Chronic venous disease (CVD) is a multifactorial condition representing one of the most common disorders among populations of Western countries. The heritability of about 17% suggests genetic risk ...factors in CVD etiology. However, so far the genetic causes are unknown. We undertook the hitherto first genome-wide association study (GWAS) for CVD, analyzing more than 1.93 M SNPs in 4,942 German individuals, followed by replication in two independent German data sets. The combined analysis of discovery and replication stages (2,269 cases and 7,765 controls) yielded robust associations within the two genes EFEMP1 and KCNH8 (rs17278665, rs727139 with P < 5 × 10
), and suggestive association within gene SKAP2 (rs2030136 with P < 5 × 10
). Association signals of rs17278665 and rs727139 reside in regions of low linkage disequilibrium containing no other genes. Data from the ENCODE and Roadmap Epigenomics projects show that tissue specific marks overlap with the variants. SNPs rs17278665 and rs2030136 are known eQTLs. Our study demonstrates that GWAS are a valuable tool to study the genetic component of CVD. With our approach, we identified two novel genome-wide significant susceptibility loci for this common disease. Particularly, the extracellular matrix glycoprotein EFEMP1 is promising for future functional studies due to its antagonistic role in vessel development and angiogenesis.
Objectives
External valvuloplasty (eVP) is a reconstructive surgical method to repair the function of the terminal and preterminal valves. We evaluated the 6-month outcomes of eVP regarding the ...diameter of the great saphenous vein (GSV).
Methods
Patients from five vein centres were included in this observational study. Follow-up involved detailed duplex sonography of the GSV. The venous clinical severity score (VCSS) and the C class of the clinical, aetiologic, anatomic and pathophysiologic (CEAP) classification were recorded.
Results
We enrolled 210 patients, with a follow-up rate of 58%; eVP was sufficient in 95.24% of the patients. The GSV diameters decreased significantly from 4.4 mm (standard deviation (SD): 1.39) to 3.9 (SD: 1.12), 4 cm distal to the saphenofemoral junction (SFJ); from 3.7 mm (SD: 1.10) to 3.5 mm (SD: 1.02) at the mid-thigh; from 3.6 mm (SD: 1.14) to 3.3 mm (SD: 0.94) at the knee and from 3.1 mm (SD: 0.99) to 2.9 mm (SD: 0.78) at the mid-calf. VCSS decreased significantly from 4.76 (SD: 2.13) preoperatively to 1.77 (SD: 1.57) 6 months postoperatively.
Conclusions
GSV function can be restored by eVP; diameters over the total length of the GSV decreased significantly.
Heritability of chronic venous disease Fiebig, Andreas; Krusche, Petra; Wolf, Andreas ...
Human genetics,
06/2010, Letnik:
127, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Varicose veins without skin changes have a prevalence of approximately 20% in Northern and Western Europe whereas advanced chronic venous insufficiency affects about 3% of the population. Genetic ...risk factors are thought to play an important role in the aetiology of both these chronic venous diseases (CVD). We evaluated the relative genetic and environmental impact upon CVD risk by estimating the heritability of the disease in 4,033 nuclear families, comprising 16,434 individuals from all over Germany. Upon clinical examination, patients were classified according to the CEAP guidelines as either C2 (simple varicose veins), C3 (oedema), C4 (skin changes without ulceration), C5 (healed ulceration), or C6 (active ulcers). The narrow-sense heritability (
h
2
) of CVD equals 17.3% (standard error 2.5%, likelihood ratio test
P
= 1.4 × 10
−13
). The proportion of disease risk attributable to age (at ascertainment) and sex, the two main risk factors for CVD, was estimated as 10.7% (Kullback–Leibler deviance
R
2
). The heritability of CVD is high, thereby suggesting a notable genetic component in the aetiology of the disease. Systematic population-based searches for CVD susceptibility genes are therefore warranted.
Zusammenfassung
Hintergrund
Die offene Varizenchirurgie kann sowohl in einem ambulanten als auch in einem stationären Setting durchgeführt werden. Aktuelle Leitlinien zur Therapie der Varikose ...nehmen zu der Frage, welche Patienten ambulant und welche stationäre zu operieren sind, nicht Stellung.
Fragestellung
Erarbeitung von Kriterienkatalogen zur Frage einer ambulanten oder stationären Varizenoperation.
Material und Methode
PubMed-Recherche zur Fragestellung und basierend auf den Literaturdaten Erarbeitung eines Delphi-Konsensus der Autoren.
Ergebnisse
Zur Frage, ob eine Varizenchirurgie ambulant oder stationär durchgeführt werden kann, existieren lediglich 2 monozentrische retrospektive Analysen sowie eine Registerstudie. In diesen Studien werden ambulante Operationen im Wesentlichen bei Patienten mit Normalgewicht und ASA-Stadium 1 durchgeführt. Gut geeignete Lokalbefunde für eine ambulante Operation sind Primäreingriffe und ein geringeres C-Stadium der CEAP-Klassifikation. Für eine stationäre Varizenoperation sprechen ausgedehnte Befunde, bei denen mehr als eine Crosse saniert werden muss, Rezidiveingriffe in der Leiste oder der Kniekehle, vorangegangene thromboembolische Ereignisse, eine erhöhte Blutungsneigung aufgrund monströser Varizen oder einer Antikoagulation, Hautkomplikationen wie ein Ulcus cruris oder eine schwere Stauungsdermatitis bzw. Dermatosklerose sowie ein BMI über 30 bei Crossektomie.
Schlussfolgerungen
Basierend auf Literaturdaten und Expertenmeinungen konnten Kriterienkataloge für eine ambulante versus stationäre offene Varizenchirurgie erarbeitet werden.
OBJECTIVE To compare the clinical efficacy and safety of endovenous laser treatment (EVLT) with high ligation and stripping (HLS) as standard treatment for great saphenous vein (GSV) insufficiency. ...DESIGN Two-center randomized controlled trial with 2-year follow-up. SETTING Interventions were performed on ambulatory and hospitalized patients at 2 vein centers, a university dermatology department (EVLT-treated group), and a specialized vein clinic (HLS-treated group). PATIENTS Random sample of 400 patients with GSV insufficiency. INTERVENTIONS Patients were assigned (1:1) to EVLT or HLS of the GSV from September 2004 through March 2007; 185 and 161 patients (limbs), respectively, were treated per protocol. MAIN OUTCOME MEASURES Clinically recurrent varicose veins after surgery (REVAS classification, primary study objective), duplex-detected saphenofemoral recurrence, clinical venous severity scoring (Homburg Varicose Vein Severity Score), hemodynamics (venous refilling time), quality of life (Chronic Venous Insufficiency Questionnaire 2), adverse effects, and visual analog scale –based evaluations of patients' satisfaction. RESULTS Clinically recurrent varicose veins after surgery were similarly observed in both groups: 16.2% (EVLT-treated group) vs 23.1% (HLS-treated group); P = .15. Duplex-detected saphenofemoral refluxes occurred significantly more frequently after EVLT (17.8% vs 1.3%; P < .001). Both treatments equally improved medical condition (Homburg Varicose Vein Severity Score) and disease-related quality of life. Endovenous laser treatment caused more adverse effects (phlebitic reaction, tightness, dyspigmentation) but revealed advantages concerning hemodynamics, recovery, and cosmetic outcome. CONCLUSIONS Both EVLT and HLS are comparably safe and effective procedures to treat GSV incompetence. The significantly higher rate and the course of duplex-detected saphenofemoral recurrences after EVLT remain a matter of further investigations. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN18322872
BACKGROUND
Endovenous laser treatment (EVLT) is a minimally invasive procedure to ablate varicose veins. The venous arterial flow index (VAFI) represents a quantitative duplex ultrasound parameter to ...characterize venous hemodynamics, which has not been investigated in EVLT so far.
OBJECTIVE
To analyze the hemodynamic improvement of EVLT of the great saphenous vein (GSV) according to VAFI measurement.
MATERIALS AND METHODS
One hundred thirty‐three participants with complete GSV insufficiency were treated with 810‐nm EVLT. VAFI as a ratio of venous and arterial flow volumes of the common femoral vessels and digital photoplethysmography (DPPG) were assessed before and 3 (n=129) and 12 months (n=71) after EVLT.
RESULTS
EVLT was performed with an energy fluence of 22.5 J/cm2, resulting in an occlusion rate of 98.4%. Duplex recurrence rates were 9.4% at 3‐month and 15.5% at 12‐month follow‐up. VAFI significantly improved from 1.395 to 1.242 and 1.167 (p<.001) 3 and 12 months after EVLT. Venous refilling time (DPPG) accordingly increased from 20.0 to 36.9 seconds (p<.001) 3 months postoperatively.
CONCLUSION
EVLT improves hemodynamic alterations in people with incompetent GSVs as demonstrated using VAFI and DPPG. VAFI might be a suitable diagnostic tool to quantify venous hemodynamics in people with varicose veins.
The authors have indicated no significant interest with commercial supporters.
The unresolved problem of recurrent saphenofemoral reflux Fischer, Reinhard; Chandler, James G; De Maeseneer, Marianne G ...
Journal of the American College of Surgeons,
07/2002, Letnik:
195, Številka:
1
Book Review, Journal Article
To evaluate a novel score (HVVSS) for varicose vein patients combining subjective symptoms, clinical findings and functional data of venous insufficiency. 91 patients (118 legs) with primary varicose ...veins of the great, small or accessory anterior saphenous vein were treated with conventional surgery. HVVSS was assessed pre- and 3 months postoperatively. The data were compared with established clinical and disease-related life quality scores (VCSS, AVVQ, CIVIQ). Test responsiveness, validity and reliability were determined using correlations with CEAP stage and venous refilling time as hemodynamic parameter, and inter-observer variability was assessed. All scores were highly responsive to varicose vein surgery (p<0.001). HVVSS(0-100) decreased from 34.1 ± 13.0 to 9.6 ± 6.9 postoperatively. The relative score change of HVVSS was superior to VCSS (69.5% vs. 58.8%, p=0.005). HVVSS revealed highly significant correlations with the clinical CEAP stage and was exclusively able to differentiate mild from severe disease as defined by venous refilling time (p=0.009). Inter-observer reliability of HVVSS was confirmed by correlation coefficients of 0.977 and 0.950 pre- and postoperatively (p<0.001). HVVSS is a suitable and reliable tool to assess disease severity in varicose vein patients and to quantify therapeutic effects of varicose vein treatment.
Chronic venous disease (CVD) is a multifactorial condition representing one of the most common disorders among populations of Western countries. The heritability of about 17% suggests genetic risk ...factors in CVD etiology. However, so far the genetic causes are unknown. We undertook the hitherto first genome-wide association study (GWAS) for CVD, analyzing more than 1.93 M SNPs in 4,942 German individuals, followed by replication in two independent German data sets. The combined analysis of discovery and replication stages (2,269 cases and 7,765 controls) yielded robust associations within the two genes EFEMP1 and KCNH8 (rs17278665, rs727139 with P < 5 x 10(-8)), and suggestive association within gene SKAP2 (rs2030136 with P < 5 x 10(-7)). Association signals of rs17278665 and rs727139 reside in regions of low linkage disequilibrium containing no other genes. Data from the ENCODE and Roadmap Epigenomics projects show that tissue specific marks overlap with the variants. SNPs rs17278665 and rs2030136 are known eQTLs. Our study demonstrates that GWAS are a valuable tool to study the genetic component of CVD. With our approach, we identified two novel genome-wide significant susceptibility loci for this common disease. Particularly, the extracellular matrix glycoprotein EFEMP1 is promising for future functional studies due to its antagonistic role in vessel development and angiogenesis.
PDF
