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13 pages, 860 KB  
Article
Preoperative Transcranial Doppler Findings and Postoperative Delirium After Cardiac Surgery in Elderly Patients: A Prospective Observational Study
by Astrid Bergmann, Yurii Ruzhyn, Jan Wiesemann, Nikolai Hulde, Janis Fliegenschmidt, Alexander Krannich and Vera von Dossow
Life 2026, 16(6), 1026; https://doi.org/10.3390/life16061026 - 19 Jun 2026
Viewed by 124
Abstract
Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial [...] Read more.
Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial hemodynamics and may provide additional information for perioperative risk assessment. In this prospective single-center observational study, 108 patients aged >70 years scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Patients who had pre-existing neurological disease, had a pathological carotid Doppler ultrasound, underwent emergency surgery, or were unable to undergo delirium screening were excluded. Preoperative bilateral TCD of the middle cerebral arteries was performed using an automated WAKIe R3 system. POD was assessed on postoperative days 1–3 using the CAM-ICU. The primary endpoint was the occurrence of POD. Twenty-one patients were excluded, leaving 87 patients for analysis. POD occurred in 14 patients (16%). All patients who developed POD had pathological preoperative TCD findings, whereas no POD occurred among patients with normal TCD examinations. Overall, 82 patients (94%) demonstrated pathological intracranial hemodynamic findings despite normal carotid Doppler ultrasound. In multivariable Firth logistic regression adjusted for age and sex, pathological TCD findings remained associated with POD; however, interpretation was limited by the small number of outcome events and quasi-complete separation. In elderly patients undergoing cardiac surgery with cardiopulmonary bypass, pathological preoperative TCD findings were frequently observed and may be associated with an increased risk of postoperative delirium. The marked discrepancy between normal carotid ultrasound and abnormal intracranial hemodynamics suggests that TCD may provide complementary information regarding cerebrovascular function. Given the limited sample size and event rate, these findings should be considered exploratory and require confirmation in larger multicenter studies. Full article
(This article belongs to the Section Medical Research)
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19 pages, 1189 KB  
Article
A Follow-Up Study of the Supraaortic and Intracranial Vessels, Cerebrovascular Reactivity, Brain Vascular Lesions and Atrophy in Patients with Rheumatoid Arthritis
by Attila Sas, Dávid Jónyer, Attila Valikovics, László Kostyál, Zsuzsanna Oláh, Katalin Hodosi, Zsófia Kardos, Csaba Oláh and Zoltán Szekanecz
J. Clin. Med. 2026, 15(12), 4691; https://doi.org/10.3390/jcm15124691 - 17 Jun 2026
Viewed by 72
Abstract
Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression [...] Read more.
Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression and vascular changes over time, using their 2017 results as baseline. Methods: In 2023, we reassessed 43 of the original 60 RA patients using laboratory testing, carotid ultrasound, functional transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) examinations. Changes over time were analyzed within the same individuals. Results: Inflammatory markers and lipid profiles showed a trend toward improvement, though changes were not statistically significant, except for a significant increase in vitamin D (p < 0.001) and a decrease in Disease Activity Score in 28 Joints (DAS28) scores (p < 0.001). Carotid ultrasound revealed a significant increase in plaque burden (p = 0.022 on the right side and p = 0.008 on the left), while carotid intima media thickness (cIMT) showed a non-significant rise. TCD measurements indicated significantly increased pulsatility (p < 0.001 on the right, p = 0.001 on the left side) and resistance (p = 0.001 on the right, p = 0.012 on the left side) indices and reduced flow velocities (p < 0.001 on the right and p = 0.001 on the left side) in bilateral middle cerebral arteries (MCAs). The cerebrovascular reserve capacity was significantly lower on the right side overall (p = 0.013), with further decline noted in the methotrexate (MTX)-treated subgroup on the left side (p = 0.043). MRI findings showed non-significant numerical trends toward worsening lacunar small-vessel disease (p = 0.405) and cerebral atrophy (p = 0.063), with higher but stable lacunar infarction scores among MTX users (p = 0.023). Conclusions: Despite improved inflammatory control, RA patients demonstrated progressive vascular and hemodynamic alterations over time, while MRI changes should be interpreted as trends. These findings support multimodal vascular monitoring in RA. Full article
(This article belongs to the Section Immunology & Rheumatology)
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15 pages, 266 KB  
Article
Carotid Intima–Media Thickness and Atherogenic Indices in Idiopathic Pulmonary Fibrosis: Evidence of Subclinical Atherosclerosis
by Aydin Balci, Yasar Inkaya and Serkan Sen
Life 2026, 16(6), 988; https://doi.org/10.3390/life16060988 - 11 Jun 2026
Viewed by 213
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by poor prognosis and accumulating evidence of systemic vascular involvement. Although cardiovascular comorbidities are recognized in IPF, the presence and extent of subclinical atherosclerosis are yet to be fully characterized. This [...] Read more.
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by poor prognosis and accumulating evidence of systemic vascular involvement. Although cardiovascular comorbidities are recognized in IPF, the presence and extent of subclinical atherosclerosis are yet to be fully characterized. This study determined whether patients with IPF exhibit increased carotid intima–media thickness (CIMT) and altered atherogenic indices compared with healthy controls. Methods: This retrospective case–control study enrolled 117 patients with IPF diagnosed based on international guidelines and 104 age- and sex-matched healthy controls. All participants underwent comprehensive pulmonary function testing, the 6-min walk test (6MWT), laboratory evaluation (including lipid profiles), and bilateral carotid Doppler ultrasonography for CIMT measurement. Atherogenic indices, including the atherogenic coefficient, cholesterol ratio risk (CRR), and atherogenic index, were calculated. Dyspnea severity was evaluated using the visual analog scale (VAS). Results: Patients with IPF exhibited significantly higher CIMT (0.78 ± 0.12 mm vs. 0.68 ± 0.10 mm, p < 0.001) and CRR (4.12 ± 1.23 vs. 3.45 ± 0.98, p < 0.001) compared with controls. After adjustment for age, sex, cumulative smoking exposure expressed as pack-years, BMI, and controlled hypertension, IPF status remained independently associated with higher CIMT (adjusted β = 0.086 mm, 95% CI: 0.057–0.115; p < 0.001) and CRR (adjusted β = 0.482, 95% CI: 0.191–0.773; p = 0.001). Furthermore, patients with IPF had significantly lower HDL cholesterol levels and higher VLDL cholesterol levels. CIMT correlated negatively with 6MWT distance (r = −0.312, p = 0.001) and positively with VAS dyspnea scores (r = 0.287, p = 0.002). Conclusions: Patients with IPF showed higher CIMT and more unfavorable atherogenic profiles than healthy controls, and these associations persisted after adjustment for major vascular risk factors. The observed relationships between CIMT, functional capacity, and dyspnea severity suggest a potential association between IPF and subclinical cardiovascular involvement. Prospective studies are warranted to clarify the clinical relevance and prognostic implications of these findings. Full article
(This article belongs to the Section Medical Research)
14 pages, 242 KB  
Article
Association Between the CALLY Index and Carotid Artery Stenosis Severity in Patients Younger and Older than 65 Years
by Demet Doğan and Erce Güler
J. Clin. Med. 2026, 15(11), 4242; https://doi.org/10.3390/jcm15114242 - 30 May 2026
Viewed by 251
Abstract
Background/Objectives: Atherosclerosis is a multifaceted inflammatory condition closely linked to immunonutritional status. The C-reactive protein–albumin–lymphocyte (CALLY) index is a composite marker of immunonutrition. We assessed the relationship between this index, age, and carotid stenosis in individuals undergoing carotid Doppler ultrasonography. Methods: [...] Read more.
Background/Objectives: Atherosclerosis is a multifaceted inflammatory condition closely linked to immunonutritional status. The C-reactive protein–albumin–lymphocyte (CALLY) index is a composite marker of immunonutrition. We assessed the relationship between this index, age, and carotid stenosis in individuals undergoing carotid Doppler ultrasonography. Methods: Individuals who underwent routine carotid Doppler ultrasonography were retrospectively analyzed. Carotid stenosis was categorized by severity, and bilateral intima–media thickness was recorded. The composite index integrating C-reactive protein, albumin, and lymphocyte parameters was derived from laboratory parameters. Traditional cardiovascular risk factors, including hypertension, diabetes mellitus, hyperlipidemia, and smoking status, were also recorded and incorporated into multivariable analyses. Sex-related differences were additionally evaluated using sex-stratified correlation analyses. Results: Among 1516 patients, 895 (59.1%) were younger than 65 years and 621 (40.9%) were aged 65 years and above. Carotid artery stenosis and intima–media thickness were significantly higher in individuals aged 65 years and above. The mean index value was significantly lower in the older group (4.0 versus 8.3; p < 0.001). Hypertension, diabetes mellitus, and hyperlipidemia were significantly more prevalent in patients with carotid stenosis (p < 0.001 for all), whereas smoking was not associated (p > 0.05). Male sex was independently associated with carotid stenosis, and sex-stratified analyses demonstrated similar inverse associations between age and CALLY index values in both sexes. In multivariable analysis, lower index values were independently associated with carotid stenosis and carotid intima–media thickness in both age groups. In the overall cohort, the index demonstrated moderate discriminatory performance (area under the curve = 0.724). Similar moderate performance was observed in the <65 (AUC = 0.681) and ≥65 (AUC = 0.685) subgroups. Conclusions: The CALLY index was independently associated with carotid stenosis and CIMT after adjustment for traditional cardiovascular risk factors. Although effect sizes were comparable between age groups, CALLY index levels were lower in older individuals. These findings suggest that the CALLY index may provide complementary information in the assessment of carotid atherosclerosis, particularly in elderly populations. However, given the retrospective cross-sectional design and moderate discriminatory performance, it should not be interpreted as a standalone, causal, or disease-specific marker. Full article
(This article belongs to the Special Issue Cardiovascular Disease in the Elderly: Prevention and Diagnosis)
14 pages, 263 KB  
Article
Analysis of the Relationship of Glycated Hemoglobin with Subclinical Atherosclerosis and Arterial Stiffness in Non-Diabetic Patients: A Retrospective Study
by Grzegorz K. Jakubiak, Natalia Pawlas, Dominika Blachut, Artur Chwalba, Andrzej Tomasik, Agata Stanek and Grzegorz Cieślar
J. Clin. Med. 2026, 15(10), 3627; https://doi.org/10.3390/jcm15103627 - 9 May 2026
Viewed by 452
Abstract
Background: Cardiometabolic diseases present a major challenge to contemporary public health. Diabetes mellitus (DM) is widely recognized as a strong cardiovascular risk factor. However, the utility of glycated hemoglobin percentage (HbA1c) for assessing cardiovascular health in individuals without DM remains uncertain. This study [...] Read more.
Background: Cardiometabolic diseases present a major challenge to contemporary public health. Diabetes mellitus (DM) is widely recognized as a strong cardiovascular risk factor. However, the utility of glycated hemoglobin percentage (HbA1c) for assessing cardiovascular health in individuals without DM remains uncertain. This study examines the association between HbA1c levels and both the presence and severity of subclinical atherosclerosis and arterial stiffness in non-diabetic individuals. Methods: A retrospective analysis was conducted on the data from 59 patients (72.88% female; mean age: 54.82 ± 17.34 years) who exhibited no signs of acute illness or exacerbation of chronic diseases. All patients were hospitalized in the Department of Internal Medicine, Angiology and Physical Medicine at the Medical University of Silesia in Katowice, Poland, between June 2022 and May 2024. HbA1c level determination, central blood pressure measurement with pulse wave analysis (PWA), carotid–femoral pulse wave velocity (cfPWV) measurement, and Doppler ultrasound of the carotid arteries and lower extremity arteries measuring the intima–media thickness (IMT) in the common carotid arteries (cIMT), common femoral arteries (cfIMT), and superficial femoral arteries (sfIMT) were performed. Spearman’s rank correlation test was applied for statistical analysis. Subsequently, a multivariate analysis model was constructed, adjusting for age, sex, body mass index (BMI), and smoking. Results: Among the assessed parameters, the strongest positive correlations were found between HbA1c and parameters such as cIMT (R = 0.532; p < 0.001), cfIMT (R = 0.63; p < 0.001), sfIMT (R = 0.539; p < 0.001), and cfPWV (R = 0.504; p < 0.001). In the multivariate analysis model, a significant relationship was found only between HbA1c and augmentation index normalized to a heart rate of 75 per minute (AIx75) (β = −0.286; 95% CI: −0.566, −0.006; p = 0.045). Conclusions: In summary, although HbA1c correlates with some parameters related to arterial stiffness and subclinical atherosclerosis in non-diabetic patients, most observed relationships are explained by confounding variables. Full article
15 pages, 406 KB  
Article
Carotid Intima–Media Thickness and Narrowing in Rheumatoid Arthritis: Impact of Age, Diabetes, and Conventional Risk Factors
by Fahad F. Almutairi, Jaber H. Alsalah, Husam K. Alzubaidi, Mohammad Mustafa, Yasser Bawazir, Khalid Bahamdein, Hassan Balubaid, Haifa Alnahdi, Khalid Khashoggi, Bander Almutairi, Shoaa Shetewi, Fahad Alrwaithi, Shadi Abushaheen, Dana Attraji, Sara Alsaylani, Huda Alamri, Rawan Abdeen, Hamzah H. Ahmed and Mohammad Khalil
Biomedicines 2026, 14(4), 817; https://doi.org/10.3390/biomedicines14040817 - 3 Apr 2026
Viewed by 508
Abstract
Background: Rheumatoid arthritis (RA) has been linked to increased cardiovascular risk; however, whether RA independently contributes to subclinical atherosclerosis remains unclear. This study aimed to evaluate carotid intima–media thickness (IMT) and carotid narrowing in RA patients compared with controls and to examine their [...] Read more.
Background: Rheumatoid arthritis (RA) has been linked to increased cardiovascular risk; however, whether RA independently contributes to subclinical atherosclerosis remains unclear. This study aimed to evaluate carotid intima–media thickness (IMT) and carotid narrowing in RA patients compared with controls and to examine their associations with conventional cardiovascular risk factors. Methods: A total of 73 RA patients and 78 healthy controls underwent carotid Doppler ultrasonography to assess IMT and carotid narrowing. Non-parametric analyses were used for between-group comparisons, and associations with clinical variables were evaluated within the RA cohort. Results: The median age was 55 years (IQR: 43–63) in the RA group and 61 years (IQR: 51–68) in controls (p = 0.012). No significant differences were observed in median right CCA IMT (RA: 0.070 mm [IQR: 0.060–0.081] vs. controls: 0.068 mm [IQR: 0.050–0.076]; p = 0.619) or left CCA IMT (RA: 0.065 mm [IQR: 0.051–0.079] vs. controls: 0.065 mm [IQR: 0.050–0.074]; p = 0.701). The prevalence of carotid narrowing was also comparable between groups (right CCA: 15.1% vs. 11.5%, p = 0.633). Within the RA cohort, age was positively correlated with right CCA IMT (Spearman’s rho = 0.375, p = 0.001), and diabetes mellitus was associated with a higher prevalence of right CCA narrowing (34.8% vs. 6.0%, p = 0.003). Conclusions: Carotid IMT and narrowing were not significantly different between RA patients and controls. In this cohort, age and diabetes mellitus were more strongly associated with subclinical carotid atherosclerosis than RA status itself. These findings emphasize the importance of comprehensive cardiovascular risk assessment in RA patients, particularly focusing on traditional risk factors. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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11 pages, 239 KB  
Article
Early Vascular Aging and Subclinical Myocardial Deformation in Children with β-Thalassemia Major: The Role of Asymmetric Dimethylarginine
by Pelin Kosger, Zeynep Canan Özdemir, Ayse Sulu, Özcan Bör and Birsen Uçar
Children 2026, 13(4), 461; https://doi.org/10.3390/children13040461 - 27 Mar 2026
Viewed by 502
Abstract
Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular [...] Read more.
Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular aging, yet their impact on myocardial deformation in pediatric patients remains incompletely characterized. Objectives: To evaluate subclinical myocardial dysfunction and arterial stiffness in children with β-TM and to investigate hemolysis-related changes in asymmetric dimethylarginine (ADMA) and L-arginine as biomarkers of endothelial dysfunction in relation to cardiovascular involvement. Methods: Twenty-four children with β-TM and 20 age-matched healthy controls were included. Cardiac structure and myocardial deformation were assessed by conventional echocardiography, tissue Doppler imaging, and speckle-tracking strain analysis. Arterial stiffness was evaluated using oscillometric pulse wave analysis and bilateral carotid intima–media thickness (CIMT). Serum ADMA and L-arginine levels were measured, and hemoglobin, reticulocyte count, and ferritin levels were recorded. Results: Children with β-thalassemia major demonstrated significantly increased arterial stiffness compared with controls, including higher PWV (4.61 ± 0.37 vs. 4.38 ± 0.31), AIx@75 (augmentation index at 75 bpm) (28.5 ± 8.34 vs. 22.8 ± 6.51), left CIMT [0.45 (0.39–0.51) vs. 0.41 (0.38–0.46)], and right CIMT [0.43 (0.39–0.54) vs. 0.40 (0.34–0.46)]. In addition, patients exhibited reduced global longitudinal strain (−19.3 ± 2.91 vs. −21.84 ± 1.91), prolonged isovolumetric relaxation time [53 (37–71) vs. 45 (37–55)], and elevated E/Em (8.44 ± 2.19 vs. 6.92 ± 1.10). ADMA levels were significantly higher in patients (0.54 ± 0.19 vs. 0.39 ± 0.22) and were positively associated with reticulocyte counts and inversely correlated with hemoglobin levels. In addition, both ADMA and ferritin levels were positively correlated with arterial stiffness indices and left ventricular filling pressures. Conclusions: Children with β-thalassemia major exhibit features suggestive of early cardiovascular aging, including impaired myocardial deformation, diastolic involvement, and increased arterial stiffness. The observed association between ADMA levels and markers of hemolysis, vascular stiffness, and myocardial deformation highlights the potential involvement of endothelial dysfunction in premature myocardial–vascular remodeling. These findings suggest that ADMA may serve as a promising biomarker for early cardiovascular risk in pediatric β-thalassemia major; however, further longitudinal and multi-center studies are needed to confirm its clinical utility for risk stratification. Full article
(This article belongs to the Section Pediatric Cardiology)
20 pages, 4332 KB  
Article
Design and Pilot Evaluation of an IoT-Based Blood Pressure Monitoring System for Rabbits
by Carlos Exequiel Garay, Gonzalo Nicolás Mansilla, Rossana Elena Madrid, Agustina González Colombres and Susana Josefina Jerez
Bioengineering 2026, 13(4), 384; https://doi.org/10.3390/bioengineering13040384 - 26 Mar 2026
Viewed by 1053
Abstract
Telemedicine, driven by the Internet of Things (IoT) and wireless connectivity, is essential for managing cardiovascular diseases, where hypertension remains the primary risk factor. In preclinical research, rabbits are superior biological models compared to rodents due to their human-like lipid metabolism. However, continuous [...] Read more.
Telemedicine, driven by the Internet of Things (IoT) and wireless connectivity, is essential for managing cardiovascular diseases, where hypertension remains the primary risk factor. In preclinical research, rabbits are superior biological models compared to rodents due to their human-like lipid metabolism. However, continuous blood pressure monitoring in this species remains challenging. The gold-standard technique (direct carotid catheterization) requires terminal procedures, and indirect methods (Doppler, oscillometric) show limited agreement with direct measurements. Furthermore, commercially available implantable telemetry platforms, while enabling real-time monitoring in freely moving animals, require costly surgical implantation, specialized proprietary hardware, and post-operative recovery periods that may confound early hemodynamic data. To address these limitations, this study presents a low-cost, customizable, and minimally invasive monitoring system utilizing a pressure transducer in the central auricular artery. The device integrates an ESP32 microcontroller with IoT technology for digital signal processing and seamless wireless data transmission to the ThingSpeak cloud platform. Unlike implantable telemetry, the proposed approach avoids surgical implantation and its associated costs and recovery time, while still enabling continuous, real-time hemodynamic tracking throughout the experimental period. A pilot evaluation against the BIOPAC MP100 reference (carotid artery) demonstrated relative errors of 1.60% for mean arterial pressure, 8.58% for systolic blood pressure, and 2.43% for diastolic blood pressure. By reducing invasiveness and enhancing remote data accessibility, this system provides a promising framework for the preclinical evaluation of antihypertensive agents and cardiovascular mechanisms, bridging the gap between edge computing and remote clinical diagnostics. Full article
(This article belongs to the Section Biosignal Processing)
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29 pages, 11181 KB  
Review
Ocular Color Doppler Ultrasound (OCDUS) in Diagnosis and Monitoring of Ophthalmological, Cerebrovascular and Systemic Diseases: A Narrative Review
by Massimo Venturini, Silvia Malnati, Noemi Teresa Catania, Andrea Coppola, Chiara Recaldini, Aroa Gnesutta, Marianna Ciani, Silvia Tamietti, Emilio Simonini, Alberta Cappelli, Simone Donati, Filippo Piacentino and Federico Fontana
J. Clin. Med. 2026, 15(6), 2458; https://doi.org/10.3390/jcm15062458 - 23 Mar 2026
Cited by 1 | Viewed by 803
Abstract
Ocular Color Doppler ultrasound (OCDUS) has been underutilized in the past as a diagnostic technique, although several OCDUS-based studies were performed in the last 30 years for diagnosis or monitoring of some ophthalmological, cerebrovascular or systemic diseases. OCDUS can provide quantitative and reproducible [...] Read more.
Ocular Color Doppler ultrasound (OCDUS) has been underutilized in the past as a diagnostic technique, although several OCDUS-based studies were performed in the last 30 years for diagnosis or monitoring of some ophthalmological, cerebrovascular or systemic diseases. OCDUS can provide quantitative and reproducible measurements of the blood flow of the main orbital vessels at the retrobulbar level. In this narrative review we aimed to investigate the relevance of OCDUS as an imaging modality in several ophthalmological, cerebrovascular and systemic diseases based on the current literature. Full article
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11 pages, 246 KB  
Article
The Role of Immune Dysregulation Markers in Cardiovascular Risk of People Living with HIV: Association Among Intima Media Changes, CD4/CD8 Ratio, and CD4+ Cell Count Nadir
by Manuela Ceccarelli, Elena Delfina Ricci, Camilla Muccini, Laura Galli, Sergio Ferrara, Alessandra Tartaglia, Benedetto Maurizio Celesia, Elio Manzillo, Alessandra Guida, Giovanni Di Filippo, Rosa Basile, Antonella Castagna and Paolo Maggi
Viruses 2026, 18(3), 383; https://doi.org/10.3390/v18030383 - 18 Mar 2026
Viewed by 693
Abstract
HIV infection can promote persistent immune activation and endothelial dysfunction, contributing to atherosclerosis. Carotid intima–media thickness (cIMT) is an established marker of subclinical atherosclerosis. We evaluated the association between cIMT severity and two routinely available markers of immune dysregulation (CD4/CD8 ratio and nadir [...] Read more.
HIV infection can promote persistent immune activation and endothelial dysfunction, contributing to atherosclerosis. Carotid intima–media thickness (cIMT) is an established marker of subclinical atherosclerosis. We evaluated the association between cIMT severity and two routinely available markers of immune dysregulation (CD4/CD8 ratio and nadir CD4+ cell count) in people living with HIV (PLWH). We conducted an Italian multicenter cross-sectional study including 1148 PLWH who underwent carotid color Doppler ultrasound. We classified cIMT as ≤0.9, 1.0–1.4, or >1.4 mm and analyzed these categories using multinomial logistic regression, reporting adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We adjusted models for age, sex, BMI, HIV acquisition risk factor, hypertension, diabetes, dyslipidemia/statin use, triglycerides, integrase inhibitor use, and ART duration. cIMT was ≤0.9 mm in 615 (53.6%) participants, 1.0–1.4 mm in 379 (33.0%), and >1.4 mm in 154 (13.4%). Using nadir CD4+ ≥ 200 cells/µL and CD4/CD8 ≥ 1.0 as reference, PLWH with nadir CD4+ < 200 and CD4/CD8 ≥ 1.0 had higher odds of cIMT 1.0–1.4 mm (aOR 1.66, 95% CI 1.02–2.69) and >1.4 mm (aOR 3.45, 95% CI 1.68–7.07). In conclusion, CD4+ nadir and this combined pattern were associated with greater cIMT severity, supporting a role for immune dysregulation in subclinical atherosclerosis. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
39 pages, 13943 KB  
Article
Characterizing Initial Cervical Spine and Neurovascular Findings in 84 Consecutive Patients with Hypermobile Ehlers–Danlos Syndrome: A Retrospective Study
by Ross A. Hauser, Morgan Griffiths, Ashley Watterson, Danielle Matias and Benjamin R. Rawlings
J. Clin. Med. 2026, 15(6), 2212; https://doi.org/10.3390/jcm15062212 - 14 Mar 2026
Viewed by 3899
Abstract
Background: Hypermobile Ehlers–Danlos syndrome (hEDS) can present as a complex interplay of widespread symptomatology and multisystem involvement, posing diagnostic and treatment challenges. Objective characterization of cervical spine and neurovascular findings in hEDS has been limited. Previous studies have emphasized upper cervical spine [...] Read more.
Background: Hypermobile Ehlers–Danlos syndrome (hEDS) can present as a complex interplay of widespread symptomatology and multisystem involvement, posing diagnostic and treatment challenges. Objective characterization of cervical spine and neurovascular findings in hEDS has been limited. Previous studies have emphasized upper cervical spine complications in hEDS, yet the relevance and mechanisms underlying associated symptomatology have not been elucidated. This study examined objective test findings in patients with hEDS at an outpatient neck clinic to explore cervical spine and neurovascular pathology that could contribute to further understanding the clinical profile of a subset of patients with hEDS. Methods: This single-center, retrospective observational study included patients with hEDS aged 20–50 years from 1 January 2022–31 December 2024, at an outpatient neck center. It excluded previous neck surgery, traumatic events, or related injury. Demographic, clinical, and diagnostic data were collected through a retrospective chart review, including measurements from standard clinical diagnostic protocols: digital motion X-ray (videofluoroscopy), cone beam CT, Doppler ultrasound, and tonometry. Results: More than 71% of patients reported ≥29 symptoms. Nearly all patients exhibited co-occurring forward head, decreased depth of curve, ligamentous cervical instability, and decreased internal jugular vein (IJV) and vagus nerve cross-sectional area (CSA). Vagus nerve CSA was found to be significantly smaller than the comparative healthy/normal population. IJV CSA was significantly smaller at C1 than at C4–C5, suggesting evidence of carotid sheath compression at C1. Conclusions: This study offers novel evidence that cervical spine pathology, IJV compression, and vagus nerve degeneration are uniformly prevalent in hEDS, which may contribute to, or be an etiological basis for, the multisystem involvement in a subset of patients with this disorder. These findings provide hypothesis-generating data to inform future mechanistic and therapeutic studies, including exploration of new diagnostic and treatment targets. Full article
(This article belongs to the Special Issue Clinical Advances in Musculoskeletal Disorders: 2nd Edition)
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17 pages, 1093 KB  
Article
Concomitant Dysregulation of Cerebral Vasoreactivity and Arterial Blood Pressure Is Closely Related in Patients with Carotid Stenosis
by Hanga Pál, Rita Magyar-Stang, Borbála Csányi, Anna Gaál, Zsuzsanna Mihály, Zsófia Czinege, Péter Sótonyi, Tamás Horváth, Balázs Dobi, Dániel Bereczki, Akos Koller and Róbert Debreczeni
Life 2026, 16(3), 472; https://doi.org/10.3390/life16030472 - 13 Mar 2026
Viewed by 862
Abstract
Background: In patients with severe atherosclerotic internal carotid artery stenosis (ICAS), the capacity of cerebral vasoreactivity (CVR)—an independent risk factor for cerebral ischemia—is reduced, and dysregulation of arterial blood pressure (ABP) may also be present. Thus, this study assessed the relationship between changes [...] Read more.
Background: In patients with severe atherosclerotic internal carotid artery stenosis (ICAS), the capacity of cerebral vasoreactivity (CVR)—an independent risk factor for cerebral ischemia—is reduced, and dysregulation of arterial blood pressure (ABP) may also be present. Thus, this study assessed the relationship between changes in cerebral blood flow velocity (BFV) in response to vasoactive stimuli (as measured by transcranial Doppler (TCD)), characterizing CVR and cardiovascular autonomic nervous system (CANS) function. Methods: Common carotid artery compression (CCC n = 26), hyperventilation (HV) and breath-holding (BH) tests (n = 31), and the Valsalva maneuver (VM n = 34) were used to assess CVR in patients with ICAS. In the middle cerebral arteries, BFV was monitored by TCD, whereas ABP was registered non-invasively. For statistical analysis, validated indices describing CANS function—namely, sympathetic index (SI), pressure recovery time (PRT), and Valsalva heart rate ratio (VHRR)—were selected based on the VM response. Several parameters were defined in order to evaluate CVR responses, including cerebral arterial resistance (CAR = ABP/BFV), which was correlated with the CVR indices using Spearman’s pairwise correlation and canonical correlation. Results: A significant correlation was found between several CVR indices of the HV-BH and VM tests and CANS indices of VM using Spearman’s pairwise correlation test. Regarding the HV-BH CVR and CANS indices of VM, a significant correlation was found between CAR values until it reached its maximum on the to-be-operated side (CARtimetomaxICAop) and VHRR (p = 0.041). A significant correlation was also found between the time elapsed until the CAR minimum value (CARtimetominICAop) and SI (p = 0.019). Concerning the CVR and CANS indices of the VM, a significant correlation was found between cerebrovascular Valsalva ratio on the to-be-operated side (CVARICAop) and PRT (p = 0.002). Canonical correlation analysis confirmed that impairments of CANS and CVR may be associated. Conclusions: In patients with severe ICAS, the potentially concomitant dysregulation of cerebrovascular reactivity and the cardiovascular autonomic nervous system can further increase cerebral ischemic risk. Full article
(This article belongs to the Section Medical Research)
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17 pages, 272 KB  
Article
Retinal Dysfunction in Hypertensive Patients with Atherosclerotic Plaque Detected by Carotid Doppler Ultrasound: An Optical Coherence Tomography Angiography Assessment
by Irina Barca, Vasile Potop and Stefan Sorin Arama
Life 2026, 16(3), 436; https://doi.org/10.3390/life16030436 - 9 Mar 2026
Viewed by 743
Abstract
Background: Our study aimed to evaluate whether OCTA can detect retinal dysfunction in hypertensive patients with atherosclerotic plaque in order to improve early detection of vascular changes and to better adjust treatment protocols. Therefore, we can potentially reduce the rate of ocular, [...] Read more.
Background: Our study aimed to evaluate whether OCTA can detect retinal dysfunction in hypertensive patients with atherosclerotic plaque in order to improve early detection of vascular changes and to better adjust treatment protocols. Therefore, we can potentially reduce the rate of ocular, cardiovascular and cerebral complications of hypertension and of dyslipidemia. Methods: We performed a study on hypertensive patients with dyslipidemia undergoing specific treatment. Ten OCTA parameters, the presence of carotid plaque on carotid Doppler ultrasound and three types of antihypertensive drugs were analyzed. An increased carotid intima-media thickness (IMT) (≥1.0 mm) or the presence of carotid plaque was defined as subclinical atherosclerosis. We correlated classes of medication with OCTA parameters and with Doppler assessment. Results: In the final study, we included 196 eyes of 98 patients; 51 subjects had carotid plaques. Three groups were formed: antihypertensive monotherapy, including Angiotensin-converting enzyme inhibitor (ACEI) or Calcium channel blocker (CCB) + statins, and combined antihypertensive therapy, including ACEI/Angiotensin Receptor Blocker (ARB) + statins. We found statistically significant results in the presence of atherosclerotic plaques as follows: increased avascular zone (FAZ) and decreased vascular flow area (VFA) in the ACEI group, increased FAZ Circularity and a reduction in Density Total in the CCB lot, higher values of non-flow area (NFA), FAZ Area and decreased Density Total in the ACEI/ARB group. Conclusions: The strongest correlations we found were between increased hypertension, decreased retinal microcirculation and the presence of atherosclerotic plaques in patients using combined antihypertensive therapy and statins. The results indicate that subjects with multiple therapies, advancing hypertensive retinopathy and atherosclerotic carotid plaques display a deficit in retinal vascularization. OCTA can provide early detection of microvascular changes in hypertension associated with dyslipidemia and carotid plaques. Thus, by correlating OCTA and carotid Doppler ultrasound, antihypertensive and statin therapy can be adjusted and disease risk stratification can be obtained. Full article
(This article belongs to the Special Issue Research on Glaucoma Diseases)
13 pages, 1056 KB  
Article
Micro- and Macro-Vascular Disease in Systemic Sclerosis and Very Early SSc (VEDOSS): Results from a Monocentric Observational Study
by Vincenzo Zaccone, Silvia Contegiacomo, Silvia Agarbati, Chiara Paolini, Carolina Clementi, Matteo Mozzicafreddo, Silvia Svegliati, Lorenzo Falsetti, Devis Benfaremo and Gianluca Moroncini
Biomedicines 2026, 14(3), 607; https://doi.org/10.3390/biomedicines14030607 - 9 Mar 2026
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Abstract
Background: Systemic sclerosis (SSc) is characterized by endothelial dysfunction leading to progressive vascular injury and fibrosis. While microvascular involvement is well established as an early disease feature, macrovascular disease has been historically underrecognized and poorly investigated in very early disease stages. Integrated [...] Read more.
Background: Systemic sclerosis (SSc) is characterized by endothelial dysfunction leading to progressive vascular injury and fibrosis. While microvascular involvement is well established as an early disease feature, macrovascular disease has been historically underrecognized and poorly investigated in very early disease stages. Integrated assessments across the SSc spectrum, including very early diagnosis of systemic sclerosis (VEDOSS), remain limited. Methods: In this cross-sectional observational study, patients with established SSc, VEDOSS, and primary Raynaud’s phenomenon (PRP) were prospectively enrolled between October 2023 and April 2025. Participants underwent comprehensive microvascular and macrovascular evaluation, including nailfold videocapillaroscopy, multisegmental arterial Doppler ultrasound (carotid, aortic, and lower limb districts), flow-mediated dilation, and measurement of endothelial biomarkers (vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and circulating endothelial cells (CECs)). Traditional cardiovascular risk was estimated using Systematic Coronary Risk Estimation 2 (SCORE2). Results: Sixty-two female subjects were included (34 SSc, 14 VEDOSS, and 14 PRP). Microvascular abnormalities followed the expected disease continuum, with capillaroscopic changes present in 57% of VEDOSS and 91% of SSc patients. Although SCORE2 estimates and carotid intima–media thickness were comparable across groups, macrovascular abnormalities were more frequent in SSc (52.9%) and VEDOSS (50%) compared with PRP (21.4%). VCAM-1, ICAM-1, and CEC levels were significantly increased in SSc compared with PRP, whereas no significant differences were observed between VEDOSS and PRP. Conclusions: These findings support a unified micro- and macro-vascular disease model in SSc and demonstrate that macrovascular involvement is detectable already in the VEDOSS phase. Conventional cardiovascular risk scores underestimate the true vascular burden, highlighting the need for disease-specific risk stratification tools integrating vascular imaging and endothelial biomarkers. Full article
(This article belongs to the Section Cell Biology and Pathology)
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11 pages, 1059 KB  
Article
Serum Osteoprotegerin Level Is Not a Localizing Biomarker of Atherosclerosis Affected by Kidney Function
by Anna Maria Bednarek, Aleksander Jerzy Owczarek, Dominika Dziadosz, Magdalena Olszanecka-Glinianowicz and Jerzy Tadeusz Chudek
Diagnostics 2026, 16(5), 786; https://doi.org/10.3390/diagnostics16050786 - 6 Mar 2026
Cited by 1 | Viewed by 622 | Correction
Abstract
Introduction: Osteoprotegerin (OPG) is recognized as an emerging biomarker for atherosclerosis. We hypothesized that atherosclerotic lesions localized across multiple vascular beds would result in greater elevations in OPG levels in the blood. Therefore, our study aimed to assess serum OPG levels and [...] Read more.
Introduction: Osteoprotegerin (OPG) is recognized as an emerging biomarker for atherosclerosis. We hypothesized that atherosclerotic lesions localized across multiple vascular beds would result in greater elevations in OPG levels in the blood. Therefore, our study aimed to assess serum OPG levels and their confounding factors in patients with hemodynamically significant multivessel atherosclerosis in varying locations. Subjects and Methods: A case–control study included 222 selected outpatients aged 50 years or older (46.4% women) with atherosclerosis confirmed by imaging (Doppler ultrasound and CT angiography) treated at a single angiology clinic. Data concerning age, smoking status, comorbidity (hypertension, diabetes mellitus, history of stroke, myocardial infarction, coronary revascularization procedures), medication, lipid profile, serum creatinine, and homocysteine levels were retrieved from medical records. Additionally, serum OPG levels were measured. Patients were divided according to serum OPG levels into terciles and the number of involved vascular beds [carotid artery disease, coronary heart disease (CHD), lower-extremity peripheral artery disease (PAD), abdominal aorta aneurysm (AAA)]. Results: The distribution of carotid artery disease, CHD, PAD, and AAA did not differ across the OPG terciles. Additionally, we did not observe differences in OPG levels between specific and multiple locations of atherosclerotic lesions. Subjects with the highest OPG levels were the oldest (75.0 ± 8.4 vs. 69.8 ± 7.1 years in the lowest tercile; p < 0.001) and were characterized by the worst kidney function (eGFR 60.8 ± 16.8 vs. 74.1 ± 13.5 mL/min/1.73 m2; p < 0.001). Conclusions: The serum OPG level did not reveal the specific location of atherosclerosis. Impaired renal function appears to be the primary determinant of serum OPG levels and a key confounder, complicating the interpretation of serum OPG as a biomarker of atherosclerosis. Full article
(This article belongs to the Special Issue Recent Advances in Biomarkers for Cardiovascular Disease)
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