Black-White Differences In Venous Thrombosis Risk: the Longitudinal Investigation of Thromboembolism Etiology (LITE)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 478-478 ◽  
Author(s):  
Neil Zakai ◽  
Pamela Lutsey ◽  
Aaron Folsom ◽  
Mary Cushman

Abstract Abstract 478 Black-White Differences in Venous Thrombosis Risk: The Longitudinal Investigation of Thromboembolism Etiology (LITE). Neil A. Zakai, Pamela L. Lutsey, Aaron R. Folsom, Mary Cushman. Introduction: Venous thrombosis (VT) is more common in blacks than whites. The reasons for this difference and whether it is explained by racial differences in VT risk factors is not known. Methods: VT was ascertained by physician review of medical records in the Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective observational study of 21,680 men and women age 45–100 years participating in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) cohorts. VT was classified as provoked if preceded within 90 days by major surgery, trauma, immobility, or associated with active cancer or chemotherapy. We used age- and sex-adjusted Cox models to evaluate whether certain VT risk factors explained the increased risk of VT in blacks vs whites. We also tested if the impact of VT risk factors differed by race using interaction terms. Most risk factors were assessed in both ARIC and CHS cohorts (body mass index (BMI), diabetes, hypertension, chronic kidney disease (CKD), factor VIII, and education) except the activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), and protein C were measured in ARIC only and C-reactive protein was measured in CHS only. Results: With up to 15 years of follow up, among 20,964 participants (5,054 blacks) without VT at baseline, 648 developed new VT (200 blacks). The age- and sex-standardized incidence of VT per 1000 person-years was higher in blacks than whites for all VT (3.18 vs 1.96), whether the VT was provoked (2.11 vs. 1.24) or unprovoked (1.12 vs. 0.74), all p <0.01. Blacks and whites had a similar incidence of pulmonary embolism (PE) (0.83 vs. 0.76, p = 0.56). Blacks had more adverse levels of many VT risk factors except CKD and a lower aPTT: BMI (29.3 vs. 26.8 kg/m2), diabetes (21 vs 11%), hypertension (59 vs 38%), CKD (5 vs. 12%), high school graduation (58 vs 80%), factor VIII (146 vs 124%), vWF (134 vs 113%), CRP (2.4 vs 1.8 mg/L) protein C (3.13 vs. 3.18 mg/L), all p <0.01. In age- and sex-adjusted Cox models, the relative risk of total VT for blacks vs. whites was 1.67 (95% CI 1.41, 1.97). When risk factors were added to age-, sex- and race-adjusted Cox models, BMI explained 36% of the excess risk of VT in blacks, factor VIII 58%, and vWF 54%. The other risk factors had a minimal impact on the HR for race. When all risk factors measured in both cohorts were considered in the same model, the association of black race with VT was attenuated (HR 1.15; 95% CI 0.94, 1.42). Of the risk factors evaluated, there were significant interactions between race and hypertension, CKD, and aPTT below the median (29s). The table lists the HR for each of these risk factors stratified by race; hypertension and CKD were stronger risk factors for VT in blacks while an aPTT less than the median was a stronger risk factor for VT in whites. Conclusions: Blacks have a higher incidence of VT than whites, whether provoked or unprovoked. The increased risk in blacks was largely explained by a greater prevalence of VT risk factors among blacks, particularly obesity, higher factor VIII and higher vWF. Further, CKD and hypertension were stronger risk factors for VT in blacks, while a shorter aPTT was a weaker risk factor for VT in blacks. Larger studies of VT in blacks addressing environmental and genetic risk factors and health-care disparities are needed to fully understand reasons for these ethnic differences in VT incidence. Disclosure: No relevant conflicts of interest to declare.

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1311-1318 ◽  
Author(s):  
Beatrice Saposnik ◽  
Jean-Luc Reny ◽  
Pascale Gaussem ◽  
Joseph Emmerich ◽  
Martine Aiach ◽  
...  

Abstract The endothelial cell protein C (PC) receptor (EPCR) facilitates PC activation by the thrombin-thrombomodulin complex. A soluble form of this receptor (sEPCR) found in plasma inhibits both activated PC (aPC) activity and PC activation by competing for PC with membrane-associated EPCR. Elevated sEPCR levels are found in approximately 20% of healthy subjects, but the mechanisms underlying this interindividual variability are unknown. We measured sEPCR levels in 100 healthy male volunteers, and observed 2 phenotypic groups of subjects. The temporal stability of sEPCR levels suggested genetic control. Extensive analysis of the EPCR gene in these subjects revealed 13 polymorphisms in complete linkage disequilibrium; these defined 3 haplotypes, 1 of which (A3) was strongly associated with high sEPCR levels. The high constitutive sEPCR levels observed in A3 haplotype carriers might reduce the efficiency of the PC system and predispose these subjects to venous thrombosis. By studying 338 patients with venous thrombosis and 338 age- and sex-matched healthy subjects, we found that the A3 haplotype was overrepresented in the patients. In multivariate analysis, subjects carrying the A3 haplotype had an increased risk of thrombosis (odds ratio [OR] = 1.8; P = .004). Thus, the A3 haplotype, which is associated with elevated plasma sEPCR levels, is a candidate risk factor for venous thrombosis.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1234-1234
Author(s):  
Daniel D. Ribeiro ◽  
Willem M. Lijfering ◽  
Frits R. Rosendaal ◽  
Suzanne C. Cannegieter

Abstract Abstract 1234 Background: Obesity (prevalence of 20–25% in Western populations), blood group non-O (present in 50% of Western populations) and factor V Leiden (present in 5% of Caucasian populations) are frequent prothrombotic risk factors and may therefore have a considerable impact on the overall incidence of venous thrombosis. We previously reported that the increased risk of venous thrombosis in individuals with a high BMI is mediated by factor VIII induced APC-resistance, and that the combination of blood group non-O with a high BMI or factor V Leiden leads to higher venous thrombosis risks than expected when these prothrombotic factors are analyzed separately (ASH Annual Meeting Abstracts. 2009;114:453). However, small numbers did not enable us to sufficiently study the risk of venous thrombosis for the combination of a high BMI with factor V Leiden and blood group non-O, or to study these effects in subgroups. Objectives: To investigate whether the presence of factor V Leiden with blood group non-O can modify the risk for venous thrombosis in individuals with different body mass index strata in a larger population based study than previously reported. To evaluate the presence of gene-environment interactions in specific subgroups. Methods: MEGA study: 4956 consecutive patients aged 18–70 years with a first episode of venous thrombosis, and 6297 age- and sex-matched controls were included. Information about BMI, blood group and factor V Leiden was available in 4062 patients and 4659 controls. Odds ratios for venous thrombosis and their 95% confidence intervals (95% CIs) were calculated for BMI tertiles with logistic regression and adjusted for age and sex (matching factors). An interaction analysis among the BMI tertiles, factor V Leiden and blood group non-O was performed. Subgroup analyses involved stratification by venous thrombosis place (i.e. deep vein thrombosis or pulmonary embolism), sex, and presence or absence of acquired venous thrombosis risk factors. Results: A progressive increase in BMI was associated with an increased risk for venous thrombosis, odds ratios 1.1 (95% CI, 0.9–1.3) for those with a BMI in the median tertile, and 1.9- (95% CI, 1.6–2.3) for those in the upper tertile, as compared to individuals in the first BMI tertile, blood group O, and no factor V Leiden (i.e. the reference group). The addition of factor V Leiden and blood group non O in the model increased the risk in all BMI tertiles; odds ratios for venous thrombosis were 3.8 (95% CI, 3.2–4.6) in the third BMI tertile of individuals with blood group non-O, and 5.4 (95% CI, 3.5–8.5) in the third BMI tertile of individuals with factor V Leiden, respectively. When both factor V Leiden and blood group non-O were present, odds ratios for venous thrombosis were 9.1 (95% CI, 5.9–14.0) in the first BMI tertile, 9.4 (95% CI, 6.6–13.5) in the second BMI tertile, and 12.5 (95% CI, 8.9–17.6) in the BMI third BMI tertile as compared to the reference group. Subgroup analyses revealed similar joint interactions of BMI with blood group non-O and factor V Leiden on venous thrombosis risk. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1271-1276 ◽  
Author(s):  
Marieke C.H. de Visser ◽  
Frits R. Rosendaal ◽  
Rogier M. Bertina

Abstract Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophilia Study (LETS), a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. All carriers of the factor V Leiden mutation were excluded. A dose-response relationship was observed between the sensitivity for APC and the risk of thrombosis: the lower the normalized APC sensitivity ratio, the higher the associated risk. The risk for the lowest quartile of normalized APC-SR (&lt;0.92), which included 16.5% of the healthy controls, compared with the highest quartile (normalized APC-SR &gt; 1.05) was greater than fourfold increased (OR = 4.4; 95% confidence interval, 2.9 to 6.6). We adjusted for VIII:C levels, which appeared to affect our APC resistance test. The adjusted (age, sex, FVIII:C) odds ratio for the lowest quartile was 2.5 (95% confidence interval, 1.5 to 4.2). So, after adjustment for factor VIII levels, a reduced response to APC remained a risk factor. Our results show that a reduced sensitivity for APC, not caused by the factor V Leiden mutation, is a risk factor for venous thrombosis.


2018 ◽  
Vol 118 (07) ◽  
pp. 1305-1315 ◽  
Author(s):  
Neil Zakai ◽  
Suzanne Judd ◽  
Brett Kissela ◽  
George Howard ◽  
Monika Safford ◽  
...  

Background Haemostatic balance represented by low protein C (PC) and elevated factor VIII (FVIII) has been inconsistently associated with stroke and coronary heart disease (CHD) risk. Objective This article assesses whether an elevated FVIII and a low PC would increase cardiovascular risk more than either individually. Patients and Methods REGARDS recruited 30,239 black and white U.S. participants aged ≥ 45 years between 2003 and 2007. FVIII and PC were measured in a case–cohort sample of 646 stroke, 654 CHD, and a 1,104-person random sample with follow-up for approximately 4.5 years. Hazard ratios (HRs) were estimated using Cox models adjusted for demographic and cardiovascular risk factors. Results Elevated FVIII (per standard deviation [SD] increase) was associated with increased risk of both stroke (HR, 1.26; 95% confidence interval [CI], 1.08, 1.46) and CHD (HR, 1.52; 95% CI, 1.29, 1.79), while there was no association of PC per SD decrease. For PC, there was a trend towards increased cardiovascular disease risk in the lowest values (bottom 5%). For stroke, there was no interaction between FVIII and low PC (p interaction = 0.55). For CHD, the adjusted HR of FVIII per SD increase was significantly greater with PC in the bottom 5% (HR, 3.59; 95% CI, 1.39, 8.29) than PC in the upper 95% (HR, 1.45; 95% CI, 1.23, 1.71; p interaction = 0.07). Conclusion Higher FVIII was associated with both CHD and stroke risk and the risk potentiated by low PC for CHD. Findings demonstrate that risks for cardiovascular diseases conferred by adverse levels of haemostasis biomarkers may be augmented by levels of other biomarkers.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1499-1499
Author(s):  
Cihan Ay ◽  
Theres Tengler ◽  
Rainer Vormittag ◽  
Ralph Simanek ◽  
Wolfgang Dorda ◽  
...  

Abstract There is accumulating evidence for an association between atherosclerosis and venous thrombosis, which may share common risk factors. The metabolic syndrome (MetSyn), a cluster of interrelated risk factors comprising abdominal obesity, elevated blood pressure, high triglycerides, reduced high-density lipoprotein cholesterol and elevated fasting glucose plasma levels is associated with atherosclerotic disease and type 2 diabetes mellitus. It induces a proinflammatory and prothrombotic state. Despite its high prevalence, data on the association with venous thromboembolism (VTE) are scarce. Therefore, we aimed to investigate the association of the MetSyn with the risk for VTE and conducted a case-control study to evaluate the prevalence of the MetSyn according to guidelines of the National Cholesterol Education Program in a high-risk population of patients with objectively confirmed recurrent VTE, who had at least one unprovoked event of deep venous thrombosis or pulmonary embolism. Age and sex-matched healthy individuals served as controls. Finally, a total of 116 patients (53 female, mean age +/−SD: 56 years +/−12) and 129 controls (66 female, mean age +/−SD: 53 years +/−11) were recruited between January 2005 and November 2005. The prevalence of the MetSyn was statistically significantly higher in patients (40/116, 35%) than in controls (26/129, 20%, p=0.012). The unadjusted odds ratio (OR) of the MetSyn for VTE was 2.1 (95% CI [1.2–3.7], p=0.012) and remained statistically significant after adjustment for factor V Leiden, prothrombin G20210A variation and elevated factor VIII activity, sex and age (OR=2.2, 95% CI [1.1–4.2], p=0.024). Furthermore, individuals with the MetSyn (n=66) had significantly higher hs-CRP (median, [interquartile range]: 0.312 mg/dL, [0.142–0.751] vs. 0.153 mg/dL, [0.073–0.330], p<0.001), fibrinogen (390 mg/dL, [342–432] vs. 343 mg/dL, [310–394], p<0.001) and factor VIII activity (182%, [157–216] vs. 159%, [133–199], p=0.005) compared to those without (n=179). In conclusion, the MetSyn was statistically significantly overrepresented in patients with VTE compared to control subjects without a history of venous or arterial thrombosis. Our data suggest that the MetSyn may contribute to the development of VTE as it was associated with a 2-fold increased risk for VTE.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3826-3826
Author(s):  
Shankaranarayana Paneesha ◽  
Aidan McManus ◽  
Roopen Arya ◽  
Nicholas Scriven ◽  
Tim Nokes ◽  
...  

Abstract The association between venous thromboembolism (VTE) and cancer is well-recognised, but the thrombosis risk factor profile of patients with cancer-associated VTE is poorly characterised; it is unclear if additional risk factors contribute to the risk of thrombosis beyond the cancer itself, or if the risk factor profile is tumour-specific. Our aim was to compare the thrombosis risk factor profiles of cancer patients with or without symptomatic VTE enrolled in VERITY, an ongoing UK prospective VTE registry. The VERITY registry records data on patients with VTE and those in whom the diagnosis of VTE is excluded. Between Jun 05 and Mar 08, 49044 patient entries were made. Individual case data for patients with cancer were extracted. Using available risk factor data, univariate analysis of 9 established risk factors for VTE (medical in-patient history/immobilisation >3 days within last 4 weeks; major surgery in the last 4 weeks; hormonal risk factor; previous history of VTE; family history of VTE; known thrombophilia; intravenous drug abuse; current smoking; and leg paralysis), comparing VTE and non-VTE cancer cases, was performed for the 4 most common cancers using SPSS. To account for the potential impact of age and sex on VTE risk, age-adjusted values were calculated for breast and prostate cancer, and age- and sex-adjusted values for colorectal and lung. A nominal level of 5% statistical significance was assumed. Of 2825 cancer cases, 1382 had an objectively confirmed diagnosis of VTE and in 1443 the diagnosis of VTE was excluded. Breast (n=498), prostate (n=374), colorectal (n=343) and lung cancer (n=275) accounted for 53% of cancer cases. Univariate associations between risk factors and symptomatic VTE were found only for prostate cancer: history of VTE (odds ratio [OR] = 3.48; 95% CI, 2.01, 6.02; p < 0.00001), family history of VTE (OR = 2.56; 95% CI, 1.02, 6.44; p = 0.046), hormonal risk factor (OR = 2.22; 95% CI, 1.00, 4.92; p = 0.049). In colorectal cancer, smoking was less likely in VTE cases (OR = 0.54; 95% CI, 0.34, 0.87; p = 0.012). Adjusting for age (and sex), univariate associations between risk factors and symptomatic VTE were again found only for prostate cancer: history of VTE (OR = 3.23; 95% CI, 1.56, 6.68; p = 0.002), with smoking less likely in age-adjusted VTE cases (OR = 0.50; 95% CI, 0.28, 0.91; p = 0.022). Our analysis of a registry population found few associations between known thrombosis risk factors and symptomatic VTE in patients with common cancers, suggesting these factors impact little on thromboembolic risk in these cancers.


1997 ◽  
Vol 78 (03) ◽  
pp. 0993-0996 ◽  
Author(s):  
P J Svensson ◽  
G Benoni ◽  
H Fredin ◽  
O Bjӧrgell ◽  
P Nilsson ◽  
...  

SummaryResistance to activated protein C (APC) caused by the R506Q mutation in factor V is the most common inherited risk factor for venous thrombosis. To elucidate whether APC-resistance is a risk factor for venous thrombosis after elective total hip replacement, the association between APC-resistance (presence of FV:Q506 allele) and postoperative thrombosis was investigated in patients (n = 198) randomised to received short (during hospitalisation, n = 100) or prolonged prophylaxis (three weeks after hospitalisation, n = 98) with low molecular weight heparin (LMWH). Among APC-resistant individuals receiving short prophylaxis, 7/10 developed thrombosis as compared to 2/12 receiving long prophylaxis (p <0.0179). Odds ratio for association between APC-resistance and thrombosis in the short prophylaxis group was 4.2 (CI 95% 1.02-17.5) (p <0.0465). Among those receiving prolonged, prophylaxis, there was no increased incidence of thrombosis associated with APC-resistance. Two unexpected observations were made. One was that APC-resistance was much more common in women (19/109) than in men (3/89) (p <0.001). The other was that even women without APC-resistance were much more thrombosis-prone than men. Thus, 24/48 of women with normal FV genotype and short prophylaxis developed thrombosis vs 8/42 among men, p = 0.002. The increased risk of thrombosis associated with female gender and APC-resistance was neutralised by the prolonged treatment. In conclusion, among patients receiving short prophylaxis, female gender was found to be a strong risk factor for venous thrombosis. Even though APC-resistance appeared to be a risk factor for postoperative thrombosis, the uneven distribution of APC-resistance between men and women, taken together with the increased risk of thrombosis among women, precluded valid conclusions to be drawn about the association between APC-resistance and an increased risk of thrombosis. Our results suggest that prolonged prophylaxis with LMWH after hip surgery is more important for women than for men.


2017 ◽  
Vol 45 (2) ◽  
pp. 206-212 ◽  
Author(s):  
Wilson Bautista-Molano ◽  
Robert Landewé ◽  
Rubén Burgos-Vargas ◽  
José Maldonado-Cocco ◽  
Anna Moltó ◽  
...  

Objective.Increased risk of comorbidities has been reported in spondyloarthritis (SpA). The objective of this study was to determine the prevalence and risk of developing comorbidities in patients with SpA in 3 Latin American (LA) countries, and to compare that prevalence with the general population.Methods.Data were analyzed from 390 patients with SpA enrolled in the Assessment of SpondyloArthritis international Society of Comorbidities in SpA study from Argentina, Colombia, and Mexico. Age- and sex-standardized prevalence (95% CI) was estimated for arterial hypertension (AHT), tuberculosis (TB), and malignancies. Age- and sex-specific data from the general population were obtained from the Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study for AHT, the Global TB report, and the GLOBOCAN project for malignancies. Data analyzed for AHT were confined to Colombia and Mexico. The prevalence in patients with SpA was compared with the prevalence in the general population per age- and sex-specific stratum, resulting in standardized risk ratios (SRR).Results.In total, 64% of the patients with SpA were male, with a mean age of 45 years (SD 14.7). The most common comorbidities in the 3 LA countries were AHT (25.3%, 95% CI 21.2–30.0), hypercholesterolemia (21.5%, 95% CI 17.6–26.0), and osteoporosis (9.4%, 95% CI 6.8–12.9). AHT prevalence in Colombia and Mexico was 21.4% (95% CI 15.4–28.9) and was higher than the general population (12.5%, 95% CI 11.4–13.7), resulting in an SRR of 1.5. TB prevalence in the 3 LA countries was 3.3% (95% CI 1.8–5.7), which was significantly higher than in the general population (0.32%), leading to an SRR of 10.3. The prevalence of malignancies was not increased.Conclusion.Patients with SpA in LA are at increased risk of AHT and TB in comparison to the general population. While this sample of patients may not be entirely representative of the patient population in each country, a systematic evaluation of these comorbidities in all patients with SpA still may help to monitor these conditions better.


Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3678-3682 ◽  
Author(s):  
Astrid van Hylckama Vlieg ◽  
Irma K. van der Linden ◽  
Rogier M. Bertina ◽  
Frits R. Rosendaal

Elevated plasma levels of factor VIII (> 150 IU/dL) are an important risk factor for deep vein thrombosis (DVT). Factor VIII is the cofactor of factor IXa in the activation of factor X. The risk of thrombosis in individuals with an elevated factor IX level is unknown. This study investigated the role of elevated factor IX levels in the development of DVT. We compared 426 patients with a first objectively diagnosed episode of DVT with 473 population controls. This study was part of a large population-based case-control study on risk factors for venous thrombosis, the Leiden Thrombophilia Study (LETS). Using the 90th percentile measured in control subjects (P90 = 129 U/dL) as a cutoff point for factor IX levels, we found a 2- to 3-fold increased risk for individuals who have factor IX levels above 129 U/dL compared with individuals having factor IX levels below this cutoff point. This risk was not affected by adjustment for possible confounders (age, sex, oral contraceptive use, and high levels of factor VIII, XI, and vitamin K-dependent proteins). After exclusion of individuals with known genetic disorders, we still found an odds ratio (OR) of 2.5 (95% confidence interval [CI]: 1.6-3.9). The risk was higher in women (OR: 2.6, CI: 1.6-4.3) than in men (OR: 1.9, CI: 1.0-3.6) and appeared highest in the group of premenopausal women not using oral contraceptives (OR: 12.4, CI: 3.3-47.2). These results show that an elevated level of factor IX is a common risk factor for DVT.


1997 ◽  
Vol 3 (4) ◽  
pp. 239-244 ◽  
Author(s):  
Kandice Kottke-Marchant ◽  
Ralph Green ◽  
Donald W. Jacobsen ◽  
Anjan Gupta ◽  
Susan R. Savon ◽  
...  

A high plasma homocysteine concentration is associated with premature vascular disease and thrombosis. The association between high homocysteine concentrations and thrombosis in patients with a normal coagulation profile is unknown. Sixty adults (37 men and 23 women, mean age 46 years) with documented thrombosis were compared with age-and sex-matched controls. Those with risk factors for thrombosis or abnormal coagulation profiles were excluded. Homocysteine concentrations were higher in cases than controls (21.8 ± 13.8 vs 11.0 ± 4.7 μmol/L, p < 0.001). A cut point for defining high homocysteine concentrations was determined at 13 μmol/L and conferred an increased odds ratio for thrombosis overall (7.8, 95% CI 3.0-20.2, p < 0.001) as well as in men (8.9, 95% CI 3.0-26.1; p < 0.001) and women (37.8, 95% CI 6.5-213.9; p < 0.01). A high plasma homocysteine is a risk factor for thrombosis in patients with a normal coagulation profile. This common abnormality should be sought in patients with otherwise unexplained thrombotic episodes. Key Words: Homocysteine—Thrombosis—Clotting.


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