Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: "the study of men born in 1913".

BACKGROUND: Risk factors for deep vein thrombosis and pulmonary embolism are mostly derived from case-control studies of hospitalized patients, and there are few long-term population-based studies. OBJECTIVE: To study the long-term risk factors for deep vein thrombosis and pulmonary embolism among middle-aged men. DESIGN: A prospective cohort study. SETTING: General community, "The Study of Men Born in 1913." SUBJECTS: A random population sample of 855 men, all aged 50 years at baseline. MAIN OUTCOME MEASURES: Eight-hundred fifty-five men participated in a screening examination in 1963 at the age of 50 years, and 792 of these men were reexamined in 1967 at the age of 54. All the men were followed up with periodic examinations until the age of 80. Objective methods were used to ascertain a diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Waist circumference (P=.004) and smoking (P = .02) predicted a venous thromboembolic event in multivariate survival analysis. Men in the highest decile of waist circumference (> or =100 cm) had an adjusted relative risk of 3.92 (95% confidence interval, 2.10-7.29; P<.001) compared with men with a waist circumference of less than 100 cm. For men who smoked 15 g of tobacco (15 cigarettes) a day or more, the adjusted relative risk was 2.82 (95% confidence interval, 1.30-6.13; P= .009) compared with nonsmokers. CONCLUSIONS: Smoking and abdominal obesity were independent risk factors for venous thromboembolic events during follow-up. In addition to the prevention of smoking and obesity, a more aggressive strategy regarding the use of prophylactic agents among smokers and obese patients, in various risk situations, may be justified.     

Venous thrombosis after long-haul flights

BACKGROUND: The risk for venous thromboembolism after long-haul flights represents a controversial issue. The aim of our study was to assess the incidence of venous thrombosis associated with long-haul flights in a prospective, controlled cohort study. METHODS: We included 964 passengers returning from long-haul flights (flight duration, > or =8 hours) and 1213 nontraveling control subjects. We excluded participants who were being treated with anticoagulant drugs or who used compression stockings. Main outcome measures were the incidence of ultrasonographically diagnosed thrombosis in the calf muscle and deep veins, symptomatic pulmonary embolism, and death. RESULTS: We diagnosed venous thrombotic events in 27 passengers (2.8%) and 12 controls (1.0%) (risk ratio [RR], 2.83; 95% confidence interval [CI], 1.46-5.49). Of these, 20 passengers (2.1%) and 10 controls (0.8%) presented with isolated calf muscle venous thrombosis (RR, 2.52; 95% CI, 1.20-5.26), whereas 7 passengers (0.7%) and 2 controls (0.2%) presented with deep venous thrombosis (RR, 4.40; 95% CI, 1.04-18.62). Symptomatic pulmonary embolism was diagnosed in 1 passenger with deep venous thrombosis (P =.44). All of these individuals had normal findings at baseline ultrasonography. Passengers with isolated calf muscle venous thrombosis or deep venous thrombosis had at least 1 risk factor for venous thrombosis (>45 years of age or elevated body mass index in 21 of 27 passengers). The follow-up after 4 weeks revealed no further venous thromboembolic event. CONCLUSIONS: Long-haul flights of 8 hours and longer double the risk for isolated calf muscle venous thrombosis. This translates into an increased risk for deep venous thrombosis as well. In our study, flight-associated thrombosis occurred exclusively in passengers with well-established risk factors for venous thrombosis.     

Isolated iliac deep venous thrombosis. Study of 48 cases seen in 7 years among 18,297 echo-Doppler evaluations of the lower limbs

Isolated iliac venous thrombosis (IIVT) is uncommon. Duplex ultrasonography of the iliac vessels is not recommended and not generally performed. OBJECTIVE: The purpose of this study was to determine the frequency of IIVT in a hospital recruitment population and to identify characteristic features of onset which might be associated with this localization in order to better target explorations. MATERIAL AND METHODS: The study included 18,297 patients referred for Duplex-ultrasonographic exploration of possible deep vein thrombosis of the lower limbs between January 1st 1994 and December 31st 2000. Selection of isolated iliac thrombosis, defined as the absence of retrograde extension to the common femoral vein, was made from the digitalized data recorded daily. The following factors were tested: sex, age, absence of clinical signs in the lower limb, presence of pulmonary signs. The raw odds ratios were calculated followed by construction of a multivariate logistic regression model. The circumstances of onset were retrieved from the patient's medical files. RESULTS: Isolated iliac venous thrombosis was discovered in 48 patients, i.e. 0.26% (95% CI 0.19%-0.35%) in the recruitment population and 0.82% (95% CI 0.61%-1.09%) among the 5827 patients with thrombosis. The common iliac was involved predominantly (35 out of 48). The left side predominated in women compared with men (24/36 versus 4/12) (p = 0.04). Specifically female circumstances (oral contraceptives, peri-obstetrical period) always led to a left localization. For the other identified circumstances (cancer, inflammatory bowel disease, orthopedic surgery, pelvic trauma), there was no predominant side. Variables explaining the multivariate model were sex, age (less than or more than 35 years), suspected pulmonary embolism, and age interaction with suspected pulmonary embolism. For women, the risk of IIVT was twice as high as for men (OR = 1.97, 95% CI 1.02-3.81). Young age was also a risk factor for IIVT and increased with suspected pulmonary embolism. The odds ratio for subjects under 35 varied from 4.20 (95% CI 1.79-9.84) without suspected pulmonary embolism to 35.01 (95% CI 14.78-82.89) with suspected pulmonary embolism. CONCLUSION: The incidence of isolated iliac venous thrombosis is very low (0.26) in this hospital recruitment population but reached 9.40% in young women under 35 with suspected pulmonary embolism. These age and sex characteristics are also the principal circumstances for the development of these thrombotic events (pregnancy, post partum period, oral contraception). Under these circumstances, it is necessary to carefully explore the iliac vessels with duplex ultrasonography.     

Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study

BACKGROUND: Oral contraceptive use increases risk for venous thromboembolism, but data on the effect of postmenopausal hormone therapy are limited. OBJECTIVE: To determine the effect of therapy with estrogen plus progestin on risk for venous thromboembolic events in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 20 clinical centers in the United States. PARTICIPANTS: 2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coronary heart disease but no previous venous thromboembolism and had not had a hysterectomy. INTERVENTION: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in one tablet (n = 1380) or placebo that was identical in appearance (n = 1383). MEASUREMENTS: Documented deep venous thrombosis or pulmonary embolism. RESULTS: During an average of 4.1 years of follow-up, 34 women in the hormone therapy group and 13 in the placebo group experienced venous thromboembolic events (relative hazard, 2.7 [95% CI, 1.4 to 5.0] [P = 0.003]; excess risk, 3.9 per 1000 woman-years [CI, 1.4 to 6.4 per 1000 woman-years]; number needed to treat for harm, 256 [CI, 157 to 692]). In multivariate analysis, the risk for venous thromboembolism was increased among women who had lower-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer (relative hazard, 3.9 [CI, 1.6 to 9.4]) and for 90 days after inpatient surgery (relative hazard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [CI, 3.0 to 10.8]). Risk was decreased with aspirin (relative hazard, 0.5 [CI, 0.2 to 0.8]) or statin use (relative hazard, 0.5 [CI, 0.2 to 0.9]). CONCLUSIONS: Postmenopausal therapy with estrogen plus progestin increases risk for venous thromboembolism in women with coronary heart disease. This risk should be considered when the risks and benefits of therapy are being weighed.     

Impact of sex and traditional cardiovascular risk factors on the risk of recurrent venous thromboembolism: results from the German MAISTHRO Registry

As arterial and venous thrombosis share common risk factors, a link between arterial and venous thrombosis has been suggested recently. Therefore, we aimed to investigate the impact of established cardiovascular risk factors on the risk of recurrent venous thromboembolism (VTE). With a cross-sectional study design, we analyzed the data of 1006 patients (582 F, 424 M) consecutively treated in our outpatient department for VTE (i.e. lower extremity deep vein thrombosis and/or pulmonary embolism) and registered in the MAISTHRO (MAin-ISar-THROmbosis) database. Of the total cohort, 324 (32.2%) patients suffered a recurrent VTE. Compared with the patients with a single thromboembolic event, patients with recurrent VTE were more frequently male (39.4 vs. 27.0%, P < 0.001). In univariate analysis, the relative risk of recurrent VTE was 1.9 [95% confidence interval (CI) 1.53-2.39] for male sex and 1.6 (1.25-1.95) for age over 50 years (PAOD). After adjustments for age, sex, thrombophilia and other common VTE risk factors, male sex [hazard ratio (HR) = 1.7 (1.38-21.9)] and arterial hypertension [HR = 1.4 (1.05-1.78)] were independent risk factors of recurrent VTE. The higher risk in men than in women persisted even after the exclusion of women with transient hormonal risk factors [HR = 1.57 (1.19-2.07)]. In contrast, no association between the presence of diabetes, obesity, hypercholesterolemia or smoking and the risk of VTE recurrence was observed. Male sex and arterial hypertension are independently associated with an increased risk of recurrent VTE after termination of anticoagulant therapy for the first VTE event.     

Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors

BACKGROUND: The recurrence rate after deep vein thrombosis (DVT) is high and the risk factors for recurrent thromboembolic events have only been investigated on a small scale. OBJECTIVES: To estimate the cumulative incidence of recurrent venous thromboembolic events after a first or a second DVT and to identify possible risk factors for recurrent venous thromboembolism. METHODS: We prospectively followed up 738 consecutive patients with an objectively verified symptomatic DVT for 3.7 to 8.8 years. Medical records and death certificates for all patients were reviewed during follow-up and recurrent DVT and pulmonary embolism were registered. RESULTS: The 5-year cumulative incidence of recurrent venous thromboembolic events was 21.5% (95% confidence interval [CI], 17.7%-25.4%) after a first DVT and 27.9% (95% CI, 19.7%-36.1%) after a second DVT. The 5-year cumulative incidence of fatal pulmonary embolism was 2.6% (95% CI, 1.1%-4.1%) after a first DVT. Proximal DVT (relative risk [RR], 2.40; 95% CI, 1.48-3.88; P<.001), cancer (RR, 1.97; 95% CI, 1.20-3.23; P<.001), and history of a venous thromboembolism (RR, 1.71; 95% CI, 1.16-2.52; P<.01) predicted an independently increased risk of recurrent events in multivariate survival analysis. Postoperative DVT (RR, 0.27; 95% CI, 0.13-0.55; P<.001) and a long duration of oral anticoagulation therapy (RR, 0.95; 95% CI, 0.92-0.98; P<.01) involved a smaller risk of recurrent events. Sex, age, initial antithrombotic therapy, or immobilization did not affect the risk of a recurrent event. CONCLUSIONS: The recurrence rate after a symptomatic DVT is high. Patients with proximal DVT, diagnosed cancer, short duration of oral anticoagulation therapy, or a history of thromboembolic events had a higher risk of recurrent events, while patients with postoperative DVT had a lower recurrence rate. This knowledge could help identify patients who might benefit most from prolonged prophylactic treatment in various risk situations.     

Factors V leiden and II 20210A in patients with symptomatic pulmonary embolism and deep vein thrombosis

PURPOSE: Factor V Leiden and factor II 20210A are inherited disorders of the clotting system that occur frequently in patients with deep vein thrombosis. We conducted this study to determine whether these factors are also common in patients with pulmonary embolism. SUBJECTS AND METHODS: We determined the prevalence of factor V Leiden and factor II 20210A in 773 consecutive patients with objectively documented symptomatic deep vein thrombosis or symptomatic pulmonary embolism, or with a combination of these disorders. RESULTS: Isolated symptomatic deep vein thrombosis occurred in 345 patients; isolated symptomatic pulmonary embolism occurred in 236; and both anomalies occurred in 192. Factor V Leiden was present in 21 (9%) of the patients with isolated symptomatic pulmonary embolism, in 30 (16%) with both manifestations, and in 63 (18%) with isolated symptomatic deep vein thrombosis (P = 0.007). Factor V Leiden was more common among patients with deep vein thrombosis (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2 to 3.7; P = 0.006) or both pulmonary embolism and deep vein thrombosis (OR = 1.8; 95% CI: 1.0 to 3.3; P = 0.07) than among patients with isolated pulmonary embolism. Factor V Leiden was less common in massive pulmonary embolism (5% [7 of 127]) than in submassive pulmonary embolism (13% [21 of 155], P = 0.03). We found no significant difference in the prevalence of factor II 20210A among the three groups. CONCLUSION: Factors V Leiden and II 20210A vary in prevalence among patients with pulmonary embolism and deep vein thrombosis, suggesting that the risk of pulmonary embolization may vary among patients who have different causes of venous thromboses.     

Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis.

OBJECTIVE: To determine whether the presence of anticardiolipin antibodies is a risk factor for ischemic stroke and venous thrombosis in healthy adult men. DESIGN: A nested, case-control study in a prospective cohort. SETTING: A nationwide study of physicians. PARTICIPANTS: The study sample was drawn from the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 male physicians. At entry, 68% of the participants submitted plasma samples that were subsequently frozen at -80 degrees C. During 60.2 months of follow-up, follow-up for nonfatal outcomes was 99.7% complete and ascertainment of fatal outcomes was 100% complete. We identified men with documented ischemic stroke, deep venous thrombosis of the leg, or pulmonary embolus and for whom a plasma sample was available. A control was matched by age, smoking history, and length of follow-up to each of the 100 patients with ischemic stroke and the 90 patients with deep venous thrombosis or pulmonary embolus. MEASUREMENTS: Plasma samples were assessed for IgG anticardiolipin antibodies by enzyme-linked immunosorbent assay. The mean anticardiolipin antibody titers of the case patients in the two diagnostic groups (ischemic stroke; venous thrombosis or pulmonary embolus) were compared with those of the control groups, and relative risks were calculated for patients in increasing percentile categories of anticardiolipin antibodies by conditional logistic regression. RESULTS: The anticardiolipin antibody titers were higher in case patients with deep venous thrombosis and pulmonary embolus than in their matched controls (P = 0.01). Persons with anticardiolipin antibody titers above the 95th percentile had a relative risk for developing deep venous thrombosis or pulmonary embolus of 5.3 (95% CI, 1.55 to 18.3; P = 0.01). The anticardiolipin antibody titers in case patients with ischemic stroke and controls were not significantly different (P > 0.2), and no clear trend of higher risks among those with elevated levels of anticardiolipin antibodies was observed. CONCLUSION: An anticardiolipin antibody level above the 95th percentile is an important risk factor for deep venous thrombosis or pulmonary embolus but not for ischemic stroke in healthy adult men.     

Pulmonary thromboembolism in Asians/Pacific Islanders in the United States: analysis of data from the National Hospital Discharge Survey and the United States Bureau of the Census

PURPOSE: To assess the rate of diagnosis of deep venous thrombosis, pulmonary embolism, and venous thromboembolism; the incidence in hospitalized patients; and mortality from pulmonary embolism among Asians/Pacific Islanders in the United States. METHODS: The number of patients discharged from hospitals with a diagnostic code for pulmonary embolism or deep venous thrombosis from 1990 through 1999 was obtained from the National Hospital Discharge Survey. Population estimates and deaths from pulmonary embolism from 1990 through 1998 were obtained from the United States Bureau of the Census. RESULTS: Rate ratios of 10-year age-adjusted rates of diagnosis of deep venous thrombosis, pulmonary embolism, and venous thromboembolism comparing Asians/Pacific Islanders with whites and African Americans ranged from 0.16 to 0.21. Rate ratios comparing incidences in hospitalized patients ranged from 0.32 to 0.42. The age-adjusted rate ratio of mortality in "others" (which included Asians/Pacific Islanders) was 0.29 (95% confidence interval [CI]: 0.01 to 0.87) compared with whites and 0.14 (95% CI: 0.0 to 0.58) compared with African Americans. CONCLUSION: Rates of deep venous thrombosis, pulmonary embolism, and venous thromboembolism; incidences in hospitalized patients; and the mortality rate from pulmonary embolism were markedly lower in Asians/Pacific Islanders than in whites and African Americans. Clinical assessment of the prior probability of venous thromboembolic disease at the bedside should probably be adjusted based on these ethnic differences.     

Activated protein C resistance determined with a thrombin generation-based test predicts for venous thrombosis in men and women

Activated protein C (APC) resistance, determined with a thrombin-generation-based APC resistance test, may explain risk differences of venous thrombosis in users of second- and third-generation oral contraceptives (OC). To clinically validate this test, we analysed the Leiden thrombophilia case-control study (474 patients with a first episode of deep vein thrombosis and 474 age- and sex-matched control subjects). Data for men and women were analysed separately. As hormonal status in women is known to strongly influence the APC sensitivity ratio (APCsr), additional strata (OC use and menopausal state) were defined. The APCsr was higher in all patients than in control subjects. Odds ratios (OR), using the 90th percentile of all control subjects (APCsr > 4.5) as cut-off, were: 7.5 [95% confidence interval (CI) 1.6-33.8] for men, 3.0 (95% CI 1.0-8.8) for premenopausal women not using OC, 4.8 (95% CI 1.6-14.7) for premenopausal women using OC and 4.7 (95% CI 1.4-15.6) for postmenopausal women. After excluding the carriers of factor V Leiden, the OR became infinite for men (no control had an APCsr > 4.5), 1.4 (95% CI 0.2-8.2) for premenopausal women not using OC, 3.4 (95% CI 1.1-10.8) for premenopausal women using OC and 3.6 (95% CI 0.6-20.5) for postmenopausal women. A high APCsr, determined with the thrombin-generation-based APC resistance test, predicts venous thrombotic risk, in populations with and without factor V Leiden. In addition, acquired APC resistance resulting from OC use predicts an increased risk for venous thrombosis independent of factor V Leiden.     

Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial

BACKGROUND: We were concerned that a fixed rather than a weight-based dosing regimen of dalteparin sodium to prevent venous thromboembolism (VTE) might result in decreased efficacy in obese patients and decreased safety in elderly patients. METHODS: We retrospectively performed subgroup analyses using the database from the Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients (PREVENT) Trial, a study of 3706 hospitalized, medically ill patients randomized to receive either dalteparin sodium, 5000 U/d, or placebo. The primary end point was a composite of symptomatic VTE, fatal pulmonary embolism, sudden death, or asymptomatic proximal deep venous thrombosis by day 21. Obesity was defined as a body mass index (calculated as weight in kilograms divided by the square of height in meters) of 30 or greater for men and 28.6 or greater for women. RESULTS: Overall, 1118 patients (30.4%) were obese and 1226 (33.3%) were 75 years or older. In obese patients, the primary end point occurred in 2.8% of the dalteparin and in 4.3% of the placebo groups (relative risk, 0.64; 95% confidence interval [CI], 0.32-1.28). In patients 75 years or older, the primary end point was reported in 4.2% of the dalteparin and in 8.0% of the placebo groups (relative risk, 0.52; 95% CI, 0.31-0.87). The dalteparin effect for the primary end point (odds ratio, 0.51; 95% CI, 0.32-0.82) was not attenuated when adjusted for age, sex, obesity, history of VTE, and varicose veins. Dalteparin was not associated with an increase in major hemorrhage by day 21 in obese (0% vs 0.7% placebo; P>.99) and in elderly (1.1% vs 0.7%; P=.12) patients. CONCLUSION: Our findings suggest that a fixed low dose of dalteparin sodium of 5000 U/d is effective and safe in preventing VTE in obese and elderly hospitalized medical patients.     

Anticardiolipin antibodies and risk of thromboembolic disease in young Jamaican women

BACKGROUND: Anticardiolipin antibodies (aCL) are a heterogeneous group of antiphospholipid antibodies that are associated with arterial and venous thrombosis. We measured aCL in women, aged 15-49 years, to determine if they are an independent risk factor for thromboembolic disease. STUDY DESIGN: Case--control study METHODS: Fifty cases were studied including venous thromboembolism (n=29), stroke and myocardial infarction (n=21), along with 148 age-matched controls. Serum samples were assayed for aCL and anti-beta2 glycoprotein 1 antibodies using the enzyme-linked immunosorbent assay (ELISA). Information on other risk factors was obtained by a standardized questionnaire. RESULTS: aCL were present in 16/50 (32%) of cases compared with 25/148 (17%) of controls (P[?]=[?]0.02). Unadjusted odds ratio (OR) and 95% confidence interval (95% CI) for thromboembolic disease associated with aCL was 2.32 (1.10--4.87). Other risk factors were hypertension, 2.93 (1.20--7.17) and a history of other heart diseases, 12.78 (1.32--123.60). Adjustment for hypertension, diabetes, oral contraceptive use, smoking, alcohol use, varicose veins, a family history of cardiovascular disease and a history of other heart diseases yielded OR (95%CI) 2.99 (1.32--6.80). beta2 glycoprotein 1-dependent aCL were also an independent risk factor, OR 4.56 (1.76--17.83). Subgroup analysis was carried out separately for cases of MI and stroke and for venous thrombosis. Adjusted OR (95% CI) associated with aCL in cases of MI and stroke was 1.76 (0.46--6.73) and 3.32 (1.15--9.54) for venous thromboembolism. CONCLUSION: aCL are a risk factor for thromboembolic disease in young Jamaican women. They confer a strong independent risk for venous thromboembolism.     

Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations

In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), body weight, height and body mass index (BMI) were evaluated as risk factors. Additionally, the joint effect of obesity together with oral contraceptive use and prothrombotic mutations on the risk of venous thrombosis were analysed. Three-thousand eight-hundred and thirty-four patients with a first venous thrombosis and 4683 control subjects were included, all non-pregnant and without active malignancies. Relative to those with a normal BMI (<25 kg/m(2)), overweight (BMI > or = 25 and BMI < 30 kg/m(2)) increased the risk of venous thrombosis 1.7-fold [odds ratio (OR)(adj(age and sex)) 1.70, 95% confidence interval (CI) 1.55-1.87] and obesity (BMI > or = 30 kg/m(2)) 2.4-fold (OR(adj) 2.44, 95% CI 2.15-2.78). An increase in body weight and body height also individually increased thrombotic risk. Obese women who used oral contraceptives had a 24-fold higher thrombotic risk (OR(adj) 23.78, 95% CI 13.35-42.34) than women with a normal BMI who did not use oral contraceptives. Relative to non-carriers of normal BMI, the joint effect of factor V Leiden and obesity led to a 7.9-fold increased risk (OR(adj) 7.86, 95% CI 4.70-13.15); for prothrombin 20210A this was a 6.6-fold increased risk (OR(adj) 6.58, 95% CI 2.31-18.69). Body height, weight and obesity increase the risk of venous thrombosis, especially obesity in women using oral contraceptives.     

Venous thromboembolism after severe injury in children

BACKGROUND: Deep vein thrombosis and pulmonary embolism are considered common complications after major trauma. Their incidence and the associated risk factors have rarely been identified in injured children. METHODS: Severely injured children (age <18 years; admitted in a pediatric intensive care unit or length of stay > or = 72 h) with a discharge diagnosis of venous thromboembolism (VTE; deep venous thrombosis and/or pulmonary embolism) were identified from the institutional trauma registry between January 1, 1999 and April 31, 2002. The study centers included a dedicated pediatric trauma center and an adult trauma center with pediatric patients. Risk factors for VTE were identified using multivariate analysis. RESULTS: VTE was found in 11 of the 3,291 admissions, for a rate of 3.3/1,000 admissions. Children with VTE were older and had higher Injury Severity Scores. Independent risk factors for VTE included thoracic injuries [odds ratio (OR): 6.9; 95% confidence interval (CI): 1.4-35.1] and spinal injuries (OR: 37.4; 95% CI: 3.5-396.7). The greatest risk of VTE was in children with central venous catheters (OR: 64.0; 95% CI: 16.8-243.9). CONCLUSION: Older children with high Injury Severity Scores, thoracic injuries, spinal injuries or venous catheters are at risk for VTE. Because VTE prophylaxis, screening and treatment are associated with complications and costs, it is essential to identify subgroups of pediatric patients in whom these strategies might be studied.     

Synergistic effects of depressed mood and obesity on long-term cardiovascular risks in 1510 obese men and women: results from the MONICA-KORA Augsburg Cohort Study 1984-1998

OBJECTIVE: To examine the contribution of depressed mood in obese subjects on the prediction of a future coronary heart disease event (CHD). DESIGN: A prospective population-based cohort study of three independent cross-sectional surveys with 6239 subjects, 45-74 years of age and free of diagnosed CHD, stroke and cancer. During a mean follow-up of 7 years, 179 CHD events occurred among men and 50 events among women. SUBJECTS: A total of 737 (23%) male and 773 (26%) female subjects suffering from obesity (BMI >or=30 kg/m2). MEASUREMENTS: Body weight determined by trained medical staff following a standardized protocol; standardized questionnaires to assess subsyndromal depressive mood and other psychosocial features. RESULTS: The main effect of obesity to predict a future CHD (hazard ratio, HR=1.38, 95% CI 1.03-1.84; P=0.031) and the interaction term of obesity by depression (HR=1.73, 95% CI 0.98-3.05; P=0.060) were borderline significant, both covariate adjusted for multiple risk factors. Relative to the male subgroup with normal body weight and no depression, the male obese group with no depression was not at significantly increased risk for CHD events (HR=1.17, 95% CI 0.76-1.80; P=0.473) whereas CHD risk in males with both obesity and depressed mood was substantially increased (HR=2.32, 95% CI 1.45-3.72, P>0.0001). The findings for women were similar, however, not significant probably owing to lack of power associated with low event rates. Combining obesity and depressed mood resulted in a relative risk to suffer from a future CHD event of HR 1.84 (95% CI 0.79-4.26; P=0.158). CONCLUSIONS: Depressed mood substantially amplifies the CHD risk of middle-aged obese, but otherwise apparently healthy men. The impact of depression on the obesity risk in women is less pronounced.     

Risk of venous thrombosis in patients with pancreatic adenocarcinoma

AIM: To estimate the risk of venous thrombosis associated with pancreatic adenocarcinoma and its consequences on treatment and survival. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 90 patients (49 males, 41 females - median age: 67 years [range: 37-94]). Pancreatic adenocarcinoma was histologically proved in 72 patients (81%) and was metastatic in 49 patients (54.4%). A venous thrombosis was observed in 24 patients (26.7%). A pulmonary embolism occurred in 4 patients with 2 deaths. The risk of venous thrombosis was significantly reduced by the use of anti-thrombotic prophylaxis (HR: 0.03 [95CI: 0.003-0.27]) and increased among patients with a biological inflammatory syndrome (HR: 9.0 [95CI: 2.30-34.4]) and metastatic disease (HR: 4.4 [95CI: 1.1-17.9]). Overall survival was not different between patients with (6.6 months) or without (6.1 months) venous thrombosis. CONCLUSION: The risk of venous thrombosis is important and may delay the treatment in patients with advanced pancreatic carcinoma. Some patients with high risk of venous thrombosis may benefit from a prophylactic anticoagulant treatment.     

Increased risk of venous thrombosis in persons with clinically diagnosed superficial vein thrombosis: results from the MEGA study

Superficial vein thrombosis (SVT) is regarded a self-limiting disorder, although the authors of recent studies showed that ultrasonographically diagnosed SVT is a precursor for venous thrombosis. We aimed to determine whether the same holds true for clinically diagnosed SVT and to what extent it is associated with thrombophilia in a population-based case-control study (ie, Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). We found that a history of clinical SVT was associated with a 6.3-fold (95% confidence interval [CI] 5.0-8.0) increased risk of deep-vein thrombosis and a 3.9-fold (95% CI 3.0-5.1) increased risk of pulmonary embolism. Blood group non-O and factor V Leiden showed a small increase in SVT risk in controls, with odds ratios of 1.3 (95% CI 0.9-2.0) and 1.5 (95% CI 0.7-3.3), respectively. In conclusion, clinically diagnosed SVT was a risk factor for venous thrombosis. Given that thrombophilia was only weakly associated with SVT, it is likely that other factors (varicosis, obesity, stasis) also play a role in its etiology.     

The risk of recurrent venous thromboembolism among heterozygous carriers of the G20210A prothrombin gene mutation

The G20210A mutation in the prothrombin gene is associated with an increased risk of a first venous thromboembolic episode; few data are available about the long-term risk for recurrent venous thromboembolism and it is not known whether or not carriers of the mutation should be recommended lifelong anticoagulant treatment after the first thrombosis. We investigated 624 patients, referred for previous objectively documented deep venous thrombosis of the legs or pulmonary embolism, to determine the risk of recurrent thromboembolism in heterozygous carriers of the G20210A mutation in the prothrombin gene after the first episode of venous thromboembolism. After exclusion of other inherited (anti-thrombin, protein C, protein S deficiency and factor V Leiden) or acquired (anti-phospholipid antibody syndrome) causes of thrombophilia, 52 heterozygous carriers of the prothrombin mutation were compared with 283 patients with normal genotype. The relative risk for recurrent venous thromboembolism was calculated between groups using a Cox's proportional hazard model. The patients with the prothrombin mutation had a risk for spontaneous recurrent venous thromboembolism similar to that of patients with normal genotype (hazard ratio 1.3; 95% CI, 0.7-2.3). The circumstances of the first event (spontaneous or secondary) did not produce any substantial variation in the risk for recurrence. In conclusion, the carriers of the prothrombin mutation should be treated with oral anticoagulants after a first deep venous thrombosis for a similar length of time as patients with a normal genotype.     

Prevalence of duplex ultrasonography detectable venous thrombosis in patients with suspected or acute pulmonary embolism

OBJECTIVES: Duplex ultrasonography performance in detecting embolic foci has not been proven satisfactory compared with phlebography or autopsic findings. In case of suspected pulmonary embolism, the embolic focus is only discovered in 11 to 18% of the cases compared with more than 30% with phlebography. For overt acute pulmonary embolism, the discovery rate is in the 30 to 45% range versus 70 to 80% with phlebography or autopsy findings. This discrepancy might result from the fact that duplex ultrasonographic explorations are generally limited to the deep collectors at the cruropopliteal level. The purpose of this study was to assess the prevalence of duplex ultrasonography detected venous thrombosis in patients with suspected or acute pulmonary embolism when the exploration includes the entire venous system from the inferior vena cava to the ankles and examines not only the deep collectors but also the muscle and superficial networks.MATERIAL AND METHODS: This study included all patients with suspected pulmonary embolism referred to the emergency unit from January 1, 1995 through December 31, 1998. The patients' hospital files were used to determine the suspected pulmonary embolism population. The acute pulmonary embolism population was defined as the patients whose files contained documented proof of pulmonary embolism (highly probable ventilation/perfusion pulmonary scintigraphy, positive pulmonary angiography, positive proximal angioscan). Thrombosis of the deep venous collectors with or without associated superficial or muscular localization was classed as "deep venous thrombi" and superficial or muscular thrombosis without involvement of the deep collectors was classed as "other venous thrombi". Subpopliteal thrombosis was classed as distal and popliteal or suprapopliteal thrombosis as proximal.RESULTS: The suspected pulmonary embolism group included 352 patients, 118 men and 234 women aged 67.6 +/- 15.4 and 70.8 +/- 20.0 years respectively (m +/- SD). The acute pulmonary embolism group included 60 patients, 17 men and 43 women aged 66.2 +/- 12.5 and 69.7 +/- 16.6 years respectively. Overall prevalence of duplex-ultrasound detected venous thrombosis was 30.4% (107/352) (95%CI: 25.6-35.2) in the suspected pulmonary embolism group and 80% (48/60) (95%CI: 69.9-90.1) in the acute pulmonary embolism group. Deep venous thrombi reaching the collectors and proximal thrombi predominated. Prevalence of "other venous thrombi" and distal venous thrombi were 6.5% (23/352) and 11.4% (40/352) respectively in the suspected pulmonary embolism group and 15.0% (9/60) and 26.7% (16/60) in the acute pulmonary embolism group. The frequency of asymptomatic venous thrombosis of the lower limbs, irrespective of the localization, was 42.1% (45/107) in the suspected pulmonary embolism group and 52.1% (25/48) in the acute pulmonary embolism group.CONCLUSIONS: The prevalence of duplex-ultrasonography detected venous thrombosis in patients with suspected or proven pulmonary embolism found in this series was equivalent to the rates reported in phlebography and autopsy series. The prevalence was higher than usually reported for duplex-ultrasonography studies limited to the cruro-popliteal level. The difference came from the "other venous thrombi" and "distal deep venous thrombi" discovered by exploring the superficial and muscular networks and the calves. This study demonstrates the contribution of duplex-ultrasonography to the diagnostic strategy for pulmonary embolism.     

Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology

PURPOSE: To determine the incidence of deep vein thrombosis and pulmonary embolism in two cohorts representing regions of the United States. METHODS: The sample comprised 21,680 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. Subjects were aged >/=45 years, resided in six communities, and were followed for 7.6 years. All hospitalizations were identified and thromboses were validated by chart review. RESULTS: The age-standardized incidence of first-time venous thromboembolism was 1.92 per 1000 person-years. Rates were higher in men than women, and increased with age in both sexes. There was no antecedent trauma, surgery, immobilization, or diagnosis of cancer for 48% (175/366) of events. The 28-day case-fatality rate was 11% (29/265) after a first venous thromboembolism and 25% (17/67) for cancer-associated thrombosis. The recurrence rate 2 years after a first venous thromboembolism was 7.7% per year (95% confidence interval [CI]: 4.5% to 10.9% per year). Cancer was the only factor independently associated with 28-day fatality (relative risk [RR] = 5.2; 95% CI: 1.4 to 19.9) or recurrent thrombosis (RR = 9.2; 95% CI: 2.0 to 41.7). CONCLUSION: The incidence of venous thromboembolism in this cohort of middle- and older-aged subjects was similar to that observed in more geographically homogeneous samples. Half of cases were idiopathic. Short-term mortality and 2-year recurrence rates were appreciable, especially among subjects with cancer. Based on this study we estimate that 187,000 cases of first-time venous thromboembolism are diagnosed yearly in the United States among those aged 45 years or older.