Journal of Vascular Diseases

Background: Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD), driven by mechanisms distinct from the general population. Fibroblast Growth Factor 23 (FGF-23), a phosphaturic hormone elevated early in CKD, has been mechanistically linked to left ventricular hypertrophy, vascular dysfunction, and disordered mineral metabolism. This study examines the associations between FGF-23 and key renal, mineral, and cardiovascular parameters and its utility in risk stratification. Methods: We conducted a cross-sectional study of 60 adults with CKD stages 1–5. Serum FGF-23 was quantified using ELISA, alongside measures of iPTH, phosphorus, calcium, and eGFR (Estimated Glomerular Filtration Rate). Cardiovascular evaluation included transthoracic echocardiography and carotid intima-media thickness (CIMT). Associations were analyzed using Spearman correlations, ROC analysis, and multivariable logistic regression. Results: FGF-23 levels were significantly associated with declining eGFR (r = –0.288; p < 0.05), elevated iPTH (Intact Parathyroid Hormone) (r = 0.361; p < 0.05), and serum phosphorus (r = 0.335; p < 0.05). Patients with structural cardiac abnormalities (left atrial enlargement or left ventricular hypertrophy) exhibited higher FGF-23 concentrations (154 vs. 128 pg/mL; p = 0.027). FGF-23 alone predicted high cardiovascular risk with moderate accuracy (AUC 0.70; sensitivity 76%; specificity 67%). A composite model including iPTH and eGFR improved discriminatory power (AUC 0.76). Conclusions: FGF-23 correlates with subclinical cardiovascular remodeling and key mineral abnormalities in CKD. Its integration with iPTH and eGFR enhances cardiovascular risk stratification, supporting its potential as a multidimensional biomarker in early CKD. However, the cross-sectional design and modest correlation strengths limit causal inference and generalizability of the findings. Full article

An ascending aortic aneurysm is a localized dilation of the ascending aorta, which poses a high risk of aortic dissection or rupture, with surgery recommended at diameters > 5.5 cm. However, events also occur at smaller sizes, suggesting additional factors—such as stenosis—may significantly influence aneurysm severity. To investigate this, a computational fluid dynamics (CFD) analysis was conducted using a patient-specific ascending aortic model (aneurysm diameter: 5.28 cm) under three aortic stenosis severities: mild, moderate, and severe. Results showed that the severe stenosis condition led to the formation of prominent recirculation zones and increased peak velocities, 2.36 m·s⁻¹ compared to 1.53 m·s⁻¹ for moderate stenosis and 1.37 m·s⁻¹ for mild stenosis. A significantly increased pressure loss coefficient was observed for the severe case. Additionally, the wall shear stress (WSS) distribution exhibited higher values along the anterior region and lower values along the posterior region. Peak WSS values were recorded at 43.46 Pa in the severe stenosis model, compared to 21.98 Pa and 13.87 Pa for the moderate and mild cases, respectively. Velocity distribution and helicity analyses demonstrate that increasing stenosis severity amplifies jet-induced flow disturbances, contributing to larger recirculation zones and greater helicity heterogeneity in the ascending aorta. Meanwhile, WSS results indicate that greater stenosis severity is also associated with elevated WSS magnitude and heterogeneity in the ascending aorta, with severe cases exhibiting the highest value. These findings highlight the need to incorporate hemodynamic metrics, alongside traditional diameter-based criteria, into rupture risk assessment frameworks. Full article

Background: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting large and medium-sized arteries, predominantly in individuals over 50 years. While it traditionally involves cranial branches of the external carotid artery, particularly the temporal arteries, growing evidence underscores frequent extracranial involvement, especially in the supra-aortic trunks. Objective: We aimed to critically review the diagnostic utility of extended Color Doppler Ultrasound (CDUS) in GCA, with a focus on vertebrobasilar involvement and current international imaging guidelines. Methods: Taking inspiration from a representative case of extracranial GCA with vertebrobasilar ischemic events, the current literature and international recommendations (e.g., EULAR, ACR, BSR and SIR) were reviewed. Results: Diagnostic accuracy significantly improves when CDUS is extended to include carotid, vertebral, subclavian and axillary arteries. Elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) correlate with large-vessel involvement and support the use of extended scanning protocols. International guidelines vary in their emphasis on extended CDUS, but consensus is growing toward ultrasound imaging-first strategies in expert hands. Conclusion: Extended CDUS is a sensitive, non-invasive first-line diagnostic tool for GCA. In patients with symptoms of the posterior cerebral circulation and elevated inflammatory indices, early comprehensive vascular imaging reduces diagnostic delay and may obviate the need for temporal artery biopsy. Full article

Background: Acute aortic occlusion (AAO) is a rare but life-threatening condition which can present with a spectrum of symptoms, ranging from mild cramping pain in the lower extremities (with or without sensory loss) to more dramatic motor loss and paraplegia. Once a diagnosis has been established, the treatment remains ambiguous, especially in a resource-limited setting. Treatment ranges from direct vascular intervention to systemic or directed thrombolysis—however, there is a lack of published literature on systemic thrombolysis, and thereby, consensus guidelines are nonexistent. Additionally, systemic thrombolysis bears a risk of hemorrhagic complications; however, the risk of death due to AAO is up to 57 times greater than the risk of intracerebral hemorrhage from systemic thrombolysis. Methods: This case report explores the prompt diagnosis of an acute aortic occlusion causing bilateral acute lower extremity ischemia in a sixty-three-year-old female patient treated with systemic thrombolysis. Results: The patient received 100 mg of tPA (without a bolus dose, over a two-hour period) in the Emergency Department (similar to that which is administered for the full-dose pulmonary embolism protocol). One hour after administration, the patient had restored flow to the bilateral lower extremities verified using bedside color-flow Doppler, with a drastic improvement in her symptoms. Two days after systemic thrombolysis, a repeat CTA showed evidence of complete resolution of her aortic clot. Her condition was complicated by a brief episode of retroperitoneal bleeding (presenting with flank pain) while on a heparin drip after admission (day two), which was resolved through discontinuation of the heparin drip and a two-unit blood transfusion. Conclusion: The patient was discharged with full function of the lower extremities on day six without anticoagulation. At her 2-week follow-up appointment, she was noted to be ambulatory without any neurodeficit, with a persistently restored arterial flow to the lower extremity. The application of systemic tPA could be paramount in the treatment of AAO in the setting of ischemic limb pathology, particularly at rural hospitals and healthcare centers where urgent direct vascular intervention may not be possible. Full article

Introduction: Isolated true subclavian artery aneurysm (SAA) is a rare form of peripheral arterial aneurysm that poses significant anatomical challenges to endovascular repair, especially in cases requiring planned vertebral artery (VA) sacrifice. The Balloon Occlusion Test (BOT) is a critical preoperative tool for evaluating collateral circulation before VA embolization. Case Report: A 74-year-old male was admitted with a pulsatile mass in the left supraclavicular fossa, and a 65 mm aneurysm of the intrathoracic segment of the left subclavian artery (LSA) involving critical arterial branches was diagnosed by computed tomography angiography. Due to his comorbidities, the patient was judged unfit for an open surgical repair of the aneurysm, and a two-stage endovascular subclavian aneurysm repair (EVSAR) was planned. The first step included embolization of the internal mammary artery and thyrocervical trunk, followed by BOT of the left VA, which confirmed an adequate perfusion of the posterior cerebral and cerebellar circulation that allowed safe VA embolization. The second step included zone 2 thoracic endograft placement (TEVAR) with LSA coverage and vascular plug occlusion of the proximal segment of the LSA and the axillary artery. Postoperative monitoring revealed no neurological deficit, and the patient was discharged home without complications. Follow-up imaging up to 24 months confirmed complete aneurysm exclusion and significant sac shrinkage. Conclusions: EVSAR with thoracic endograft and VA sacrifice, preceded by BOT, may be a safe and effective minimally invasive approach for the treatment of intrathoracic SAA. Full article

Background/Objectives: Unruptured intracranial aneurysms (UIAs) carry a risk of subarachnoid hemorrhage (SAH), which has a high mortality rate of up to 45% and significant long-term disability among survivors. Traditional surgical clipping and endovascular treatment (EVT) are widely used, but both have limitations: EVT shows higher recurrence and retreatment rates, while open clipping poses higher procedural risks. Minimally invasive craniotomy (MIC) techniques are emerging as a promising third option, offering potential benefits in terms of safety, durability, and recovery. This study aims to compare MIC and EVT for UIAs to evaluate their relative efficacy, safety, and long-term outcomes. Methods: A systematic literature review was conducted using PubMed and Scopus. Inclusion criteria encompassed original, peer-reviewed studies reporting clinical outcomes of UIA treatments. Data extracted included study characteristics, treatment modality, complication rates, recurrence, retreatment, and patient outcomes. Results: MIC demonstrated low complication rates (1.6–5.88%), for which the percentage was significantly lower than that for stent-assisted coiling (37%) and flow diversion (17%), while maintaining similar efficacy to traditional clipping. New EVT techniques such as WEB devices showed less procedural risks (0.7%) but higher retreatment rates. Conclusions: This review shows that while traditional craniotomy for aneurysm clipping carries higher perioperative risk than EVT, most studies have failed to compare long-term recurrences. MIC has significantly lower perioperative complications rates, comparable to EVT, and provides the same durability with improved cosmetic results. MIC should be considered when selecting patients as an alternative to EVT, particularly for unruptured anterior circulation aneurysms. Further prospective studies are needed to guide treatment decisions. Full article

Background/Objectives: Tick-borne diseases (TBDs) are increasingly recognized as causes of both systemic and neurologic illness. While their impact on vascular health is established, their role in cerebrovascular disease remains underexplored. This review aims to synthesize clinical evidence linking TBDs with cerebrovascular events, focusing on mechanisms of injury, pathogen-specific associations, and treatment outcomes. Methods: A narrative review was conducted using Boolean keyword searches across PubMed, Scopus, EMBASE, and Web of Science. Relevant literature on ischemic and hemorrhagic stroke, cerebral vasculitis, and stroke mimics associated with TBDs was examined. The review included case reports, observational studies, and mechanistic research. Pathogen-specific data and disease characteristics were extracted and summarized. Results: Several tick-borne pathogens were associated with cerebrovascular complications. Borrelia burgdorferi was most commonly implicated and typically presented with large-vessel vasculitis. Rickettsia, Ehrlichia, and Anaplasma species caused endothelial injury through immune-mediated inflammation. Powassan virus and Crimean–Congo hemorrhagic fever virus exhibited central nervous system involvement and hemorrhagic potential. Babesia species contributed to vascular injury through thrombocytopenia and embolic complications. Neuroimaging frequently demonstrated multifocal stenoses and vessel wall inflammation. Antimicrobial treatment, particularly with doxycycline or ceftriaxone, was often effective, especially when administered early. Supportive care for stroke symptoms varied by presentation and underlying pathogen. Conclusions: Cerebrovascular disease caused by tick-borne pathogens is an underrecognized but potentially reversible condition. Despite diverse etiologies, most pathogens share a final common pathway of endothelial dysfunction. Early recognition and targeted antimicrobial therapy, combined with supportive stroke care, are essential to improving patient outcomes. Full article

Background: Load carriage is an activity of daily living, can be an occupational risk, and is a popular method of resistance training. Type of carry could be related to vascular and blood pressure (BP) responses and may be related to cardiovascular risk. As physical activity is recommended by clinicians and exercise physiologists, understanding the vascular responses in relation to type of carry is important to consider in terms of risk. The purpose of this study was to compare the vascular health and BP responses to the farmer’s handle (load at the side of the body) and zercher (load in front of the body) carry and to examine sex differences in the responses. Methods: A total of 38 adults (22 females and 16 males) completed farmer’s handle and zercher load carriage with pre- and post-vascular measurements using pulse wave analysis. Results: We found that load carriage with weight in front of the body (zercher) elicits a larger increase in arterial stiffness (AIx@75), and load carriage with the load on the side of the body (farmer’s handle) elicits a larger increase in peripheral systolic BP. There were no sex differences in the responses to carry. Females exercise (3.1 vs. 4.8) and weight train (1.5 vs. 2.6) fewer times per week and had a lower resting systolic BP (121.5 ± 10.3 vs. 131.3 ± 8.3 mmHg) (p < 0.05). Both types of load carriage increased peripheral systolic BP, central systolic BP, and vascular stiffness (p < 0.05). Conclusions: Location of load carriage is important to consider based on potential cardiac risk of patients. Full article

Background: Premature atherosclerosis (PreAS) is generally defined as a disease affecting those under the age of 50 and has an outsized impact on quality-adjusted life years. We sought to better understand what individuals are at the highest risk for PreAS by examining differences in demographics and comorbidities compared to traditional atherosclerosis (TradAS). Study Design: An Institutional Review Board (IRB) approved retrospective study was conducted using retrospective data from a large regional health system. Patients who received a diagnosis of cerebrovascular disease (CeVD), coronary artery disease (CAD) or peripheral arterial disease (PAD) between 2012 and 2023 were included. Results: The review identified 136,328 patients in which 17,008 or 13% presented with PreAS (diagnosed from age 18 up to, and including, age 50). Rates of comorbidities were as follows (PreAs/TradAS): hypertension 63%/86%, diabetes 29%/35%. hyperlipidemia 45%/67%, chronic kidney disease 15%/26%, tobacco use 52%/60% and substance use 25%/9%. Differences in race, ethnicity and gender were as follows (PreAS/TradAS): White 59%/80%, Black 22%/10% and Latinx 17%/6%; male 51%/55%, and female 49%/45%. Conclusions: Patients with PreAS had lower rates of diseases that typically progress with aging, including hypertension, hyperlipidemia, chronic kidney disease, and diabetes. Tobacco use was less prevalent in the PreAS group and there was a significantly higher rate of illicit substance use in the PreAS population. Race and ethnicity were notably different with Black and Hispanic patients representing a significantly larger proportion of those with PreAS relative to TradAS. Our findings suggest risk factors beyond those classically described may play key roles in causing patients to develop PreAS. Full article

The concepts of “isolated” or “idiopathic” heat failure (CHF/HF) and more recently of “non-dilated cardiomyopathy” lack a clear description of the specific characteristics that help condense the disease into a nomenclature-based list applicable to population studies. This ensued in the absence of primary preventive investigations of CHF/HF. Moreover, in the large spectrum of cardiovascular diseases (CVD), the conditions attributable to coronary heart diseases (CHD) from those related to CHF/HF or other causes are not in general disentangled. We review here current results prompting the operational idea to index heart diseases of uncertain etiology (HDUEs) from a population-based perspective in several contributions, where CHF/HF represented 50% of HDUEs, approximately 10% of all CVD mortality and approximately 5% of all-cause mortality. We wish to stimulate new studies that compare CHD with CHF/HF only, exploiting population data, excluding baseline prevalent heart diseases, including incidence cases and separately studies with large numbers of recruited individuals. These analyses may well be complemented by the use of the Fine-Gray variant of the Cox predictive model that, by the sub-distribution of hazard models, may enable identifying risk factors as the determinants of competition between groups of diseases. The aim is to better define the differences between CHD and CHF/HF along with the possible etiology and even specific risk factors of these independent CHF/HF cases. A surge of interest among the investigators should thus be stimulated. Eventually, also for this “character” (in Pirandello’s acception), an author may hopefully be found, thus complementing with etiology an apparently orphan condition. Full article

Coronary artery bypass grafting (CABG) has evolved into a cornerstone treatment for coronary artery disease, with graft selection playing a critical role in long-term outcomes. Multiple arterial grafting (MAG) represents a significant advancement over single arterial grafting, utilizing conduits such as the internal thoracic artery and radial artery to enhance graft durability and patient survival. This review examines the outcomes, challenges, and controversies associated with MAG, highlighting its superior patency rates and reduced need for repeat revascularization procedures. While the technique provides long-term survival benefits, concerns such as the complexity of surgical techniques, increased operative time, and higher resource utilization underscore the importance of surgeon expertise and institutional infrastructure. Patient selection remains critical, as factors like age, comorbidities, and gender influence outcomes and highlight disparities in access to MAG. Emerging evidence addresses debates regarding optimal graft choice and balancing long-term benefits against short-term risks. Future directions focus on ongoing clinical trials, innovations in minimally invasive and robotic-assisted CABG, and technological advancements aimed at improving graft patency. Professional guidelines and best practices underscore the need for personalized approaches to optimize MAG’s potential. This article underscores the promise of MAG in redefining CABG care, paving the way for enhanced patient outcomes and broadened applicability. This article highlights the promise of MAG in transforming CABG care, leading to improved patient outcomes and expanded applicability. Full article

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most common malignancies associated with thrombotic events. While there is research present on various techniques of portal vein reconstruction, there is limited published data on the techniques and/or considerations of reconstruction in the setting of complete portal vein occlusion. We therefore sought to analyze and present our experience of this clinical scenario. Methods: This was a retrospective analysis of a prospectively collected database. All patients who underwent portal vein resection and/or reconstruction during a pancreatic resection were included. Post-operatively, all patients underwent a contrast-enhanced CT scan on post-operative day 1 to assess for any portal vein thrombus. Results: Pancreatic resection with portal vein reconstruction was performed in 183 patients. Complete PV occlusion was seen in 12 patients at the time of surgery. In those patients with an occluded PV, reconstruction options included primary repair with end-end anastomosis (n = 2) or use of an interposition graft (n = 9). Interposition graft conduits included the left renal vein (n = 6), tubularized bovine pericardium (n = 3), and femoral vein (n = 1). Post-operative portal vein thrombus was seen in 4/12 patients. The majority of patients (n = 7) were discharged on therapeutic anticoagulation, 4 were discharged on an antiplatelet, and 1 patient received neither. Conclusions: Based on our series, we would recommend attempting PV reconstruction in these patients with an interposition graft (with autologous left renal vein or bovine pericardium). We believe that with this technique, the post-operative thrombosis risk is similar to PV reconstructions in non-occluded patients. Full article

Background and aim: Low-density lipoprotein cholesterol (LDL-C) is an important and well-established modifiable risk factor for cardiovascular disease, including peripheral artery disease (PAD). We aimed at evaluating the lipid profile at admission in PAD patients with an indication for invasive treatment. Methods: Among patients with PAD diagnosis admitted to the vascular surgery department, those receiving statins and those with LDL-C values in the recommended target (<55 mg/dL) were identified. The correlation of LDL-C values with different clinical variables was investigated. Results: Of the 399 patients, 259 (65%) were on statin therapy. According to multivariate linear regression analysis, diabetes (p = 0.004), previous CAD history (p < 0.001), and statin therapy (p < 0.001) were independently associated with LDL-C levels. Patients with LDL-C < 55 mg/dL at admission were 89 (22% of the overall cohort). Among these patients, diabetes (48.3% versus 35.8%, p = 0.036), CAD history (52.8% versus 30%, p < 0.001), and statin use (91% versus 57.4%, p < 0.001) were more frequent as compared with patients not at target. Conclusion: Despite the very high cardiovascular risk of our group, the rate of statin prescription was very low and far from ideal. Only a small percentage of patients achieved target LDL-C values. Patients with coexistent diabetes and CAD had lower LDL-C values, suggesting management by specialists with greater attention to lipid profile and pointing out an urgent need for information on cardiovascular disease management. Full article

Aortic aneurysm is a vascular disease with a complex pathogenesis which is usually asymptomatic but can lead to high mortality with sudden rupture. This review comprehensively examines the molecular mechanisms of aortic aneurysms in the context of extracellular matrix destruction, smooth muscle cell apoptosis, chronic inflammation, oxidative stress, genetic mutations, and epigenetic regulations. In addition, the potential of molecular biomarkers in diagnosis and prognosis and targeted treatment strategies are evaluated. Animal models and translational findings form the basis for establishing a bridge between preclinical and clinical applications. This study aims to provide insight into the integration of molecular findings into clinical practice in light of the current literature and to guide future research. Full article

Background/Objectives: Radial artery occlusion (RAO) following hemostasis after coronary procedures is the most common complication, with a highly variable incidence (1–33%). While it is well established that the patent hemostasis technique reduces RAO rates, it remains unclear which device should be preferred. The wide variety of available radial hemostasis devices makes it necessary to identify those associated with a lower incidence of complications. Methods: Literature from 2016 to 2021 was reviewed through a systematic search in PubMed, CINAHL, Cochrane, and Embase databases. Only randomized controlled trials (RCTs) involving adult patients undergoing percutaneous transradial coronary procedures were included. Devices considered included pneumatic compression devices, manual compression, elastic bandages, and hemostatic dressings. The review process followed PRISMA guidelines. Two random-effects frequentist network meta-analyses were conducted to compare the effects of 16 and 9 radial hemostasis devices on RAO incidence at 24 h and 30 days after the procedure. Results: A total of 17 RCTs were included. The network meta-analysis (NMA) showed a protective effect at the 24 h endpoint for both double-balloon devices and pneumatic compression devices adjusted to mean arterial pressure. At the 30-day endpoint, significant differences were observed among pneumatic compression, chitosan-based PADs, mechanical compression devices, and adjustable elastic bandages. Conclusions: Although some treatments with specific devices significantly differ from the reference treatment, the limited availability of data to assess RAO at 30 days and a certain heterogeneity between devices indicate the need for further investigation. Full article

Late ruptures of abdominal aortic aneurysms post-endovascular aneurysm repair present a significant risk, occurring in about 0.9% of cases. The typical timeframe leading to rupture is roughly 37 months, with the primary factors often linked to endoleaks, especially types I and III, which sustain pressure within the aneurysm sac. The approaches to managing late ruptures consist of endovascular approaches, open surgical interventions, and conservative care, each customised to the patient’s specific characteristics. When feasible endovascular repair is favoured, additional stent grafts are deployed to seal endoleaks and offer lower perioperative mortality rates compared to those for open surgery. Open repair is considered when endovascular solutions fail or are not feasible. Conservative management with active monitoring and supportive treatment can be considered for haemodynamically stable non-surgical patients. Endovascular repair methods like fenestrated/branched EVAR (F/BEVAR) and parallel grafting (PGEVAR) are effective for complicated anatomies and show high technical success with reduced morbidity compared to that with open repairs. Chimney techniques and physician-modified endografts may help regain and broaden the sealing zone. Limb extensions with or without embolisation, interposition endografting, and whole-body relining are helpful options for type IB and type 3–5 endoleaks. Open surgical repair carries a higher perioperative mortality but may be essential in preventing death due to rupture following failed EVAR. The choice depends on the patient’s clinical stability and fitness for surgery in the absence of a viable endovascular alternative. This article discusses the available options for treating late rupture after EVAR, emphasising the importance of individualised treatment plans and the need for rigorous postoperative surveillance to prevent such complications. Full article

Patients with End-Stage Renal Disease (ESRD) represent a very fragile population, presenting with higher rates of complications and morbidity following vascular interventions. This study aims to analyze post-operative outcomes, such as mortality, readmissions, and amputations, in patients with Peripheral Arterial Disease (PAD) and ESRD on dialysis. Methods: A retrospective cohort study was conducted of patients with PAD and ESRD on dialysis who underwent vascular interventions between 2015 and 2017. This study focused on post-operative outcomes, including mortality, readmissions, and amputations. The data were analyzed to identify patterns and correlations. Results: This study found that patients with PAD and ESRD have long hospital stays, high amputation rates, high readmission rates, and treatment failure. Above-knee amputation (AKA) and female gender were associated with higher mortality rates, while prior stroke was associated with higher odds of readmissions. Conclusions: This study highlights the need for further studies with larger patient populations to identify independent predictors of negative outcomes. The findings suggest that specific factors, such as AKA, female gender, and prior stroke, significantly impact post-operative outcomes in this patient population. Full article

Objectives: This study investigates the effects of cluster set resistance training (RT) on heart rate variability (HRV) parameters in young, healthy individuals. Methods: This trial was registered in the Brazilian Clinical Trials Registry (ReBEC) under the identification number RBR-9857xj3 on 7 December 2024. Sixteen participants (seven female, 25 ± 2 years old) performed both cluster set and traditional RT protocols with equal relative intensity (85% 10RM), volume load (4 × 10 repetitions), and rest intervals (120 s). Cluster set configuration involved the introduction of a shorter rest interval between a cluster of sets [4 × (2 × 5) with 90 s inter-set rest and 30 s intra-set rest]. HRV parameters (RMSSD, HFnu, SD1, LFnu, LF/HF ratio, and SD2) were assessed before and 30 min post-exercise. The rating of perceived exertion (RPE) was assessed immediately after RT protocols. Results: The traditional RT protocol led to a significant reduction in parasympathetic activity (RMSSD, HFnu, SD1) and an increase in sympathetic activity (LFnu, LF/HF ratio, and SD2) (p < 0.05), whereas the cluster set RT protocol did not alter HRV parameters. Additionally, RPE was significantly higher (p < 0.001) in the traditional RT protocol. Conclusion: This study suggests that the cluster set may have a less pronounced impact on HRV parameters 30 min post-exercise compared to traditional sets. These findings can guide exercise physiologists in designing resistance training programs for clinical populations by prescribing protocols that minimize cardiac autonomic stress. Full article

Peripheral artery disease (PAD) is a chronic progressive accumulation of atherosclerotic lesions with varying degrees of arterial obstruction determining ischemic symptoms of the involved extremities. PAD is associated with decreased bioavailable nitric oxide due to endothelial cell dysfunction and the development and progression of vascular arterial stiffening (VAS). Atherosclerosis also plays an essential role in the development and progression of vascular arterial stiffening (VAS), which is associated with endothelial cell activation and dysfunction that results in a proinflammatory endothelium with a decreased ability to produce bioavailable nitric oxide (NO). NO is one of three gasotransmitters, along with carbon monoxide and hydrogen sulfide, that promotes vasodilation. NO plays a crucial role in the regulation of PAD, and a deficiency in its bioavailability is strongly linked to the development of atherosclerosis, VAS, and PAD. A decreased arterial patency may also occur due to a reduction in the elasticity or diameter of the vessel wall due to the progressive nature of VAS and atherosclerosis in PAD. Progressive atherosclerosis and VAS promote narrowing over time, which leads to impairment of vasorelaxation and extremity blood flow. This narrative review examines how atherosclerosis, aging and hypertension, metabolic syndrome and type 2 diabetes, tobacco smoking, and endothelial cell activation and dysfunction with decreased NO and VAS with its increased damaging pulsatile pulse pressure result in microvessel remodeling. Further, the role of ischemia and ischemia–reperfusion injury is discussed and how it contributes to ischemic skeletal muscle remodeling, ischemic neuropathy, and pain perception in PAD. Full article