2 – Epidemiology and risk factors

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Chronic venous disease

Beyond Epidemiology of severe stages of chronic venous insufficiency in the Bonn Vein Study
E. Rabe / Germany

The author presented the Bonn Vein Study, a population-based, cross-sectional, one-year study with participants from a single random sample out of population registers. The 3072 participants ranged in age from 18 to 79 years (43.9% male, 56.1% female). The response rate was 59%. The CEAP classification and duplex scanning were used.

Chronic venous disorders are very common in the general population. The prevalence was 87.5% for telangiectases, 23% for varicose veins, 17% for chronic vein insufficiency (CVI) (C3-C6), and 0.7% for C5-6 (venous leg ulcers) in both males and females. The most important risk factors for telangiectases and varicose veins were age (over 60), female gender, pregnancies, and family history of varicose veins. The most important risk factors for CVI besides age (over 50) were obesity and urban residence.

Symptoms and signs of chronic venous disorders: what can we learn from epidemiologic studies?
E. Rabe, F. Pannier / Germany

The authors presented an epidemiological study from Germany to evaluate the prevalence and risk factors associated with venous insufficiency in the general population (screening of 3072 individuals aged 18 to 79) of the city of Bonn and two rural cities. The prevalence was determined by means of the response to a specific questionnaire and one duplex ultrasound study.

The majority of symptoms associated with venous insufficiency appeared in patients at stages C3 to C6 of the CEAP. The presence of varicose veins relates to genetic factors, obesity, female gender, and advanced age. Obesity, low social class, living in a city, and sedentary lifestyle were associated with CVI. The authors intend to continue the study to answer questions like: Why do symptoms vary in patients with the same type of varicose veins and degree of reflux?

Chronic venous insufficiency: clinical presentations among Malaysian patients
N.C. Liew, K. Moissinac, L. Lee / Malaysia

The authors have produced a venous registry of 343 patients (520 limbs) with symptoms of CVI. The incidence of CVI among the Asian population is not known. In this series, patients tend to present late: 50% belong to CEAP classes C4-C6. Postthrombotic syndrome is not infrequent, affecting 5% of the general population. Better education of the general population so that medical advice is sought at earlier disease stages may perhaps alter the spectrum of patients presenting to a venous clinic.

Venous thrombosis

Prevalence and indicators of deep vein thrombosis in medical patients
K. Sato, K. Hanzawa, T. Okamoto, F. Asami, M. Takekubo, O. Namura, J. Hayashi / Japan

In Japan, venous thromboembolism (VTE) is thought to be a rare disease, and thromboprophylaxis is not routinely used in clinical practice. In this study, the authors aimed to determine the risk of VTE in hospitalized medical patients and to identify indicators of this risk.

Of 158 patients (mean age 60 years) bedridden for at least 48 h in an internal medicine ward with an acute medical condition and who underwent compression ultrasonography, 68 (43%) had thrombosis. Older age was associated with a higher thrombotic risk. This incidence is particularly high, but it included 26 isolated soleal vein thromboses, 5 superficial vein thromboses, and 5 upper limb thromboses after catheter insertion. These results suggest Japanese and Westerners have a similarly high risk and underline the importance of preventing thromboembolic risk in medical patients.

Prevalence of calf deep vein thrombosis in residents in rural Japan, and diameter of soleus vein indicates a risk of calf
DVT in Mid Niigata prefecture Earthquake 2004

K. Hanzawa, J. Hayashi, I. Fuse, F. Aizawa / Japan

During earthquakes, people often take refuge in their cars, sometimes for many days because of the frequent aftershocks over the following days. After an earthquake in 2004, 11 persons taking refuge in their cars suffered from pulmonary embolism (PE), of which four died. This prompted a Japanese team to conduct investigations on VTE risk in such a context. They performed systematic ultrasonography of the calf in all residents taking refuge in their cars one week after the quake and found 30% of them to have calf deep vein thrombosis (DVT). One year after the quake, a similar study was performed in 1365 persons living in the affected area. Prevalence of calf vein DVT was 7.8%. The authors found a correlation between the Richter scale value at the place of residence and the risk of thrombosis. The same study was performed in a control group in another city 100 km from the area of the quake. In this city, only 1.8% of tested subjects had DVT. Also, the authors found the diameter of the soleal veins to be associated with DVT risk. In particular, in the area hit by the quake, soleal vein diameters were significantly higher in subjects who took refuge in their car than in those who did not. It was higher in patients with calf DVT than in those without DVT, with a 2.5 (95% CI 1.7 to 4.0) odds-ratio at the cut-off of 9 mm. The proportion of subjects with an increased soleal vein diameter (above 9 mm) was higher in the quake area than in the control study, and one year after the quake a significant association between the soleal vein diameter and the risk of DVT was also found.

The high proportion of calf DVT, even asymptomatic, observed after confinement in cars for several days might represent a danger for the exposed population. Although the criteria for selection of controls were not clearly stated, the risk of thrombosis during the following year seems to be higher than in unexposed patients.

Risk profile of patients with deep vein thrombosis diagnosed in ambulatory care – Data from the German TULIPA Registry
H. Gerlach, S.M. Schellong, V. Hach-Wunderle, E. Rabe, H.B. Riess, H. Carnarius, N. Banik, R. Bauersachs / Germany

Nowadays, patients with DVT are managed on an outpatient basis. The aim of the German TULIPA registry (comprising 4976 patients referred by their GP for a clinically suspected DVT to 341 ambulatory care vascular medicine physicians) was to provide information on patient risk profiles in such a setting.

Prevalence of classic risk factors was higher in patients with DVT at ultrasonography than in those without. Male gender, older age, a recent history of plaster cast, surgery, confinement to bed, or acute disease were associated with DVT, as well as a family history of VTE, active malignancy or the use of estrogens, corticosteroids or anticancer therapy. However, odd-ratios for the association between these risk factors and DVT were lower than usually reported, most of them being between 1.4 and 1.8. Varicose veins and long distance travel were not associated with DVT in this study.

These results are not surprising, due to the study design. In fact, this was not a case-control study. All patients were referred by their GP because DVT was suspected, partly because of the patients’ risk factors. This reduced the contrast between patients with and without DVT, those without DVT not being good controls for an association study.

Importance of combination of persistent underlying factors in deep vein thrombosis
H. Yasuhara, N. Ohara, T. Hattori, O. Shigeta / Japan

In a cohort study of 122 patients with lower limb DVT, the authors aimed to 1) identify factors linked with an associated PE at the time of DVT diagnosis; 2) identify factors associated with a higher risk of VTE recurrence during a mean 21-month follow-up. 67 patients (55%) had an associated PE. Those patients with recurrent DVT, prolonged bed rest, or who underwent venous catheter insertion were more prone to associated PE. This was also true for patients with persistent underlying risk factors (coagulopathy, active malignancy, collagen disease, or iliac compression): hazard ratio 1.6. During follow-up, patients with a history of VTE (hazard ratio 3.9) had a higher risk of DVT recurrence, as had those with one of the predefined persistent underlying risk factors: hazard ratio 3.6.

These data confirm that a stratification of patients based on VTE history and the presence or absence of transient or persistent risk factors for VTE is useful in predicting severity and the risk of DVT recurrence, and have the potential to improve management.

Risk of recurrent deep venous thrombosis in patients with genetic thrombophilias
J.R. Gonzalez-Porras, I. Alberca, M.L. Lopez, F. Lozano / Spain

259 patients with DVT were included in the investigation. Genetic polymorphisms of factor V Leiden, G20210A prothrombin and 677T methylene tetrahydrofolate reductase and their influence on DVT recurrence were assessed. The authors concluded that the double defect, and homozygosity or double heterozygosity for factor V Leiden and G20210A were associated with an increased risk of recurrent DVT. Patients who were heterozygous for factor V Leiden or G20210 had a risk of recurrent DVT similar to that of patients who had neither mutation. The 677T MTHFR mutation alone or combined with hyperhomocysteinemia was not associated with an increased risk of recurrent DVT. In conclusion, the authors recommended active (LMW-heparin or warfarin) thromboprophylaxis for all patients at high risk of re-thrombosis.

A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk of venous thrombosis
J. Corral, J.R. Gonzalez-Porras, R. Gonzales, I. Alberca, F. Lozano, V. Vicente / Spain

Z-dependent protease inhibitor (ZPI) is a new hemostatic serpin with anticoagulant activity. There were 6 genetic mutations affecting the ZPI gene. All of them induced ZPI deficiency and significantly increased the risk of DVT. The ZPI mutation is the root cause of primary DVT in 0.9% cases.

Deep venous thrombosis incidence in patients immobilized by multiple sclerosis: a prospective study
G. Arpaia, P. Bavera, D. Caputo, L. Mendozzi, R. Cavarretta, G.B. Agus / Italy

Patients affected by multiple sclerosis experience a progressive reduction in walking capacity and spend increasing time in a wheelchair or in the sitting position. Leg swelling occurs in a short time often with pain and can lead to DVT. Up to now, DVT in these patients has been underestimated and not much considered by neurologists. The aim of this prospective study was to screen 200 patients with multiple sclerosis: 100 with usual rehabilitation, 100 with the same but also wearing below-knee stockings. The author presented preliminary data on 50 patients with a follow-up of 6 months and evaluation by duplex scan at several levels (below-knee deep veins, popliteal, and femoral veins). DVT (either distal or proximal) was found in 13 patients (19.6%) at the end of the 4 weeks of rehabilitation.

Factors to predict the risk of venous thromboembolism recurrence
G. Palareti / Italy

The optimal duration of oral anticoagulant therapy (OAT) to prevent recurrences after a first unprovoked venous thromboembolism (VTE) event is still uncertain. The author reported data from a recently published, prospective, open label, randomized controlled study to assess whether the D-dimer (DD) test may be used to establish OAT duration. The DD test was performed 1 month after anticoagulation withdrawal in patients with a first unprovoked proximal deep venous thrombosis or pulmonary embolism who had received OAT for 3 months. Patients with a normal DD did not receive OAT. Patients with abnormal DD were randomized to receive further such treatment or not. DD was abnormal in 223/608 (36.7%) patients. Recurrent VTE occurred in 24/385 patients with abnormal DD. The adjusted hazard ratio of patients with abnormal DD who stopped anticoagulation versus those with normal DD was 2.27 (1.15-4.46; P=0.02). In conclusion, the DD test after OAT withdrawal can assess the risk of VTE recurrence. Patients with abnormal DD have a higher risk of recurrence and should benefit from prolonged anticoagulation.

Incidence and clinical predictors of deep vein thrombosis in patients hospitalized with heart failure in Japan
S. Ota, N. Yamada, M. Nakamura, N. Isaka, M. Ito / Japan

The aim of this study was to estimate the incidence of venous thromboembolism (VTE) in in-hospital patients with heart failure (HF). This study was performed in 108 patients admitted to hospital with class 2 to 4 HF. They underwent systematic compression ultrasonography during their stay. Despite the use of anticoagulant therapy in 21 patients (mainly warfarin for their underlying cardiac condition), the overall incidence of DVT was 13%. This correlated with the severity of HF: 5.4%, 7.1% and 23.2% in NYHA classes 2, 3 and 4, respectively. In a multivariate analysis, class 4 HF and anticoagulation were independent predictors of risk, with odds-ratios of 18 (95% CI, 3.0 to 117) and 0.22 (95% CI, 0.1 to 0.9), respectively. Because LMWH use is restricted in Japan, where VTE is thought to be a rare disease, this Japanese study provides valuable confirmation of the high incidence of VTE in hospitalized HF patients and highlights the need for thromboprophylaxis in such patients.