCS) are widely utilized as sugar substitutes due to their intense sweetness, thermal stability, and applicability in weight management and diabetic-friendly products. However, increasing evidence has raised concerns about their potential long-term effects on metabolic health, glucose regulation, cardiovascular function, carcinogenicity, and gut microbiota composition. This review systematically evaluates the pharmacokinetics, metabolic effects, and associated health outcomes of major LCS. Mechanistically, LCS exert effects via sweet taste receptor-mediated pathways, altering glucose absorption, insulin secretion, and intracellular signaling cascades. Additionally, LCS influence gut microbiota composition, with certain agents promoting dysbiosis and glucose intolerance. While some findings support the metabolic benefits of selected LCS, others underscore potential risks, necessitating cautious interpretation. In conclusion, while LCS offer viable alternatives to sugar, their health effects are context-dependent and may vary across different sweeteners and populations. Long-term, high-quality clinical trials are essential to elucidate their safety and efficacy. Full article

Background/Objectives: Radial artery access (RAA) is widely used for catheter-based procedures due to its safety and convenience, but complex regional pain syndrome (CRPS) remains a rare, underrecognized complication—particularly in women. CRPS manifests as prolonged, severe pain and autonomic symptoms, often associated with nerve irritation near the carpal tunnel. This study aimed to evaluate whether modifying the puncture site to a high radial artery puncture (HRAP) reduces the risk of CRPS in patients undergoing transarterial micro-embolization (TAME) for frozen shoulder. Methods: We retrospectively reviewed 97 patients (47 women and 50 men) who underwent transarterial micro-embolization (TAME) via conventional RAA for frozen shoulder between February and June 2019. The occurrence of CRPS and vascular complications was recorded. All punctures were ultrasound-guided. Results: Among women treated via conventional RAA, five developed CRPS and one had radial artery occlusion. CRPS symptoms included intense puncture site pain (mean duration was 47 days), which severely impaired daily function. No complications occurred in men. Following the adoption of HRAP, no cases of CRPS, prolonged pain, or vascular complications were observed in the consecutive 101 women treated. Conclusions: Our findings suggest HRAP reduces CRPS risk by avoiding superficial nerve branches and targeting deeper arterial segments with fewer sensory structures. This ultrasound-guided modification is simple, does not require additional training, and may be widely applicable in both musculoskeletal and cardiovascular interventions. HRAP may help minimize neuropathic complications in broader patient populations. Full article

Background/Objectives: Hypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, their short half-life requires frequent dosing and incurs high treatment costs. This study evaluates a novel peptide-based Anti-PCSK9 product aimed at providing sustained LDL-C reduction. Methods: A novel PCSK9 based-peptide conjugated to diphtheria toxoid (DT) was evaluated in various preclinical models: high-fat diet-fed C57BL/6 mice, APOB100/hCETP transgenic mice, BALB/c mice and normocholesterolemic non-human primates. Immunogenicity (Anti-PCSK9 antibody titers, binding affinity by SPR), pharmacodynamics (LDL-C levels, inhibition of PCSK9-LDLR interaction) and safety were assessed. Toxicity was evaluated in rodents, rabbits and dogs through clinical monitoring, histopathology, organ function and safety pharmacology studies. Results: The Anti-PCSK9 product induced robust and long-lasting immune response in all models antibody titers in BALB/c mice peaked by week 6 and persisted for 12 months. LDL-C reductions of 44% in APOB100/hCETP mice and 37% in C57BL/6 mice correlated with high antibody titers and strong PCSK9-binding affinities (85 and 49 RU), leading to 59% and 58% inhibition of PCSK9-LDLR interaction, respectively. Non-human primates showed sustained responses. No systemic toxicity was observed; injection-site reactions were mild and reversible. No adverse effects were detected on cardiovascular, neurological, or respiratory systems. Conclusions: This peptide-based Anti-PCSK9 therapy offers sustained efficacy and safety, representing a promising long-acting alternative for managing hypercholesterolemia. Full article

Background/Objectives: Knee osteoarthritis (OA) significantly affects quality of life and poses substantial treatment challenges in patients with severe comorbidities that contraindicate total knee arthroplasty. Transarterial periarticular embolization (TAE) has developed as a minimally invasive alternative targeting pathological periarticular hypervascularity. Bilateral embolization in a single session has not yet been clearly documented. This case report describes the application of bilateral genicular artery embolization using bioresorbable gelatin microspheres. Case report: A 68-year-old male patient with severe bilateral knee OA and multiple cardiovascular comorbidities underwent simultaneous bilateral TAE using Nexsphere-F microspheres (100–300 µm). Embolization targeted hypervascular genicular branches identified through digital subtraction angiography preserving normal capsular and osseous perfusion. Results: At one-month follow-up, the patient’s pain score decreased dramatically (VAS from 8/10 to 2/10), accompanied by marked functional improvement (WOMAC score: from 64 to 84; KOOS score: from 49 to 72). No intraoperative or postoperative complications occurred and the patient required no analgesics post-procedure. Conclusions: Bilateral, same-session genicular artery embolization using bioresorbable gelatin microspheres provided short-term clinical benefits in a patient with advanced knee OA contraindicated for surgery. Full article

The renin-angiotensin system (RAS) has evolved from being considered solely a peripheral endocrine system for cardiovascular control to being recognized as a complex molecular network with important functions in the central nervous system (CNS) and peripheral nervous system (PNS). Here we examine the organization, mechanisms of action, and clinical implications of cerebral RAS in physiological conditions and in various neurological pathologies. The cerebral RAS operates autonomously, synthesizing its main components locally due to restrictions imposed by the blood–brain barrier. The key elements of the system are (pro)renin; (pro)renin receptor (PRR); angiotensinogen; angiotensin-converting enzyme types 1 and 2 (ACE1 and ACE2); angiotensin I (AngI), angiotensin II (AngII), angiotensin III (AngIII), angiotensin IV (AngIV), angiotensin A (AngA), and angiotensin 1-7 (Ang(1-7)) peptides; RAS-regulating aminopeptidases; and AT1 (AT1R), AT2 (AT2R), AT4 (AT4R/IRAP), and Mas (MasR) receptors. More recently, alamandine and its MrgD receptor have been included. They are distributed in specific brain regions such as the hypothalamus, hippocampus, cerebral cortex, and brainstem. The system is organized into two opposing axes: the classical axis (renin/ACE1/AngII/AT1R) with vasoconstrictive, proinflammatory, and prooxidative effects, and the alternative axes AngII/AT2R, AngIV/AT4R/IRAP, ACE2/Ang(1-7)/MasR and alamandine/MrgD receptor, with vasodilatory, anti-inflammatory, and neuroprotective properties. This functional duality allows us to understand its role in neurological physiopathology. RAS dysregulation is implicated in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and neuropsychiatric disorders such as depression and anxiety. In brain aging, an imbalance toward hyperactivation of the renin/ACE1/AngII/AT1R axis is observed, contributing to cognitive impairment and neuroinflammation. Epidemiological studies and clinical trials have shown that pharmacological modulation of the RAS using ACE inhibitors (ACEIs) and AT1R antagonists (ARA-II) not only controls blood pressure but also offers neuroprotective benefits, reducing the incidence of cognitive decline and dementia. These effects are attributed to direct mechanisms on the CNS, including reduction of oxidative stress, decreased neuroinflammation, and improved cerebral blood flow. Full article