Enhanced oxidative stress in coronary heart disease and chronic heart failure as indicated by an increased 8-epi-PGF(2alpha)

The role of oxidation injury as an important factor in the pathophysiology of cardiomyopathy (CMP) has recently gained increasing interest. Semiquantitative analysis for isoprostane, 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)), and oxidised low-density lipoprotein (ox-LDL) of coronary vascular tissue samples derived from CMP patients revealed an increased extent and intensity of uptake as compared to the respective controls. To evaluate oxidative stress in vivo, we examined plasma, serum, salivary, and urinary 8-epi-PGF(2alpha) in patients with dilated CMP (n=20) and ischemic CMP (n=20) with decreased left ventricular ejection fraction (LVEF). Patients with coronary heart disease (CHD) (n=20) and 20 healthy, age-matched, and sex-matched controls were investigated in parallel. 8-Epi-PGF(2alpha) levels were correlated with the functional severity of heart failure [New York Heart Association (NYHA) classification] and LVEF. 8-Epi-PGF(2alpha) levels were matched according to risk factors (smoking and hypercholesterolemia) and were significantly higher in patients with CMP as compared to healthy controls and patients with CHD in all investigated compartments. A positive correlation between NYHA stages and 8-epi-PGF(2alpha), as well as a negative correlation to LVEF, could be demonstrated in a subgroup analysis. These findings reflect the enhanced oxidation injury in patients with CMP and, to a lesser extent, in CHD as compared to healthy controls, thus highly indicating the relevance of oxidative stress for the pathogenesis and progression of cardiovascular disease.     

Clinical features of venous insufficiency and the risk of venous thrombosis in older people

Venous thrombosis is common in older age, with an incidence of 0·5–1% per year in those aged >70 years. Stasis of blood flow is an important contributor to the development of thrombosis and may be due to venous insufficiency in the legs. The risk of thrombosis associated with clinical features of venous insufficiency, i.e., varicose veins, leg ulcers and leg oedema, obtained with a standardized interview was assessed in the Age and Thrombosis Acquired and Genetic risk factors in the Elderly (AT‐AGE) study. The AT‐AGE study is a case–control study in individuals aged 70 years and older (401 cases with a first‐time venous thrombosis and 431 control subjects). We calculated odds ratios (ORs) and corresponding 95% confidence intervals (CI) adjusted for age, sex and study centre. Varicose veins and leg ulcer were associated with a 1·6‐fold (95% CI 1·2–2·3) and 3·3‐fold increased risk of thrombosis (95% CI 1·6–6·7), respectively, while the risk was increased 3·0‐fold (95% CI 2·1–4·5) in the presence of leg oedema. The risk of thrombosis was highest when all three risk factors occurred simultaneously (OR: 10·5; 95% CI 1·3–86·1). In conclusion, clinical features of venous insufficiency, i.e., varicose veins, leg ulcers and leg oedema, are risk factors for venous thrombosis in older people.     

Insulin resistance, adipokines, and oxidative stress in nondiabetic, hypercholesterolemic patients: leptin as an 8-epi-prostaglandin F2alpha determinant

Limited data are available on the association of insulin resistance, adipokines, and in vivo lipid peroxidation. We investigated the relationships between insulin resistance, adipokines (leptin, adiponectin, and resistin), and oxidative stress in nondiabetic, hypercholesterolemic patients. Seventy-six nondiabetic patients with hypercholesterolemia participated in this cross-sectional study. Fasting glucose and insulin concentrations were analyzed. Serum leptin, adiponectin, and resistin concentrations and urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) were determined using enzyme-linked immunosorbent assay. We divided all subjects into 3 groups, classified by the tertiles of homeostasis model assessment of insulin resistance (HOMA-IR) values, and clinical parameter comparisons were made among the 3 groups. The results showed that serum leptin (P < .001) and adiponectin levels (P < .05) were significantly different among the groups, although serum resistin was not different. Furthermore, the group with the highest HOMA-IR had a significantly higher urinary 8-epi-PGF(2alpha) excretion than the group with the lowest HOMA-IR (P = .017). Circulating leptin was positively correlated with urinary 8-epi-PGF(2alpha) (r = 0.323, P < .01) and HOMA-IR (r = 0.524, P < .001). Circulating adiponectin was negatively correlated with body mass index (r = -0.252, P < .05) and HOMA-IR (r = -0.228, P < .05). We could not find a relationship between circulating adiponectin or resistin and urinary 8-epi-PGF(2alpha) excretion. Stepwise multiple linear regression analysis showed that leptin was associated with the urinary 8-epi-PGF(2alpha) excretion after adjusting for age, sex, body mass index, blood lipids, and HOMA-IR (P = .002). In conclusion, our results show that more insulin-resistant state of nondiabetic, hypercholesterolemic patients is associated with decreased adiponectin and increased leptin and urinary 8-epi-PGF(2alpha) levels, although no relationship with resistin was observed. Furthermore, serum leptin independently contributed to urinary 8-epi-PGF(2alpha) excretion.     

The isoprostane, 8-epi-PGF2 alpha, is accumulated in coronary arteries isolated from patients with coronary heart disease.

OBJECTIVE: In the present study we wanted to know whether 8-epi-PGF2 alpha, which belongs to the class of isoprostanes formed by free radical-mediated peroxidation of arachidonic acid and arachidonyl-containing phospholipids, is enriched in isolated coronary arteries of patients suffering from coronary heart disease (CHD, n = 23) who received allograft heart transplants as compared to vessels derived from patients with dilative cardiomyopathy (CMP, n = 19) or from healthy heart donors (controls, n = 6). METHODS: Sections from the isolated coronary arteries were analysed by semiquantitative immunohistochemistry by determining the area and intensity of positive reaction for 8-epi-PGF2 alpha in the vascular intima and media. In addition, the 8-epi-PGF2 alpha content was determined using a specific immunoassay after extraction and purification. RESULTS: The immunohistochemical results indicated that 8-epi-PGF2 alpha is significantly enriched in arteries from patients suffering from CHD as compared to CMP (P < 0.0001). In controls, significantly less immunostaining was observed. Furthermore, a significant positive correlation between semiquantitative immunohistochemistry and radioimmunological determination was observed too. CONCLUSIONS: From our findings we conclude that 8-epi-PGF2 alpha is especially accumulated in coronary arteries from CHD patients and therefore is likely to be involved in atherogenesis.     

The influence of environmental factors in chronic venous insufficiency

The present article focuses on the prevalence and risk factors for varicose veins and the severe stage of chronic venous insufficiency (CVI). The evaluation was made by reviewing the results of specific well-designed studies performed on the general population (case-control studies, cross-sectional studies, and large case series). Data from the literature were compared with the results of a recent multicenter cross-sectional study in Poland, in which 40,095 individuals from 803 registers of primary care physicians were clinically examined and assigned a clinical CEAP class. Analysis of the associations between varicose veins or severe CVI prevalence and factors that are usually considered as representing a risk for the development of CVI was performed. In Poland, a prevalence of varicose veins and severe CVI (skin changes, leg ulcer) similar to that observed in the other developed countries was reported. It was more common in women, but female sex was not found to be a strong risk factor. Among the risk factors most closely associated with CVI were age, family history of varicose veins, and constipation, whatever the sex. This is in keeping with findings from recent epidemiologic studies. Obesity and lack of physical activity were strongly associated with CVI in women, more so than in men. The number of pregnancies (more than 2 pregnancies) significantly distinguished between women with and without CVI. Regarding these latter risk factors, the Polish results do not contradict the commonly held beliefs that are found in the literature. A modest association was found with female sex, previous injury in legs (DVT), and remaining in the standing position for a long time, although these parameters are usually among those mostly agreed as being risk factors. The role of the prolonged sitting position was not established. The Polish epidemiologic survey provided updated figures on the prevalence of and risk factors for varicose veins and severe CVI, using clear and globally accepted clinical definitions for the venous disease based on the CEAP classification.     

Improvements of Venous Tone with Pycnogenol in Chronic Venous Insufficiency: An Ex Vivo Study on Venous Segments

This study evaluated the stretching and dilatation of venous segments ex vivo in subjects with primary varicose veins in comparison with comparable segments from subjects that used the supplement Pycnogenol (150 mg/d) for 3 months before surgery. Subjects with varicose veins and chronic venous insufficiency voluntarily used Pycnogenol for a period of at least 3 months. The segments of veins removed with surgery (in 30 subjects that had used Pycnogenol and in 10 comparable control subjects that had not used the supplement) were compared with normal, unused vein segments harvested for bypass grafting. The segments were suspended and a weight was attached to the distal part of the veins for 3 minutes and dilated with pressurized water. Digital images were recorded; the veins were measured before and after stretching to evaluate elongation. The manipulation of the vein segment was minimal. Tests were completed within 20 minutes after harvesting the veins. All segments were 4 cm long. The stretching test indicated a significantly higher level of passive elongation in control, varicose segments (2.29; 0.65 mm) in comparison with 1.39; 0.2 mm in vein segments from Pycnogenol-using patients. The dilation test showed an average higher dilation (2.19; 0.3 mm) in control varicose veins in comparison with varicose veins from Pycnogenol-using patients (1.32; 0.7 mm) (p < 0.05). Stretching and dilatation were lower in veins from Pycnogenol-using subjects (p < 0.05). The measurement of destretching and the recovery after dilatation indicated a better tone and recovery of the original size/shape in varicose segments from patients using Pycnogenol. Varicose segments had a more significant persistent dilatation and elongation in comparison with normal vein segments. Pycnogenol seems to decrease passive dilatation and stretching and gives vein walls a greater tonic recovery and elasticity that allows the vein to recover its original shape after dynamic stresses.     

Differences in prostaglandin E2, prostaglandin F2 alpha and prostacyclin contents and their response to thyrotrophin stimulation and in prostaglandin-stimulated cyclic AMP response in normal and Grave's thyroid slices

The human thyroid contained prostaglandin (PG) E2, PGF2 alpha and 6-oxo-PGF1 alpha, an end-metabolite of prostacyclin (PGI2), the 6-oxo-PGF1 alpha content being the highest of these prostaglandins. Graves's thyroid contained a significantly higher amount of PGF2 alpha and lower amounts of PGE2 and 6-oxo-PGF1 alpha than the normal thyroid. Thyrotrophin acutely augmented the thyroid contents of PGE2, PGF2 alpha and 6-oxo-PGF1 alpha. The TSH-stimulated increases in PGE2 and 6-oxo-PGF1 alpha were lower but the TSH-stimulated increase in PGF2 alpha was significantly higher in Graves's thyroid than in the normal thyroid. Prostaglandin E2 and PGI2 stimulated human thyroid cyclic AMP synthesis, with the magnitudes of PGE2- and PGI2-stimulated increases in cyclic AMP being equal in normal and Graves's thyroid. Prostaglandin F2 alpha did not stimulate cyclic AMP synthesis significantly. These results provide evidence that prostaglandins play important roles in thyroid physiology and the pathophysiology of Graves's disease.     

Prevalence and risk factors of varicose veins in Japanese women

The prevalence and risk factors of varicose veins in Japan were investigated in 541 Japanese women. Varicose veins were defined as any dilated, tortuous, and elongated veins of the lower extremity and classified into four types. The total prevalence rate was 45%. Saphenous type was observed in 22%, segment type in 35%, reticular type in 28%, and web type in 16%. Varicose veins in Japan seem to be less common than in the United States and Europe but more prevalent than in Africa. Concerning risk factors for varices, age, sex, heredity, and childbirth were related to the incidence of varicosities, as reported by others. However, these risk factors were shown to differ according to type of varicose veins.     

Impaired ambulatory venous function in lymphedema assessed by near-infrared spectroscopy.

AIM: The aim of this study was to investigate venous function in patients with leg lymphedema during exercise using near-infrared spectroscopy (NIRS), compared with that of patients with chronic venous insufficiency (CVI). METHODS: Forty-three legs of 33 patients (5 males, 28 females; mean age: 53 years) with leg lymphedema without varicose veins or deep vein thrombosis underwent a treadmill walking test with simultaneous NIRS. For comparison, 136 legs of 91 patients (35 males, 56 females; mean age: 56 years) with varicose veins as a CVI group and 45 legs of 38 healthy volunteers (23 males, 15 females; mean age: 50 years) were also evaluated in the same method. Deoxygenated hemoglobin (HHb) was continuously measured during exercise, and the ambulatory venous retention index (AVRI) of each leg was obtained from the serial changes in HHb. RESULTS: The mean AVRI of the lymphedema group was significantly higher than that of healthy legs and significantly lower than of legs with moderate or severe CVI. Furthermore, it was similar to that in the mild CVI group. CONCLUSIONS: Venous function is impaired in exercising legs with lymphedema, and corresponds to that in legs with mild venous insufficiency. The treatment of lymphedema should take CVI into consideration.     

Varicose symptoms without varicose veins: the hypotonic phlebopathy, epidemiology and pathophysiology. The Acireale project

Ever since 1982 the authors have been interested in varicose symptoms without varicose veins. Carrying out several pilot studies with infrared photoplethysmography (PPG) and strain gauge plethysmography they suggest that the pathophysiology of this behaviour could be caused by the reduction of the venous wall tone. They propose the name of Hypotonic Phlebopathy (HP). The diagnosis criteria are focused by symptoms (heavy legs in upright position, restless leg syndrome, sub-oedema and/or evening oedema) and signs detected by PPG, s.g plethysmography and duplex scanning (reduction of the muscle-venous calf pump and increase of the venous wall compliance). Epidemiology, assessed between 1989 and 1992 (Acireale Project), showed a 15.90% morbidity, with higher prevalence in females; the most important risk factors are pregnancy and family history. HP is not rare in males; the principal risk factor is work involving standing for long periods. These behaviours have been independently confirmed by two studies carried out in France in 1992, which showed a 15% prevalence in a similar group of subjects with functional venous insufficiency. The authors suggest the introduction of the term of Hypotonic Phlebopathy, the symptoms of which are significantly improved by phlebotonic drugs, especially when they are stronger. CEAP classification: C(0-S); E(P); A(0); P(unclassifiable); Clinical score (1-2); Anatomical score (0); Disability score (1).     

Prostaglandin E, thromboxane B2 and 6-oxo-prostaglandin F1 alpha in amniotic fluid and maternal plasma of rhesus monkeys (Macaca mulatta) during the latter third of gestation.

The concentrations of prostaglandin E (PGE), thromboxane B2 (TXB2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) were measured by radioimmunoassay in serial samples of amniotic fluid and maternal peripheral plasma in the latter third of pregnancy in rhesus monkeys (Macaca mulatta). The samples were collected under ketamine-induced anaesthesia. The concentration of PGE was undetectable in amniotic fluid until a few days before delivery when a large increase was observed in three of the five animals. There were small increases of TXB2 and 6-oxo-PGF1 alpha in amniotic fluid before delivery. In maternal plasma the concentrations of PGE, TXB2 and 6-oxo-PGF1 alpha were generally higher and more variable than in amniotic fluid and did not increase with advancing gestation. It is suggested that increased production of primary prostaglandins occurs before, and is involved in, the onset of parturition in the rhesus monkey.     

Quantitative air-plethysmographic venous function and ambulatory venous pressure in patients with primary varicose vein.

AIM: The purpose of this study was to investigate the relationship between air-plethysmographic volume parameters under standard exercise loading and foot venous pressure parameters under ideal exercise loading in patients with primary varicose veins. METHODS: Seventy-one lower limbs in 39 patients with primary varicose veins and 8 lower limbs in 4 healthy controls were examined. The patients included 12 males and 27 females, ranging in age from 36 to 79 years. Eighteen limbs were asymptomatic (class 0) limbs, 28 limbs had symptoms of swelling or heaviness (class 1), and 25 had skin lesions (class 2+3). The patients and controls were examined with duplex scanning, air-plethysmography, and ambulatory foot venous pressure measurement. RESULTS: The mean ambulatory venous pressure (AVP) was significantly higher in the class 2+3 limbs than in the other classes, but it was not significantly higher in class 1 than in class 0. There were no significant differences between the class 2+3 limbs and class 1 limbs in any of the air-plethysmographic parameters. However, the VFI in the class 0 limbs was significantly different from that in the other 2 groups. Among all parameters examined, the venous filling index (VFI) was the most closely correlated with the AVP. All air-plethysmographic parameters were negatively correlated with the VRT. CONCLUSIONS: Among non-invasive air-plethysmographic volume parameters, VFI is the most reliable indicator for quantitative evaluation of calf pump function.     

The generation of the F2-isoprostane 8-epi-PGF2alpha by human platelets on collagen stimulation

F-isoprostanes are prostaglandin (PG) F2-like compounds formed via non-enzymatic peroxidation of arachidonic acid, although some F2-isoprostane production may be cyclo-oxygenase (COX)-mediated. Of these substances 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) has received the most attention as it induces vasoconstriction and mitogenesis, and influences pathophysiological mechanisms relevant to arterial disease. Using improved methods for F2-isoprostane determination we examined collagen-stimulated platelet production of F2-isoprostanes in platelet-rich plasma (PRP), distinguishing between the free and esterified forms of these substances. Collagen stimulation caused marked release to the plasma (platelet-poor; PPP) of free 8-epi-PGF2alpha (2 +/- 2 pg/mg platelet protein vs 174 +/- 53 pg/mg protein, control (i.e. non-stimulated) vs collagen-stimulated, P < 0.05) and of free 9alpha ,11alpha-PGF (37 +/- 19 pg/mg protein vs 1948 +/- 643 pg/mg protein, control vs stimulated, P < 0.05), a COX derived product. Neither free nor esterified 9alpha, 11beta-PGF and 9beta, 11alpha-PGF2alpha were detectable in control or collagen stimulated samples. Sample concentrations of the esters of 8-epi-PGF2alpha and 9alpha, 11alpha-PGF2alpha were unaltered by collagen stimulation. These data confirm a previous report that activated platelets release the F2-isoprostane 8-epi-PGF2alpha, accompanying the release of a COX-derived product, 9alpha, 11alpha-PGF2alpha.     

The generation of the F(2)-isoprostane 8-epi-PGF(2alpha) by human platelets on collagen stimulation

F(2)-isoprostanes are prostaglandin (PG) F(2)-like compounds formed via non-enzymatic peroxidation of arachidonic acid, although some F(2)-isoprostane production may be cyclo-oxygenase (COX)-mediated. Of these substances 8-epi-prostaglandin F(2)alpha (8-epi-PGF(2alpha)) has received the most attention as it induces vasoconstriction and mitogenesis, and influences pathophysiological mechanisms relevant to arterial disease. Using improved methods for F(2)-isoprostane determination we examined collagen-stimulated platelet production of F(2)-isoprostanes in platelet-rich plasma (PRP), distinguishing between the free and esterified forms of these substances. Collagen stimulation caused marked release to the plasma (platelet-poor; PPP) of free 8-epi-PGF(2alpha) (2 +/- 2 pg/mg platelet protein vs 174 +/- 53 pg/mg protein, control (i.e. non-stimulated) vs collagen-stimulated, P < 0.05) and of free 9alpha ,11alpha-PGF (37 +/- 19 pg/mg protein vs 1948 +/- 643 pg/mg protein, control vs stimulated, P < 0.05), a COX derived product. Neither free nor esterified 9alpha, 11beta-PGF and 9beta, 11alpha-PGF(2alpha) were detectable in control or collagen stimulated samples. Sample concentrations of the esters of 8-epi-PGF(2alpha) and 9alpha, 11alpha-PGF(2alpha) were unaltered by collagen stimulation. These data confirm a previous report that activated platelets release the F2-isoprostane 8-epi-PGF(2alpha), accompanying the release of a COX-derived product, 9alpha, 11alpha-PGF(2alpha).     

Haemostatic factors and risk of varicose veins and chronic venous insufficiency: Edinburgh Vein Study.

Despite much research, the aetiology of venous disease is still poorly understood. Since haemostatic factors are involved in the processes of fibrinolysis and platelet aggregation, it is conceivable that such processes may be implicated in the pathology of varicose veins and chronic venous insufficiency (CVI). The Edinburgh Vein Study examined 1566 men and women aged 18-64 years that were randomly selected from the lists of 12 general practitioners. Each subject completed a questionnaire, underwent a comprehensive clinical examination and had a blood sample taken for the analysis of plasma fibrinogen, tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) antigens. Subjects with trunk varicose veins and those with CVI had higher levels of each haemostatic factor compared with those with no trunk varices and no CVI. Although unit increases in t-PA and vWF were initially associated with a significantly increased risk of CVI in men, and both factors with an elevated risk of trunk varices in women, multiple adjustment for age, smoking status and body mass index reduced the odds ratios to non-significance. However, this does not entirely rule out the possibility of a pathogenic role for haemostatic factors in venous disease, but rather indicates the need for further experimental and epidemiological studies.     

Incidence of varicose veins in Finland

BACKGROUND: Incidence of varicose veins in the population is unknown. The study aimed at estimating the incidence of varicose veins in complete cohorts of 40-60 year-olds in a general population. PATIENTS AND METHODS: The study was conducted in the city of Tampere, Finland. A validated questionnaire (with 93% sensitivity and 92% specificity) was used in a general population of 6874 individuals (aged 40, 50 or 60). Initially, 3065 of them had no varicose veins and 78% were followed-up for 5 years. RESULTS: 157 individuals reported new varicose veins during the follow-up. The overall incidence was 13.5 per 1000 person years (8.5 for men and 19.2 for women). Female sex was an independent and statistically significant risk indicator of varicose veins (adjusted odds ratio, OR 2.4). The incidence was significantly higher at the age of 50-55 years (OR 1.6). Higher body mass index seemed to be related to higher risk of new varicose veins (OR 1.2-1.8), but the association failed to reach statistical significance. The level of education did not affect the incidence. CONCLUSIONS: New varicose veins appear also in the middle-aged population, and the rate is linked with the female gender, especially at the beginning of the 6th decade.     

Venous insufficiency and hemorheology. Influence of venous stasis on erythrocyte aggregation and disaggregation

The aim of this study was to assess the rheological properties of blood in patients with superficial venous insufficiency, in the very exact place of the hemodynamic disturbance i.e. in the veins of the lower limbs. MATERIAL AND METHODS: Several hemorheological parameters were studied in 20 patients (12 females and 8 males, 20 to 44 years old) with varicose veins of the lower limbs (insufficiency of the superficial venous system and no history of thrombosis). The results were compared to those obtained in 20 healthy controls matched for sex, age, weight and schedule for blood withdrawal. Two blood samples were obtained from the veins of the lower limbs of each subject: the first one at rest and the second after 10 minutes of "venous stasis" (standing position and 100 mm Hg tourniquet), in a temperature controlled room (22 degrees C). Every blood test was performed within one hour after blood withdrawal: --hematocrit (microcentrifugation) and fibrinogen (nephelometry); --plasma viscosity in a 37 degrees C temperature controlled capillary viscometer (Myrenne KSPV4); --erythrocyte filterability using the Hemorheometer (8% hematocrit and polycarbonate nuclepore membrane with a pore diameter of 5 microns); --erythrocyte aggregation and disaggregation (Myrenne AMM1 aggregometer and Erythroaggregometer SEFAM). RESULTS: 1. Hematocrit was not significantly different between both groups of subjects at rest. However, it increased significantly after venous stasis in patients with varicose veins (44.2% vs 41.8%, p. less than 0.05) and that was not found in controls. 2. At rest, the fibrinogen level was higher in patients than in controls (3.54 milligrams vs 2.41 milligrams, p less than 0.01). After statis, a significant increased was found only in the patients group (3.93 milligrams, p less than 0.05). 3. In a similar way, plasma viscosity at rest was significantly higher in patients (1.23 mPa.s) than in controls (1.11 mPa.s, p less than 0.01), and after stasis a further increase was found in the patients group (1.32 mPa.s, p less than 0.01). 4. Also the erythrocyte filterability index was altered at rest in patients (20.9) when compared to controls (15.1, p less than 0.01). A significant increase of this index was only found in the patients group (23, p less than 0.01). 5. Every aggregation parameters were significantly different at rest when comparing subjects groups, the most significant difference concerning the threshold of disaggregation (171.2 s-1 vs 106.8 S-1, p less than 0.001. Erythrocyte aggregation index was increased after stasis in patients but not in controls, with both 600 S-1 and 3 S-1 shear rates. 6. Positive correlations were found between low shear rate aggregation index on one hand and fibrinogen (r = 0.61), plasma viscosity (r = 0.51) and erythrocyte filterability index (r = 0.47) on the other hand...     

Increased mast cell infiltration in familial varicose veins: pathogenetic implications?

AIM: Increased infiltration of activated mast cells has been recently implicated in the pathophysiology of varicose veins. The aim of the present study was to investigate a possible association between mast cell infiltration of primary varicose veins and clinical features, which could clarify further varicose vein pathophysiology. METHODS: Seventeen patients, operated on for primary varicose veins and greater saphenous vein incompetence, participated in the study. Mast cells, distributed within the adventitia of grossly abnormal segments of the greater saphenous vein and calf varicosities removed during surgery, were identified and measured in stained tissue sections. The mast cell count, expressed as mast cells per 10 high-power fields, was subsequently associated with clinical features, including age, gender, body mass index, familial varicose veins, duration of varicose vein disease and relation to previous pregnancies, leg symptoms and findings on physical examination, clinical class and score of chronic venous insufficiency (CEAP classification). RESULTS: Patients with family history of varicose veins (n=7) had a significantly increased mast cell infiltration (median, interquartile range) of the abnormal venous segments (16, 8.4) in comparison with those (n=10) without such a history (9.2, 7.3), p=0.005. Mast cell infiltration had a significant inverse association with age (r= -0.49, p=0.046), but not with the remaining clinical features. CONCLUSION: Our findings support the hypothesis that the increased mast cell infiltration in varicose veins is not a consequence of venous hypertension. Furthermore, the increased mast cell infiltration in familial varicose veins implies a rather primary role and therefore the presence of a distinct pathophysiology. Further investigation testing the activity of mast cells in cases of family history might reveal another step in the pathogenic mechanism of varicose veins, leading to a more rational treatment.     

Superficial vein thrombosis: risk factors,diagnosis, and treatment

Superficial vein thrombosis (SVT) risk factors are close to those of venous thromboembolism (VTE). Diagnosis is made in a clinical setting but ultrasonography is useful to eliminate concomitant deep vein thrombosis (DVT). For SVT of the lower limbs, which is the main location, varicose veins represent the principal cause but underlying conditions (e.g.: autoimmune diseases, malignancy or thrombophilia) must be sought in idiopathic, migrant or recurrent SVT and in the absence of varicose veins. Concomitant DVT and pulmonary embolism can occur in approximately 15% and 5% respectively. Historical treatments consist of anti-inflammatory agents plus elastic stockings and, in case of varicose veins, thrombectomy and stripping. Other treatments (anticoagulants, vein ligation) were assessed to limit the VTE risk. A one-month prophylactic dose of low molecular weight heparin plus elastic stockings could be the appropriate strategy in most cases. Other studies are needed before definitive conclusions can be drawn.     

Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome.

BACKGROUND: The metabolic syndrome (MetS) is a major target for prevention of atherosclerotic cardiovascular diseases and visceral fat accumulation is an underlying component of MetS. The aim of this study was to investigate the association of systemic oxidative stress with visceral fat accumulation and MetS. METHODS AND RESULTS: The study group consisted of Japanese men (n=44; 51.2+/-11.4 years) and women (n=61; 55.4 +/-13.4 years). Urinary 8-epi-prostaglandin F2alpha (8-epi-PGF2 alpha) concentration, a biomarker of systemic oxidative stress, was significantly high in the subjects with MetS. As the urinary concentration of 8-epi-PGF2alpha increased, the number of criteria for MetS were significantly met (abdominal obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol, hypertension, and high fasting glucose). Among parameters associated with MetS, the correlation coefficient of visceral fat area (VFA) with urinary 8-epi-PGF2alpha concentration was the highest (r=0.636, p<0.0001). In non-obese subjects, the correlation coefficient of VFA with urinary 8-epi-PGF2alpha concentration was higher (r=0.728, p<0.0001), although there was no significant correlation between subcutaneous fat area and urinary 8-epi-PGF2 alpha. Stepwise multiple regression analysis identified VFA as the strongest and independent determinant of urinary 8-epi-PGF2 alpha (p<0.0001) followed by adiponectin (p=0.0212) and, high sensitive C-reactive protein (p=0.0365). CONCLUSIONS: Systemic oxidative stress, as measured by urinary 8-epi-PGF2alpha , is strongly associated with visceral fat accumulation and MetS.