@article {712, title = {Anticardiolipin antibodies as a risk factor for venous thromboembolism in a population-based prospective study.}, journal = {Br J Haematol}, volume = {119}, year = {2002}, month = {2002 Dec}, pages = {1005-10}, abstract = {

Anticardiolipin antibodies, one of the family of {\textquoteright}antiphospholipid{\textquoteright} antibodies, increase the risk of venous thromboembolism in the presence of autoimmune disease. Our objective was to determine prospectively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults. We conducted a nested case-control study (n = 317 patients and n = 655 control subjects) in a longitudinal study of over 20 000 participants. Baseline (prediagnosis) anticardiolipin IgG and IgM antibodies were assessed by enzyme-linked immunoassays. Venous thromboembolism was validated using standardized criteria for venous thrombosis and pulmonary embolism. There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence, overall or in any subgroup. For example, the multivariate-adjusted relative risk was 0.88 (95\% confidence interval, 0.43, 1.78) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion, in this general population sample, an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism.

}, keywords = {Aged, Aged, 80 and over, Antibodies, Anticardiolipin, Case-Control Studies, Female, Humans, Immunoglobulin G, Immunoglobulin M, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Prospective Studies, Reference Values, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {0007-1048}, doi = {10.1046/j.1365-2141.2002.03949.x}, author = {Runchey, Shauna S and Folsom, Aaron R and Tsai, Michael Y and Cushman, Mary and McGovern, Paul D} } @article {716, title = {Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE).}, journal = {Am J Med}, volume = {113}, year = {2002}, month = {2002 Dec 01}, pages = {636-42}, abstract = {

PURPOSE: We sought to assess prospectively whether higher levels of blood coagulation factors and inflammation markers are risk factors for venous thromboembolism.

SUBJECTS AND METHODS: In two pooled population-based cohort studies, we measured levels of factor VII, factor VIII, von Willebrand factor, fibrinogen, and C-reactive protein, and white blood cell count, in samples obtained from 19,237 adults with no baseline history of venous thromboembolism, cancer, or warfarin use. The endpoint was validated venous thromboembolism during follow-up (median, 7.8 years).

RESULTS: A total of 159 venous thromboembolism events occurred. Factor VIII and von Willebrand factor were linearly associated with increased risk of venous thromboembolism (P for trend <0.0001). As compared with those in the lowest quartile, the multivariate-adjusted hazard ratio (HR) of venous thromboembolism was 2.6 (95\% confidence interval [CI]: 1.6 to 4.3) for factor VIII levels in the highest quartile and 3.8 (95\% CI: 2.0 to 7.2) for the highest fifth percentile. For von Willebrand factor, the hazard ratios in middle-aged subjects were 4.6 (95\% CI: 2.2 to 9.2) for the highest quartile and 7.6 (95\% CI: 3.1 to 18) for the highest fifth percentile. Factor VII levels above the 95th percentile, as compared with the lowest quartile, also conveyed a higher risk of venous thromboembolism (HR = 2.4; 95\% CI: 1.2 to 4.8). In contrast, there was no association of venous thromboembolism with fibrinogen or C-reactive protein levels, or white cell count.

CONCLUSIONS: In this prospective study, elevated factor VIII and von Willebrand factor levels were common, independent, and dose-dependent risk factors for venous thromboembolism, and an elevated factor VII level was a possible risk factor. Venous thromboembolism, unlike arterial disease, was not related to inflammatory markers.

}, keywords = {Aged, Biomarkers, Blood Coagulation Factors, C-Reactive Protein, Cohort Studies, Confidence Intervals, Factor VII, Female, Fibrinogen, Humans, Inflammation Mediators, Longitudinal Studies, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Risk Assessment, Risk Factors, Sensitivity and Specificity, Thromboembolism, Venous Thrombosis, von Willebrand Factor}, issn = {0002-9343}, doi = {10.1016/s0002-9343(02)01345-1}, author = {Tsai, Albert W and Cushman, Mary and Rosamond, Wayne D and Heckbert, Susan R and Tracy, Russell P and Aleksic, Nena and Folsom, Aaron R} } @article {710, title = {Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism.}, journal = {Am J Hematol}, volume = {71}, year = {2002}, month = {2002 Dec}, pages = {285-90}, abstract = {

Case-control studies have indicated increased risk of venous thrombosis associated with the prothrombin gene G20210A polymorphism and with elevated plasma prothrombin levels. We sought to confirm these results in a prospective population-based study of 21,690 persons. We measured G20210A and prothrombin antigen on pre-event blood samples of 302 participants who developed venous thromboembolism (VTE) and 626 participants who remained free of VTE. Approximately 4.0\% of cases and 2.4\% of controls carried the G20210A polymorphism, but only one of 137 African Americans did. The odds ratio in whites was 1.87 (95\% CI = 0.85, 4.11)--higher for those who reported a prior history of VTE (OR = 5.44) than those reporting no VTE history (OR = 1.41) and in those with idiopathic VTE (OR = 2.51) than those with secondary VTE (OR = 1.38). There was no association between venous thromboembolism and plasma prothrombin antigen level. We estimated that the G20210A polymorphism may account for approximately 2.5\% of venous thromboembolism events in United States whites.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Case-Control Studies, European Continental Ancestry Group, Genotype, Humans, Incidence, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Prospective Studies, Prothrombin, Recurrence, Research Design, Risk Factors, Thromboembolism, United States}, issn = {0361-8609}, doi = {10.1002/ajh.10229}, author = {Folsom, Aaron R and Cushman, Mary and Tsai, Michael Y and Heckbert, Susan R and Aleksic, Nena} } @article {684, title = {A prospective study of venous thromboembolism in relation to factor V Leiden and related factors.}, journal = {Blood}, volume = {99}, year = {2002}, month = {2002 Apr 15}, pages = {2720-5}, abstract = {

The aim of this study was to examine the occurrence of venous thromboembolism (VTE) in relation to factor V-related risk factors. Using a nested case-control design combining 2 population-based prospective studies, we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor V antigen in 335 participants who developed VTE during 8 years of follow-up and 688 controls. The overall odds ratio (OR) of VTE was 3.67 (95\% CI, 2.20-6.12) in participants carrying factor V Leiden compared with noncarriers. APC resistance measured after predilution with factor V-deficient plasma conferred an OR of 2.58 (95\% CI, 1.62-4.10). All 3 participants homozygous for the HR2 haplotype had a VTE, and the OR of VTE for homozygosity was estimated to be 5.5 (95\% CI, 2.45-12.5). Carriers of the HR2 haplotype otherwise were not at increased risk of VTE overall (OR = 1.05; 95\% CI, 0.64-1.72), but double heterozygotes for HR2 and factor V Leiden carried an OR of idiopathic VTE of 16.3 (95\% CI, 1.7-159) compared with noncarriers. Factor V antigen also was not associated with VTE overall, but for participants with the combination of high factor V antigen plus factor V Leiden the OR of idiopathic VTE was 11.5 (95\% CI, 4.2-31.4). In the general population, APC resistance and factor V Leiden were important VTE risk factors; homozygosity for the HR2 haplotype may be a risk factor but was rare; otherwise, HR2 haplotype and factor V antigen were not risk factors except in carriers of factor V Leiden.

}, keywords = {Activated Protein C Resistance, Aged, Cohort Studies, Continental Population Groups, Factor V, Genotype, Haplotypes, Humans, Incidence, Longitudinal Studies, Middle Aged, Odds Ratio, Prospective Studies, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {0006-4971}, doi = {10.1182/blood.v99.8.2720}, author = {Folsom, Aaron R and Cushman, Mary and Tsai, Michael Y and Aleksic, Nena and Heckbert, Susan R and Boland, Lori L and Tsai, Albert W and Yanez, N David and Rosamond, Wayne D} } @article {693, title = {Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {22}, year = {2002}, month = {2002 Jun 01}, pages = {1018-22}, abstract = {

Although deficiencies of protein C and antithrombin, 2 natural plasma anticoagulants, are known risk factors for venous thrombosis, population-based prospective incidence data on these associations are lacking. Venous thromboembolic events have been identified in adults in 2 longitudinal cohort studies, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). Incidence was examined in relation to prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic events that were not due to cancer in the ARIC Study. The age-adjusted incidence was elevated 3.36-fold (95\% CI 1.24 to 9.11) in the 1.1\% of subjects with protein C values <2.0 mg/L compared with subjects with higher values. In contrast, in the ARIC Study and the CHS, there was no association between low plasma antithrombin and venous thromboembolism. In conclusion, in this population-based study, a low protein C, but not antithrombin, level has been determined to be associated with an increased incidence of venous thromboembolism. Attributable risk estimates suggest that low protein C levels account for approximately 2.5\% of venous thromboembolic events in the ARIC population.

}, keywords = {Adult, Aged, Aged, 80 and over, Antithrombins, Arteriosclerosis, Cohort Studies, Humans, Incidence, Longitudinal Studies, Middle Aged, Odds Ratio, Population Surveillance, Prospective Studies, Protein C, Protein C Deficiency, Pulmonary Embolism, Thromboembolism, Venous Thrombosis}, issn = {1524-4636}, doi = {10.1161/01.atv.0000017470.08363.ab}, author = {Folsom, Aaron R and Aleksic, Nena and Wang, Lu and Cushman, Mary and Wu, Kenneth K and White, Richard H} } @article {743, title = {Prospective study of fibrinolytic markers and venous thromboembolism.}, journal = {J Clin Epidemiol}, volume = {56}, year = {2003}, month = {2003 Jun}, pages = {598-603}, abstract = {

Prior research has conflicted on whether increased levels of plasma fibrinolytic factors may identify patients at risk of venous thromboembolism (VTE). We therefore performed a nested case-control study of VTE within two prospective population-based studies. In 308 participants who developed VTE and 640 controls, we measured PAI-1 antigen, tPA/PAI-1 complex, plasmin-alpha 2-antiplasmin (PAP), and the PAI-1 -675 4G/5G promoter polymorphism on pre-event blood samples. There was no overall association between any of these fibrinolytic variables and VTE, after adjustment for age or for multiple VTE risk factors. There was weak evidence for an interaction of PAP with elevated factor VIIIc and elevated D-dimer in augmenting VTE risk. We conclude that, for the most part, these fibrinolytic markers do not identify healthy subjects at risk for VTE.

}, keywords = {Aged, alpha-2-Antiplasmin, Antifibrinolytic Agents, Biomarkers, Caenorhabditis elegans Proteins, Case-Control Studies, Female, Fibrinolysin, Fibrinolysis, Humans, Male, Middle Aged, Odds Ratio, Plasminogen Activator Inhibitor 1, Prognosis, Prospective Studies, Protein-Tyrosine Kinases, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {0895-4356}, doi = {10.1016/s0895-4356(03)00052-0}, author = {Folsom, Aaron R and Cushman, Mary and Heckbert, Susan R and Rosamond, Wayne D and Aleksic, Nena} } @article {942, title = {Frailty and risk of venous thromboembolism in older adults.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {62}, year = {2007}, month = {2007 Jan}, pages = {79-82}, abstract = {

BACKGROUND: Frailty is a common risk factor for morbidity and mortality in elderly persons. Recent evidence links frailty to activation of coagulation and inflammatory pathways. We aimed to determine whether frailty in community-dwelling older adults is a risk factor for venous thromboembolism (VTE).

METHODS: We conducted a prospective cohort study in four U.S. communities involving 4859 participants 65 years old and older. At baseline, in 1989-1993, we assessed frailty based on weight loss, grip strength, feelings of exhaustion, walk time, and physical activity. Incident VTE (deep vein thrombosis or pulmonary embolus) through 2002 was identified by review of hospital records.

RESULTS: Fifty-two percent of the sample was classified as having intermediate or definite frailty. After adjustment for age, race, sex, body mass index, and diabetes, the relative risk of total VTE (n = 150) for people who were frail compared with no frailty was 1.31 (95\% confidence interval [CI], 0.93-1.84). The comparably adjusted relative risk for idiopathic VTE (n = 58) was 1.79 (95\% CI, 1.02-3.13).

CONCLUSIONS: The incidence rates of idiopathic VTE was higher in community-dwelling older adults with baseline frailty compared with no frailty. Further studies of the clotting process in frailty may allow the development of an improved strategy to determine VTE risk in this vulnerable subset of older adults.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Female, Follow-Up Studies, Frail Elderly, Humans, Male, Morbidity, Motor Activity, Prospective Studies, Risk Factors, Thromboembolism, United States, Venous Thrombosis}, issn = {1079-5006}, doi = {10.1093/gerona/62.1.79}, author = {Folsom, Aaron R and Boland, Lori L and Cushman, Mary and Heckbert, Susan R and Rosamond, Wayne D and Walston, Jeremy D} } @article {1001, title = {Chronic kidney disease increases risk for venous thromboembolism.}, journal = {J Am Soc Nephrol}, volume = {19}, year = {2008}, month = {2008 Jan}, pages = {135-40}, abstract = {

Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95\% confidence interval [CI] 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95\% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95\% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Diabetic Nephropathies, Factor VIII, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Failure, Chronic, Longitudinal Studies, Male, Middle Aged, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {1533-3450}, doi = {10.1681/ASN.2007030308}, author = {Wattanakit, Keattiyoat and Cushman, Mary and Stehman-Breen, Catherine and Heckbert, Susan R and Folsom, Aaron R} }