Search Results (954)

Background: This prospective cohort study examines the association between hyperuricemia (HU) and cardiovascular diseases. The aim of the current study was to assess whether there might be a correlation between hyperuricemia and cardiovascular risk and future cardiovascular events. Methods: We analyzed data from 4082 participants, dividing them into two groups based on serum uric acid levels. Results: Our findings reveal that participants with elevated serum uric acid or xanthine oxidase inhibitor (XOI) therapy had a significantly higher incidence of cardiovascular events such as coronary artery disease (8.4% vs. 3.3%), stroke (2.6% vs. 1.2%), heart failure (3.4% vs. 0.9%), and chronic kidney insufficiency (4.5% vs. 1.9%) compared to those with normal uric acid levels. Moreover, group 2, which had higher serum uric acid levels, also exhibited a higher burden of established cardiovascular risk factors, including hypertension, obesity, and diabetes. These results support the hypothesis that HU is not only a marker for metabolic dysfunction but may also serve as an independent risk factor for cardiovascular morbidity and mortality. Conclusions: We propose that routine measurement of uric acid levels could be a valuable tool for early identification of high-risk cardiovascular patients, particularly in individuals with multiple metabolic risk factors. Further prospective studies are needed to explore the potential benefits of early XOI therapy in reducing cardiovascular events. Full article

This research represents the first in the Republic of Kazakhstan focusing on Afghan war veterans identified as being at risk for Post-Traumatic Stress Disorder (PTSD). A comprehensive investigation was undertaken regarding the comorbidity of PTSD symptoms, somatic diseases (cardiovascular and others), and mental disorders. The study’s sample comprised 293 Afghan war veterans, while the control group consisted of 149 males without combat experience. The research methodology incorporated data extracted from medical records, a demographic questionnaire, the Mississippi PTSD Scale (military and civilian versions), the Spielberger–Khanin Anxiety Inventory, the Beck Depression Inventory (BDI), and the SCL-90-R questionnaire. Subclinical symptoms indicative of chronic PTSD were identified in 25.2% of veterans, as assessed by the Mississippi PTSD Scale. According to the Spielberger–Khanin questionnaire, veterans with subclinical PTSD exhibited a moderate level of situational (44.96 ± 6.39 points) and personal anxiety (44.14 ± 5.49 points), which were significantly higher than those observed in the control group (29.87 ± 6.50, p₂ < 0.001, 36.13 ± 6.82, p₂ = 0.003). Furthermore, based on the BDI, these veterans demonstrated an elevated level of depression (13.32 ± 1.36) in comparison to veterans without PTSD (8.61 ± 0.65, p < 0.001) and the control group (4.06 ± 0.75, p < 0.0001). The findings indicate that veterans exhibiting a high level of PTSD are characterized by a more pronounced manifestation of psychopathological indicators, as assessed by the SCL-90-R questionnaire. Compared to the control group, veterans exhibiting PTSD symptoms were found to have a comorbidity with somatic diseases: stage 3 hypertension in 45.2% vs. 21.3% (p₂ < 0.001), coronary heart disease in 45.5% vs. 13.4% (p₂ < 0.001), and type 2 diabetes mellitus in 20.3% vs. 6.1% (p₂ = 0.001). Consequently, Afghan war veterans should be regarded as a high-risk group for cardiovascular diseases (including hypertension and coronary heart disease), cerebrovascular diseases, and mental health disorders. Accordingly, a comprehensive approach is necessary to identify PTSD symptoms alongside concomitant anxiety–depressive disorders and somatic diseases in individuals who have experienced traumatic events. Full article

Background/Objectives: Our objective was to describe the safety and efficacy of enteral droxidopa, a norepinephrine prodrug, for intravenous (IV) vasopressor weaning in intensive care unit (ICU) patients. Methods: This was a single-center, retrospective descriptive study of adult ICU patients. Patients who received ≥ 4 consecutive doses of droxidopa for IV vasopressor weaning were included. The cessation of the IV vasopressor without re-initiation within 72 h of droxidopa initiation was the primary outcome. The adverse events assessed included hypotension, hypertension, and arrhythmias. Results: Forty-six patients were included, with a median age of 61. Forty-two patients (91%) were on midodrine at the time of droxidopa initiation. The median daily midodrine dose was 80 mg. The median time from ICU admission to droxidopa initiation was 17 days. Patients were on a median of one IV vasopressor at the time of droxidopa initiation, with norepinephrine as the most common agent (50%). The median initial daily droxidopa dose was 300 mg, with a median maximum daily dose of 900 mg. Vasopressor support was discontinued within 72 h of droxidopa initiation in 46% of patients, with a median time to IV vasopressor cessation of 3.3 days. There were no incidences of hypotension, hypertension, arrhythmias, or ICU readmissions related to droxidopa. Droxidopa was continued upon discharge in 29% of patients. Conclusions: Droxidopa may be a safe and effective option to facilitate the weaning of IV vasopressor support in patients who are refractory or intolerant to midodrine. Larger prospective studies are needed to confirm these findings. Full article

Zilebesiran represents an innovative antihypertensive therapy employing small interfering RNA (siRNA) to inhibit hepatic angiotensinogen, a key regulator of the renin–angiotensin–aldosterone system. By directly targeting the source of angiotensin II production, zilebesiran offers a novel mechanism distinct from conventional antihypertensive treatments. In the clinical studies KARDIA-1 and KARDIA-2, zilebesiran demonstrated clinically significant reductions in systolic blood pressure, with effects lasting up to 24 weeks after a single subcutaneous injection. In KARDIA-1, doses of 300 mg and 600 mg administered every 6 months resulted in reductions of over 15 mmHg in systolic blood pressure at 3 months compared with placebo. KARDIA-2 further showed an additional reduction of up to 12.1 mmHg at 3 months when zilebesiran was used as an adjunct to standard antihypertensive therapy. KARDIA-3 is currently evaluating the therapy in a larger global population to assess its impact on major cardiovascular outcomes. Zilebesiran has demonstrated a favorable safety profile with minimal adverse events, offering potential advantages for patients with resistant or uncontrolled hypertension and those at high cardiovascular risk, especially where adherence to daily oral medications is challenging. Beyond blood pressure reduction, zilebesiran may protect target organs, including the heart, kidneys, and retina. In conclusion, zilebesiran represents a promising siRNA-based therapy that may redefine the management of difficult-to-control hypertension, offering durable, targeted, and patient-friendly treatment with broad cardiovascular benefits. Future studies will clarify its long-term safety, efficacy across diverse populations, and integration into personalized hypertension management strategies. Full article

Semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist, is widely prescribed for weight loss in non-diabetic populations. Given the link between obesity and overactive bladder (OAB), we explored whether GLP-1 use would improve adverse urinary events beyond its weight loss benefit for non-diabetic adults undergoing onabotulinumtoxin A (BTX-A) treatment for OAB. Using the TriNetX database, we conducted a retrospective cohort study of non-diabetic OAB patients treated with BTX-A alone or with concurrent GLP-1 therapy. Propensity score matching (1:1) was adjusted for age, race, ethnicity, hypertension, and BMI/obesity. After matching, 992 patients were included in each group. GLP-1 use was associated with a lower incidence of urinary retention (8.6% vs. 4.9%, risk difference 3.66%, p = 0.0044) and urinary tract infection (13.3% vs. 8.8%, risk difference 4.54%, p = 0.00224), with corresponding improved one-year retention-free and UTI-free survival on Kaplan–Meier (KM) analysis. Antispasmodic initiation rates were similar (11.8% vs. 10.3%, risk difference 1.55%, p = 0.6921), and KM analysis showed no significant difference. These findings suggest that GLP-1 receptor agonist use may improve select urinary adverse events in non-diabetic adults undergoing BTX-A treatment for OAB and support further investigation into its potential adjunctive role in OAB management with longer follow-up. Full article

Background: Hypertension remains a leading cause of cardiovascular morbidity and mortality, disproportionately affecting low- and middle-income countries (LMICs), where healthcare access and awareness are limited. Excessive sodium intake, often from discretionary salt used in cooking, contributes significantly to this burden. Salt substitutes, typically formulated by partially replacing sodium chloride with potassium chloride or other minerals, offer a cost-effective dietary intervention to lower blood pressure (BP) and reduce cardiovascular risk, particularly in resource-constrained settings. Objective: This review examines the efficacy of low-sodium salt substitutes (LSSS) in reducing blood pressure (BP) and its effects on cardiovascular (CV) outcomes, safety concerns, and challenges to their implementation in LMICs. Methods: We conducted a comprehensive narrative review of studies published between 1994 and 2024 using PubMed, Embase, and Scopus databases. Eligible studies included randomized controlled trials, systematic reviews, observational studies, and implementation research that evaluated the effects of LSSS on BP, CV outcomes, safety, and feasibility in LMIC contexts. Thematic synthesis was used to summarize the findings. Key Findings: Salt substitutes consistently lowered systolic and diastolic BP across diverse populations, with mean reductions ranging from 3 to 5 mmHg. Trials have also demonstrated reductions in stroke incidence, CV events, and all-cause mortality. However, the benefits were mostly derived from studies conducted in China and other upper-middle-income settings. Safety concerns (particularly hyperkalemia in individuals with chronic kidney disease or RAAS inhibitors) warrant targeted risk screening and public education. Implementation barriers in LMICs include cost, limited availability, poor awareness, and a lack of regulatory oversight. Conclusions: Salt substitutes present a promising, scalable strategy to reduce BP and CV disease burden in LMICs. However, their adoption must be context-specific, culturally sensitive, and supported by government subsidies, regulatory frameworks, and educational campaigns. Future trials should evaluate the long-term safety and cost-effectiveness in underrepresented LMIC populations to guide equitable public health interventions. Full article

Background: Prostate cancer is the most frequent malignancy in men, with an incidence of 21% of all diagnosed tumors in this population in Spain. Between 10 and 20% of patients with prostate cancer develop castration-resistant prostate cancer (CRPC). Abiraterone is widely used in CRPC and metastatic prostate cancer, but data on its renal safety are limited. Methods: We performed a single-center, retrospective observational study including patients with advanced prostate cancer who initiated abiraterone between January 2013 and July 2024 at Hospital Clínico San Carlos (Madrid, Spain). Patients were followed until December 2024. Renal events were defined as acute kidney injury (AKI), electrolyte imbalance, new onset or worsening hypertension (HTN), and/or volume overload. Risk factors and associations with mortality were analyzed using multivariate models. Results: Seventy-nine patients were included (mean age 76 ± 9.5 years; 70.9% CRPC; 89.9% metastatic disease). Median follow-up was 17 months. Renal events occurred in 63.3% of patients. Independent risk factors were metastatic disease (OR 13.335; 95% CI 1.418–124.444; p < 0.0235) and HTN (OR 3.336; 95% CI 1.091–10.206; p < 0.0347). Electrolyte imbalance occurred in 36.7% of patients. AKI developed in 30.4% of patients, of whom 50% progressed to chronic kidney disease. New/worsening HTN occurred in 25.5%, and volume overload occurred in 16.5%. Abiraterone discontinuation due to renal events was rare (4%). At the end of follow-up, 18.9% of patients had died. In a multivariate Cox analysis, AKI was identified as an independent predictor of mortality [HR 3.044 (95% CI 1.001–9.260); p = 0.05]. Conclusions: Renal events are common in patients treated with abiraterone, especially in those with metastatic disease and hypertension. AKI independently predicted mortality. Close monitoring of renal function and blood pressure is essential in this population. Full article

Hepatocellular carcinoma (HCC) is characterized by a complex disruption of hemostatic balance, increasing the risk of both thrombotic and hemorrhagic events. Thrombotic complications, most notably portal vein thrombosis (PVT) and venous thromboembolism (VTE), have a significant impact on clinical outcomes and therapeutic strategies. Cirrhosis contributes to the precarious equilibrium between pro- and anticoagulant forces through impaired synthesis of coagulation factors, endothelial dysfunction, and systemic inflammation. In the presence of HCC tumor-driven mechanisms, such as tissue factor expression, extracellular vesicle release, platelet activation, and suppression of fibrinolysis exacerbate this prothrombotic state. In this scenario, advanced diagnostic tools such as thrombin generation assay (TGA) and rotational thromboelastometry (ROTEM) offer a more accurate assessment of coagulation dynamics than conventional tests, enabling better risk stratification especially for therapeutic purposes. Anticoagulant therapy has demonstrated clinical benefit in selected cases of non-malignant PVT and VTE, particularly when liver function is preserved. While prophylactic strategies are still under investigation, data suggest they may be safely implemented in selected surgical patients. In the setting of immunotherapy, especially regimens involving anti-VEGF agents, anticoagulation may be considered with careful management of bleeding risk due to portal hypertension. An individualized approach to anticoagulation, supported by functional coagulation testing, is gaining acceptance as a means to safely reduce thrombotic burden and potentially improve outcomes in patients with HCC. Full article

Background/Objectives: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown blood pressure (BP) reduction in type 2 diabetes (T2D). However, head-to-head comparisons in hypertensive patients remain limited. This study assessed the effects of SGLT2i and GLP-1RA on systolic BP (SBP), diastolic BP (DBP), antihypertensive regimen modifications, and adverse events in Saudi patients with both conditions. Methods: A retrospective cohort study was conducted between January 2022 and April 2024 using records from two hospitals. Adults with T2D and hypertension who initiated SGLT2i or GLP-1RA and had ≥2 BP readings were included. BP changes were analyzed with ANOVA; adverse events and treatment discontinuation were assessed with Chi-square and Kaplan–Meier analysis. Results: Of 505 patients, 291 (57.6%) received SGLT2i and 214 received GLP-1RA. Both classes significantly reduced SBP (p < 0.001), and DBP decreased significantly only in the SGLT2i group (p < 0.001). Antihypertensive regimen reduction occurred in 6.9% of patients, most commonly among SGLT2i users (74.3%), while 76.8% remained on the same regimen; the remaining patients had other modifications such as dosage adjustments or changes in individual agents. Adverse events occurred in 6.3% of patients with no group differences. Therapy discontinuation was higher with GLP-1RA (12.6%) versus SGLT2i (2.4%, p < 0.001). Conclusions: Both SGLT2i and GLP-1RA might be considered in patients with T2D and hypertension, with SGLT2i potentially offering additional benefits for DBP reduction and simplifying antihypertensive regimens, which could support clinical decision-making in real-world practice. Full article

Introduction: Sickle cell anemia (SCA) is a hereditary hemoglobinopathy caused by a mutation in the beta-globin gene, resulting in the production of hemoglobin S. Intracranial hemorrhage (ICH) is a severe complication for patients with SCA, but there is a paucity of literature on its epidemiology, risk factors, and clinical outcomes. To address this knowledge gap, we conducted a comprehensive analysis using the Nationwide Inpatient Sample (NIS) database to evaluate the epidemiology, prevalence, predictors, and clinical outcomes of ICH in adults with SCA. Methods: We conducted a retrospective cohort study using the NIS database from 2016 to 2020 to identify hospitalizations with SCA, using the ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes. Subsequently, we derived the prevalence and predictors of ICH in SCA adults. Results: Out of 468,070 admissions of adult hospitalizations (Aged ≥ 18 years) with SCA between 2016 and 2020 in the United States, 825 (0.17%) had ICH (nontraumatic intraparenchymal and/or subarachnoid bleeding). 410 (49.7%) were males, and 380 (46.0%) belonged to the age group of more than 45 years. The mean length of stay was 14.9 days, and 210 deaths occurred during the index hospitalization, resulting in a 25.4% inpatient mortality rate as compared to 0.6% in SCA-non-ICH patients (p < 0.001). Across all adult SCA hospitalizations during 2016–2020 (n = 468,070), ICH accounted for 210 of 2940 inpatient SCA deaths (7.1%). On multivariate logistic regression analysis, hypertension (OR:2.08, 95% CI: 1.2–3.3), prior history of ischemic stroke (OR: 17.06, 95% CI: 7.5–38.5), and a Charlson comorbidity index of more than one (OR: 2.9, 95% CI: 2.4–3.5) are significant predictors of ICH in adults with SCA. Conclusions: This study highlights the high prevalence of ICH in addition to the well-known thrombotic phenomenon among SCA patients. Stroke prevention and hypertension control are of paramount importance for the prevention of this catastrophic event in patients with SCA. Full article

Background/Objectives: Ischemic cardiomyopathy is a major cause of morbidity and mortality. Obesity is paradoxically associated with better outcomes, while clustering of cardiometabolic risk factors (CMRFs)—diabetes mellitus, arterial hypertension, and hyperlipidemia—is associated with worse prognosis in heart failure (HF) patients. The interplay between vascular function, obesity and clustering of CMRFs in ischemic HF is not thoroughly investigated. Methods: In a prospective, single-center cohort study, 560 patients with ischemic cardiomyopathy were followed for a median of 43 months. Baseline BMI, CMRFs and markers of vascular function including flow-mediated dilation (FMD), and carotid–femoral pulse wave velocity (cf-PWV) were assessed. Major adverse cardiovascular events (MACE), including death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure or other cardiovascular causes, were recorded. Cox proportional hazards models and cubic spline analyses evaluated associations and nonlinear relationships. Results: Obesity was independently associated with a 50% lower risk of MACE (HR 0.50; 95% CI 0.32–0.981; p = 0.01) and improvement of FMD by 1% corresponded to a 7% reduction in MACE risk (HR 0.93; 95% CI 0.87–0.99; p = 0.03) after adjusting for multiple confounders. Clustering of all three CMRFs predicted greater MACE risk (HR 1.42; 95% CI 1.03–1.95; p = 0.03). No significant differences in FMD or cf-PWV were observed across BMI groups. cf-PWV values were impaired among patients with all 3 CMRFs but cf-PWV did not predict MACE. Conclusions: Higher BMI and FMD each independently predict improved outcomes in ischemic cardiomyopathy. The clustering of cardiometabolic risk factors is a strong predictor of adverse events. Full article

Background/Objectives: Roxadustat is a new treatment for the anemia of chronic kidney disease (CKD) that has comparable efficacy to erythropoietic-stimulating agents (ESAs), with the advantage of oral administration and increased iron bioavailability. It appears to be a safe treatment in terms of the development of major adverse cardiovascular events (MACEs); however, its long-term safety has not been fully evaluated. In this meta-analysis we evaluate its safety in dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD patients, considering the comparator used and treatment duration. Methods: The safety of Roxadustat was assessed based on the incidence of serious (SAEs) and non-serious adverse events (AEs). A random-effects method was used to estimate the odds ratios (ORs) and their 95% CIs. Results: Fifteen different randomized controlled clinical trials were included, with a total of 10,284 patients with CKD stages 3–5 treated with Roxadustat, 5604 on dialysis and 4680 not on dialysis. The overall incidence of AEs in the Roxadustat group did not change significantly (OR = 1.13; 1.00–1.27); however, the incidence of SAEs was significantly higher than in the control group (OR = 1.13; 1.04–1.23). Specifically, the incidence of hypertension (OR = 1.39; 1.13–1.73) and hyperkalemia (OR = 1.31; 1.02–1.69) was higher in the Roxadustat group than in the placebo group of NDD patients. All AEs except MACEs and hyperkalemia increased with treatment > 30 weeks. No differences were found in the incidence of any adverse effects studied compared with ESAs. Conclusions: Roxadustat is associated with an increased risk of SAEs, including hypertension and hyperkalemia in NDD patients. Therefore, monitoring potassium levels and blood pressure is recommended in these patients. Full article

Bevacizumab is often used off-label in pediatric neuro-oncology, and evidence for indications of bevacizumab use in pediatric neuro-oncology is often fragmented. Therefore, this review aims to provide an organized summary of efficacy across different types of tumors, highlight outcomes, and link findings to the underlying biology. Gaps in the literature were also identified to guide future research. We narratively synthesized various pediatric studies, and the following tumor categories were identified for discussion: low-grade glioma, high-grade glioma, diffuse intrinsic pontine glioma, schwannoma, medulloblastoma, radiation necrosis, and cerebral edema. Key outcomes considered included overall survival, event-free survival, progression-free survival, vision and/or hearing improvements, steroid use, quality of life, and toxicity. The greatest benefits were observed in cases such as recurrent medulloblastoma in combination with temozolomide and irinotecan, optic pathway glioma visual function, and diminished steroid use in radiation necrosis. Results were poorer in cases of newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas. The medication was overall well tolerated, with adverse events like hypertension, proteinuria, and epistaxis often being manageable with surveillance. In consideration of the results, bevacizumab should be considered based on the tumor profile, and its outcome measured along functional endpoints, besides radiological evolution. Continued investigations into outcome measures, as well as combination with targeted treatments and optimizing therapy, will contribute to improving outcomes in this vulnerable population. Full article

Serum uric acid (SUA) overproduction, leading to hyperuricemia, represents a metabolic dysfunction of frequent detection in a number of diseases characterized by an elevated cardiovascular risk, such as metabolic syndrome, essential hypertension, dyslipidemia, obesity, and diabetes mellitus. Similar findings have been also reported for the Atherogenic Index of Plasma (AIP), i.e., a biomarker derived from the logarithmic transformation of the ratio between plasma triglycerides and high-density plasma lipoprotein cholesterol. Both SUA and AIP have been found to be sensitive predictors of fatal and non-fatal cardiovascular events and all-cause mortality, their association representing a highly sensitive marker potentiating the predictive value of each single factor. Although a number of studies have investigated the relationships between SUA and AIP, the association between these two metabolic variables still remains in several indistinct aspects. The present paper, after briefly summarizing the main features of the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, will review the main study results related to SUA as cardiovascular risk factors. It will also report the original data collected in the PAMELA study on (1) the association between SUA and AIP and (2) the relationships between AIP and normal and elevated blood pressure, metabolic profile, and target organ damage associated with hypertension. Full article

Ischemic stroke is a leading cause of disability worldwide, often triggered by atherothrombotic or embolic events. A growing body of evidence highlights the role of neuroinflammation as a central mechanism in post-stroke damage, influenced by modifiable systemic risk factors. Emerging evidence suggests that oxidative stress mediates the impact of several modifiable risk factors by activating redox-sensitive pathways (such as NF-κB), impairing nitric oxide bioavailability, and promoting matrix metalloproteinase activity that disrupts vascular integrity and contributes to ischemic injury. In this context, our meta-analysis examined major modifiable risk factors for ischemic stroke, with a particular focus on their shared ability to promote oxidative stress and neuroinflammatory cascades. By emphasizing these redox-dependent mechanisms, our work supports the biological plausibility of exploring antioxidant strategies as complementary approaches to mitigate stroke risk. Hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, and transient ischemic attacks all contribute to oxidative damage through mechanisms such as endothelial dysfunction, vascular inflammation, and excessive free radical exposure. We searched PubMed, PubMed Central, Web of Science, and Scopus for observational studies published within the last five years, identifying 23 studies (691,524 participants) meeting eligibility criteria. Using a random-effects model, we found significant associations between stroke risk and hypertension (OR = 1.58, 95% CI: 1.28–1.94), smoking (OR = 1.61, 95% CI: 1.13–2.28), type 2 diabetes (OR = 1.53, 95% CI: 1.29–1.81), atrial fibrillation (OR = 1.88, 95% CI: 1.28–2.75), and prior transient ischemic attack (OR = 1.62, 95% CI: 1.24–2.11). These risk factors are known to contribute to systemic inflammation, potentially exacerbating neuroinflammatory cascades post-stroke. Despite limitations such as heterogeneity and low certainty of evidence, our findings reinforce the relevance of targeting inflammation-driven risk factors in stroke prevention strategies and future research. Full article