Monocyte chemoattractant protein 1 plasma concentration in blood from varicose veins decreases under venoactive drug treatment.

BACKGROUND: Vein-specific inflammation leads to vascular smooth muscle cells proliferation and extracellular matrix degradation of vein wall. This process is known as remodeling and is promoted by "trapped" leukocytes. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine responsible for trafficking of leukocytes from blood to vein wall. The aim of this study was to measure the MCP-1 concentration in varicose veins blood before and after venoactive drug therapy and to compare it with a concentration of blood from varicose veins of subjects who did not receive drug treatment. METHODS: Non-randomized comparative study was conducted on 30 patients with primary varicose veins. 20 patients of the study group received diosmin 900 mg/hesperidin 100 mg once daily. 10 controls received no treatment. MCP-1 level was measured (pg/mL) in the blood from varicose veins twice, at the day of inclusion and after 60 days. Legs discomfort related to chronic venous disease (CVD) symptoms was measured with 10-cm Visual Analogue Scale (VAS) at inclusion and at completion of the study. RESULTS: Median (interquartile range, IQR) MCP-1 concentrations in treatment and control groups at inclusion were 171.9 (124.4-216.0) and 157.0 (120.1-163.1), resp., P=0.285. After 60 days of treatment MCP-1 level decreased, but non-significantly to 152.3 (124.1-178.3). In patients who did not receive treatment chemokine level slightly increased to 163.0 (134.0-172.9). Median changes over time were -6.6 (-30.9-7.4) and 10.6 (-3.7-19.2) in the study and control groups, resp. (P=0.048). After 60 days in 12 of 19 and 2 of 9 patients of treatments and control groups MCP-1 decreased (P=0.103). Odds ratio for MCP-1 decreasing was 9.5 (95% CI 1.1-81.5, P=0.043) for those who received venoactive drug. Mean (± standard deviation [SD]) legs discomfort significantly dropped in the study group from 5.7 (±2.5) to 1.9 (±2.2) (P=0.0003), while in controls no changes were registered: 3.4 (±1.3) and 3.5 (± 1.4), resp., P=0.28). Mean difference of VAS at baseline and at follow-up was -3.5 (±2.6) and 0.9 (±2.1), resp. (P<0.0001). CONCLUSIONS: Plasma concentration of MCP-1 in varicose veins blood demonstrates a tendency to decrease under two months treatment with a venoactive drug. Future studies are needed to reveal a possible role of MCP-1 as a target considering its role in varicose veins pathogenesis.

Risk factors for venous symptoms in Russian patients with chronic venous disease.

Objectives: The study aimed to investigate risk factors for venous symptoms in Russian patients with chronic venous disease (CVD).Methods: Data on 487 patients with CVD aged 18 years and more were extracted from the database of a cross-sectional population-based study on the prevalence of CVD in a rural settlement. Risk factors for venous symptoms were calculated by multiple regression analysis. The study is registered at clinicaltrials.gov as NCT03900234, 1 April 2019.Results: A total of 259 patients (53.2%) had venous symptoms. Female gender, hard labour (HRs 1.8 and 1.4, p < .01), age, family history of CVD and being employed (HRs 1.009, 1.3, 1.27, p < .05) are risk factors for development of symptoms. After calculating for different complaints separately, female gender was confirmed as a risk factor for all symptoms. Family history of CVD with HR 1.4 is a risk factor for heaviness (p < .01) and fatigue (p < 0.05). Employment predicts heaviness, sensation of swelling and night cramps - HRs 1.38, 1.7 and 1.9 respectively (p < .05). Hard labour is a risk factor for sensation of swelling with HR 2.1 (p < .05), pain and night cramps (HRs 2.2 and 4.4, p < .01). Prolonged standing is associated with sensation of swelling - HR 1.05 (p < .05). Superficial venous reflux is a predictor only for venous pain (HR 2.4, p < .01).Conclusions: This study presents independent risk factors for venous symptoms in CVD patients. It demonstrates that different symptoms are associated with different factors.

Genome-wide association study in ethnic Russians suggests an association of the MHC class III genomic region with the risk of primary varicose veins.

Heredity is a well-known risk factor for varicose veins, but genetic basis of this condition remains poorly studied. Our aim was to conduct a large-scale genetic association study for primary varicose veins (PVVs) in the population of ethnic Russians. An initial scan using Illumina HumanExome-12 v1.0 BeadChip was performed for 273 patients with PVVs and 250 controls without a history of chronic venous disease and other venous disorders. After quality control and removal of monomorphic markers, 25,424 common and 48,232 rare variants were included in the analysis. 42 single nucleotide polymorphisms (SNPs) were genotyped in the independent replication cohort of 447 PVVs patients and 443 controls. Association of common variants with PVVs was investigated by logistic regression, and the impact of rare variants was analyzed using sequence kernel association test. No effect of low frequency alleles has been revealed in our study. Common variant analysis identified a promising signal at chromosome 6 within classical major histocompatibility complex (MHC) class III subregion. The most strongly associated SNP in a combined analysis that reached a suggestive significance level of 3.2e-05 was polymorphism rs4151657 in the complement factor B gene. Testing for potential pleiotropy with other traits indicated that the same causal variant in this region increases the risk of rheumatoid arthritis and has a negative impact on human height. Our results provide suggestive evidence for the involvement of the MHC class III genes in the pathogenesis of PVVs. Further independent studies are needed to confirm our pilot findings.

Prevalence and Risk Factors for Chronic Venous Disease in the General Russian Population.

OBJECTIVE/BACKGROUND: The aim was to establish the prevalence of chronic venous disease (CVD) and its risk factors in the general population. METHODS: This was a population based, cross sectional study. In total, 703 residents aged > 18 years from the rural community of Kryukovo (Central Russia) were enrolled. Medical history was taken and clinical examination performed, documenting venous signs/symptoms. The CEAP classification of the most affected limb was used. Duplex ultrasound was performed to register morphological changes and reflux in deep and superficial veins. RESULTS: There were 63% women and 37% men (mean age 53.5 years). CVD was found in 69.3%. Of all participants 4.7% were C0S and 34.3% were C1. Chronic venous insufficiency (C3-C6) was found in 8.2% and venous ulcers (C5-C6) in 1.1%. Venous pain, heaviness, fatigue, itching, and the sensation of swelling were documented in 14.8%, 36.3%, 32.8%, 7.0% and 29.1% of patients respectively. Family history was the significant risk factor for both CVD (hazard ratio [HR] 1.3) and primary varicose vein disease (HR 1.6; p < .01). Female sex was a risk factor only for CVD (HR 1.3; p < .01) but not for varicose veins. Age was a risk factor for CVD (HR 1.01) and for varicose veins (HR 1.02; p < .01). For women, number of births (HR 1.05; p < .05) and menopause (HR 1.3; p < .01) were risk factors for CVD. Menopause was a risk factor for varicose veins (HR 2.0; p < .05). CONCLUSION: This study provides data on the prevalence of CVD, venous abnormalities and risk factors in Russia. The results contribute to already established data, giving a more complete outlook on the global prevalence of CVD.

Short-term results of isolated phlebectomy with preservation of incompetent great saphenous vein (ASVAL procedure) in primary varicose veins disease.

Objective To establish an effect of isolated phlebectomy in patients with incompetent great saphenous vein (Ambulatory Selective Varices Ablation under Local anesthesia (ASVAL) procedure) on the reflux and diameter of the trunk and to assess recurrence rate of varicose veins at one year. Material and methods We conducted a prospective study on patients with primary varicose veins and with C2 or C2,3 or C2,3,4 or C2,4 classes of chronic venous disease and great saphenous vein incompetence. The study included 67 patients (51 women and 16 men; 75 limbs in total). Age varied from 17 to 71 years; mean age was 46.8 years (SD 13.9). We recorded the presence or absence of reflux in the great saphenous vein with duplex ultrasound before and after surgery. The recurrence of varicose veins was evaluated at 12 months. All the patients underwent isolated phlebectomy with preservation of incompetent great saphenous vein (ASVAL procedure) under local anesthesia. Results At one year after removing of tributaries of the incompetent trunk, 66% of them were competent. Reflux persisted in 17% of great saphenous veins with reflux above mid-thigh and in 61% of trunks with reflux extended below the mid-thigh (p = 0.0004). The diameter of all the veins decreased significantly no matter reflux disappeared or not. Varicose veins reoccurred in 13.5% cases. In 6.5% of limbs with a reflux above the mid-thigh, the recurrence was registered at one year, while in the limbs with the reflux below the mid-thigh at a baseline, the recurrence rate was 25% (p = 0.036). Conclusion Isolated phlebectomy with a preservation of incompetent great saphenous vein leads to disappearance of reflux in a majority of cases and to significant decrease of vein diameter in all the cases. ASVAL procedure could be considered as a less aggressive and less expensive approach in selected cases. Clear indications for isolated phlebectomy need to be established.