Giacomo Buso

Background: Chronic venous disease (CVD) is a prevalent condition associated with significant morbidity and impaired quality of life. Venoactive nutraceuticals are widely used as part of conservative management and are cited in major guidelines, yet recommendations remain heterogeneous and clinical practice varies substantially. This study aimed to establish expert consensus on the clinical use of these agents in CVD within the Italian vascular community. Methods: A three-round modified Delphi was conducted among 21 Italian vascular specialists (May–July 2025). Consensus was defined as ≥70% agreement. Statements addressed CEAP classification, symptom assessment, use and perceived effectiveness of individual agents, combination regimens, and topical formulations. Results: Consensus supported routine use of CEAP and its 2020 revision, the clinical distinction between CVD (C0–C2) and chronic venous insufficiency (CVI) (C3–C6), and systematic classification of patients as symptomatic or asymptomatic. Strong agreement endorsed the use of selected venoactive nutraceuticals across all CEAP classes and supported combination therapy as more effective than monotherapy. An oral fixed-dose combination of diosmin, ruscus, melilotus, Vitis vinifera, and horse chestnut extract, pre-selected as a test case to evaluate the plausibility of combining agents with complementary mechanisms, was considered a reasonable first-line conservative option. Topical preparations were endorsed across C1–C6, particularly for CVI and to reduce heaviness, reflecting their perceived value as safe adjuncts despite the limited availability of high-quality evidence. No consensus was reached for ruscus, horse chestnut, hydroxyethylrutosides, red vine leaf extract, anthocyanosides, or β-arbutin in monotherapy. The panel agreed on the need to update clinical guidelines to reflect emerging evidence on venoactive nutraceuticals. Conclusions: This Delphi provides structured expert consensus on the use of venoactive nutraceuticals in CVD. Combination therapy integrating multiple physiological effects is considered more effective than single agents. Further research is required to validate combination regimens and topical formulations and to determine their impact on patient-reported outcomes.

Vascular Ehlers–Danlos syndrome (vEDS) is a rare autosomal dominant connective tissue disease resulting from pathogenic variants in the collagen type III alpha 1 chain (COL3A1) gene, encoding type III procollagen. Patients with vEDS present with severe tissue fragility that can result in arterial aneurysm, dissection, or rupture, especially of medium-caliber vessels. Although early reports have indicated a very high mortality rate in affected patients, with an estimated median survival of around 50 years, recent times have seen a remarkable improvement in outcomes in this population. This shift could be related to greater awareness of the disease among patients and physicians, with improved management both in terms of follow-up and treatment of complications. Increasing use of drugs acting on the cardiovascular system may also have contributed to this improvement. In particular, celiprolol, a β1 cardio-selective blocker with a β2-agonist vasodilator effect, has been shown to reduce rates of vascular events in patients with vEDS. However, the evidence on the true benefits and possible mechanisms responsible for the protective effect of celiprolol in this specific setting remains limited. Drugs targeting the extracellular matrix organization and autophagy–lysosome pathways are currently under investigation and could play a role in the future. This narrative review aims to summarize current evidence and future perspectives on vEDS medical treatment, with a specific focus on vascular prevention.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04–1.27], p < 0.001 and HR 1.25 [1.09–1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

Neutrophils play a role in cardiovascular (CV) disease. However, relatively scant evidence exists in the setting of peripheral artery disease (PAD). The aims of this study were to measure biomarkers of neutrophil activation in patients with symptomatic chronic PAD compared with healthy controls, to assess their association with PAD severity, and to evaluate their prognostic value in patients with PAD. The following circulating markers of neutrophil degranulation were tested: polymorphonuclear neutrophil (PMN) elastase, neutrophil gelatinase-associated lipocalin (NGAL), and myeloperoxidase (MPO). Neutrophil extracellular traps (NETs) were quantified by measuring circulating MPO–DNA complexes. Patients with PAD underwent a comprehensive series of vascular tests. The occurrence of 6-month major adverse CV (MACE) and limb events (MALE) was assessed. Overall, 110 participants were included, 66 of which had PAD. After adjustment for conventional CV risk factors, PMN-elastase (adjusted odds ratio [OR]: 1.008; 95% confidence interval [CI]: 1.002–1.015; p = 0.006), NGAL (adjusted OR: 1.045; 95%CI: 1.024–1.066; p < 0.001), and MPO (adjusted OR: 1.013; 95%CI: 1.001–1.024; p = 0.028) were significantly associated with PAD presence. PMN-elastase (adjusted hazard ratio [HR]: 1.010; 95%CI: 1.000–1.020; p = 0.040) and MPO (adjusted HR: 1.027; 95%CI: 1.004–1.051; p = 0.019) were predictive of 6-month MACE and/or MALE. MPO displayed fair prognostic performance on receiver operating characteristic (ROC) curve analyses, with an area under the curve (AUC) of 0.74 (95%CI: 0.56–0.91) and a sensitivity and specificity of 0.80 and 0.65, respectively, for a cut-off of 108.37 ng/mL. MPO–DNA showed a weak inverse correlation with transcutaneous oximetry (TcPO2) on proximal foot (adjusted ρ −0.287; p = 0.032). In conclusion, in patients with symptomatic chronic PAD, enhanced neutrophil activity may be associated with an increased risk of acute CV events, rather than correlate with disease severity. Further research is needed to clarify the role of neutrophils in PAD natural history.

In recent years, increasing attention has been paid to the role of neutrophils in cardiovascular (CV) disease (CVD) with evidence supporting their role in the initiation, progression, and rupture of atherosclerotic plaque. Although these cells have long been considered as terminally differentiated cells with a relatively limited spectrum of action, recent research has revealed intriguing novel cellular functions, including neutrophil extracellular trap (NET) generation and inflammasome activation, which have been linked to several human diseases, including CVD. While most research to date has focused on the role of neutrophils in coronary artery and cerebrovascular diseases, much less information is available on lower limb peripheral artery disease (PAD). PAD is a widespread condition associated with great morbidity and mortality, though physician and patient awareness of the disease remains low. To date, several studies have produced some evidence on the role of certain biomarkers of neutrophil activation in this clinical setting. However, the etiopathogenetic role of neutrophils, and in particular of some of the newly discovered mechanisms, has yet to be fully elucidated. In the future, complementary assessment of neutrophil activity should improve CV risk stratification and provide personalized treatments to patients with PAD. This review aims to summarize the basic principles and recent advances in the understanding of neutrophil biology, current knowledge about the role of neutrophils in atherosclerosis, as well as available evidence on their role of PAD.

Introduction: Lipedema is a poorly known condition. Diagnosis is based almost exclusively on clinical criteria, which may be subjective and not always reliable. This study aimed to investigate regional body composition (BC) by dual-energy X-ray absorptiometry (DXA) in patients with lipedema and healthy controls and to determine cut-off values of fat mass (FM) indices to provide an additional tool for the diagnosis and staging of this condition. Methods: This study is a single-center case-control study performed at Lausanne University Hospital, Switzerland. Women with clinically diagnosed lipedema underwent regional BC assessment by DXA. The control group without clinical lipedema was matched for age and body mass index (BMI) at a ratio of 1:2 and underwent similar examination. Regional FM (legs, arms, legs and arms, trunk, android and gynoid FM) was measured in (kg) and divided by FM index (FMI) (kg/m2) and total FM (kg). The trunk/legs and android/gynoid ratios were calculated. For all indices of FM distribution showing a significant difference between cases and controls, we defined the receiver operating characteristic (ROC) curves, calculating the area under the curve (AUC), sensitivity, specificity, and Youden’s index. Types and stages of lipedema were compared in terms of FM indices. Correlation analyses between all FM distribution indices and lipedema stages were performed. Results: We included 222 women (74 with lipedema and 148 controls). Overall, the mean age was 41 years (standard deviation [SD] 11), and mean BMI was 30.9 kg/m2 (SD 7.6). A statistically significant difference was observed for all DXA-derived indices of FM distribution between groups, except for arm FM indices. The ROC curve analysis of leg FM/total FM, as a potential indicator of lipedema, resulted in an AUC of 0.90 (95% confidence interval 0.86–0.94). According to Youden’s index, optimal cut-off value identifying lipedema was 0.384. Sensitivity and specificity were 0.95 and 0.73, respectively. We found no significant differences between lipedema types and stages in terms of FM indices, nor significant correlations between the latter and lipedema stages. Discussion/Conclusion: BC assessment by DXA, and particularly calculation of the leg FM/total FM index, is a simple tool that may help clinicians rule out lipedema in doubtful cases.