@article {691, title = {Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 May 27}, pages = {1182-9}, abstract = {

BACKGROUND: The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies.

METHODS: To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998.

RESULTS: There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95\% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95\% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95\% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P<.001 for the trend). Diabetes was also associated with an increased risk of VTE (adjusted hazard ratio, 1.5 [95\% CI, 1.0-2.1]).

CONCLUSIONS: Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.

}, keywords = {Aged, Arteriosclerosis, Female, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Pulmonary Embolism, Risk Factors, United States, Venous Thrombosis}, issn = {0003-9926}, doi = {10.1001/archinte.162.10.1182}, author = {Tsai, Albert W and Cushman, Mary and Rosamond, Wayne D and Heckbert, Susan R and Polak, Joseph F and Folsom, Aaron R} } @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 {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 {726, title = {Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Am J Hematol}, volume = {72}, year = {2003}, month = {2003 Mar}, pages = {192-200}, abstract = {

We sought to examine prospectively the association of serum homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphism with risk of venous thromboembolism (VTE). We studied these relationships in a nested case-control study of 303 VTE cases and 635 matched controls from a population-based cohort of 21,680 adults from six U.S. communities. The highest quintile of serum homocysteine carried a non-statistically significant adjusted odds ratio of 1.55 (95\% CI, 0.93-2.58) compared to the lowest quintile in the overall cohort but a significant association among adults aged 45-64 years (OR = 2.05, 95\% CI, 1.10-3.83) and an inverse association in those > or = 65 years of age. Carriers of the MTHFR C677T polymorphism were not at higher risk for VTE than those with normal genotype (OR = 0.74, 95\% CI = 0.56-0.98). Our prospective data showed, at most, a weak relationship between homocysteine and VTE risk, with associations larger among younger participants. MTHFR C677T was not a risk factor for VTE.

}, keywords = {Aged, Aging, Animals, Case-Control Studies, Cohort Studies, Factor V, Female, Genotype, Homocysteine, Humans, Longitudinal Studies, Male, Methylenetetrahydrofolate Reductase (NADPH2), Middle Aged, Odds Ratio, Oxidoreductases Acting on CH-NH Group Donors, Polymorphism, Genetic, Prospective Studies, Risk Factors, Venous Thrombosis}, issn = {0361-8609}, doi = {10.1002/ajh.10287}, author = {Tsai, Albert W and Cushman, Mary and Tsai, Michael Y and Heckbert, Susan R and Rosamond, Wayne D and Aleksic, Nena and Yanez, N David and Psaty, Bruce M and Folsom, Aaron R} } @article {793, title = {Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology.}, journal = {Am J Med}, volume = {117}, year = {2004}, month = {2004 Jul 01}, pages = {19-25}, abstract = {

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.

}, keywords = {Aged, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Neoplasms, Population Surveillance, Pulmonary Embolism, Recurrence, Risk Factors, Survival Rate, Venous Thrombosis}, issn = {0002-9343}, doi = {10.1016/j.amjmed.2004.01.018}, author = {Cushman, Mary and Tsai, Albert W and White, Richard H and Heckbert, Susan R and Rosamond, Wayne D and Enright, Paul and Folsom, Aaron R} }