Homocysteine Is Associated With Future Venous Thromboembolism in 2 Prospective Cohorts of Women.
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ABSTRACT:
SUBMITTER: Aday AW
PROVIDER: S-EPMC8222168 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Red cell distribution width (RDW) is associated with venous thromboembolism (VTE), but the underlying mechanism(s) is unclear. Iron deficiency is associated with high RDW, and studies suggest an association between iron deficiency and VTE. To assess whether iron deficiency is a risk factor for VTE that explains the association between RDW and VTE, we conducted a nested case-control study of 390 patients with VTE and 802 age- and sex-matched controls selected from the population-based cohort of the Tromsø Study. Physical measurements and blood samples were collected from 1994 to 1995. Logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE by RDW, hepcidin, and ferritin light chain (FtL). RDW was inversely associated with hepcidin, FtL, and hemoglobin. The risk of VTE increased linearly across categories of higher plasma hepcidin levels. Participants with hepcidin in the highest quartile had an OR for VTE of 1.32 (95% CI, 1.00-2.42), and those in the >90% percentile had an OR for VTE of 1.66 (95% CI, 1.14-2.42) compared with the reference group (quartiles 2 and 3). The risk estimates remained similar after adjustment for C-reactive protein. The risk of VTE increased by categories of higher RDW and was strengthened after inclusion of hepcidin and FtL in the multivariable model. Our findings reject the hypothesis that iron deficiency explains the association between RDW and VTE and suggest, in contrast, that high body iron levels might increase the risk of VTE.
| S-EPMC5998931 | biostudies-literature
Project description:BackgroundVenous thromboembolism is a common complication of cancer, but the risk of developing venous thromboembolism varies greatly among individuals and depends on numerous factors, including type of cancer. We aimed to develop and externally validate a clinical prediction model for cancer-associated venous thromboembolism.MethodsWe used data from the prospective Vienna Cancer and Thrombosis Study (CATS) cohort (n=1423) to select prognostic variables for inclusion in the model. We then validated the model in the prospective Multinational Cohort Study to Identify Cancer Patients at High Risk of Venous Thromboembolism (MICA) cohort (n=832). We calculated c-indices to show how the predicted incidence of objectively confirmed venous thromboembolism at 6 months compared with the cumulative 6-month incidences observed in both cohorts.FindingsTwo variables were selected for inclusion in the final clinical prediction model: tumour-site risk category (low or intermediate vs high vs very high) and continuous D-dimer concentrations. The multivariable subdistribution hazard ratios were 1·96 (95% CI 1·41-2·72; p=0·0001) for high or very high versus low or intermediate and 1·32 (95% CI 1·12-1·56; p=0·001) per doubling of D-dimer concentration. The cross-validated c-indices of the final model were 0·66 (95% CI 0·63-0·67) in CATS and 0·68 (0·62-0·74) in MICA. The clinical prediction model was adequately calibrated in both cohorts.InterpretationAn externally validated clinical prediction model incorporating only one clinical factor (tumour-site category) and one biomarker (D-dimer) predicted the risk of venous thromboembolism in ambulatory patients with solid cancers. This simple model is a considerable improvement on previous models for predicting cancer-associated venous thromboembolism, and could aid physicians in selection of patients who will likely benefit from thromboprophylaxis.FundingAustrian Science Fund, Austrian National Bank Memorial Fund, and participating hospitals.
| S-EPMC7338218 | biostudies-literature
Project description:PurposeVenous thromboembolism (VTE) is a leading cause of death among patients with cancer. The Khorana score was developed for assessing the risk of VTE in outpatients with cancer receiving chemotherapy, but its accuracy in identifying patients at high risk has been questioned. The aim of this study was to develop and validate a clinical-genetic score that improves the assessment of VTE risk in oncology outpatients within 6 months of diagnosis.MethodsThe new score was developed using the data of 364 outpatients belonging to the Spanish ONCOTHROMB 12-01 population. In this cohort, clinical data associated with the risk of VTE were collected at the time of diagnosis, including the Khorana score. These patients were also genotyped for the 51 genetic variants known to be associated with VTE. Multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to VTE risk, allowing a clinical-genetic risk score (the ONCOTHROMB score) to be developed. The Khorana and the ONCOTHROMB scores were then compared via the area under the receiver operating characteristic curve (AUC), calibration, and the number of patients needed to treat. The new score was then validated in a study of 263 patients in the Vienna Cancer and Thrombosis Study population.ResultsNine genetic variants, tumor site, TNM stage, and a body mass index of > 25 kg/m2 were found to be associated with VTE and were used to build the ONCOTHROMB score, which better predicted the overall risk of VTE than did the Khorana score (AUC, 0.781 v 0.580; P < .001). Similar AUC results were recorded in the validation study the Vienna Cancer and Thrombosis Study cohort involving patients with the same type of tumor (AUC for the ONCOTHROMB score v the Khorana score: 0.686 v 0.577; P < .001) and with all type of tumors (AUC for the ONCOTHROMB score v the Khorana score: 0.720 v 0.561; P < .0001).ConclusionThe ONCOTHROMB score for VTE risk in outpatients with cancer, which takes into account both clinical and genetic variables, better identifies patients who might benefit from primary thromboprophylaxis than does the Khorana score.
| S-EPMC10414737 | biostudies-literature
Project description:BackgroundSeverely ill patients with SARS-CoV-2 have an increased risk of venous thromboembolism (VTE) i.e., deep vein thrombosis and pulmonary embolism. However, the VTE risk in patients with mild and moderate COVID-19, hospitalized or managed at home, remain uncertain. The aims of this study were to assess the rate and the risk factors symptomatic VTE, in patients with mild and moderate COVID-19 and to compare them to a cohort of similar patients without COVID-19.MethodsPatients presenting to the emergency department (ED) of participating centers for confirmed or probable mild or moderate COVID-19 and not having acute VTE were included. This COVID-19 cohort was retrospectively compared to a prospective cohort of similar ED patients using propensity score matching. The main outcome was the rate of symptomatic VTE within the 28 days after ED presentation.ResultsA total of 2292 patients were included in the COVID-19 cohort. The 28-day incidence of symptomatic VTE was 1.3% (n = 29/2292, 95%CI: 0.9 to 1.8), 2.3% (n = 20/866, 95%CI: 1.5 to 3.5) in moderate COVID-19 patients and 0.6% (n = 9/1426; 95%CI: 0.3 to 1.2) in mild COVID-19 patients managed as outpatients. An age over 65 years and hospitalization were independent risk factors of VTE. After adjustment, patients in the COVID-19 cohort had an absolute increase in over symptomatic VTE risk of +1.69% (95%CI, 0.88 to 2.51) versus patients in the comparison cohort (n = 1539).ConclusionsPatients with moderate COVID-19 presenting to the ED had a high risk of subsequent VTE.Trial registrationEthics committee of the CHU of Angers (N°2020/87).
| S-EPMC8498792 | biostudies-literature
Project description:BACKGROUND:Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. METHODS AND RESULTS:We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria ?30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well. CONCLUSIONS:Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.
| S-EPMC3520022 | biostudies-literature
Project description:ObjectiveTo prospectively assess the incidence of both symptomatic and asymptomatic venous thromboembolism (VTE) in patients with amyotrophic lateral sclerosis (ALS) and to identify risk factors.MethodsFifty outpatients with ALS were recruited consecutively and prospectively evaluated with bilateral venous duplex ultrasonography (VDU) of the proximal leg veins at enrollment and 6 and 12 months. The primary outcome measure was clinically important VTE, defined as asymptomatic proximal deep vein thrombosis (DVT) by screening VDU, symptomatically proven DVT or pulmonary embolism (PE), or fatal PE. For each patient, person-days of follow-up were recorded from enrollment until the date of VTE, death, loss to follow-up, or final 12-month visit.ResultsDuring the 1-year follow-up period, VTE was detected in 4 patients (1 symptomatic DVT, 1 symptomatic PE, and 2 asymptomatic DVTs) over 13,011 person-days of follow-up, representing an 11.2% 1-year incidence. Subjects with leg-onset ALS or significant leg weakness had a 1-year VTE incidence rate of 35.8% and 35.5%, respectively. VTE risk was significantly increased for those patients with decreased lower extremity Revised ALS Functional Rating Scale subscore (p = 0.03), decreased Lower Extremity Activity Scale score (p = 0.02), and decreased average lower limb Medical Research Council scale strength score (p = 0.03).ConclusionsOur data suggest that clinically important VTE is common in patients with ALS, particularly those with leg weakness and reduced mobility. Given these results, the potential benefits of routine VTE screening and primary prophylaxis in high-risk patients with ALS with leg weakness should be explored in future studies. In the meantime, physicians should have a low threshold for considering VTE in patients with ALS with leg weakness.
| S-EPMC4032202 | biostudies-literature
Project description:ObjectiveTo characterize risk factors of venous thromboembolism (VTE) and to examine effects of VTE on survival of women with cervical cancer.MethodsThis is a retrospective study examining consecutive stage I-IV cervical cancer cases diagnosed between 2000 and 2014. Cumulative risk of VTE after cervical cancer diagnosis was evaluated by a time-dependent analysis, expressing adjusted-hazard ratio [HR] and 95% confidence interval [CI]. Survival analysis was performed to determine independent risk factors for progression-free survival (PFS) and disease-specific overall survival (OS).ResultsVTE was recorded in 98 (12.3%, 95%CI 11.6-22.8) out of 798 cases with 1-, 2-, and 5-year cumulative incidences after cervical cancer diagnosis being 8.4%, 11.3%, and 18.7%, respectively. On multivariable analysis, advanced-stage disease (2-year cumulative risk, distant metastatic disease 44.8% [HR 4.13, 95%CI 1.06-10.7, P=0.003], and locally-advanced disease 13.4% [HR 2.46, 95%CI 1.17-4.43, P=0.004]) were independently associated with increased risk of VTE compared to early-stage disease (stage IA1-IB1 4.1%). In addition, low albumin level (HR per unit change, 0.59, 95%CI 0.40-0.85, P=0.005) and chemotherapy treatment (HR 2.46, 95%CI 1.30-4.66, P=0.006) remained independent risk factors associated with increased risk of VTE. On univariate analysis, VTE was significantly associated with decreased PFS (5-year rates, 22.3% versus 68.7%, P<0.001) and OS (5-year rates, 55.1% versus 90.0%, P<0.001). On multivariable analysis, VTE remained an independent prognostic factor associated with decreased PFS (HR 1.95, 95%CI 1.43-2.67, P<0.001) and OS (HR 3.54, 95%CI 2.04-6.13, P<0.001).ConclusionVTE represents aggressive tumor behavior and poor patient condition, and is an independent prognostic factor for decreased survival in women with cervical cancer.
| S-EPMC7643406 | biostudies-literature
Project description:Essentials The association of venous thromboembolism (VTE) with subsequent physical function remains unclear. We prospectively evaluated this relationship among women from the Nurses' Health Studies. We found a decline in physical function over four years in women with incident VTE. This decline was somewhat greater among women specifically reporting a pulmonary embolism. Background Physical function is integral to healthy aging; however, limited research has examined the association of venous thromboembolism(VTE) with subsequent physical function. Objectives To prospectively evaluate the relationship between VTE and decline in physical function among 80 836 women from the Nurses' Health Study(NHS), ages 46-72 in 1992, and 84 304 women from the Nurses' Health Study II(NHS II), ages 29-48 in 1993. Methods Physical function was measured by the Medical Outcomes Short Form-36 physical function scale, administered every 4 years. We compared change in physical function for women with vs. without an incident VTE in each 4-year follow-up period using multivariable linear regression. Results We observed a decline in physical function over 4 years when comparing women with vs. those without incident VTE in both older (NHS) and younger (NHS II) women (multivariable-adjusted mean difference NHS, -6.5 points [95% CI -7.4, -5.6] per 4 years; NHS II, -3.8 [95% CI -5.6, -2.0]). This difference appeared greater among women specifically reporting a pulmonary embolism (NHS, -7.4 [95% CI -8.7, -6.1]; NHS II, -4.8 [95% CI -6.8, -2.8]), and was equivalent to 6.2 years of aging. Whereas longer-term slopes of physical function decline following a VTE were not different from the slopes of decline in women without a VTE, the absolute level of physical function of women with VTE was worse at the end of follow-up compared to women without VTE. Conclusions In this prospective cohort, incident VTE was strongly associated with an acute decline in physical function. These results suggest it may be clinically important to consider approaches to ameliorating functional deficits shortly after VTE diagnosis.
| S-EPMC6286689 | biostudies-literature
Project description:ObjectiveTo identify risk factors for venous thromboembolism (VTE) and to examine the association of VTE and survival in women with uterine carcinosarcoma.MethodsThis multicenter retrospective study examined 906 women who underwent primary surgical treatment for stage I-IV uterine carcinosarcoma. Time-dependent analyses were performed for cumulative incidence of VTE after surgery on multivariate models.ResultsThere were 72 (7.9%) women who developed VTE after surgery with 1-, 2-, and 5-year cumulative incidences being 5.1%, 7.3%, and 10.2%, respectively. On multivariate analysis, older age (hazard ratio [HR] per year 1.03, P=0.012), non-Asian race (HR 6.28, P<0.001), large body habitus (HR per kg/m2 1.04, P=0.014), residual disease at surgery (HR 3.04, P=0.003), tumor size ≥5cm (HR 2.73, P=0.003), and stage IV disease (HR 2.12, P=0.025) were independently associated with increased risk of developing VTE. A risk pattern analysis identified that obese Non-Asian women with large tumors (13.7% of population) had the highest incidence of VTE (2-year cumulative rate, 26.1%) whereas Asian women with no residual disease (47.1% of population) had the lowest (2-year cumulative rate, 1.6%) (P<0.001). Presence of carcinoma/sarcoma in metastatic sites was significantly associated with increased risk of VTE compared to carcinoma alone (2-year rates, 31.2% versus 8.4%, P=0.049). VTE was independently associated with decreased progression-free survival on multivariate models (5-year rates, 24.9% versus 47.2%, HR 1.46, 95%CI 1.05-2.04, P=0.026).ConclusionOur study suggests that VTE represents a surrogate marker of aggressive tumor behavior and diminished patient condition in uterine carcinosarcoma; obese Non-Asian women with large tumors carry a disproportionally high risk of VTE, suggesting that long-term prophylaxis may benefit this population.
| S-EPMC7529359 | biostudies-literature
Project description: Not available
| S-EPMC1895668 | biostudies-literature