Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology

Summary.  Background:  In a recent case–control study, the odds of metabolic syndrome (MetSyn) among deep vein thrombosis cases were almost twice those among controls. We tested the hypothesis that the incidence of non-cancer-related venous thromboembolism (VTE) is higher among adults with MetSyn and further, that associations are stronger for idiopathic than secondary VTE. Methods:  A total of 20 374 middle-aged and elderly adults were followed for over 12 years for incident VTE in the Longitudinal Investigation of Thromboembolism Etiology (LITE). All hospitalizations were identified and VTEs validated by chart review. Baseline MetSyn was defined using ATP III guidelines, including ≥3 of the following components: abdominal obesity, elevated blood pressure, low HDL-cholesterol, high triglycerides and high glucose. Because sex modified the relation between MetSyn and VTE (p_interaction = 0.001), proportional hazards regression analyses were stratified by sex to assess the associations of MetSyn and its components with risk of incident non-cancer-related VTE, adjusting for potential confounders. Results:  Incident VTE ( n  = 358) included 196 idiopathic events. Baseline MetSyn was associated with risk of total VTE (hazard ratio (HR) = 1.84, 95% CI = 1.30, 2.59) and idiopathic VTE (HR = 1.59, 95% CI = 1.02, 2.47) among men, but not women. The association was largely attributable to abdominal obesity (HR of VTE = 2.10, 95% CI = 1.51, 2.93, in men; HR of VTE = 1.70, 95% CI = 1.24, 2.34, in women), with no additional contribution by the other MetSyn components. Conclusion:  Although abdominal obesity was associated with increased risk of VTE in both men and women, MetSyn and its other components do not seem important in VTE etiology.     

Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø study

Summary.  Background:  Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV is increased in acute myocardial infarction, and has been identified as an independent risk factor for future myocardial infarction and stroke. Objectives: The purpose of the study was to determine the impact of platelet count and MPV on the incidence of venous thromboembolism (VTE) in a prospective, population-based study. Methods:  Platelet count, MPV and baseline characteristics were registered in 25 923 subjects aged 25–96 years who participated in the Tromsø Study in 1994–1995. Incident VTE events were registered to the end of follow-up (1 September 2007). Results:  There were 445 validated incident VTE events (1.6 per 1000 person-years), of which 186 (42%) were unprovoked, during a mean of 10.8 years of follow-up. Subjects with MPV ≥ 9.5 fL had a 1.3-fold [95% confidence interval (CI) 1.0–1.7] higher risk of total VTE and a 1.5-fold (95% CI 1.1–2.3) higher risk of unprovoked VTE than subjects with MPV < 8.5 fL in analyses adjusted for age, sex, smoking, body mass index, and platelet count. Increasing MPV was associated with increased risk of total VTE ( P for trend = 0.09) and unprovoked VTE ( P for trend = 0.03) in analyses adjusted for age and sex. There was no significant association between increasing platelet count and risk of VTE. Conclusions:  An increasing MPV was identified as a predictor for VTE, in particular VTE of unprovoked origin. The present findings support the concept that platelet reactivity is important in the pathogenesis of VTE.     

High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism

Summary.  Background:  The assessment of the risk of recurrent venous thromboembolism (VTE) is important to determine the optimal duration of secondary prophylaxis. The risk can be estimated by measuring individual parameters reflecting hypercoagulability. Because of the large numbers of such putative parameters, the assessment in individual patients is complex. Application of global assays reflecting the pro-/anti-coagulant balance in vivo would be desirable. Objectives:  To investigate the relationship between recurrent VTE and thrombin generation (TG). Patients-methods:  Two hundred and fifty-four patients were followed-up after a first episode of unprovoked, objectively documented VTE for a period of 2.7 years after discontinuation of treatment with vitamin K antagonists. TG was measured 1 month after discontinuation of treatment as endogenous thrombin potential (ETP), peak thrombin and lag-time in the presence or absence of thrombomodulin. The study outcome was objectively documented symptomatic recurrent VTE. Results:  Patients with ETP or peak (measured in the presence of thrombomodulin) of >960 n m _*min or >193 n m had hazard ratios (HR) (95% CI) for recurrent VTE of 3.41 (1.34–8.68) or 4.57 (1.70–12.2) as compared with those with an ETP <563 n m _*min or peak <115 n m . Patients with lag-time <14.5 min had HR of 3.19 (1.29–7.89) as compared with those with lag-time >20.8 min. HR for ETP, peak or lag-time measured in the absence of thrombomodulin were smaller than those measured in the presence of thrombomodulin. Conclusions:  The measurement of TG helps to identify patients at higher risk of VTE recurrence. The increased risk may be better appreciated if the test is performed in the presence of thrombomodulin.     

The relationship between unprovoked venous thromboembolism, age, and acute myocardial infarction

Summary.  Background:  Patients with unprovoked venous thromboembolism (VTE) may be at increased risk of acute myocardial infarction (AMI). However, the nature and clinical significance of this association remain unclear, particularly as it relates to age of presentation. Methods: We performed a longitudinal matched cohort study utilizing multiple administrative databases. Ontario residents aged 20–64 years diagnosed with unprovoked VTE from 1 April 1991 to 31 March 1995 ( n  = 6065) were matched to a population cohort ( n  = 12 040) in 1 : 2 fashion on the basis of age, gender, socioeconomic class, cardiovascular risk factors and other comorbidities. The primary outcome was a comparison of relative risk of AMI over 10-year follow-up in subjects with unprovoked VTE (overall and stratified by age) vs. controls. Secondary outcomes included risk of death or the composite endpoint of AMI and/or death. Results: Patients 20–39 years of age presenting with unprovoked VTE had an increased risk of AMI [adjusted hazard ratio (HR) 3.92, 95% confidence interval (CI) 1.65–9.35] as compared to controls; the association was applicable to those without atherosclerotic risk factors at baseline. There was no significant relationship between unprovoked VTE and AMI among patients 40–64 years old, with or without atherosclerotic risk factors. Irrespective of age, patients with unprovoked VTE had an increased risk of all-cause death or our composite endpoint of AMI and/or death as compared to patients without VTE. Conclusions: Unprovoked VTE is associated with a nearly 4-fold higher risk of subsequent AMI among younger patient populations. Future studies must explore the risk–benefit tradeoffs of long-term surveillance and management options among such patient populations.     

Prevalence of abdominal obesity in primary care: the IDEA UK study

Background: Abdominal obesity is known to be a risk factor for cardiovascular and metabolic diseases. However, despite the importance of abdominal obesity as a risk factor for cardiovascular and metabolic disease, there are currently no UK‐specific data on its prevalence in patients attending primary care. Aim: The aim of the International Day for the Evaluation of Abdominal obesity (IDEA)‐UK observational study was to determine the distribution of waist circumference – a marker of abdominal obesity – and its relationship with cardiovascular risk markers in a UK‐based primary care population. Methods: Patients underwent measurements of height, weight and waist circumference and provided data on reported cardiovascular disease (CVD), diabetes, hypertension and dyslipidaemia. Results: A total of 1731 patients were assessed within the study, of which 719 were male and 1012 were female. Of these 1731 patients, 1718 had complete datasets for the presence of reported cardiovascular risk factors. Median waist circumference in the male and female populations respectively was 99.0 cm [interquartile range (IQR) 91.0?108.0 cm] and 89.0 cm (IQR 79.0?100 cm). In all, 38.8% of men and 51.2% of women were abdominally obese (waist circumference > 102 cm and > 88 cm respectively) according to the US National Cholesterol Education Program (NCEP) guidelines. Within both male and female populations, the incidence of reported CVD, lipid disorders, hypertension and diabetes increased with increasing quartiles for waist circumference. Conclusion: Increased waist circumference is widespread in patients attending primary care in the UK and is associated with elevated levels of reported diabetes, hypertension, lipid disorders and CVD.     

The incidence of venous thromboembolism among patients with primary lung cancer

Background:  The incidence of venous thromboembolism (VTE) by lung cancer histology and stage is unknown. Objectives:  To determine the incidence of VTE and the risk factors associated with development of VTE in a large population-based study of patients with non-small cell and small cell lung cancer. Methods:  The California Cancer Registry was merged with the Patient Discharge Data Set to determine the incidence of VTE among lung cancer cases diagnosed between 1993 and 1999. Results:  Among 91 933 patients with newly diagnosed lung cancer, the 1-year and 2-year cumulative VTE incidences were 3.0% and 3.4%, respectively, with a person-time rate of 7.2 events/100 patient-years during the first 6 months. The 1-year incidence of VTE was significantly increased in comparison to the general population [standardized incidence ratio = 21.2, 95% confidence interval (CI) = 20.4–22.0]. In a multivariate model, significant predictors of developing VTE within 1 year of non-small cell lung cancer (NSCLC) diagnosis were: younger age, the number of chronic medical comorbidities [hazard ratio (HR) = 2.8 if 3 vs. 0, 95% CI = 2.5–3.1], advancing cancer stage (HR = 4.0 for metastatic vs. local disease, 95% CI = 3.4–4.6) and adenocarcinoma histology (HR = 1.9 vs. squamous cell, 95% CI = 1.7–2.1). In multivariate models, VTE was a significant predictor of death within 2 years for both NSCLC and small cell lung cancer (SCLC), HR = 2.3, 95% CI = 2.2–2.4, and HR = 1.5, 95% CI = 1.3–1.7, respectively. Conclusions:  Approximately 3% of lung cancer patients developed VTE within 2 years. The diagnosis of VTE was associated with a higher risk of death within 2 years for NSCLC and SCLC.     

High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS)

Summary.  Background:  In cancer patients, laboratory parameters that predict venous thromboembolism (VTE) are scarce. Increased platelet count has been found to be a risk factor for VTE in cancer patients receiving chemotherapy (CHT). We have assessed high platelet count as a risk predictor for VTE in patients with cancer undergoing discriminative anti-cancer treatments and investigated whether platelet count correlates with thrombopoietin (TPO) levels. Design and methods:  The Cancer and Thrombosis Study (CATS) is an ongoing prospective observational study of patients with newly diagnosed cancer or progression of disease, which started in October 2003. Occurrence of VTE and information on the patients' anti-cancer treatment during follow-up were recorded. Results: Between October 2003 and February 2008, 665 patients with solid tumors were included (314 female/351 male, mean age 62 years). VTE occurred in 44 patients (18 female/26 male, mean age 62 years). The cumulative probability of VTE after 1 year was 34.3% in patients with a platelet count (PC) above the 95th percentile representing 443 × 10⁹/L compared with 5.9% in those below 443 × 10⁹/L. High platelet count [hazard ratio (HR): 3.50, 95% confidence interval (CI): 1.52–8.06, P  = 0.0032], soluble P-selectin [HR: 2.66, 95% CI: 1.42–4.96, P  = 0.0021] and surgery [HR: 4.05, 95% CI: 1.74–9.46, P  = 0.0012] were statistically significant risk factors for VTE in multivariable analysis along with leucocyte count, age, gender, radio- and CHT. We found no correlation between platelet count and TPO levels. Conclusions:  High PC is a clinically important, independent risk predictor for VTE in cancer patients. PC was not found to be associated with TPO levels.     

The long-term risk of cancer in patients with a first episode of venous thromboembolism

Summary.  Background: In patients with venous thromboembolism (VTE), 15–20% will have prevalent cancer when VTE is diagnosed but little is known about such patients' long-term risk, time course and predictors of new cancer. Patients and methods: We studied an inception cohort of patients with a first VTE who were not diagnosed with cancer within 3 months after VTE and who had follow-up for up to 120 months. We determined the annual risk for a new cancer [number of events and 95% confidence interval (CI)] per 100 person-years in all patients and in those with unprovoked VTE and identified predictors for new cancer. Results: We studied 1852 patients with VTE who received anticoagulant therapy for 12 months (mean) and were followed for 4.2 years (mean). During follow-up, there were 105 (5.7%) patients diagnosed with new cancer during the period after the initial 3 months from diagnosis, for an annual risk of 1.32 (CI, 1.09–1.60) per 100 person-years. The risk for new cancer appeared uniform over time. The annual risk for new cancer was more than 2-fold higher in patients presenting with unprovoked compared with those with provoked VTE [1.76 (CI, 1.39–2.20) vs. 0.83 (CI, 0.58–1.16) per 100 person-years; P  < 0.001]. Clinical predictors for new cancer were increasing age [hazard ratio (HR), 1.23; CI, 1.05–1.44] and unprovoked VTE (HR, 1.86; CI, 1.21–2.87). Conclusion: In patients with a first VTE and without prevalent cancer, the risk for new cancer is about 1–2% per year, appears to be uniform over time, and is higher in patients with unprovoked VTE and those with advanced age.     

Lipid biomarkers, hormone therapy and the risk of venous thromboembolism in women

Summary.  Background: Published reports of a relationship between lipids and incident venous thromboembolism (VTE) are conflicting. Objectives: To clarify the relationship between lipids and VTE risk in healthy women, including potential effect modification by hormone therapy (HT). Patients/methods: Among 27 081 initially healthy women followed prospectively for incident VTE, we measured a full panel of lipid biomarkers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and apolipoproteins A-I (apo A-I) and B₁₀₀. Results: During a median follow-up of 11.4 years, VTE occurred in 355 women. We observed no relationship between any of the lipids and VTE risk. However, when unprovoked VTE was considered separately ( n  = 161), both HDL-C and apo A-I were positively associated with risk. Fully adjusted hazard ratios (HR) and 95% confidence intervals (CI) for extreme tertiles of HDL-C and apo A-I were 1.75 (1.13–2.73) and 1.70 (1.10–2.62), respectively. After stratifying by HT use, this relationship was present only among HT users; the HRs for unprovoked VTE for extreme tertiles of HDL-C and apo A-I were 3.58 (1.69–7.58) and 2.88 (1.29–6.42) among users, but only 0.79 (0.39–1.62) and 0.89 (0.50–1.57) among non-users. The interactions were statistically significant (each P _interaction <0.05). Conclusions: We observed little evidence that lipid levels predict risk of incident VTE among non-users of HT. High levels of HDL-C and apo A-I associate with unprovoked VTE risk among HT users. This observation likely reflects prothrombotic effects of HT that are concomitant with HDL-C and apo A-I levels, rather than direct effects of those lipids.     

Managing cardiovascular risk in patients with metabolic syndrome

Metabolic syndrome consists of a cluster of cardiovascular (CV) and metabolic risk factors (e.g., abdominal obesity, hypertension, elevated levels of fasting plasma glucose and triglycerides, and low levels of high-density lipoprotein cholesterol [HDL-C]) and is associated with an increased risk for type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Because the risks for CVD and type 2 DM are highly variable among patients with metabolic syndrome, it is essential to assess a patient's risks before identifying specific treatment or lifestyle interventions. The major risk factors for CVD are smoking, hypertension, elevated levels of total and low-density lipoprotein cholesterol, low levels of HDL-C, and older age. In patients at low risk for CV events, lifestyle interventions (i.e., weight loss and increased physical activity) may be sufficient to control the components of metabolic syndrome and to reduce the risk for type 2 DM and CVD. Patients who are at high risk, however, must receive aggressive drug therapy in addition to lifestyle interventions. The following factors need to be targeted: obesity (particularly abdominal obesity), dyslipidemia, hypertension, and prothrombotic/proinflammatory states. Drugs with various and complementary mechanisms of action, including drugs targeting lipid metabolism, may be effective in controlling these factors and thereby delaying or preventing CV events and type 2 DM.     

Insulin resistance and risk of venous thromboembolism: results of a population‐based cohort study

Summary. Background: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity. Objective: We aimed to investigate whether insulin resistance is a risk factor for VTE. Methods: For this analysis we used the PREVEND prospective community‐based observational cohort study. Insulin resistance was measured as HOMA‐IR (homeostasis model assessment of insulin resistance) and fasting insulin. VTE was assessed using databases of the national registries of hospital discharge diagnoses, death certificates and the regional anticoagulation clinic. Results: Out of 7393 subjects, 114 developed VTE during a median follow‐up of 10.5 years. High HOMA‐IR was associated with increased risk of VTE after adjustment for traditional cardiovascular risk factors, CRP and markers of endothelial dysfunction (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 1.09–1.75; P = 0.007). When body mass index (BMI) was added to the model, BMI was a strong risk predictor for VTE (HR, 1.53; 95% CI, 1.24–1.88; P < 0.001) whereas HOMA‐IR no longer showed such an association (HR, 1.11; 95% CI, 0.85–1.43; P = 0.45). Results were similar for fasting insulin. Conclusion: Our population‐based cohort study shows an increased risk of VTE in subjects with increasing insulin resistance but not independently of BMI.     

Venous thromboembolism in association with features of the metabolic syndrome

BACKGROUND: Central obesity, diabetes mellitus, dyslipidaemia and chronic hypertension--features of the metabolic syndrome--have been individually associated with venous thromboembolism (VTE). However, whether each of these factors additively increases the risk of VTE is uncertain. AIM: To determine whether features of the metabolic syndrome independently increase the risk of VTE. DESIGN: Prospective cohort study derived from the Heart Outcomes Prevention Evaluation 2 (HOPE-2) randomized clinical trial. SETTING: One hundred and forty-five clinical centres in 13 countries. METHODS: We studied 5522 adults aged > or =55 years with cardiovascular disease or diabetes mellitus. At enrollment, 35% had 0-1 features of the metabolic syndrome, 30% had two, 24% had three and 11% had four. We defined symptomatic VTE as an objectively confirmed new episode of deep-vein thrombosis or pulmonary embolism. RESULTS: VTE occurred in 88 individuals during a median 5.0 years of follow-up. The incidence rate of VTE (per 100 person-years) was 0.30 with 0-1 features, 0.36 with two features, 0.38 with three features and 0.40 with four features of the metabolic syndrome (trend p = 0.43). Relative to the presence of 0-1 features of the metabolic syndrome, the adjusted hazard ratio (95%CI) for VTE was 1.22 (0.71-2.08) with two features, 1.25 (0.70-2.24) with three features, and 1.26 (0.59-2.69) with four features. DISCUSSION: The number of features of the metabolic syndrome present was not a clinically important risk factor for VTE in older adults with vascular arterial disease.     

Cigarette smoking and the risk of venous thromboembolism: The Tromsø Study

Summary. Background: Conflicting findings have been reported on the association between smoking and the risk of venous thromboembolism (VTE). Objectives: To conduct a prospective, population‐based cohort study to investigate the association between cigarette smoking and the risk of incident VTE. Patients/Methods: Information on smoking habits was assessed by self‐administered questionnaires in 24 576 subjects, aged 25–96 years, participating in the fourth Tromsø Study in 1994–1995. Incident cases of VTE were registered until the end of follow‐up at 1 September 2007. Results: A total of 389 incident VTE events (1.61 per 1000 person‐years) were registered during follow‐up (median of 12.5 years). Heavy smokers (> 20 pack‐years) had a hazard ratio (HR) of 1.46 (95% confidence interval [CI] 1.04–2.05) for total VTE, and and an HR of 1.75 (95% CI 1.14–2.69) for provoked VTE, as compared with never smokers. The risk of provoked VTE increased with more pack‐years of smoking (P = 0.02). Smoking was not associated with risk of unprovoked VTE. The number of pack‐years was associated with increased risk of cancer and myocardial infarction, whereas the association between pack‐years of smoking and VTE disappeared when failure times were censored at the occurrence of cancer or myocardial infarction. Conclusions: Heavy smoking was apparently a risk factor for provoked VTE in analyses with VTE events as the only outcome. The lack of association between smoking and risk of VTE in analyses censored at the occurrence of cancer or myocardial infarction may suggest that smoking‐attributable diseases or other predisposing factors are essential for smoking to convey a risk of VTE.     

Circulating preptin levels in normal,impaired glucose tolerance,and type 2 diabetic subjects

Despite the fact that controversy remains around the underlying pathophysiological processes leading to the development of the metabolic syndrome (insulin resistance and/or hyperinsulinemia versus abdominal obesity), there is increased recognition that abdominal obesity is the most prevalent form of the metabolic syndrome. Although it has been well established that there is a greater prevalence of chronic metabolic diseases such as diabetes and cardiovascular diseases in obese patients than among normal weight individuals, obesity is a remarkably heterogeneous condition and not every obese patient is characterized by co‐morbidities. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a major correlate of a cluster of diabetogenic, atherogenic, prothrombotic and proinflammatory metabolic abnormalities referred to as the metabolic syndrome. Due to its anatomic location and peculiar metabolic, hyperlipolytic activity, the expanded visceral adipose depot is a key correlate of the altered cardiometabolic risk profile observed among individuals with a high‐risk abdominal obesity phenotype. Evidence suggests that this dysmetabolic profile is predictive of a substantially increased risk of coronary heart disease even in the absence of classical risk factors. Finally, a moderate weight loss in initially abdominally obese patients is associated with a preferential mobilization of visceral adipose tissue, which in turn leads to substantial improvements in the metabolic risk profile predictive of a reduced risk of coronary heart disease and of type 2 diabetes.     

Peak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study

Summary.  Background : Thrombin is an enzyme that is essential for the acceleration of the coagulation cascade and the conversion of fibrinogen to clottable fibrin. Objectives : We evaluated the relationship of basal peak thrombin generation with the risk of future venous thromboembolism (VTE), and determined whether associations were independent of other coagulation markers. Methods : The Longitudinal Investigation of Thromboembolism Etiology (LITE) study investigated VTE in two prospective population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS). Peak thrombin generation was measured on stored plasma in a nested case–control sample (434 cases and 1004 controls). Logistic regression was used to estimate the relationship of peak thrombin generation with VTE, adjusted for age, sex, race, center, and body mass index. Mediation was evaluated by additionally adjusting for factor VIII and D-dimer. Results : Relative to the first quartile of peak thrombin generation, the odds ratio (OR) of VTE for those above the median was 1.74 [95% confidence interval (CI) 1.28–2.37]. The association was modestly attenuated by adjustment for FVIII and D-dimer (OR 1.47, 95% CI 1.05–2.05). Associations appeared to be stronger for idiopathic than for secondary VTE. Elevated peak thrombin generation more than added to the VTE risk associated with FV Leiden or low activated partial thromboplastin time. Conclusions : In this prospective study of two independent cohorts, elevated basal peak thrombin generation was associated with subsequent risk of VTE, independently of established VTE risk factors.     

Prevalence and risk factors of non-fatal venous thromboembolism in the active population of the VITA Project

Summary.  Cost-effective strategies for the identification of subjects at risk of venous thromboembolism (VTE) in the active population are still lacking. Our objectives were to identify risk factors for venous thromboembolism in active subjects. We analyzed data from a population-based sample of 15 055 Caucasians aged 18–65 years randomly selected from the census list of the township of Vicenza, Italy. A validated methodology was used to retrospectively identify subjects with previous VTE. Body mass index (BMI), smoking, oral contraceptive use, previous superficial vein thrombophlebitis (SVT) and familial history of VTE, all at the age of first thrombosis, were ascertained by direct interview and by review of available medical records. Ninety-two deep vein thromboses [prevalence: 61.1/10 000, 95% confidence interval (CI) 49.2–74.9], three upper deep vein thrombosis (prevalence: 1.9/10 000, 95% CI 0.4–5.8) and 21 pulmonary embolism (prevalence: 13.9/10 000, 95% CI 8.6–21.3) were identified. After age and sex adjustment, clinically identifiable risk factors were: history of SVT [odds ratio (OR) = 6.8], oral contraceptive use (OR = 4.7), family history of VTE (OR = 4.5), smoking (OR = 1.7) and BMI above the third tertile (OR vs. mid-tertile 2.9). While previous SVT and BMI were associated with VTE in all circumstantial situations (surgery/trauma, pregnancy or idiopathic VTE), for oral contraceptive use, positive family history and smoking the degree of association varied significantly depending on the situation. Non-fatal VTE affects 0.7% of the subjects belonging to an active population, 56% of cases being potentially preventable. In 30% of VTE cases, at least two easily recognizable risk factors are present. Clinical assessment of risk factors remains the mainstay of VTE prevention.     

ABO blood group, other risk factors and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE)

Summary.  Background:  Numerous case–control studies have reported higher prevalence of non-O blood type among venous thromboembolism (VTE) patients than controls, but potential mechanisms or effect modifiers for the association are not fully established. Patients/methods:  Using a nested case–control design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, ABO blood type and other VTE risk factors were measured on pre-event blood samples of 492 participants who subsequently developed VTE and 1008 participants who remained free of VTE. Results:  A total of 64.4% of cases and 52.5% of controls had non-O blood type. Among controls, mean values of factor VIIIc (FVIIIc) and von Willebrand factor among the non-O blood type group were higher than among the O group. Compared with O blood type, the age-adjusted odds ratio (OR) of VTE for non-O blood type was 1.64 (95% CI, 1.32–2.05) and was similar for the two parent studies and race groups. Further adjustment for sex, race, body mass index, diabetes mellitus and FVIIIc reduced the OR: 1.31 (95% CI, 1.02–1.68). Factor V Leiden (FV Leiden) appeared to modify the non-O blood type association with VTE in a supra-additive fashion, with an age-, sex- and race-adjusted OR of 6.77 (95% CI, 3.65–12.6) for having both risk factors. Conclusions:  Non-O blood type was independently associated with risk of VTE, and added to the risk associated with FV Leiden.     

Abdominal fat distribution and disease: an overview of epidemiological data.

Recent prospective, epidemiological research has demonstrated the power of an increased waist/hip circumference ratio (WHR) to predict both cardiovascular disease (CVD) and non-insulin dependent diabetes mellitus (NIDDM) in men and women. Obesity, defined as an increased total body fat mass, seems to interact synergistically in the development of NIDDM, but not of CVD. Increased WHR with obesity (abdominal obesity) seems to be associated with a cluster of metabolic risk factors, as well as hypertension. This metabolic syndrome is closely linked to visceral fat mass. Increased WHR without obesity may instead be associated with lift style factors such as smoking, alcohol intake, physical inactivity, coagulation abnormalities, psychosocial, psychological and psychiatric factors. Direct observations show, and the risk factor associations further strengthen the assumption, that abdominal (visceral) obesity is more closely associated to NIDDM than CVD, while an increased WHR without obesity may be more closely linked to CVD than NIDDM. It remains to be established to what extent, if any, an increased WHR in lean men, and particularly in lean women, indicates fat distribution. Other components of the WHR measurement might be of more importance in this connection.     

Clinical outcome in patients with venous thromboembolism and hidden cancer: findings from the RIETE Registry

Summary.  Introduction:  Although extensive screening in patients with venous thromboembolism (VTE) may result in early identification of hidden cancer, it is unknown whether the prognosis of these patients may be favorably influenced. Patients and methods:  RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We compared the 3-month outcome of patients with hidden cancer with that in patients in whom no symptoms of cancer were noted. Results:  Of 17 475 patients with acute VTE, 2852 (16%) had cancer diagnosed before VTE or during admission. Hidden cancer was detected in 178 (1.2%) of the remaining 14 623 patients. The most common sites were lung, prostate, colorectum, or hematologic, and 51% had metastases. As compared with patients in whom no symptoms of cancer were noted, those with hidden cancer had an increased incidence of recurrent VTE (11.4% vs. 2.1%; P  <   0.001), major bleeding (5.1% vs. 2.1%; P  =   0.007), and mortality (20% vs. 5.4%; P  <   0.001). In the multivariate analysis, patients aged 60–75 years [odds ratio 1.8; 95% CI 1.2–2.7], with idiopathic VTE (odds ratio 3.0; 95% CI 2.2–4.2), with bilateral thrombosis (odds ratio 2.3; 95% CI 1.3–4.1) or with anemia (odds ratio 1.9; 95% CI 1.4–2.6) were at an increased risk for hidden cancer. Conclusions:  VTE patients with hidden cancer have an increased incidence of recurrences, major bleeding or death during the first 3 months of therapy. With four simple, easily obtainable variables, it is possible to identify a subgroup of VTE patients with a higher risk for hidden cancer.     

Relation of coronary atherosclerosis and metabolic syndrome in asymptomatic subjects: evaluation with coronary CT angiography

To assess the relationship between metabolic syndrome (MetS) and coronary atherosclerosis using coronary CT angiography (CCTA) as the evaluation tool in asymptomatic cardiovascular disease (CVD) free subjects. The presence and extent of coronary atherosclerosis in 755 asymptomatic self-referred subjects were measured using CCTA. The relationships between coronary atherosclerosis, MetS, and other clinical factors were assessed. To further investigate the relationship between MetS and the presence and extent of coronary plaque, subjects were divided into 3 subgroups according to the number of metabolic factors (MF0, 1–2 or ≥3) and the number of coronary segments with plaque (segment involvement score: SIS0, 1, ≥2). MetS showed significant association with the presence of coronary plaque after adjustment for other clinical factors [odds radio (OR) 1.791 (1.159–2.775), P = 0.009]. Among metabolic components, abdominal obesity and high blood pressure were significantly associated with the presence of coronary plaque [OR 1.708 (1.189–2.455), P = 0.004; OR 1.677 (1.165–2.415), P = 0.005]. Coronary plaque was more frequently found in subgroups with a higher number of metabolic factors (32.4, 36.7 and 52.1 %). Higher SISs were also found in subjects with more MetS components (SIS1: 14.6, 16.2 and 27.2 %; SIS ≥ 2: 17, 19.7 and 23.7 %). In asymptomatic CVD free subjects, MetS and number of metabolic factors were related with an increased risk of the presence and the extent of coronary plaque. Abdominal obesity and high blood pressure were significantly associated with the presence of coronary plaque.