Predominance of left‐sided deep vein thrombosis and body weight

Venous thrombosis poses a heavy medical burden. The incidence of venous thrombosis is one to two per thousand persons per year [1]. Over the years, many risk factors for this multicausal disease have been studied [2]. In 1851, Virchow observed a left-sided predominance of deep vein thrombosis (DVT) of the legs and hypothesized that compression of the left common iliac vein by the right common iliac artery could be the underlying cause [3]. In 1957, May and Thurner noted the presence of venous webs or spurs in the left common iliac vein in autopsies due to compression of the left iliac vein between the right iliac artery and fifth lumbar vertebra [4]. In pregnant women, the flow velocity in the left veins is decreased in the supine position [5], probably induced by the pregnant uterus compressing the common iliac vein [6]. This finding may explain the strong tendency of leftover right-sided thrombosis observed in pregnant women, in whom 80–90%of deep venous thromboses occur in the left leg [7,8]. Some cohort studies among DVT patients also reported a higher incidence of thrombosis in the left than in the right leg, of approximately 60 vs. 40% [9,10]. Obesity, defined as a body mass index (BMI) of 30 kg m or more, increases the risk of DVT by more than 2-fold [11]. We hypothesized that the intra-abdominal fat that is abundant in obesity mimics the compression of the left common iliac vein by the right common iliac artery induced by a pregnant uterus. Therefore, we investigated the distribution between leftand right-sided DVT in a large population-based cohort of patients with DVT, and assessed whether obesity modulates the risk of developing left-sided thrombosis. All analyses were carried out as part of the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), a large population-based case-control study. Between March 1999 and September 2004, all consecutive patients with a first episode of venous thrombosis were recruited from six anticoagulation clinics in the Netherlands. These clinics monitor the anticoagulant treatment for all outpatients within a well-defined geographical area. Eligible participants were between 18 and 70 years of age at the time of inclusion. Patients who died (n = 310) and those who were at the end stage of their disease (n = 86) and who were therefore unable to fill in a questionnaire were excluded. Of the 6256 eligible patients, 5183 (82.8%) were willing to participate. The study was approved by the Medical Ethics Committee of the Leiden University Medical Center, Leiden, the Netherlands. All participants provided written informed consent. Risk factors for venous thrombosis, including surgery, injury, pregnancy and oral contraceptive use, were reported in a standardized mailed questionnaire covering a period of 1 year before the venous thrombotic event. The questionnaire contained information about the weight and height of the participants, fromwhich we calculated BMI by dividing weight (kg) by squared height (m). For this analysis we compared the incidence of leftvs. right-sided DVT of the leg among patients with isolated DVT and excluded subjects with a diagnosis of pulmonary embolism, thrombosis in both legs, arm vein thrombosis and patients who were pregnant at the time of thrombosis or in the previous year. We calculated the incidence of leftand right-sided deep vein thrombosis with their corresponding 95% confidence intervals in all patients. To assess whether obesity modulates this distribution, we stratified for the presence of obesity as defined by a BMI of 30 kg m or more and tested this difference by using the Student t-test. Furthermore, we conducted logistic regression analyses with the side of thrombosis as the dependent variable and adjusted for risk factors such as age, sex, surgery, injury, BMI and oral contraceptive use. Of the 5183 patients with venous thrombosis, 2863 patients were diagnosed with an isolated leg DVT. After exclusion of women who had been pregnant prior to the DVT (n = 122) or for whom data regarding pregnancy were missing (n = 33) and cases in whom the side of thrombosis was not recorded (n = 132), we included 2576 patients in the analysis. The average age was 49 years (IQR 40.1–59.3) and the average BMI was 26.9 kg m (IQR 23.9–29.4); half of the patients were female. Correspondence: Willemien Thijs, Leiden University Medical Center, Department of Pulmonology, PO Box 9600, 2300 RC Leiden, the Netherlands. Tel: +31 71 5262950; fax: +31 71 5266927. E-mail: w.thijs@lumc.nl