Risk Factors For Incident Venous Thromboembolism Research Articles

Severe alpha‐1‐antitrypsin deficiency increases the risk of venous thromboembolism

BackgroundSevere alpha‐1‐antitrypsin deficiency (AATD), phenotype PiZZ, is associated with increased risk of liver disease and chronic obstructive pulmonary disease (COPD), but the risk of venous thromboembolism (VTE) is unknown. Our aim was to evaluate the risk of VTE in individuals with severe AATD compared with control subjects from the general population. MethodsIndividuals with severe AATD (n = 1577) were recruited from the Swedish national AATD register. Control subjects (n = 5969) were selected from the OLIN (Obstructive Lung Disease in Northern Sweden) studies, that include a random general population sample. Longitudinal data on VTE and diagnoses were obtained from the Swedish National Patient Registry. Associations were analyzed using multivariable Cox regression. ResultsAt inclusion, 46% of the AATD individuals and 53% of the controls were never‐smokers. COPD was present in 46% of the AATD individuals compared with 4% of the controls. During a median follow‐up of 18 years, 116 (7%) of the AATD individuals and 89 (1%) of the control subjects developed VTE, unadjusted hazard ratio 6.5 (95% confidence interval 4.9–8.6). Risk factors for incident VTE were male gender, age, COPD, cancer, and liver disease. Adjusting for these factors, the AATD individuals had a significantly higher risk of incident VTE, adjusted hazard ratio 4.2 (95% confidence interval 2.9–6.2) as compared with the controls. ConclusionSubjects with severe AATD have considerably increased risk of developing VTE compared with the general population, even after accounting for risk factors. This calls for optimized risk factor management and clinical follow‐up of this patient group.

Myocardial Infarction as a Transient Risk Factor for Incident Venous Thromboembolism: Results from a Population-Based Case-Crossover Study.

Patients with myocardial infarction (MI) are at increased short-term risk of venous thromboembolism (VTE). The mechanisms behind this association are unclear. We aimed to investigate the impact of acute MI as a transient risk factor for incident VTE while taking other concomitant VTE risk factors into account. We conducted a case-crossover study of VTE patients (n = 707) recruited from the fourth survey of the Tromsø Study. VTE risk factors and hospitalizations were registered during the 90-day period preceding the VTE diagnosis (hazard period) and in four 90-day control periods. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to acute MI and after adjustment for other risk factors. Additionally, we applied a mediation analysis to quantify how much the known transient risk factors account for the observed effect of MI on VTE risk. MI was recorded in 13 (1.8%) of the hazard periods and in 6 (0.2%) of the control periods, which yielded a crude OR of 11.9 (95% CI: 3.9-36.7). Adjustment for immobilization and infection yielded an OR of 2.7 (95% CI: 0.6-11.2). The OR was attenuated to 2.6 (95% CI: 0.6-11.9) after further adjustment for major surgery, trauma, red blood cell transfusion, and central venous catheterization. Approximately 60% of the association between MI and VTE was mediated through infection and immobilization. In conclusion, our findings suggest that the increased VTE risk after MI may to a large extent be explained by concomitant conditions related to MI, particularly infections and immobilization.

Abstract P270: Body Size Throughout the Life Course and Risk of Venous Thromboembolism

Introduction: Adult body mass index (BMI) is strongly associated with venous thromboembolism (VTE), however whether earlier-life adiposity or other measures of adult adiposity are associated with VTE risk remains unknown. Hypothesis: Since BMI is a strong risk factor for incident VTE, we hypothesized that early life body size as well as other measures of adult adiposity may also be positively associated with VTE risk. Methods: We evaluated associations of childhood somatotype, BMI at age 18, change in BMI since age 18, and measures of waist and hip circumference with incident VTE among 47,415 women age 40-67 years at baseline from the Nurses’ Health Study (NHS), 47,539 women age 29-48 years from the Nurses’ Health Study II (NHS II), and 32,707 men age 39-76 years from the Health Professionals Follow-Up Study (HPFS) without a prior VTE. We calculated multivariable-adjusted hazard ratios (HR) of VTE using Cox proportional hazards models. Results: Over ≥25 years of follow-up, there were 1,191 incident VTE cases in NHS, 763 cases in NHS II, and 1,350 cases in HPFS. Adult BMI was strongly associated with VTE in all three cohorts (HRs comparing ≥35 kg/m 2 vs. <22.5 kg/m 2 : NHS: 3.03 [95% CI: 2.58, 3.55], NHS II: 3.88 [95% CI: 3.36, 4.48], HPFS: 2.49 [95% CI: 1.83, 3.29]; all P trend< 0.01). Waist circumference, hip circumference, and height were associated with greater VTE risk, even after adjusting for adult BMI (all P trend< 0.01) (Table). Somatotype at ages 5 and 10, BMI at age 18, and change in BMI since age 18 were not significantly associated with VTE risk, after accounting for adult BMI. Conclusions: Adult BMI, waist circumference, hip circumference, and height were independently, positively associated with incident VTE risk. Early life body size was not significantly associated with VTE risk after accounting for adult BMI, indicating that BMI and adiposity are likely more important acutely that cumulatively over time in the etiology of VTE. Clinically, encouraging weight loss in adults

Risk factors for incident venous thromboembolism in active cancer patients: A population based case–control study

BackgroundIndependent risk factors for cancer-associated incident venous thromboembolism (VTE) and their magnitude of risk are not fully characterized. AimTo identify non-cancer and cancer-specific risk factors for cancer-associated incident VTE. MethodsIn a population-based retrospective case–control study, we used Rochester Epidemiology Project and Mayo Clinic Cancer Registry resources to identify all Olmsted County, MN residents with active cancer-associated incident VTE, 1973–2000 (cases; n=570) and 1–3 residents with active cancer matched to each case on age, sex, date and duration of active cancer (controls; n=604). Using conditional logistic regression, we tested cancer and non-cancer characteristics for an association with VTE, including a cancer site VTE risk score. ResultsIn the multivariable model, higher cancer site VTE risk score (OR=1.4 per 2-fold increase), cancer stage≥2 (OR=2.2), liver metastasis (OR=2.7), chemotherapy (OR=1.8) and progesterone use (OR=2.1) were independently associated with VTE, as were BMI<18.5kg/m2 (OR=1.9) or ≥35kg/m2 (OR=4.0), hospitalization (OR=7.9), nursing home confinement (OR=4.7), central venous (CV) catheter (OR=8.5) and any recent infection (OR=1.7). In a subgroup analysis, platelet count≥350×109/L at time of cancer diagnosis was marginally associated with VTE (OR=2.3, p=0.07). ConclusionCancer site, cancer stage≥2, liver metastasis, chemotherapy, progesterone, being underweight or obese, hospitalization/nursing home confinement, CV catheter, and infection are independent risk factors for incident VTE in active cancer patients.

Epidemiology of venous thromboembolism.

Thrombosis can affect any venous circulation. Venous thromboembolism (VTE) includes deep-vein thrombosis of the leg or pelvis, and its complication, pulmonary embolism. VTE is a fairly common disease, particularly in older age, and is associated with reduced survival, substantial health-care costs, and a high rate of recurrence. VTE is a complex (multifactorial) disease, involving interactions between acquired or inherited predispositions to thrombosis and various risk factors. Major risk factors for incident VTE include hospitalization for surgery or acute illness, active cancer, neurological disease with leg paresis, nursing-home confinement, trauma or fracture, superficial vein thrombosis, and-in women-pregnancy and puerperium, oral contraception, and hormone therapy. Although independent risk factors for incident VTE and predictors of VTE recurrence have been identified, and effective primary and secondary prophylaxis is available, the occurrence of VTE seems to be fairly constant, or even increasing.

Is Diabetes Mellitus an Independent Risk Factor for Venous Thromboembolism?

Although diabetes mellitus is reported as a risk factor for venous thromboembolism (VTE), persons with diabetes are frequently hospitalized for medical illness or surgery, or confined to a nursing home, all major VTE risk factors. Consequently, we tested diabetes for an independent association with incident VTE. Using Rochester Epidemiology Project resources, we identified all Olmsted County, Minn residents who met objective criteria for incident VTE over the 25-year period, 1976 to 2000 (n=1922), and 1 to 2 resident controls per case, matched on age, gender, and length of medical history (n=2115). Complete medical histories in the community were reviewed for previously identified independent VTE risk factors and diabetes-related variables. We tested diabetes and diabetes complications (retinopathy, nephropathy or neuropathy, and ketoacidosis) as potential VTE risk factors, both alone and after adjusting for VTE risk factors. Univariately, diabetes by clinical diagnosis or by stricter criteria (fasting ambulatory blood glucose >/=140 mg/dL or antidiabetic drug therapy), and diabetes complications, were associated with overall incident VTE. However, after controlling for hospitalization for major surgery or medical illness and nursing home confinement, diabetes was no longer associated with VTE. Diabetes mellitus and diabetes complications are not independent risk factors for incident VTE.

Novel Risk Factors for Venous Thromboembolism (VTE): A Population-Based Case-Control Study.

Background: While several uncommon disorders (e.g., myeloproliferative diseases, connective tissue disease, etc.) have been suggested as potential risk factors for VTE, the independence and magnitude of any risk is uncertain.Objective: To test uncommon characteristics as potential independent risk factors for VTE, and estimate the magnitude of risk for each.Methods: Using the resources of the Rochester Epidemiology Project, we identified all incident cases of deep vein thrombosis and pulmonary embolism over the 6-year period, 1992–1997. For each objectively confirmed case (n=562), we identified up to two Olmsted County residents without VTE who most closely matched a case on age, gender, and medical record number (n=755). Because medical record numbers are assigned sequentially, such matching assures a similar duration of medical follow-up. For all cases and controls, we reviewed the complete medical records in the community for over 125 baseline characteristics which were tested for an association with VTE using conditional logistic regression.Results: The mean ± SD (range) ages for cases and controls were 65.71 ± 18.85 (0–102) and 64.90 ± 18.66 (0–102) years, respectively, and 55.5% were female. Novel univariate risk factors for incident VTE included former tobacco smoker, ischemic heart disease, valvular heart disease, chronic lung disease, all-cause pulmonary hypertension, chronic renal disease, myeloproliferative disorders, any infection, femoral artery catheterization (angiography or percutaneous intervention), ICU admission and angiotensin converting enzyme (ACE) inhibitor therapy. Among infections, septicemia, pneumonia, and ENT, cardiovascular, GI, urinary tract and skin/soft tissue infections were univariately associated with VTE; reproductive tract infection was not. Diabetes mellitus, hyperlipidemia, lipid-lowering drugs (including statins), inflammatory bowel disease, asthma, connective tissue disease, and influenza were not univariately associated with VTE, and beta-blocker therapy was not protective. A multivariate analysis will test these characteristics as potential independent VTE risk factors.Conclusions: Several novel characteristics are univariately associated with VTE. Such novel characteristics may provide new insights into VTE mechanisms if, upon further analysis, these characteristics are independent VTE risk factors.

Thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population‐based case–control study

Dysfunction of the protein C anticoagulant system is associated with venous thromboembolism (VTE) and thrombomodulin (TM) is a critical cofactor within the protein C system. The aim of this study was to test the hypotheses that polymorphisms or haplotypes within the TM gene are common risk factors for VTE. We screened the TM putative promoter, exon and 3'-untranslated region for sequence variations in a random sample (n = 266) of consecutive idiopathic, objectively confirmed non-Olmsted County VTE patients referred to the Mayo Clinic. We then genotyped a sample of Olmsted County, MN residents with a first lifetime, objectively confirmed VTE in the 25-year period, 1966-90 (n = 223), and a sample of Olmsted County residents without VTE (n = 237) for polymorphisms either discovered in the screening population or previously published, and tested for an association of VTE with TM genotype or haplotypes using unconditional logistic regression and generalized linear models, respectively. We also genotyped these Olmsted County cases and controls at 20 'null' genetic maker loci and tested for population admixture. Nine novel and three previously described mutations were identified in the screening population. Mutations within the TM promoter, EGF(1-5), serine/threonine-rich, transmembrane, and cytoplasm regions were absent or uncommon. TM845G-->A (Ala25Thr; lectin region), TM2136T-->C (Ala455Val; EGF(6) region), TM2470C deletion (3'-untranslated region), and 4363A-->G (3'-flanking region) were more common, but were not associated with VTE by genotype or haplotype. Null genetic marker allele frequencies did not differ significantly among cases and controls. We conclude that polymorphisms or haplotypes within the TM gene are not common risk factors for incident VTE.

Atherosclerosis as a Risk Factor for Venous Thromboembolism (VTE): A Population-Based Cohort Study.

While atherosclerosis has been suggested as a risk factor for VTE, previously identified mechanisms for atherosclerosis and VTE differ dramatically.Objectives: To compare (a) VTE-free survival and (b) observed vs. expected number of VTE events, among adult patients with and without aortic atherosclerosis.Design/Setting: Population-based prospective cohort study in Olmsted County, MN.Patients: Age- and sex-stratified random sample of the adult (≥45 years old) Olmsted County population identified over the three-year period, 1993–1995 (n=573), performed as part of the Stroke Prevention: Assessment of Risk in the Community (SPARC) study.Measurements: The SPARC study included a baseline clinical evaluation (interviews, review of medical records), blood pressure measurements, blood sampling, and transesophageal echocardiography (TEE). The Risk Factors for VTE in the Community study identified all incident VTE among Olmsted County residents over the 32-year period, 1966–1997, from which expected VTE events by age and sex were calculated.Results: Over 2830 person-years of follow-up, 12 SPARC patients developed VTE (7 idiopathic). The 4-year VTE-free survival was 99% and 98% for those with and those without any TEE-detected aortic atherosclerosis. Adjusting for age in a Cox proportional hazards model, lack of aortic atherosclerosis was significantly associated with subsequent VTE (p=0.01). Among the 276 patients without atherosclerosis observed for 1423 person-years, 7 VTE were observed compared to 2.6 expected (RR=2.7, 95%CI: 1.1, 5.6). Among the 291 patients with atherosclerosis (plaque ≥2mm), 4 VTE were observed compared to 5.8 expected (RR=0.7, 95%CI: 0.2, 1.8).Conclusions: Atherosclerosis is not a risk factor for incident VTE.