Search Results (1,006)

Background: Alcohol-associated liver disease (AALD) represents significant health burdens worldwide. This study aims to provide a comprehensive overview of the AALD outcomes that were incompletely understood. Methods: The current study utilizes data from the National Health and Nutrition and Examination Survey (NHANES) from 2011–2020, using a stratified, multistage probability cluster design. AALD in the NHANES was defined using clinical laboratory data and self-reported alcohol use, among which fibrosis-4 score of >2.67. Analysis is conducted using weighted, logistic, and Cox linear regression. Results: The initial sample included 23,206 participants aged 20 and older, with recorded cardiovascular status and AST/ALT levels. Participants reporting AALD had a higher percentage of college degrees (p < 0.001) and were more likely to be daily smokers. Asians exhibited the highest rates of AALD compared to other demographics (p < 0.001). The prevalence in private insurance is significantly greater than Medicaid, but the usage trends have been increasing in Medicaid. The trends of advanced fibrosis have been increasing in blacks and Asians, while they have been decreasing among whites and Mexicans. Those with AALD also had higher mean systolic and diastolic blood pressure, as well as elevated fasting glucose levels (p < 0.001). The mortality rate among AALD participants with heart diseases was 25%, compared to 3% among those without (p < 0.001). After adjusting for potential confounding variables, no statistically significant associations were found between AALD status and HF or CAD. However, a clinically significant increase in the odds of stroke was observed within the AALD group (p < 0.001). Conclusions: Our findings indicate Asians have the highest rates of AALD. The trends of advanced fibrosis have been increasing in blacks and Asians. There is an increased prevalence of AALD with heart diseases and a significant increase in mortality with stroke. Full article

Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone EVT to elucidate patient characteristics and factors associated with a favorable functional outcome after EVT. Methods: We reviewed all cases of EVT at our institution between February 2018 and February 2022 in the extended time window from 6–24 h. Demographic, clinical, imaging, and procedure co-variates were included. A favorable clinical outcome was defined as a modified Rankin scale of 0–2. We included patients with M1 or internal carotid artery occlusion treated with EVT within 6–24 h after symptom onset. We used a univariate and multivariate logistic regression analysis to identify patient factors associated with a favorable clinical outcome at 90 days. Results: Our study included evaluation of 121 patients who underwent EVT at our comprehensive stroke center. Our analysis demonstrates that a higher recanalization score based on the modified Thrombolysis In Cerebral Infarction (mTICI) scale (2B-3) was a strong indicator of a favorable outcome (OR 7.33; CI 2.06–26.07; p = 0.0021). Our data also showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.0095) and the presence of pre-existing hypertension (p = 0.0035) may also be predictors of an unfavorable outcome (mRS > 2) per our multivariate analysis. Conclusion: Patients without pre-existing hypertension had more favorable outcomes following EVT in the expanded time window. This is consistent with other multicenter data in the expanded time window that demonstrates greater odds of a poor outcome with elevated pre-, peri-, and post-endovascular-treatment blood pressure. Our data also demonstrate that the mTICI score is a strong predictor of favorable outcome, even after controlling for other variables. A lower baseline NIHSS at the time of thrombectomy may also indicate a favorable outcome. Furthermore, the presence of clinical or radiographic mismatch based on the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and NIHSS per DAWN and DEFUSE-3 criteria did not emerge as a predictor of favorable outcome, which is congruent with recent randomized controlled trials and meta-analyses. Full article

Recent studies have demonstrated that the development and progression of hypertensive kidney injury comprise not only elevated systemic blood pressure but also a complex interplay of cellular, molecular, and genetic mechanisms. In this report, we outline the key emerging pathways—ranging from dysregulated renin–angiotensin system signaling, oxidative stress, immune-mediated inflammation, and metabolic abnormalities to epigenetic alterations and genetic susceptibilities—that contribute to kidney damage in hypertensive conditions. In addition, we also discuss precision medicine approaches like biomarker-directed therapies, pharmacologically targeted therapies, and device-based innovations for modulating these pathways. This integrative review emphasizes the application of omics technologies and genetically guided interventions to better stratify patients and offer personalized care for hypertensive kidney disease. Full article

Background/Objectives: Nelumbo nucifera Gaertn. (lotus) seeds have traditionally been used to treat hypertension, though their mechanisms remain unclear. This study investigated the antihypertensive effects of lotus seed extract (LSE) and its mechanisms in rats with N^ω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Methods: Male Sprague Dawley rats received L-NAME (40 mg/kg/day) in drinking water and were treated orally with LSE (5, 10, or 100 mg/kg/day), captopril (5 mg/kg/day), or a combination of LSE and captopril (2.5 mg/kg/day each) for 5 weeks. Hemodynamic parameters and histological changes in the left ventricle and aorta were assessed. Mechanistic studies included measurements of plasma nitric oxide (NO) metabolites, malondialdehyde (MDA), superoxide dismutase (SOD) activity, angiotensin II (Ang II), angiotensin-converting enzyme (ACE) activity, and protein expression via western blot. Results: L-NAME elevated systolic blood pressure and induced cardiovascular remodeling, oxidative stress, and renin-angiotensin system activation. LSE treatment reduced blood pressure, improved antioxidant status, increased NO bioavailability, and downregulated gp91^phox and AT₁R expression. The combination of low-dose LSE and captopril produced stronger effects than LSE alone, with efficacy comparable to captopril. Conclusions: These findings suggest that LSE exerts antihypertensive effects via antioxidant activity and inhibition of the renin-angiotensin system, supporting its potential as an adjunct therapy for hypertension. Full article

Preeclampsia with severe features presents major anesthetic challenges, particularly in category 1 cesarean sections, in which rapid, safe, and hemodynamically stable induction is critical. Neuraxial techniques may be controversial due to neurological symptoms, making general anesthesia a viable option. However, traditional general anesthesia may exacerbate hypertension and increase maternal and fetal risks. Two primigravida patients with elevated blood pressure and neurological symptoms underwent category 1 cesarean delivery under TIVA-TCI with propofol, using the Marsh model. Hemodynamic stability, drug dosing, and maternal–neonatal outcomes were monitored. Sufentanil was administered for analgesia; neuromuscular blockade was achieved with rocuronium and reversed with sugammadex. No BIS or TOF monitoring was available. Both patients maintained stable hemodynamics and oxygenation throughout surgery. Intubation was successfully performed at an effect-site concentration of 3.5 µg/mL. Neonatal Apgar scores were within acceptable limits. No major complications occurred intraoperatively or postoperatively. TCI allowed individualized dosing and smooth emergence. TIVA-TCI with propofol appears to be a viable alternative to volatile-based general anesthesia in category 1 emergencies for cesarean sections for patients with preeclampsia with severe features, especially when neuraxial anesthesia is controversial. It offers hemodynamic stability and controlled depth of anesthesia, though its use requires experience and may not be optimal in cases requiring ultra-rapid induction. Full article

HIV infection and hypertensive disorders of pregnancy (HDP), particularly preeclampsia (PE) with severe features, are leading causes of maternal mortality worldwide. This study investigates the role of asymmetric dimethylarginine (ADMA) and prostacyclin (PGI2) concentrations in endothelial impairment in normotensive pregnant versus PE women within an HIV endemic setting in KwaZulu-Natal Province, South Africa. The study population (n = 84) was grouped according to pregnancy type, i.e., normotensive (n = 42) and PE (n = 42), and further stratified by HIV status. Clinical factors were maternal age, weight, blood pressure (both systolic and diastolic) levels, and gestational age. Plasma concentrations of ADMA and PGI2 were measured using the enzyme-linked immunoassay (ELISA). Differences in outcomes were analyzed using the Mann–Whitney U and Kruskal–Wallis test together with Dunn’s multiple-comparison post hoc test. The non-parametric data were presented as medians and interquartile ranges. Gravidity, gestational age, and systolic and diastolic blood pressures were significantly different across the study groups where p < 0.05 was deemed significant. Furthermore, the concentration of ADMA was significantly elevated in PE HIV-positive vs. PE HIV-negative (p = 0.0174) groups. PGI2 did not show a significant difference in PE compared to normotensive pregnancies (p = 0.8826) but was significantly different across all groups (p = 0.0212). An increase in plasma ADMA levels was observed in the preeclampsia HIV-negative group compared to the normotensive HIV-negative group. This is linked to the role played by ADMA in endothelial impairment, a characteristic of PE development. PGI2 levels were decreased in PE compared to the normotensive group regardless of HIV status. These findings draw attention to the importance of endothelial indicators in pathogenesis and possibly early prediction of PE development. Full article

Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In this prospective cohort, preterm-born children (≤35 weeks’ gestation) with (n = 19) and without (n = 38) neonatal AKI were evaluated at 7–12 years. A term-born control group (n = 44) was included for biomarker comparison. Assessments included perinatal data, anthropometry, office and ambulatory blood pressure monitoring (ABPM), and renal ultrasonography. Kidney function was evaluated using serum creatinine (sCr), cystatin C, and estimated glomerular filtration rate (eGFR). Tubular injury was assessed using urinary kidney injury molecule-1/Cr (KIM-1/Cr), neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr), and trefoil factor 3/Cr (TFF3/Cr) ratios, as well as serum TFF3. Results: Conventional kidney function markers were similar among groups. However, the AKI group had higher serum cystatin C, lower cystatin C–based eGFR, and elevated urinary KIM-1/Cr and NGAL/Cr compared to no-AKI and term controls. Serum TFF3 was also higher in the AKI group. ABPM revealed higher nocturnal systolic blood pressure and blood pressure load in the AKI group. Kidney size did not differ between preterm subgroups. Conclusions: Neonatal AKI in preterm infants is associated with subtle alterations and potential renal stress or injury at school age, detectable only with sensitive biomarkers and ABPM. Further prospective studies are needed to validate these biomarkers and determine their role in predicting long-term outcomes in preterm infants with neonatal AKI. Full article

Objective: This study aimed to determine the possibility of creating a new animal model in which diabetic retinopathy (DR) progresses due to hypertension caused by salt loading. Methods: Male Spontaneously Diabetic Torii (SDT) fatty rats were divided into two groups: one group received 0.3% saline water starting at 8 weeks of age for a duration of 16 weeks (salt SDT fatty group), while the control group was provided with tap water (SDT fatty group). In addition, Sprague-Dawley (SD) rats receiving tap water served as normal controls. Retinal function was assessed by electroretinography (ERG) at 8 and 24 weeks of age. At 24 weeks, following perfusion with fluorescein dextran, the eyes were enucleated, and retinal flat mounts were prepared for vascular evaluation. Retinal thickness and the number of retinal folds were assessed histologically, and ultrastructural changes in the retina were examined using transmission electron microscopy. Results: Saline administration did not lead to significant changes in food consumption or body weight among the groups. In the salt SDT fatty group, blood pressure was significantly elevated, while blood glucose levels showed a slight reduction. ERG analysis showed that the amplitude of oscillatory potential (OP)1 waves was suppressed, and the latencies of OP3, OP4, and OP5 waves were prolonged. Although no significant changes were noted in retinal thickness or the number of retinal folds, thickening of the retinal capillary basement membrane was evident in the salt SDT fatty group. Conclusions: Hypertension induced by 0.3% saline promotes DR progression in SDT fatty rats. This model may help clarify the role of hypertension in DR. Full article

Objectives: To determine whether plasma concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are elevated in adults with prediabetes, we explored their association with tissue advanced glycation end-products (AGEs) and assessed the influence of Mediterranean diet adherence. Methods: This cross-sectional single-centre study included 92 adults with prediabetes and 86 age-/sex-matched normoglycaemic controls. Anthropometry, blood pressure, biochemical indices, and skin autofluorescence-derived AGEs were measured. Serum AEA and 2-AG were quantified by competitive ELISA, while Mediterranean diet adherence was assessed using the Mediterranean Diet Serving Score (MDSS). Results: Prediabetes was associated with higher AEA (p = 0.004) but not 2-AG (p = 0.520). Also, AEA correlated positively with AGE values (r = 0.36; p = 0.002) and increased across AGE-based cardiovascular risk categories. In multivariable models, both prediabetes status and AGE burden independently predicted AEA. Participants achieving MDSS ≥ 14 exhibited lower AEA (p = 0.038); 2-AG remained unaffected. Finally, the multivariable analysis confirmed that both prediabetes (β = 11.9; p = 0.005) and AGE values (β = 0.25; p = 0.003) are positively associated with plasma AEA levels, independent of age, sex, BMI, and fasting plasma glucose levels. Conclusions: Circulating AEA, but not 2-AG, is elevated in prediabetes and independently linked to cumulative AGE burden, suggesting early endocannabinoid activation contributes to cardiometabolic risk. High adherence to a Mediterranean diet may mitigate this dysregulation. Full article

Primary aldosteronism (PA), the most common cause of secondary hypertension, is increasingly recognized as an independent driver of adverse cardiac remodeling, mediated through mechanisms beyond elevated blood pressure alone. Chronic aldosterone excess leads to myocardial fibrosis, left ventricular hypertrophy, and diastolic dysfunction via mineralocorticoid receptor activation, oxidative stress, inflammation, and extracellular matrix dysregulation. These changes culminate in a distinct cardiomyopathy phenotype, often underrecognized in early stages. Multimodality cardiac imaging, led primarily by conventional and speckle-tracking echocardiography, and complemented by exploratory cardiac magnetic resonance (CMR) techniques such as T1 mapping and late gadolinium enhancement, enables non-invasive assessment of structural, functional, and tissue-level changes in aldosterone-mediated myocardial damage. While numerous studies have established the diagnostic and prognostic relevance of imaging in PA, several gaps remain. Specifically, the relative sensitivity of different modalities in detecting subclinical myocardial changes, the long-term prognostic significance of imaging biomarkers, and the differential impact of adrenalectomy versus medical therapy on cardiac reverse remodeling require further clarification. Moreover, the lack of standardized imaging-based criteria for defining and monitoring PA-related cardiomyopathy hinders widespread clinical implementation. This narrative review aims to synthesize current knowledge on the pathophysiological mechanisms of aldosterone-induced cardiac remodeling, delineate the strengths and limitations of existing imaging modalities, and critically evaluate the comparative effects of surgical and pharmacologic interventions. Emphasis is placed on early detection strategies, identification of imaging biomarkers with prognostic utility, and integration of multimodal imaging into clinical decision-making pathways. By outlining current evidence and highlighting key unmet needs, this review provides a framework for future research aimed at advancing personalized care and improving cardiovascular outcomes in patients with PA. Full article

Background/Objectives: Elevated serum uric acid levels are associated with the occurrence, development, and adverse events of coronary heart disease (CHD) and CHD risk factors. However, the extent of any pathogenic effect of the serum uric acid on CHD and whether CHD risk factors play a confounding or mediating role are still unclear. Methods: The potential causal associations of serum uric acid with CHD were evaluated via cross-trait linkage disequilibrium score regression analysis and Mendelian randomization. The pleiotropy of genetic tools was analyzed via a Bayesian colocalization approach. Moreover, we utilized two-step MR to identify risk factors mediating the relationship between uric acid and CHD. Results: Mendelian randomization results derived from two genetic instrument selection strategies support that serum uric acid levels have a significant causal relationship with coronary artery disease, stable angina pectoris, and myocardial infarction. This causal relationship was partially mediated by diastolic blood pressure, mean arterial pressure, and serum triglycerides. Transcriptomic analysis revealed that serum uric acid may directly contribute to the development of atherosclerosis by inducing transcriptomic changes in macrophages. Conclusions: Our findings highlight that the control of serum urate concentration in the long-term management of CHD patients may be necessary. Well-designed clinical trials and foundational research are presently required to furnish conclusive proof regarding the specific clinical scenarios in which adequate reduction in urate concentrations can confer cardiovascular advantages. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg·kg⁻¹·day⁻¹) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure. Full article

The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The present study investigates the pharmacological properties of Bothrops atrox venom (VBA), focusing specifically on its impact on renal blood flow. Following the renal perfusion procedure, kidney tissues were processed for histopathological examination. Statistical analysis of all evaluated parameters was conducted using ANOVA and Student’s t-test, with significance set at p < 0.005. Administration of VBA resulted in a marked reduction in both perfusion pressure and renal vascular resistance. In contrast, there was a significant elevation in urinary output and glomerular filtration rate. Histological changes observed in the perfused kidneys were mild. The involvement of nitric oxide in the pressor effects of Bothrops atrox venom was not investigated in renal perfusion systems or in in vivo models. Treatment with VBA led to elevated nitrite levels in the bloodstream of the experimental animals. This effect was completely inhibited following pharmacological blockade with L-NAME. Based on these findings, we conclude that VBA alters renal function and promotes increased nitric oxide production. Full article

Background: Blood pressure (BP) variability has been increasingly recognized as a predictor of cardiovascular and renal outcomes. However, the relevance of specific dynamic indices such as the maximum slope of systolic blood pressure (max SBP slope), derived through partial Fourier series modeling, in relation to early renal damage remains underexplored. Methods: A total of 389 patients with essential hypertension were enrolled and stratified according to the estimated glomerular filtration rate (eGFR) ≥ or <90 mL/min/1.73 m² and the presence of subclinical renal damage, defined by elevated urinary albumin excretion (AER) and/or reduced eGFR. All participants underwent clinical and biochemical evaluation, as well as 24-h ambulatory blood pressure monitoring (ABPM), including advanced hemodynamic analysis using Fourier-based modeling. Results: Patients with eGFR < 90 mL/min/1.73 m² were older and exhibited higher waist circumference, uricemia, albuminuria, and systolic BP values, including the elevated max SBP slope (12.8 vs. 10.8 mmHg/h, p = 0.028). Subclinical renal damage was associated with older age; male sex; smoking; and higher levels of uricemia, clinical, and ambulatory BP, and the max SBP slope (14.2 vs. 10.7 mmHg/h, p = 0.007). The max SBP slope positively correlated with AER (r = 0.215, p < 0.001) and inversely with eGFR (r = −0.153, p = 0.002). In multivariate linear regression, the max SBP slope remained independently associated with AER (β = 0.220, p < 0.001), along with mean 24-h SBP, male sex, and the day–night SBP percentage dip. Logistic regression confirmed these associations with subclinical renal damage (max SBP slope OR: 1.536; 95% CI: 1.241–2.004; p = 0.001). Conclusions: The max SBP slope, a dynamic index of BP derived via Fourier analysis, is independently associated with markers of subclinical renal damage in hypertensive patients. This suggests that incorporating such advanced metrics into ABPM evaluation may improve early risk stratification and help identify individuals at greater risk of renal impairment, even in the absence of overt kidney disease. Full article