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1.
Int J Obes (Lond) ; 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33935282

RESUMO

AIMS: To evaluate whether the association between plasma branched-chain amino acids (BCAA) and intrahepatic lipid (IHL) was affected by physical activity level. Furthermore, to investigate if a conventional exercise training program, a subcategory of physical activity, could lower plasma BCAA along with alterations in IHL content in patients with type 2 diabetes (T2DM) and people with nonalcoholic fatty liver (NAFL). METHODS: To investigate the effect of physical activity on the association between plasma BCAA and IHL content, linear regression analyses were performed in 1983 individuals from the Netherlands Epidemiology of Obesity (NEO) stratified by physical activity frequency. Furthermore, the effect of a 12-week supervised combined aerobic resistance-exercise program on plasma BCAA, insulin sensitivity (hyperinsulinemic-euglycemic clamp), and IHL (proton-magnetic resonance spectroscopy (1H-MRS)) was investigated in seven patients with T2DM, seven individuals with NAFL and seven BMI-matched control participants (CON). RESULTS: We observed positive associations between plasma valine, isoleucine and leucine level, and IHL content (1.29 (95% CI: 1.21, 1.38), 1.52 (95% CI: 1.43, 1.61), and 1.54 (95% CI: 1.44, 1.64) times IHL, respectively, per standard deviation of plasma amino acid level). Similar associations were observed in less active versus more active individuals. Exercise training did not change plasma BCAA levels among groups, but reduced IHL content in NAFL (from 11.6 ± 3.0% pre-exercise to 8.1 ± 2.0% post exercise, p < 0.05) and CON (from 2.4 ± 0.6% pre-exercise to 1.6 ± 1.4% post exercise, p < 0.05), and improved peripheral insulin sensitivity in NAFL as well by ~23% (p < 0.05). CONCLUSIONS: The association between plasma BCAA levels and IHL is not affected by physical activity level. Exercise training reduced IHL without affecting plasma BCAA levels in individuals with NAFL and CON. We conclude that exercise training-induced reduction in IHL content is not related to changes in plasma BCAA levels. TRIAL REGISTRATION: Trial registry number: NCT01317576.

2.
Am J Epidemiol ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33878166

RESUMO

Statistical correction for measurement error in epidemiologic studies is possible, provided that information about the measurement error model and its parameters are available. Such information is commonly obtained from a randomly sampled internal validation sample. It is however unknown whether randomly sampling the internal validation sample is the optimal sampling strategy. We conducted a simulation study to investigate various internal validation sampling strategies in conjunction with regression calibration. Our simulation study showed that for an internal validation study sample of 40% of the main study's sample size, stratified random and extremes sampling had a small efficiency gain over random sampling (10% and 12% decrease on average over all scenarios, respectively). The efficiency gain was more pronounced in smaller validation samples of 10% of the main study's sample size, i.e., a 31% and 36% decrease on average over all scenarios, for stratified random and extremes sampling, respectively. To mitigate the bias due to measurement error in epidemiologic studies, small efficiency gains can be achieved for internal validation sampling strategies other than random, but only when measurement error is non-differential. For regression calibration, the gain in efficiency is, however, at the cost of a higher percentage bias and lower coverage.

4.
J Cardiovasc Magn Reson ; 23(1): 46, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33866975

RESUMO

BACKGROUND: Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. METHODS: From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45-65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP < 130/80 mmHg and reference values for elevated BP subgroups (≥ 130/80 and < 140/90 mmHg; and ≥ 140/90 mmHg). Differences between groups were tested with independent samples t-test or ANOVA. Due to an oversampling of obese individuals in this study, PWV values are based on a weighted analysis making them representative of the general population. RESULTS: Normal mean PWV was 6.0 m/s [95% CI 5.8-6.1]. PWV increased with advancing age and BP categories (both p < 0.001). There was no difference between sex in normal PWV, however in the BP > 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants < 55 years old compared to participants ≥ 55 years, indicating an increasing variability of PWV with age. PWV upper limits were particularly elevated in participants ≥ 55 years old in the high blood pressure subgroups. CONCLUSION: This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population.

5.
Br J Haematol ; 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33748963

RESUMO

Glucocorticoid treatment increases venous thromboembolism (VTE) risk. Whether this is due to the medication or the underlying disease, or affects the risk of VTE recurrence, has been difficult to determine. The aim of our present study was to quantify the risk for first and recurrent VTE associated with oral glucocorticoids use, considering the underlying disease. A total of 2547 patients with VTE from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study were linked to the Dutch Pharmaceutical Statistics register. The risk of first VTE during periods of exposure with oral glucocorticoids was estimated by the self-controlled case series method and that of recurrent VTE was examined in a cohort design. The incidence rate ratio (IRR) of first VTE in the period of glucocorticoid treatment was 3·51 [95% confidence interval (CI) 2·55-4·80]. This IRR was 2·53 (95% CI 1·10-5·72) in the week before treatment started, 5·28 (95% CI 2·89-9·53) in the first 7 days of treatment, remained elevated afterwards and decreased to 1·55 (95% CI 0·85-3·12) after 6 months, as compared to unexposed periods. The hazard ratio for recurrence was 2·72 (95% CI 1·64-4·78) in treatment periods as compared with no treatment. The increased risk of VTE associated with oral glucocorticoid treatment is due to a combined effect of the treatment and the underlying disease, remaining high during the first months of prescription.

6.
BMC Med ; 19(1): 69, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33731105

RESUMO

BACKGROUND: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease. METHODS: We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions. RESULTS: We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures. CONCLUSIONS: Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.

7.
J Investig Med ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753535

RESUMO

Clinical research is a discipline prone to the use of technical terms that may be particularly at risk for misunderstanding given the complex interpretation that is required. In this century, what is happening with the word 'pragmatic' when describing a randomized controlled trial (RCT) with medicines deserves a public reflection. Explanatory trials are conducted in ideal conditions to assess the comparative efficacy of interventions and are useful to explain whether interventions work. Pragmatic trials are those conducted in a way that resembles usual clinical practice conditions to assess the comparative effectiveness of interventions in a manner directly applicable for decision-makers. This, however, did not prevent 36% of authors of placebo-controlled, or prelicensing trials to identify their medicines RCTs as pragmatic in the title of their articles. The current situation is such that scientific literature has accepted that 'pragmatic' can convey the original meaning-that obtained in trials mimicking usual clinical practice-and a distorted one-that is focused on streamlining any trial procedure. Those involved in clinical trials should emphasize the importance of precision in the use of terms when describing RCTs through standardized solutions when possible. Unless clinical trial stakeholders agree when it would be correct to label an RCT as pragmatic, in a short period of time the term will be in danger of becoming meaningless. It is suggested that the Enhancing the Quality and Transparency of Health Research (EQUATOR) network, the Consolidated Standards of Reporting Trials (CONSORT) group and the International Committee of Medical Journal Editors (ICMJE) could address this topic and provide a consensus way forward.

8.
Clin Nutr ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33593663

RESUMO

BACKGROUND & AIMS: Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (α-tocopherol, α-TOH) competitively reacts with lipid peroxyl radicals to mitigate oxidative damage, and forms oxidized vitamin E metabolites. Accordingly, we aimed to investigate the associations between α-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population. METHODS: This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. α-TOH metabolites in blood (α-TOH and α-CEHC-SO3) and urine [sulfate (SO3) and glucuronide (GLU) of both α-TLHQ (oxidized) and α-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS). Measures of glucose homeostasis (HOMA-B, HOMA-IR, Insulinogenic index and Matsuda index) were obtained from fasting and postprandial blood samples. Multivariable linear regression analyses were performed to assess the associations of α-TOH metabolites and measures of glucose homeostasis. RESULTS: We included 498 participants (45% men) with mean (SD) age of 55.8 (6.1) years who did not use glucose-lowering medication. While blood α-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (α-TLHQ-SO3/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher α-TLHQ-SO3 was associated with 0.92 (95% CI: 0.87, 0.97) fold lower HOMA-IR and 1.06 (1.01, 1.11) fold higher Matsuda index, respectively. Similar results were obtained for the urinary α-TLHQ to α-CEHC ratio as a measure of oxidized-over-enzymatic conversion of α-TOH. CONCLUSION: Higher urinary levels of oxidized α-TOH metabolites as well as higher oxidized-to-enzymatic α-TOH metabolite ratio, but not circulating α-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating α-TOH, estimates of the conversion of α-TOH might be informative in relation to health and disease.

9.
Blood ; 137(17): 2394-2402, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512453

RESUMO

Genetic risk score (GRS) analysis is a popular approach to derive individual risk prediction models for complex diseases. In venous thrombosis (VT), such type of analysis shall integrate information at the ABO blood group locus, which is one of the major susceptibility loci. However, there is no consensus about which single nucleotide polymorphisms (SNPs) must be investigated when properly assessing association between ABO locus and VT risk. Using comprehensive haplotype analyses of ABO blood group tagging SNPs in 5425 cases and 8445 controls from 6 studies, we demonstrate that using only rs8176719 (tagging O1) to correctly assess the impact of ABO locus on VT risk is suboptimal, because 5% of rs8176719-delG carriers do not have an increased risk of developing VT. Instead, we recommend the use of 4 SNPs, rs2519093 (tagging A1), rs1053878 (A2), rs8176743 (B), and rs41302905 (O2), when assessing the impact of ABO locus on VT risk to avoid any risk misestimation. Compared with the O1 haplotype, the A2 haplotype is associated with a modest increase in VT risk (odds ratio, âˆ¼1.2), the A1 and B haplotypes are associated with an âˆ¼1.8-fold increased risk, whereas the O2 haplotype tends to be slightly protective (odds ratio, âˆ¼0.80). In addition, although the A1 and B blood groups are associated with increased von Willebrand factor and factor VIII plasma levels, only the A1 blood group is associated with ICAM levels, but in an opposite direction, leaving additional avenues to be explored to fully understand the spectrum of biological effects mediated by ABO locus on cardiovascular traits.

12.
Metabolites ; 10(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256233

RESUMO

Metabolomics studies have seen a steady growth due to the development and implementation of affordable and high-quality metabolomics platforms. In large metabolite panels, measurement values are frequently missing and, if neglected or sub-optimally imputed, can cause biased study results. We provided a publicly available, user-friendly R script to streamline the imputation of missing endogenous, unannotated, and xenobiotic metabolites. We evaluated the multivariate imputation by chained equations (MICE) and k-nearest neighbors (kNN) analyses implemented in our script by simulations using measured metabolites data from the Netherlands Epidemiology of Obesity (NEO) study (n = 599). We simulated missing values in four unique metabolites from different pathways with different correlation structures in three sample sizes (599, 150, 50) with three missing percentages (15%, 30%, 60%), and using two missing mechanisms (completely at random and not at random). Based on the simulations, we found that for MICE, larger sample size was the primary factor decreasing bias and error. For kNN, the primary factor reducing bias and error was the metabolite correlation with its predictor metabolites. MICE provided consistently higher performance measures particularly for larger datasets (n > 50). In conclusion, we presented an imputation workflow in a publicly available R script to impute untargeted metabolomics data. Our simulations provided insight into the effects of sample size, percentage missing, and correlation structure on the accuracy of the two imputation methods.

13.
Ned Tijdschr Geneeskd ; 1642020 12 10.
Artigo em Holandês | MEDLINE | ID: mdl-33332045

RESUMO

Our view on causes of venous thrombosis changed drastically by the discovery of Factor V Leiden, since unlike other genetic causes of hereditary thrombophilia its prevalence is several percent. It led to major research activities, and the insight that thrombosis is a multicausal disease, invariably the result of an interplay of genetic and environmental factors. Another consequence was a hype of testing of thrombosis patients, and women before starting oral contraceptives. Factor V Leiden became the most performed diagnisticgenetic test worldwide. However, there was no medical rationale for this massive testing. In young women the absolute risk of thrombosis is so low, that enormous numbers of women would need to be tested to prevent one thrombotic event. And tests after a first event in patients were nearly always useless, since Factor V Leiden does not affect the risk of recurrence. It took decennia before the hype faded.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33347586

RESUMO

OBJECTIVE: We investigated the role of blood pressure, vessel wall stiffness [pulse wave velocity (PWV)] and subclinical atherosclerosis markers [carotid intima-media thickness (cIMT), popliteal vessel wall thickness (pVWT)] as mediators of the association of obesity with OA. METHODS: We used cross-sectional data from a subset of the population-based NEO study (n = 6334). We classified clinical hand and knee OA by the ACR criteria, and structural knee OA, effusion and bone marrow lesions on MRI (n = 1285). cIMT was assessed with ultrasonography. pVWT was estimated on knee MRI (n = 1285), and PWV by abdominal velocity-encoded MRIs (n = 2580), in subpopulations. Associations between BMI and OA were assessed with logistic regression analyses, adjusted for age, sex and education. Blood pressure, cIMT, pVWT and PWV were added to the model to estimate mediation. RESULTS: The population consisted of 55% women, with a mean (s.d.) age of 56(6) years. Clinical hand OA was present in 8%, clinical knee OA in 10%, and structural knee OA in 12% of participants. BMI was positively associated with all OA outcomes. cIMT partially mediated the association of BMI with clinical hand OA [10.6 (6.2; 30.5)%], structural knee OA [3.1 (1.9; 7.3)%] and effusion [10.8 (6.0; 37.6)%]. Diastolic blood pressure [2.1 (1.6; 3.0)%] minimally mediated the association between BMI and clinical knee OA. PWV and pVWT did not mediate the association between BMI and OA. CONCLUSIONS: cIMT and diastolic blood pressure minimally mediated the association of BMI with OA. This suggests that such mediation is trivial in the middle-aged population.

15.
Clin Infect Dis ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33249450

RESUMO

Controlled human infection (CHI) models for the novel coronavirus (SARS-CoV-2) have been proposed as a tool to accelerate the development of vaccines and drugs. Such models carry inherent risks. Participants may develop severe disease or complications after deliberate infection. Prolonged isolation may negatively impact their wellbeing. Through secondary infection of study personnel or participant household contacts, the experimental virus strain may cause a community outbreak. We identified risks associated with such a SARS-CoV-2 CHI model and assessed their likelihood and impact and propose strategies that mitigate these risks. In this report, we show that risks can be minimized with proper risk mitigation strategies; the residual risk however should be weighed carefully against the scientific and social values of such a CHI model.

16.
J Thromb Haemost ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217158

RESUMO

BACKGROUND: Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands. OBJECTIVE: This observational cohort study aimed to assess all-cause and cause-specific mortality in patients with hemophilia in the Netherlands between 2001-2018 and to compare mortality and life-expectancy with previous survival assessments from 1973 onwards. PATIENTS/METHODS: All 1066 patients with hemophilia who participated in a nationwide survey in 2001 were followed until July 2018. RESULTS: Information on 1031 individuals (97%) was available, of whom 142 (14%) deceased during follow-up. Compared with the general Dutch male population, mortality of patients with hemophilia was still increased (standardized mortality ratio: 1.4, 95% confidence interval: 1.2-1.7). Intracranial bleeding and malignancies were the most common causes of death. Estimated median life expectancy of patients with hemophilia was 77 years, six years lower than the median life expectancy of the general Dutch male population (83 years). Over the past 45 years, death rates of patients with hemophilia have consistently decreased, approaching the survival experience of the general population. Over the past decades, mortality due to human immunodeficiency virus and hepatitis C virus infections has decreased, death due to intracranial hemorrhages has increased and death due to ischemic heart disease has remained consistently low over time. CONCLUSIONS: Survival in patients with hemophilia in the Netherlands has improved over time but is still lower than that of the general population.

17.
Thromb Res ; 197: 172-178, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33221577

RESUMO

BACKGROUND: Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels. OBJECTIVES: To disentangle the role of genetic (sex, blood group) and acquired factors (comorbidities, body mass index, reduced kidney function, hormone use, and inflammation) in regulating von Willebrand factor antigen (VWF:Ag) and factor VIII activity (FVIII:C) levels in the normal population. METHODS: Analysis were performed in a large population sample (2923 individuals) from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), after exclusion of individuals with active cancer and women who were pregnant or within nine months postpartum. The increase of VWF:Ag and FVIII:C with age was evaluated by linear regression after the age of 40 years. Analyses were adjusted for acquired factors and stratified for sex and blood group. RESULTS: VWF:Ag and FVIII:C increased with age: increase per decade of age for VWF:Ag 18 IU/dL (95%CI 15-20) and for FVIII:C 12 IU/dL (95%CI 10-14). After adjustment for acquired factors, the increase per decade was 13 IU/dL (95%CI 10-16) for VWF:Ag and 9 IU/dL (95%CI 6-11) for FVIII:C. The stratified analysis for blood group showed higher increase in the non-O group, but these differences were annulled after adjustment for acquired factors. CONCLUSIONS: VWF:Ag and FVIII:C increase with age. Carriers of blood group non-O present a steeper increase of VWF:Ag and FVIII:C with age, that is mediated by acquired factors.

18.
PLoS One ; 15(11): e0242062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33196677

RESUMO

OBJECTIVE: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. METHODS: Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. RESULTS: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 ß = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 ß = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 ß = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 ß = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. INTERPRETATION: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses.

19.
J Thromb Haemost ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33174335

RESUMO

OBJECTIVE: This study aimed at evaluating the effect of thrombophilia on the risk of VTE in patients undergoing any type of orthopedic surgery. BACKGROUND: Patients undergoing orthopedic surgery are at high risk for venous thromboembolism (VTE). Whilst patients with thrombophilia have an increased risk of VTE, it is currently unclear whether there is a synergetic effect in patients with thrombophilia who undergo orthopedic surgery. METHODS: Data from a large population-based case-control study (the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis [MEGA] study) were used. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex and body mass index (BMI) (ORadj) were calculated for patients undergoing any orthopedic intervention. RESULTS: Of 4,721 cases and 5,638 controls, 263 cases and 94 controls underwent orthopedic surgery. Patients who had any orthopedic intervention in the year prior to the index date were at higher risk of VTE (ORadj 3.7; 95% CI, 2.9-4.8) than those who did not undergo any orthopedic surgery. There was an additionally increased risk in patients with factor V Leiden (OR 17.5, 95% CI 4.1-73.6), non-O blood group (OR 11.2; 95%CI 3.4-34.0) or elevated plasma levels of factor VIII (OR 18.6; CI 7.4-46.9) all relative to patients without these defects, not undergoing orthopedic surgery. CONCLUSIONS: Patients with factor V Leiden, high levels of factor VIII or blood group non-O were found to have a high risk of VTE after orthopedic surgery. Identification of these patients may enable individualized thromboprophylactic treatment, to efficiently reduce VTE risk.

20.
Thromb Res ; 197: 132-137, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33212380

RESUMO

BACKGROUND: Deep vein thrombosis (DVT) is a common multi-factorial disease with a partially understood aetiology. Although the roles of high factor (F)VIII and von Willebrand factor (VWF) levels are recognized, that of ADAMTS13 is still unclear. AIM: To assess the association between ADAMTS13 activity levels, VWF antigen (VWF:Ag) and FVIII coagulant activity (FVIII:C) levels and DVT. MATERIALS AND METHODS: 365 Italian DVT patients and 292 age- and sex-matched controls were considered. Plasma ADAMTS13 activity was measured using FRETS-VWF73 assay. VWF:Ag and FVIII:C were measured using immunoassay and one-stage clotting assay (ACL TOP analyzer), respectively. Quartile analyses were performed to evaluate the individual association between ADAMTS13 activity, VWF:Ag, FVIII:C and DVT. The combined effect of high VWF levels (> 4th quartile) and low ADAMTS13 levels (< 1st quartile) was evaluated using binary variables. All models were age- and sex-adjusted. Estimated risks were reported as Odds ratio (OR) with 95% confidence intervals (CI). RESULTS: ADAMTS13 activity was lower in DVT patients (94% vs. 98% of controls). Patients with an ADAMTS13 activity <1st quartile (86%) showed a 1.6-fold increased risk of DVT (95%CI, 1.05-2.55). The combination of low ADAMTS13 activity and high VWF:Ag levels was associated with a 15-fold increased risk (95%CI, 7.80-33.80). VWF:Ag and FVIII:C were associated to DVT with a dose-response relationship. CONCLUSIONS: ADAMTS13 activity < 86% was associated with a moderate risk of DVT. The co-presence of low ADAMTS13 activity and high VWF levels resulted in a strong synergistic effect on DVT risk. The association of VWF:Ag and FVIII:C with DVT was confirmed.

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