Chronic venous disease is a common disease, the prevalence of which increases with age, and can cause debilitating symptoms that adversely affect the quality of life. The risk factors include family history, female sex, obesity, pregnancy, parity, and history of deep vein thrombosis. Moreover, it is associated with venous obstruction, reflux, or both, which, in turn, leads to ambulatory venous hypertension. Chronic venous disease is the leading cause of leg ulcers, which place a significant cost burden on the health care system. Compression therapy remains the cornerstone of treatment, particularly for more advanced disease. Superficial saphenous vein reflux can be associated with significant symptoms. Catheter techniques, both thermal and nonthermal, have demonstrated efficacy and safety in successful closure and symptom improvement. Deep vein obstruction can be broadly divided into thrombotic and nonthrombotic and can lead to symptomatic chronic venous disease. Recanalization using balloons and stents has been increasingly used and studied in such patients. It is critical to develop training opportunities and guidelines to improve evidence-based and appropriate care for cardiologists treating chronic venous disease.

UNASSIGNED: Micronized purified flavonoid fraction (MPFF) is a widely prescribed and extensively investigated venoactive drug (VAD). The standard dosage for MPFF is 500 mg administered twice daily. However, a new daily dose of 1000 mg has just been introduced.
UNASSIGNED: This study investigated whether a daily dose of 1000 mg MPFF could be implemented and embraced by the public and still has the same therapeutic effects as conventional pharmaceuticals.
UNASSIGNED: For this meta-analysis, we searched MEDLINE, Embase, Science of Web, Cochrane, and PubMed databases and forward and backward citations for studies published between database inception and March 2023. Three randomized controlled trials (RCTs) of comparison of different dosages of MPFF to evaluate whether there is a significant difference between them were included, without language or date restrictions. Due to the small sample size of the study included, we conducted a simple sensitivity test using a one-by-one exclusion method, and the results showed that the study did not affect the final consolidation conclusion. The quality of the evidence was assessed using the Cochrane risk-of-bias tool.
UNASSIGNED: Out of 232 studies, 99 were eligible and 39 RCTs had data, all with low to moderate bias. Overall, 1924 patients (experimental group: 967, control group: 957) in 3 RCTs met the criteria. There is no significant difference in patient compliance, efficacy, clinical adverse events, and quality of life scores between MPFF 1000 mg once daily and MPFF 500 mg twice daily (standardized mean difference [SMD]: 0.049 [0.048, 0.145], p=0.321, risk ratio [RR]: 0.981 [0.855, 1.125], p=0.904, and SMD: 0.063 [0.034, 0.160], p=0.203).
UNASSIGNED: In symptomatic chronic venous disease patients, MPFF 1000 mg once daily and MPFF 500 mg twice daily improve patient compliance, lower limb discomfort, clinical adverse events, and quality of life scores similarly. Regular medical care should recommend MPFF 1000 mg daily more often.
CONCLUSIONS: Micronized purified flavonoid fraction (MPFF) is a popular venoactive medication (VAD) in modern medicine.MPFF is effective in treating lower extremity venous problems.Currently, besides conventional 500 mg tablets, there exist alternative dosage forms such as solutions, chewable tablets, and other novel formulations for MPFF.The excessive frequency and amount of medication may have a negative impact on patient adherence.

Sclerotherapy is the treatment of choice for telangiectasias and reticular veins. The most common side effects of this procedure are hyperpigmentation and matting, which are feared owing to their aesthetic damage and difficulty of treatment. Combined treatments with laser and hypertonic glucose sclerotherapy have been described with excellent results, but limited to treatment of veins of ≤2 mm in diameter. Cryo laser after foam sclerotherapy is a procedure to treat reticular veins in the lower extremities that utilizes first foam sclerotherapy with polidocanol than immediately followed by transdermal Nd:YAG 1064 laser treatment and we can treat veins ≤5 mm. This report presents a successful case of varicose vein treatment using combined transdermal laser and sclerotherapy with foam sclerotherapy with polidocanol to treat veins >2.5 mm in diameter.

OBJECTIVE: Patients with chronic venous disease (CVD) can present with different underlying hemodynamic abnormalities affecting the deep, superficial, and perforator veins. This review explores the relationship between reflux patterns, extent of venous reflux, and clinical manifestations of CVD.
METHODS: The Medline and EMBASE databases were searched systematically from 1946 to April 1, 2024. References of shortlisted papers were searched for relevant articles. Studies were included if they were in English language, included participants ≥16 years of age, documented reflux patterns in two or more of the following: deep, superficial, and/or perforator systems, and related patterns to presentation or severity. Exclusion criteria included patients with isolated deep venous thrombosis, post-thrombotic syndrome or stenotic or obstructive disease.
RESULTS: We identified 18 studies (11,177 participants; range, 55-3016). Meta-analysis showed significant odds ratios (OR) for C4-6 disease being associated with deep reflux (OR, 2.41; 95% confidence interval [CI], 1.53-3.78) and perforator reflux (OR, 3.37; 95% CI, 2.16-5.27), but not superficial reflux (OR, 2.11; 95% CI, 0.87-5.14), vs C0-3 disease. Severe CVD (C4-6) was significantly associated with isolated deep, combined deep and superficial, and combined superficial and perforator reflux. The greatest risk of CVD progression (defined as de novo development of varicose veins and progression to greater CVD severity) was shown by two studies to be related to combined deep and superficial reflux.
CONCLUSIONS: Although limited by the heterogenous nature of the studies, this review confirms that reflux pattern is a significant predictor of clinical class, and higher clinical, etiological, anatomical, and pathophysiological stages are associated with a higher prevalence of superficial, deep, and perforator reflux. Isolated deep and combined reflux also seem to be to predict the onset of leg ulceration. Future studies should relate reflux patterns to treatment outcomes, including recurrence risk. This work could help to inform health policies and management guidelines so that reflux patterns, in conjunction with other demographic and hemodynamic parameters, could be used to risk stratify patients and identify individuals who may benefit from earlier treatment.

BACKGROUND: Micronized purified flavonoid fraction (MPFF) is the most widely prescribed and well-studied venoactive drug available for the treatment of chronic venous disease (CVD). Photoplethysmography (PPG) is used to quantitatively measure venous hemodynamics and provide information about the overall function of the venous system. The aim of this study was to use digital PPG to evaluate the effects of MPFF on venous hemodynamics in patients with CVD.
METHODS: Patients diagnosed with CVD at an outpatient clinic in Bursa, Turkey between February 2018 and July 2020 were assessed for inclusion in this retrospective analysis. Patients who complied with the advised treatment strategy (MPFF 1,000 mg tablets taken orally once daily and compression garments) and attended follow-up visits were included in the analysis. Digital PPG was used to measure venous refilling time (VRT) and venous pumping capacity (VPC) at diagnosis and 6 months of follow-up. The Venous Clinical Severity Score (VCSS) was also obtained at these visits, and patients completed the 20-item Chronic Venous Insufficiency Questionnaire (CIVIQ-20).
RESULTS: In total, 721 patients (mean age 52 years) with C0-C4 CVD were included in the study. PPG showed that VRT and VPC increased significantly from 19.0 sec to 2.0%, respectively, at diagnosis to 27.4 and 4.9%, respectively, at 6 months (both P < 0.05). Mean VCSS improved significantly from 7.9 at diagnosis to 3.1 at 6 months (P < 0.05). Mean CIVIQ-20 score also improved significantly at the 6-month follow-up (20.1 vs 38.6 at diagnosis; P < 0.01).
CONCLUSIONS: In patients with C0-C4 CVD, 6 months of MPFF treatment plus the wearing of compression garments was associated with statistically significant improvements in venous hemodynamic parameters measured by PPG, as well as measures of clinical severity and quality of life.

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OBJECTIVE: Inflammation and endothelial dysfunction are important venous changes in patients with chronic venous disease (CVD). The use of the venoactive drugs remains an important treatment modality for patients with CVD, reducing the severity of the CVD-related symptoms and swelling but also reducing inflammation and protecting endothelial cells. In this research, the effects of the serum obtained from patients with CVD before and after sulodexide treatment were evaluated for in vivo and in vitro inflammatory markers and endothelial cell function.
METHODS: Inflammatory markers (IL-6, matrix metalloproteinase-9 [MMP-9], vascular cell adhesion molecule-1 [VCAM-1], and von Willebrand factor [vWF]) from the incompetent great saphenous veins (GSVs) and from the systemic venous circulation were studied in 10 patients with CVD (C2s) before and after 2 months of sulodexide (2 × 500 lipasemic units/d) therapy. Serum obtained from the vein blood before and after sulodexide treatment was evaluated for in vitro cultured human umbilical vein endothelial cell function.
RESULTS: The serum collected from lower leg incompetent GSVs had significantly elevated levels of VCAM-1 (+29%, P < .001) compared with the serum from the systemic circulation. Endothelial cells exposed to the serum from the incompetent lower leg veins of the untreated CVD patients demonstrated higher stimulated synthesis of MMP-9 (+17%, P < .01), as well as increased markers of senescence (prolongation of population doubling time, β-galactosidase activity, and expression of p21 and p53 genes). CVD serum-induced senescent endothelial cells had a higher expression of genes regulating IL-6, MMP-9, VCAM-1, and vWF synthesis. The overall proinflammatory effect on endothelial cells by the serum collected from the incompetent GSVs was stronger as compared with the serum from the systemic circulation. Serum collected from the veins after sulodexide treatment caused lower levels of endothelial cell inflammatory markers as well as respective gene expression than serum obtained at the beginning of the study (before sulodexide treatment). Sulodexide application also reduced the inflammatory secretory activity of the senescent endothelial cells. Sulodexide treatment resulted in the decrease of the majority of the studied inflammatory parameters in both lower limb incompetent vein and systemic blood.
CONCLUSIONS: In patients with CVD, there are significant differences between circulating inflammatory markers analyzed from the lower leg incompetent GSV segments compared with the systemic circulation, indicating a higher inflammatory condition in CVD. Treatment with sulodexide reduces the proinflammatory and endothelial cell activation properties of the serum from patients with CVD.
CONCLUSIONS: The study documented the significant proinflammatory human vascular endothelial cell activation when exposed to the serum collected from the varicose veins as compared with the serum from the systemic circulation in patients with chronic venous disease (CVD). The inflammatory marker expression, endothelial dysfunction, and endothelial cell senescence transformation can be successfully controlled and downregulated by patients\' exposure to the glycosaminoglycan (sulodexide) treatment. Further studies are needed to confirm if glycosaminoglycan application can prevent further CVD clinical progression due to potential CVD-related pathological processes\' modulation and their downregulation.

Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) and appear as abnormally enlarged and tortuous superficial veins. VVs result from functional abnormalities in the venous circulation of the lower extremities, such as venous hypertension, venous valve incompetence, and venous reflux. Previous studies indicate that enhanced angiogenesis and inflammation contribute to the progression and onset of VVs; however, dysregulations in signaling pathways associated with these processes in VVs patients are poorly understood. Therefore, in our study, we aimed to identify key regulators of angiogenesis and inflammation that are dysregulated in patients with VVs. Expression levels of 18 genes were analyzed in peripheral blood mononuclear cells (PBMC) using real-time PCR, as well as plasma levels of 6 proteins were investigated using ELISA. Higher levels of CCL5, PDGFA, VEGFC, TGF-alpha, TGF-beta 1, and VEGF-A, as well as lower levels of VEGFB and VEGF-C, were found to be statistically significant in the VV group compared to the control subjects without VVs. None of the analyzed factors was associated with the venous localization of the varicosities. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors in PBMC and plasma from VVs patients, providing new insight into molecular mechanisms that could contribute to the development of VVs and point out promising candidates for circulatory biomarkers of this disease.

OBJECTIVE: The aim of this study was to understand the prevalence of chronic venous disease (CVD) of lower limbs in young men at high-altitude in Xizang, and to provide prevention measures.
METHODS: The convenient sampling method was used to conduct a questionnaire survey among males aged 18 to 40 above an altitude of 3000 meters in Xizang in April 2023. The contents of the questionnaire included basic information, symptoms of CVD of lower limbs, protection status and training needs. Multivariate logistic regression model was calculated to evaluate the risk factors for CVD.
RESULTS: A total of 350 survey questionnaires were received, and 326 valid samples were collected. The prevalence of CVD of lower limbs (C1-C6) was 37.42% (95%CI: 32.17%-42.68%), the ratio of C0 to C5 were 62.58%, 27.30%, 3.07%, 4.60%, 2.15% and 0.31%, respectively, no one reached C6. The top three symptoms of CVD were lower limb fatigue (18.10%), heaviness (15.34%) and pain (13.19%). 46.01% of respondents were unaware of CVD, and 12.88% of respondents did not have any protective measures of CVD. Multivariate logistic regression showed that age (OR = 1.076, 95%CI: 1.018-1.137, p = .009), preference for spicy food (OR = 1.747, 95%CI: 1.083-2.818, p = .022), unbalanced diet (OR = 1.877, 95%CI: 1.049-3.358, p = .034) and physical exercise (OR 0.610, 95%CI: 0.377-0.986, p = .044) were the independent risk factors for CVD.
CONCLUSIONS: This study provided data on the prevalence of CVD in young men at high-altitude and the risk factors for CVD. The findings of this study may facilitate the development of individualized clinical assessments and targeted prevention programs.