Incident Venous Thromboembolism Events Research Articles

Thyroid function, as assessed by TSH, and future risk of venous thromboembolism: the Tromsø study.

The relationship between thyroid function and the risk of venous thromboembolism (VTE) has not been addressed in population-based cohorts. We investigated the association between TSH levels and the risk of VTE in a general adult population. Population-based cohort study. TSH was measured in 11 962 subjects aged 25-89 years who participated in Tromsø 4-6 starting in 1994-1995. Incident VTE events were recorded through 31st December 2010. Cox's regression models with TSH as a time-varying covariate were used to calculate hazard ratios (HRs) of VTE by TSH categories (low TSH: <0.05 mU/l; moderately reduced TSH: 0.05-0.19 mU/l; normal TSH: 0.20-4.00 mU/l; moderately elevated TSH: 4.01-5.00 mU/l; and high TSH: >5.00 mU/l) and within the normal range of TSH, modeling TSH as a continuous variable. There were 289 VTEs during 8.2 years of median follow-up. Subjects with low (prevalence: 0.22%) and high (3.01%) TSH had slightly higher risk estimates for VTE than did subjects with normal TSH (multivariable HRs: 2.16, 95% CI 0.69-6.76 and 1.55, 95% CI 0.87-2.77 respectively), but the CIs were wide. Moreover, there was no association between TSH within the normal range and VTE (HR per 1 mU/l increase: 0.95, 95% CI 0.82-1.11). Serum levels of TSH within the normal range were not associated with a risk of VTE, whereas low and high TSH levels were rare and associated with a moderately higher risk of VTE. The present findings suggest that only a minor proportion of the VTE risk in the population can be attributed to thyroid dysfunction.

Red cell distribution width is associated with incident venous thromboembolism (VTE) and case-fatality after VTE in a general population

Recent studies suggest an association between red cell distribution width (RDW) and incident venous thromboembolism (VTE). We aimed to investigate the impact of RDW on risk of incident and recurrent VTE, and case-fatality, in a general population. RDW was measured in 26,223 participants enrolled in the Tromsø Study in 1994-1995. Incident and recurrent VTE events and deaths during follow-up were registered until January 1, 2012. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). There were 647 incident VTE events during a median of 16.8 years of follow-up. Individuals with RDW in the highest quartile (RDW≥13.3%) had 50% higher risk of an incident VTE than those in the lowest quartile (RDW≤12.3%). The association was strongest for unprovoked deep-vein thrombosis (HR highest vs lowest quartile of RDW: 1.8, 95% CI 1.1-3.1). VTE patients with baseline RDW≥13.3% had 30% higher risk of all-cause mortality after the initial VTE event than VTE patients with RDW<13.3%. There were no association between RDW and risk of recurrent VTE. Our findings suggest that high RDW is a risk factor of incident VTE, and that RDW is a predictor of all-cause mortality in VTE patients.

Inflammation markers and incident venous thromboembolism: the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort

Inflammation biomarkers are associated with the venous thromboembolism (VTE) risk factors obesity and age; however, the relationships of inflammation with VTE risk remain controversial. To examine associations of four inflammation biomarkers, i.e. C-reactive protein (CRP), serum albumin, white blood cell (WBC) count, and platelet count (PLTC), with incident VTE, and to determine whether they mediate the association of age or obesity with VTE. Hazards models adjusted for VTE risk factors were used to calculate the prospective association of each biomarker with incident VTE in 30,239 participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Mediation of the associations of obesity and age with VTE were examined by bootstrapping. Over a period of 4.6 years, there were 268 incident VTE events. After adjustment for VTE risk factors, the hazard ratios (HRs) were 1.25 (95% confidence interval [CI] 1.09-1.43) per standard deviation (SD) higher log-CRP and 1.25 (95% CI 1.06-1.48) per SD lower albumin; there were no associations for WBC count or PLTC. The association of body mass index (BMI), but not age, with VTE was partially mediated by CRP and albumin. In risk factor-adjusted models, the percentage attenuations of the BMI HR for VTE after introduction of CRP or albumin into the models were 15.4% (95% CI 7.7-33.3%) and 41.0% (95% CI 12.8-79.5%), respectively. Higher CRP levels and lower serum albumin levels were associated with increased VTE risk, and statistically mediated part of the association of BMI with VTE. These data suggest that inflammation may be a potential mechanism underlying the relationship between obesity and VTE risk.

Family history of myocardial infarction and cause-specific risk of myocardial infarction and venous thromboembolism: the Tromsø Study.

A family history of myocardial infarction (FHMI) has been shown to increase the risk of venous thromboembolism (VTE). The mechanism underlying the association remains unclear. Therefore, we aimed to determine the risks of MI and VTE by FHMI using a cause-specific model and to explore whether atherosclerotic risk factors could explain the association between FHMI and VTE in a population-based cohort. The study included 21 624 subjects recruited from the Tromsø Study in 1994 to 1995 and 2001 to 2002. Incident MI and VTE events were registered from date of enrollment to end of follow-up, December 31, 2010. There were 1311 MIs and 428 VTEs during a median follow-up of 15.8 years. FHMI was associated with a 52% increased risk of MI (adjusted hazard ratio, 1.52; 95% confidence interval, 1.35-1.70) and a 26% increased risk of VTE (adjusted hazard ratio, 1.26; 95% confidence interval, 1.02-1.55) in the cause-specific Cox model. Similar results were found using the traditional Cox model. The risk estimates by status of FHMI were highest for unprovoked deep vein thrombosis (adjusted hazard ratio, 1.69; 95% confidence interval, 1.12-2.56), and the risk increased with increasing number of affected relatives. Modifiable atherosclerotic risk factors slightly altered the association between FHMI and MI but had a negligible effect on the association between FHMI and VTE. FHMI was associated with increased risk of both MI and VTE in a cause-specific model. Apparently, the association between FHMI and VTE applied to unprovoked deep vein thrombosis and was not explained by modifiable atherosclerotic risk factors.

High Fish plus Fish Oil Intake Is Associated with Slightly Reduced Risk of Venous Thromboembolism: The Tromsø Study

Current knowledge of the effect of fish consumption on risk of venous thromboembolism (VTE) is scarce and diverging. Therefore, the purpose of the present study was to investigate the impact of fish consumption and fish oil supplements on the risk of VTE in a population-based cohort. Weekly intake of fish for dinner and intake of fish oil supplements during the previous year were registered in 23,621 persons aged 25–97 y who participated in the Tromsø Study from 1994 to 1995. Incident VTE events were registered throughout follow-up (31 December 2010). Cox-regression models were used to calculate HRs for VTE, adjusted for age, body mass index, sex, triglycerides, HDL cholesterol, physical activity, and education level. During a median of 15.8 y of follow-up there were 536 incident VTE events. High fish consumption was associated with a slightly reduced risk of VTE. Participants who ate fish ≥3 times/wk had 22% lower risk of VTE than those who consumed fish 1–1.9 times/wk (multivariable HR: 0.78; 95% CI: 0.60, 1.01; P = 0.06). The addition of fish oil supplements strengthened the inverse association with risk of VTE. Participants who consumed fish ≥3 times/wk who additionally used fish oil supplements had 48% lower risk than those who consumed fish 1–1.9 times/wk but did not use fish oil supplements (HR: 0.52; 95% CI: 0.34, 0.79; P = 0.002). In conclusion, a high weekly intake (≥3 times/wk) of fish was associated with a slightly reduced risk of VTE, and the addition of fish oil supplements strengthened the inverse effect.

Hyperglycemia, assessed according to HbA1c, and future risk of venous thromboembolism: the Tromsø study

HbA1c , a marker of average plasma glucose level during the previous 8-12weeks, is associated with the future risk of cardiovascular disease and all-cause mortality. To examine the association between hyperglycemia, assessed according to HbA1c , and the future risk of venous thromboembolism (VTE) in a population-based cohort. HbA1c was measured in 16156 unique subjects (25-87years) who participated in one or more surveys of the Tromsø study (Tromsø4, 1994-1995; Tromsø5, 2001-2002; and Tromsø6, 2007-2008). All subjects were followed, and incident VTE events were recorded up to 31 December 2010. There were 333 validated first VTE events, of which 137 were unprovoked, during a median follow-up of 7.1years. HbA1c was not associated with the future risk of VTE in analyses treating HbA1c as a continuous variable, or in categorized analyses. The risk of VTE increased by 5% per one standard deviation (0.7%) increase in HbA1c (multivariable-adjusted hazard ratio [HR]1.05; 95% confidence interval [CI]0.97-1.14), and subjects with HbA1c ≥6.5% had a 27% higher risk than those with HbA1c <5.7% (multivariable-adjusted HR1.27; 95%CI0.72-2.26). There was no significant linear trend for an increased risk of VTE across categories of HbA1c (P=0.27). Serum levels of HbA1c were not associated with the future risk of VTE in multivariable analysis. Our findings suggest that hyperglycemia does not play an important role in the pathogenesis of VTE.

Carotid Atherosclerosis Predicts Future Myocardial Infarction But Not Venous Thromboembolism

Objective—Recent studies have suggested that arterial and venous thrombosis share common risk factors. Although carotid atherosclerosis is associated with arterial cardiovascular events, its role in venous thromboembolic disease is unclear. We wanted to investigate and compare the effect of carotid atherosclerosis on the risk of myocardial infarction (MI) and venous thromboembolism (VTE) in a general population, taking into account competing risks.Approach and Results—Mean intima-media thickness and total plaque area in the right carotid artery were measured with ultrasound in 6257 people aged 25 to 84 years who participated in a population-based health study, the Tromsø Study, from 1994 to 1995. Incident MI and VTE events were registered from date of enrollment to end of follow-up on December 31, 2010. Cox proportional hazards regression models using age as time scale were used to estimate cause-specific hazard ratios with 95% confidence intervals for MI and VTE by increasing levels of intima-media thickness and total plaque area. There were 894 incident MI cases and 256 VTE events during a median of 15.4 years of follow-up. The risk of MI increased significantly across quartiles of mean intima-media thickness (Pfor trend &lt;0.001) and with increasing total plaque area (Pfor trend &lt;0.001), but neither intima-media thickness (Pfor trend=0.94) nor total plaque area (Pfor trend=0.45) was associated with VTE risk in multivariable-adjusted analysis.Conclusions—In this study, carotid atherosclerosis was strongly associated with future MI but not with VTE. Our findings suggest that carotid atherosclerosis does not represent a link between arterial and venous thrombosis.

Fish intake and venous thromboembolism: A Danish follow-up study

Data on the association between fish intake and venous thromboembolism (VTE) is sparse and inconsistent. To investigate whether intake of total, lean or fatty fish is associated with development of incident VTE. This study is based on the Danish follow-up study Diet, Cancer and Health including 27,178 men and 29,876 women aged 50-64 with no history of cancer. Participants were included between 1993 and 1997 and followed through 2006. Information on fish intake and potential confounders was obtained from baseline questionnaires. The outcome was incident VTE (all) and idiopathic VTE. We used Cox proportional hazard models with age as time axis. Separate analyses were performed for men and women. Adjustment was made for BMI, smoking, physical activity, energy intake and women's use of hormone replacement therapy. During follow-up, 641 incident VTE events were verified. We found no association between total fish intake and VTE, but moderate intake of fatty fish was associated with a statistically non-significant 20-40% lower risk of idiopathic VTE compared with consumption of a low intake (less than 8g) of fatty fish per day. Intake of neither total nor fatty fish was statistically significantly associated with the incidence rate of VTE. However, intake of fatty fish may be associated with a reduction of the risk of idiopathic VTE.

Venous Thromboembolism Incidence In The Cooperative Study Of Sickle Cell Disease: The Untold Story

BackgroundAn increased risk of venous thromboembolism (VTE) among individuals with sickle cell disease (SCD) has only recently been recognized. Unlike arterial thrombosis such as stroke which primarily occurs in children with SCD, VTE risk in SCD appears to increase in young adulthood. To date, no studies have described the incidence of VTE in adolescents and adults with SCD. We performed a secondary analysis of the largest prospective cohort of SCD patients, the Cooperative Study of Sickle Cell Disease (CSSCD), to estimate the incidence rate and age-specific cumulative incidence of first VTE among SS/Sβ0 patients aged 15 or older. MethodsWe used available data from Phase 1 of the CSSCD,1 a multi-institution longitudinal prospective study conducted from 1978-1988, to identify cases of first VTE in patients aged 15 or older at enrollment with SS/Sβ0 genotype. Individuals with a history of prior VTE were excluded. VTE was defined as any pulmonary embolism (PE) or deep venous thrombosis (DVT) identified by ICD-9 code except in the case of pregnancy where VTE events were explicitly collected. Because the definition of acute chest syndrome (ACS) in the CSSCD also included PE and because the ICD-9 code for PE was also used for pulmonary infarct in cases of potential ACS, PE cases that were identified during an admission for ACS were included only if a negative chest X-ray was recorded. The date of VTE was recorded as being the date of the annual visit for any interim VTE or as the date of discharge for any VTE that occurred during a hospitalization. 95% Confidence intervals (CI) for incidence rates were calculated using a Poisson distribution assumption. Kaplan-Meier failure curves were generated to estimate age-specific cumulative incidence. ResultsA total of 1,133 individuals with SS/Sβ0 aged ≥ 15 years with 6,608 years of follow-up were included for analysis. During this study period, 43 incident VTE events were identified. The median age at VTE was 26.3 years (range 17-47 years) and 25 (58%) were female. The overall incidence rate for VTE was 6.5 events/1000 person-years (CI 4.7, 8.8). The Kaplan-Meier failure curve for VTE is shown below. The cumulative incidence of first VTE was estimated as 9.0% (CI 6.4-12.7) by age 30 and 14.1% (CI 10.2-19.2) by age 40. [Display omitted] ConclusionsThe incidence rate of first VTE among SS/Sβ0 patients aged ≥ 15 years appears to be high, with an estimated cumulative incidence by age 40 that far exceeds that for Factor V Leiden carriers (estimated 6.2% by age 65).2 This study underscores the thrombophilic state of SCD and emphasizes the need for further research into the risk factors for VTE in the SCD population.1. Gaston M, Rosse WF. The cooperative study of sickle cell disease: review of study design and objectives. Am J Pediatr Hematol Oncol 1982; 4: 197-201.2. Heit JA, Sobell JL, Li H, Sommer S. The incidence of venous thromboembolism among Factor V Leiden carriers: a community-based cohort study. J Throm Haemost 2004; 3: 305-11.This Abstract was prepared using CSSCD Research Materials obtained from the NHLBI via BioLINCC (https://biolincc.nhlbi.nih.gov/). Disclosures:Naik:NHLBI: Research Funding. Haywood:NHLBI: Research Funding. Lanzkron:GlycoMimetics, Inc.: Research Funding.

White Blood Cell Count Measured Prior to Cancer Development Is Associated with Future Risk of Venous Thromboembolism – The Tromsø Study

BackgroundElevated white blood cell (WBC) count is associated with risk of venous thromboembolism (VTE) in cancer patients initiating chemotherapy. It is not known whether the risk of VTE by WBC count in cancer patients is causal or merely a consequence of the malignant disease. To address this question, we studied the association between WBC count, measured prior to cancer development, and risk of VTE in subjects who did and did not develop cancer during follow-up in a prospective population-based study.MethodsBaseline characteristics, including WBC and neutrophil counts, were measured in 24304 initially cancer-free subjects who participated in the Tromsø Study in 1994-1995. Incident cancer diagnosis and VTE events were registered up to September 1, 2007. In the cancer cohort, WBC and neutrophil counts were measured in average 7.1 years before cancer development. Cox-regression models were used to calculate hazard ratios (HRs) for VTE by WBC and neutrophil counts as categorized variables (<40th, 40-80th, and >80th percentile) with 95% confidence intervals (CIs).ResultsDuring follow-up, 1720 subjects developed cancer and there were 388 VTE events, of which 116 occurred in the cancer-group (6.9 per 1000 person-years) and 272 in the cancer-free group (1.1 per 1000 person-years). In those who developed cancer, WBC count above the 80th percentile (≥8.6x109 cells/L) was associated with a 2.4-fold higher risk (HR 2.36, 95% CI: 1.44-3.87) of VTE compared to WBC count below the 40th percentile (<6.4x109 cells/L). No association was found between WBC count and VTE in those who stayed cancer-free (HR 0.94, 95% CI 0.65-1.36). Similar findings were observed for neutrophils.CommentPre-cancer WBC count was associated with risk of VTE in cancer patients, but not in cancer-free subjects. Our findings suggest that leukocytes may play a causal role in cancer-related VTE rather than only reflecting the low-grade inflammation associated with cancer.

Venous thromboembolism in patients with pancreatic cancer: Incidence and effect on survival in east Asian ethnic groups.

151 Background: Pancreatic cancer is known to be most frequently associated with venous thromboembolism (VTE), with the incidence of 10~20% in Western countries. As for the East Asian ethnic groups, just one small retrospective study showed lower incidence (5.3%) than other ethnic groups. However, there have been no large retrospective cohort studies of VTE in pancreatic cancer of East Asian ethnic group. Methods: We retrospectively reviewed the medical records of patients diagnosed with pancreatic adenocarcinoma in 2005~2010 at Severance Hospital, Seoul, Korea. Principal outcomes were incident VTE events and mortality. Cox proportional hazards models were used to analyze associations between specific risk factors and principal outcomes. Results: We investigated 1334 patients with pancreatic adenocarcinoma and 218 (16.3%) patients were excluded due to incomplete medical records and loss to follow-up. Among 1116 eligible patients, the overall and 1-year cumulative VTE incidence were 13.9% and 11.2% respectively. The incidence rate during the half year, 1-year and 2-years were 23.4, 17.7, 15.6 events per 100 person-years, respectively. Among total of 155 VTE patients, abdominal VTE was 52.9%, deep vein thrombosis was 21.3%, pulmonary thromboembolism was 19.4%, and head and neck VTE was 18.7%. In multivariable analyses, significant predictors of developing VTE included advanced metastatic stage (HR=2.08, 95% CI 1.37 to 3.17) and treatment of chemotherapy or radiotherapy, including CCRT (HR=1.52, 95% CI 16 to 1.99). VTE was a significant risk factor of 1-year and overall mortality (HR=1.44, 95% CI 1.15 to 1.79 and HR=1.45, 95% CI 1.21 to 1.73). Among 155 VTE patients, head and neck (H&amp;N) VTE revealed highest risk of overall mortality (HR=2.05, 95% CI 1.27 to 3.33, versus non-H&amp;N VTE). Conclusions: Approximately 13.9% of pancreatic adenocarcinoma patients developed VTE in East Asian ethnic group and this incidence was not significantly different from other ethnic groups. Advanced metastatic stage was the strongest predictor of VTE which would be a significant risk factor of 1-year mortality. Among VTE patients, head and neck VTE was 18.7% and showed the highest risk of overall death.

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

Conflicting findings have been reported on the association between smoking and the risk of venous thromboembolism (VTE). To conduct a prospective, population-based cohort study to investigate the association between cigarette smoking and the risk of incident VTE. 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. 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. 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.

C0065 White blood cell count measured prior to cancer development is associated with future risk of venous thromboembolism in cancer patients' the Tromsø study

Background: Leukocytosis is an independent risk factor for mortality in cancer patients. Elevated white blood cell (WBC) count, and neutrophils in particular, is also associated with increased risk of venous thromboembolism (VTE) in patients with manifest cancer initiating chemotherapy. It is not known whether the risk of VTE by WBC in cancer patients is causal or merely a consequence of the disease. To address this question we studied the association between WBC count, measured prior to cancer development, and risk of VTE in subjects without and with development of cancer during follow-up in a prospective population-based study. Methods: Baseline characteristics, including total WBC and neutrophil counts, were measured in 24463 initially cancer-free subjects who participated in the Tromso study in 1994–1995. Cancer diagnosed at least one year after WBC measurements and incident venous thromboembolism occurring after the cancer diagnoses were registered up to September 1st, 2007. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. Results: There were 1647 subjects who developed cancer and 353 incident VTE events, ofwhich 84 (24%) occurred in the cancer-group (15.6 per 1000 person-years) and 269 (76%) in the cancer-free group (1.15 per 1000person-years) during follow-up. The risk of VTE increased by 29%per one standard deviation (1SD=2.38×109 cells/L) increase in total WBC (multivariable HR 1.29; 95% CI 1.14–1.46) among cancer patients. WBC count≥8.5×109 cells/L was associated with a 2-fold higher adjusted risk of VTE compared to WBC countb6.5×109 cells/L (HR 2.0, 95% CI 1.163.72). Similar findings were observed for neutrophils. No association was found betweenWBC count and VTE in cancer-free subjects. Comment: Total WBC and neutrophil counts measured prior to cancer development were associated with risk of VTE in cancer patients, but not in cancer-free subjects. Our findings suggest that neutrophils may play a causative role inVTE among cancer patients rather thanonly reflecting the low-grade inflammation associated with cancer.

Cystatin C is associated with risk of venous thromboembolism in subjects with normal kidney function - the Tromso study

Previous studies have shown an association between impaired kidney function, assessed by cystatin C-based estimated glomerular filtration rate, and venous thromboembolism. The aim of this study was to investigate whether serum cystatin C was associated with a risk of venous thromboembolism among subjects with normal kidney function in a prospective population-based study. Cystatin C was measured in serum from 3251 men and women with normal kidney function, aged 25-84 years, who participated in the Tromsø study in 1994-1995. Normal kidney function was defined as a creatinine-based estimated glomerular filtration rate greater than 90 mL/min/1.73 m(2) and absence of microalbuminuria. Incident venous thromboembolism was registered from the date of inclusion through to the end of follow-up, September 1, 2007. Cox-regression models were used to calculate hazard ratios with 95% confidence intervals for venous thromboembolism. There were 83 incident venous thromboembolic events, of which 53 (63.9 %) were provoked, during a median of 12.3 years of follow-up. A one standard deviation (0.11 mg/L) increase in serum cystatin C levels was associated with a 43% (hazard ratio 1.43; 95% confidence interval 1.17-1.72) increased risk of total venous thromboembolism. Subjects with cystatin C levels in the top quartile (≥ 0.87 mg/L) had a 2.5-fold (hazard ratio 2.51; 95% confidence interval 1.27-4.96) increased risk of venous thromboembolism compared to those with levels in the bottom quartile (≤ 0.72 mg/L) in adjusted analysis. The risk estimates were even higher for provoked venous thromboembolism (hazard ratio 3.11; 95% confidence interval 1.23-7.86). Serum cystatin C levels were associated with the risk of venous thromboembolism in subjects with normal kidney function. Our findings suggest that elevated serum cystatin C levels may promote venous thrombosis beyond reflecting impaired kidney function.

Impact of Interim Hospitalizations on Risk of Venous Thromboembolism (VTE) Recurrence: A Nested Case-Cohort Study

Abstract 1241 Background:Hospitalization (with or without surgery) is a major risk factor for incident venous thromboembolism (VTE); however, the contribution of interim hospitalization to risk of recurrent VTE is unknown. Objective:To estimate risk of recurrent VTE related to interim hospitalization by conducting a population-based longitudinal review of provider-linked detailed medical records. Methods:We performed a nested case-cohort study. The cohort consisted of all Olmsted County residents with incident VTE 1988–2000 and ≥1 day follow-up. Cases were cohort members with recurrent VTE. Subjects were followed for all interim hospitalizations and warfarin use from incident VTE until earliest of emigration, death, recurrent VTE, or 12/31/2005. Data were analyzed using Cox proportional hazards and time dependent covariates to test for the effects of interim hospitalization and prophylaxis on VTE recurrence, adjusting for gender and age at incident VTE. Analyses were limited to subjects who survived free of death and recurrent VTE for ≥ 6 months. Results:Of 1262 incident VTE events (cohort), there were 309 VTE recurrences (cases). We randomly sampled 272 subjects from the cohort and 163 cases. Of the random samples, 210 incident events and 83 cases survived ≥ 6 months free of death and recurrent VTE and form our analysis population. The rate of secondary (interim) prophylaxis was approximately 50% for both incident events and cases, and was not predictive of recurrence (p=0.73). Male gender and interim hospitalization were associated with increased VTE recurrence even after adjusting for age at incident VTE and use of secondary warfarin prophylaxis. The hazard of recurrent VTE was nearly 10-fold higher for subjects with interim hospitalization versus those with none (HR: 9.6; 95% CI: 6.6, 13.8); men had a 1.5-fold increased recurrence rate compared with women (HR: 1.5; 95% CI: 1.1, 2.1). Conclusions:Our results, for the first time, show the importance of interim hospitalization as a predictor of VTE recurrence. Disclosures:No relevant conflicts of interest to declare.

Risk assessment models for cancer‐associated venous thromboembolism

Venous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high-risk patients to prevent incident (first-time) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as well as ambulatory cancer patients receiving thalidomide or lenalidomide in combination with high-dose dexamethasone or chemotherapy, in the absence of contraindications to anticoagulation. However, the majority of cancer patients are ambulatory, and currently primary thromboprophylaxis is not recommended for these patients, even those considered at very high risk. In this concise review, the authors discuss risk stratification models that have been specifically developed to identify cancer patients at high risk for VTE, and thus might be useful in future studies designed to determine the potential benefit of primary thromboprophylaxis.

Coffee consumption and the risk of venous thromboembolism: the Tromsø study

Several studies have investigated the association between coffee consumption and cardiovascular disease, but little is known about coffee intake and the risk of venous thromboembolism (VTE). The aim of this prospective cohort study was to investigate the association between coffee consumption and the risk of incident VTE in a general population. Information about coffee consumption habits was obtained with a self-administered questionnaire in 26, 755 subjects, aged 25-97 years, who participated in the fourth survey of the Tromsø study (1994-1995). Incident VTE events were registered until the end of follow-up, 1 September 2007. There were 462 incident VTE events (1.60 per 1000 person-years, 95% confidence interval [CI] 1.46-1.75) during a median of 12.5 years of follow-up. A daily consumption of three to four cups was borderline associated (hazard ratio [HR] 0.70; 95% CI 0.48-1.02) and a daily consumption of five to six cups (HR 0.67; 95% CI 0.45-0.97) was significantly associated with reduced risk of VTE as compared with coffee abstainers in multivariable analysis adjusted for age, sex, body mass index (BMI), smoking status, physical activity, diabetes, history of cardiovascular disease and cancer. Similar risk estimates were found for provoked and unprovoked VTE, and in sex-stratified analyses. Our findings suggest a possible U-shaped relationship between coffee consumption and VTE, and that moderate coffee consumption may be associated with a reduced risk of VTE. However, more studies are needed to establish whether moderate coffee consumption is inversely associated with the risk of VTE.

Venous Thromboembolism in Uterine Cancer

To determine the incidence, time course, and risk factors associated with the development of venous thromboembolism (VTE) and the effect of VTE on survival in women with uterine cancer. Using the California Cancer Registry, the date, stage, and histology of all incident uterine cancer cases during 1993-1999 were identified. These cases were linked with the state's hospital discharge database, allowing identification of incident VTE events, after excluding cases with a previous history of VTE. Proportional hazards modeling was used to analyze the association of baseline risk factors with the development of VTE (<1 year), using major surgery as a time-dependent covariate. In a similar model for death (<2 years), VTE was included as a time-dependent covariate. Among 18,440 cases with uterine cancer, the 2-year cumulative incidence of VTE was 2.7%. The cumulative incidence varied from 1.5% among women with local stage disease to 10.5% among women with advanced disease. Among cases diagnosed with local disease, risk factors for the development of VTE within 1 year in localized disease included major surgery (hazard ratio [HR]=2.1, P<0.01), presence of long-term comorbidities (HR=2.9 for ≥3 comorbidities, P<0.0001), black race (HR=2.0, P<0.006), and sarcoma histology (HR=1.7, P<0.04). Among cases with regional disease, presence of comorbidities, black race, and sarcomas or nonendometrioid carcinomas were all associated with significantly higher risk of VTE. In advanced disease, the presence of any comorbidities and black race were the strongest predictors (HR=2.4 and 1.9, respectively). Women (aged<45 years) with advanced disease had a notably high 2-year incidence of 18%. Age did not predict VTE in localized and regional diseases. For all stages of cancer, development of VTE within 2 years was a significant predictor of decreased survival, and the magnitude of the risk was greatest among the cases diagnosed with localized disease (HR=6.1; confidence interval, 4.6-8.1). The incidence of VTE in women with uterine cancer was high, particularly in younger women with metastatic disease. The strong association between development of VTE and death suggests a close coupling between the biological aggressiveness of the cancer and the activation of thrombosis.

Joint Effects of Obesity and Body Height on the Risk of Venous Thromboembolism

The goal of this study was to investigate the combined effect of obesity and body height on the risk of venous thromboembolism (VTE) in a prospective population-based study. Personal characteristics, including measures of obesity and body height, were collected in 26 714 men and women, aged 25 to 97 years, who participated in the Tromsø Study in 1994 to 1995. Incident VTE events were registered through September 1, 2007. There were 461 incident VTE events during a median of 12.5 years of follow-up. A tall stature was associated with increased risk of VTE in normal-weight (body mass index <25 kg/m(2)) and obese (body mass index ≥30 kg/m(2)) men, but not in women. The combination of obesity and tall stature synergistically increased the risk of VTE in both sexes. Tall (≥182 cm), obese men had a 5-fold (multivariable hazard ratio 5.16; 95% CI 2.39 to 11.14) increased risk of VTE compared with normal-weight men with short (≤172 cm) stature. Tall (≥168 cm), obese women had an almost 3-fold (multivariable hazard ratio 2.89; 95% CI 1.31 to 6.35) increased risk of VTE compared with normal-weight, short (≤159 cm) women. The combination of obesity and a tall stature was associated with a substantially increased risk of VTE, especially in men, suggesting synergistic effects of obesity and height on risk of VTE in both sexes.

High-sensitivity C-reactive protein is not a risk factor for venous thromboembolism: the Tromso study

High-sensitivity C-reactive protein is associated with risk of arterial cardiovascular disease but conflicting results have been reported on its role in venous thromboembolic disease. The objective of our study was to investigate the association between high-sensitivity C-reactive protein levels and risk of future venous thromboembolism in a prospective cohort recruited from a general population. High-sensitivity C-reactive protein was measured in serum samples from 6,426 men and women, aged 25-84 years, recruited from the Tromsø Study in the period 1994-1995. Incident venous thromboembolism events (n=209) were registered during a median of 12.5 years of follow up. Cox's proportional hazards regression models were used to estimate age- and gender-and multivariable-adjusted hazard ratios with 95% confidence intervals for total venous thromboembolism, and for provoked and unprovoked venous thromboembolism by increasing levels of high-sensitivity C-reactive protein. There was no increased risk of venous thromboembolism per 1 standard deviation increase in high-sensitivity C-reactive protein (hazard ratio 1.08; 95% confidence interval 0.95-1.23) or across quartiles of high-sensitivity C-reactive protein (P for trend 0.6) in analyses adjusted for age and gender. Further adjustment for body mass index, smoking and diabetes did not alter the risk estimates. Moreover, high-sensitivity C-reactive protein was not associated with venous thromboembolism in either gender specific analysis or in separate analyses of provoked and unprovoked venous thromboembolism events. In this prospective study, serum levels of high-sensitivity C-reactive protein were not associated with future development of venous thromboembolism. Our findings do not suggest a causal role for C-reactive protein in the pathogenesis of venous thromboembolism.