A.M. van Rij

Incidence of deep vein thrombosis after varicose vein surgery.

Varicose vein surgery is generally considered to have little risk of postoperative deep vein thrombosis (DVT). This prospective study examined the incidence of DVT in patients undergoing varicose vein surgery.

Duplex Ultrasound Investigation of the Veins of the Lower Limbs after Treatment for Varicose Veins – UIP Consensus Document

OBJECTIVES Duplex ultrasound has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this article was an initiative of the Union Internationale de Phlébologie (UIP). The aim was to obtain a consensus of international experts on the methodology and terminology to be used for assessment after treatment of incompetent superficial and perforating veins in the lower limb by ultrasound imaging. DESIGN The study design was consensus meetings leading to a consensus document. METHODS The UIP invited group submitted relevant literature references and written contributions concerning the methodology, terminology and value of duplex imaging after treatment. The authors prepared a draft document that was circulated to a larger group of experts and revised according to the comments received. Eventually, all participants agreed upon the final version of the article. RESULTS Formal analysis of the results of interventions for varicose veins relies on adequate preoperative assessment and a careful description of the procedure employed. The timing of investigations of outcome should be classified as immediate (1-4 weeks), short-term (1 year), midterm (2-3 years) and long-term (5 years or more). The examination should employ standard methodology and formally described variables, which can be tailored to the intervention that was undertaken. The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination and reporting after various treatments for varicose veins, including novel treatments under scientific study. CONCLUSIONS Duplex ultrasonography is a fundamental component of the investigation of the lower limb venous system after treatment for varicose veins.

Recurrent Varicose Veins: Patterns of Reflux and Clinical Severity

Duplex scanning was used to determine patterns of recurrent varicose veins in 264 limbs and to relate these to clinical factors. All limbs had previously undergone sapheno-femoral ligation in the groin. A recurrent sapheno-femoral junction was present in 172 (65.2%). Incompetence was found in long or short saphenous veins in 232 limbs (87.9%), perforators in 176 (66.7%), and deep veins in 156 (59.1%). Residual long saphenous veins were present in 43.4% and 73.6% of limbs that were with and without stripped long saphenous veins, respectively. An incompetent thigh perforator was present in 14.0% and 15.3% of these two groups, respectively. Multiple sites of incompetence were observed in the majority (75.4%). In general, no particular reflux pattern in the groin was related to an increased incidence of ulceration. However, ulceration was more frequent in limbs with deep reflux to knee or below-knee levels. None of those with isolated reflux in the groin that was unrelated to the common femoral vein had ulceration. The pattern of reflux was unrelated to striping or non-striping of the long saphenous veins and the time since initial surgery. A history of deep vein thrombosis was invariably associated with some degree of deep reflux. A system of recurrent patterns in the groin is described for the purpose of surgical audit. In 15.1%, recurrence was attributed with some confidence to inadequate surgery. These results indicate that the pattern of recurrence is highly variable and often with multiple sites of incompetence. In a few instances, the pattern of recurrence was associated with specific clinical factors. A full work-up including duplex scanning is recommended.

Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial.

BackgroundThe use of repeated intravenous infusions of EDTA, which has become known as “chelation therapy,” has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication. Methods and ResultsA double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal propor-tion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%). ConclusionsChelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication.

Twenty-eight loci that influence serum urate levels: analysis of association with gout

Objectives Twenty-eight genetic loci are associated with serum urate levels in Europeans. Evidence for association with gout at most loci is absent, equivocal or not replicated. Our aim was to test the loci for association with gout meeting the American College of Rheumatology gout classification criteria in New Zealand European and Polynesian case-control sample sets. Methods 648 European cases and 1550 controls, and 888 Polynesian (Ma¯ori and Pacific) cases and 1095 controls were genotyped. Association with gout was tested by logistic regression adjusting for age and sex. Power was adequate (>0.7) to detect effects of OR>1.3. Results We focused on 24 loci without previous consistent evidence for association with gout. In Europeans, we detected association at seven loci, one of which was the first report of association with gout (IGF1R). In Polynesian, association was detected at three loci. Meta-analysis revealed association at eight loci—two had not previously been associated with gout (PDZK1 and MAF). In participants with higher Polynesian ancestry, there was association in an opposing direction to Europeans at PRKAG2 and HLF (HLF is the first report of association with gout). There was obvious inconsistency of gout association at four loci (GCKR, INHBC, SLC22A11, SLC16A9) that display very similar effects on urate levels. Conclusions We provide the first evidence for association with gout at four loci (IGF1R, PDZK1, MAF, HLF). Understanding why there is lack of correlation between urate and gout effect sizes will be important in understanding the aetiology of gout.

Obesity and Impaired Venous Function

OBJECTIVES The clinical severity of venous disease is often worse in obese patients. The objectives of this study were to compare lower limb venous physiology assessed by air plethysmography in a large group of obese and normal-weight patients; to consider the effect of posture on these measures and on foot vein pressure in a smaller cohort. METHODS Venous function was assessed using air plethysmography and duplex scanning in 934 consecutive patients presenting for assessment of venous disease. These were grouped into obese or non-obese categories. A smaller group of twenty patients with a range of body weights were randomly selected from a database of patients with varicose veins. Foot vein pressures and femoral vein diameter were measured standing, sitting, lying and ambulating. RESULTS Venous disease was more clinically severe in the obese limbs (CEAP C5&6 non-obese group 20.5%, obese group 35.4%, p<0.001 chi(2)). Venous reflux was worse in the obese but measures of muscle pump function were better. Residual volumes and fractions were better in the obese (mean residual volume, non-obese 60 SD 36, obese 50 SD 42, p<0.001 t test). In the smaller study group weight correlated with the diameter of the superficial femoral vein (r=0.50), ambulatory venous pressure (r=0.45), venous filling index (r=0.49) and the ejection volume (r=0.38, p<0.05). The foot venous pressure was significantly greater in the obese in all positions. CONCLUSION The CEAP clinical stage of venous disease is more advanced in obese patients than non-obese patients with comparable anatomical patterns of venous incompetence. This may be the result of raised intra-abdominal pressure reported in previous studies, leading to greater reflux, increased vein diameter and venous pressures.

Quantitation of malondialdehyde (MDA) in plasma, by ion-pairing reverse phase high performance liquid chromatography

An ion-pairing high performance liquid chromatography method is described for the separation and quantitation of malondialdehyde in plasma. The MDA is determined as the thiobarbiturate chromogen formed by reaction of the plasma with 2-thiobarbituric acid under acid and heating conditions. However, under these conditions other interfering chromogens can also be formed. Using DEAE-cellulose chromatography followed by ion-pairing HPLC, we have been able to separate and quantitate the levels of MDA-TBA chromogen formed in plasma from other interfering chromogens. Measurements of MDA levels in the plasma of six normal individuals by HPLC gives a mean value of 4.57 +/- 0.33 nmole/ml, whereas the spectrophotometric determined value is 8.83 +/- 1.15 nmole/ml. These data suggest that some reevaluation of the numerous papers published on MDA levels in plasma using spectrophotometric methods may be necessary.

Elevated Plasma Active Matrix Metalloproteinase-9 Level Is Associated With Coronary Artery In-Stent Restenosis

Objective—This study aimed to determine whether the plasma levels of matrix metalloproteinase-9 (MMP-9) or tissue inhibitor of metalloproteinases-1 (TIMP-1) were altered in patients with a history of symptomatic in-stent restenosis (ISR). Methods and Results—A group of 158 patients with a history of ISR were compared with 128 symptom-free patients. Plasma samples and a detailed risk factor history were collected. Plasma samples were analyzed for pro–MMP-9 and latent MMP-9 and active MMP-9, latent MMP-3, and TIMP-1. Several variables were associated with ISR, including index coronary disease extent and severity (number of diseased vessels and American College of Cardiology/American Heart Association lesion classification), number, diameter, and total length of stent(s) inserted, and plasma high-density lipoprotein cholesterol. Plasma active MMP-9 (odds ratio, 1.96; 95% CI, 1.43 to 2.69) showed independent risk association with ISR. Patients with multiple sites of ISR had significantly higher levels of active MMP-9 compared with patients with only a single ISR lesion or no ISR. Conclusion—Plasma active MMP-9 levels may be a useful independent predictor of bare metal stent ISR.

Novel rare mutations and promoter haplotypes in ABCA1 contribute to low-HDL-C levels

The ATP‐binding cassette A1 (ABCA1) protein regulates plasma high‐density lipoprotein (HDL) levels. Mutations in ABCA1 can cause HDL deficiency and increase the risk of premature coronary artery disease. Single nucleotide polymorphisms (SNPs) in ABCA1 are associated with variation in plasma HDL levels. We investigated the prevalence of mutations and common SNPs in ABCA1 in 154 low‐HDL individuals and 102 high‐HDL individuals. Mutations were identified in five of the low‐HDL subjects, three having novel variants (I659V, R2004K, and A2028V) and two with a previously identified variant (R1068H). Analysis of four SNPs in the ABCA1 gene promoter (C‐564T, G‐407C, G‐278C, and C‐14T) identified the C‐14T SNP and the TCCT haplotype to be over‐represented in low‐HDL individuals. The R1587K SNP was over‐represented in low‐HDL individuals, and the V825I and I883M SNPs over‐represented in high‐HDL individuals. We conclude that sequence variation in ABCA1 contributes significantly to variation in HDL levels.

Evidence for a genetic role in varicose veins and chronic venous insufficiency

There is a strong body of circumstantial evidence which implicates genetics in the aetiology and pathology of varicose veins and venous ulcer disease. The aim of this review is to consider the current knowledge of the genetic associations and the ways in which new genetic technologies may be applied to advancing our understanding of the cause and progression of these venous diseases. A number of publications have used a candidate gene approach to identify genes implicated in venous disease. Although these studies have opened up important new insights, there has been a general failure to replicate results in an independent cohort of patients. With our limited knowledge of the biological pathways involved in the pathogenesis of venous disease we are not in a strong position to formulate truly erudite a priori candidate gene hypothesis-directed studies. A genome wide association study should therefore be considered to help further our understanding of the genetic basis of venous disease. Due to the large sample sizes required for discovery and validation, using the new generations of molecular technologies, it will be necessary to form collaborating groups in order to successfully advance the field of venous disease genetics.