scholarly journals Plasma levels of growth differentiation factor 15 are associated with future risk of venous thromboembolism

Blood ◽  
2020 ◽  
Vol 136 (16) ◽  
pp. 1863-1870
Author(s):  
Ellen-Sofie Hansen ◽  
Kristian Hindberg ◽  
Nadezhda Latysheva ◽  
Pål Aukrust ◽  
Thor Ueland ◽  
...  

Abstract Growth differentiation factor 15 (GDF-15), a marker of inflammation and oxidative stress, has emerged as a biomarker for arterial cardiovascular disease. However, the association between GDF-15 and venous thromboembolism (VTE) remains uncertain. We therefore investigated the association between plasma GDF-15 levels and future risk of incident VTE and explored the potential of a causal association using Mendelian randomization (MR). We conducted a population-based nested case-control study comprising 416 VTE patients and 848 age- and sex-matched controls derived from the Tromsø Study. Logistic regression was used to calculate odds ratios (ORs) for VTE across GDF-15 quartiles. For the MR, we used data from the International Network on Venous Thrombosis (INVENT) consortium to examine whether single nucleotide polymorphisms (SNPs) associated with GDF-15 levels with genome-wide significance were related to VTE. We found that the ORs for VTE increased across GDF-15 quartiles (Ptrend = .002). Participants with GDF-15 values in the highest quartile (≥358 pg/mL) had an OR for VTE of 2.05 (95% confidence interval, 1.37-3.08) compared with those with GDF-15 in the lowest quartile (<200 pg/mL) in the age- and sex-adjusted model. ORs remained essentially the same after further adjustment for body mass index, smoking, hormone therapy, physical activity, and C-reactive protein. Similar results were obtained for provoked/unprovoked events, deep vein thrombosis, and pulmonary embolism. GDF-15 levels, as predicted by the SNPs, were not associated with VTE in MR. Our results indicate that high GDF-15 levels are associated with increased risk of VTE, but MR suggests that this association is not causal.

2019 ◽  
Vol 120 (01) ◽  
pp. 156-167 ◽  
Author(s):  
Shih-Yi Lin ◽  
Yun-Lung Chang ◽  
Hung-Chieh Yeh ◽  
Cheng-Li Lin ◽  
Chia-Hung Kao

Abstract Background The risk of venous thromboembolism (VTE) in generally ill patients, both under outpatient and inpatient care, following blood transfusion has not been determined. Methods This retrospective population-based cohort study was conducted using the National Health Insurance Research Database. We studied patients who received blood transfusion, defined as red blood cell transfusion of any type, from January 1, 2000 to December 31, 2011. The index date was defined as the date of blood transfusion. The primary outcome was VTE. Propensity score matching and Cox proportional hazard models were used. Results A total of 41,866 patients who underwent blood transfusion and 41,866 matched controls were studied. Generally, the blood transfusion cohort has 2.98 times higher risk of VTE than the control cohort (95% confidence interval [CI] = 1.23–7.22). The blood transfusion cohort had respectively 1.99 and 1.64 times higher risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) compared with the control cohort (DVT, 95% CI = 1.65–2.41; PE, 95% CI = 1.19–2.26). Patients in the blood transfusion cohort who did not use warfarin were 1.95 times more likely to develop VTE than those in the control cohort (adjusted hazard ratio [HR]: 1.95, 95% CI = 1.65–2.31). Patients in the blood transfusion cohort were 1.74 times more likely to die than those in the control cohort (adjusted HR: 1.74, 95% CI = 1.48–2.05). Conclusion Blood transfusion is associated with an increased risk of VTE. The risk of VTE decreased in those who took warfarin.


2017 ◽  
Vol 176 (5) ◽  
pp. 625-634 ◽  
Author(s):  
Gunhild Lerstad ◽  
Ellen E Brodin ◽  
Johan Svartberg ◽  
Rolf Jorde ◽  
Jan Brox ◽  
...  

ObjectiveThe relationship between serum levels of calcium, parathyroid hormone (PTH) and risk of venous thromboembolism (VTE) has not been addressed in population-based cohorts. We investigated the associations between serum levels of calcium and PTH, with future risk of VTE in a general adult population.DesignPopulation-based cohort.MethodsA total of 27 712 subjects (25–87 years) who participated in Tromsø 4 (1994–1995) and Tromsø 5 (2001–2002) surveys were included in the study, and total calcium and PTH were measured in 27 685 and 8547 subjects respectively. Incident VTE was recorded through December 31, 2012. Cox-regression models with calcium and PTH as time-varying exposures were used to calculate hazard ratios (HR) of VTE by quartiles of calcium and PTH. Quartiles of calcium and PTH were also combined to assess the effect of discordants of both PTH and calcium (e.g. highest and lowest quartiles of both calcium and PTH) on VTE risk using the middle two quartiles as reference.ResultsThere were 712 VTEs during 15.0 years of median follow-up. Serum levels of calcium and PTH were not associated with risk of VTE. However, subjects with discordant high serum levels of both calcium and PTH (calcium ≥2.45 mmol/L and PTH ≥4.0 pmol/L) had increased risk of VTE compared to those in subjects with normal calcium and PTH (multivariable HR: 1.78, 95% CI: 1.12–2.84).ConclusionsSerum levels of calcium and PTH separately were not associated with future risk of VTE, but subjects with high levels of both calcium and PTH had increased risk of VTE compared to those in subjects with normal levels.


2015 ◽  
Vol 113 (01) ◽  
pp. 185-192 ◽  
Author(s):  
Chun-Cheng Wang ◽  
Cheng-Li Lin ◽  
Guei-Jane Wang ◽  
Chiz-Tzung Chang ◽  
Fung-Chang Sung ◽  
...  

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.


2012 ◽  
Vol 107 (03) ◽  
pp. 485-493 ◽  
Author(s):  
Sigrid K. Brækkan ◽  
Ida J. Hansen-Krone ◽  
John-Bjarne Hansen ◽  
Kristin F. Enga

SummaryEmotional states of depression and loneliness are reported to be associated with higher risk and optimism with lower risk of arterial cardiovascular disease (CVD) and death. The relation between emotional states and risk of venous thromboembolism (VTE) has not been explored previously. We aimed to investigate the associations between self-reported emotional states and risk of incident VTE in a population-based, prospective study. The frequency of feeling depressed, lonely and happy/optimistic were registered by self-administered questionnaires, along with major co-morbidities and lifestyle habits, in 25,964 subjects aged 25–96 years, enrolled in the Tromsø Study in 1994–1995. Incident VTE-events were registered from the date of inclusion until September 1, 2007. There were 440 incident VTE-events during a median of 12.4 years of follow-up. Subjects who often felt depressed had 1.6-fold (95% CI:1.02–2.50) higher risk of VTE compared to those not depressed in analyses adjusted for other risk factors (age, sex , body mass index, oes-trogens), lifestyle (smoking, alcohol consumption, educational level) and co-morbidities (diabetes, CVD, and cancer). Often feeling lonely was not associated with VTE. However, the incidence rate of VTE in subjects who concurrently felt often lonely and depressed was higher than for depression alone (age-and sex-adjusted incidence rate: 3.27 vs. 2.21). Oppositely, subjects who often felt happy/optimistic had 40% reduced risk of VTE (HR 0.60, 95% CI: 0.41–0.87). Our findings suggest that self-reported emotional states are associated with risk of VTE. Depressive feelings were associated with increased risk, while happiness/ optimism was associated with reduced risk of VTE.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Mengkun Chen ◽  
Ning Ding ◽  
Lena Mathews ◽  
Ron C Hoogeveen ◽  
Christie M Ballantyne ◽  
...  

Introduction: Growth differentiation factor 15 (GDF-15) is a marker of oxidative stress and inflammation and has been associated with several cardiovascular disease (CVD) phenotypes. However, conflicting results have been reported regarding the association of GDF-15 with incident atrial fibrillation (AF) in the general population. Hypotheses: Higher GDF-15 level is associated with increased risk of incident AF independent of potential confounders. Methods: In 10,101 White and Black ARIC participants (mean age 60 years and 20.9% Blacks) free of AF at baseline (1993-95), we quantified the association of GDF-15 and incident AF using three Cox proportional hazards models. GDF-15 was measured by SOMA scan assay. AF was defined by hospitalizations with AF diagnosis or death certificates (ICD-9 codes: 427.31-427.32; ICD-10 codes: I48.x) or AF diagnosis by ECG at subsequent ARIC visits. Results: There were 2165 cases of incident AF over a median follow-up of 20.7 years (incidence rate 12.1 cases/1,000 person-years). After adjusting for demographic characteristics and cardiovascular risk factors, log GDF-15 was significantly associated with incident AF (hazard ratio 1.42 (1.25-1.63) for top vs. bottom quartile) (Model 1 in Table ). The result was robust even further adjusting for history of other CVD phenotypes and cardiac markers (Models 2 and 3 in Table ). In Model 3, quartiles of high-sensitive cardiac troponin T (hs-cTnT) did not demonstrate significant associations with incident AF. Conclusions: In community-based population, elevated GDF-15 level was independently and robustly associated with incident AF (even more strongly than troponin). These results suggest the involvement of GDF-15 in the development of AF and the potential of GDF-15 as a risk marker to identify individuals at high risk of AF.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jingyi Gong ◽  
Zsofia Drobni ◽  
Raza Alvi ◽  
Sean Murphy ◽  
Sarah Hartmann ◽  
...  

Introduction: Immune checkpoint inhibitors (ICI) lead to immune activation, increased inflammation and cancer cell death. Both immune activation and inflammation are critical pathobiological drivers for venous thromboembolism (VTE). There are no robust data testing the effect of ICIs on the risk of developing VTE. Methods: This is a retrospective study of 2854 patients who received ICIs at Massachusetts General Hospital, Boston, MA. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard criteria. A case-crossover design was applied with an “at-risk period” defined as the two-year period after and the “control period” as the two years prior to treatment. Incidence rate ratio (IRR) was calculated using Poisson’s regression. Results: Immune checkpoint inhibitor use increased VTE risk by 1.84-fold from 4.85 per 100-person years to 8.91 per 100 person-years (IRR 1.84, 95% confidence interval: 1.54 - 2.19, p <0.001). Of the individual components, there was a 2.44-fold increase in DVT risk (2.30 to 5.58 per 100 person-years) and 1.68-fold increase in PE risk (2.96 to 5.00 per 100 person-years). Comparing patients with and without a VTE event, those with a VTE event after ICI initiation had a higher rate of prior VTE, lung cancer, urothelial cancer, and a higher platelet count and white blood cell count at baseline. At 6 months post ICI initiation, 165 (8.6%) patients had a VTE event and of these patients 136 (7.1%) had no prior VTE. Conclusions: Patients with cancer treated with ICIs are at increased risk of developing VTE. Whether prophylaxis for VTE among patients starting an ICI reduces this risk is unclear.


TH Open ◽  
2019 ◽  
Vol 03 (01) ◽  
pp. e50-e57
Author(s):  
Vânia Morelli ◽  
Joakim Sejrup ◽  
Birgit Småbrekke ◽  
Ludvig Rinde ◽  
Gro Grimnes ◽  
...  

AbstractStroke is associated with a short-term increased risk of subsequent venous thromboembolism (VTE). It is unclear to what extent this association is mediated by stroke-related complications that are potential triggers for VTE, such as immobilization and infection. We aimed to investigate the role of acute stroke as a trigger for incident VTE while taking other concomitant VTE triggers into account. We conducted a population-based case-crossover study with 707 VTE patients. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios with 95% confidence intervals (CIs) for VTE according to triggers. Stroke was registered in 30 of the 707 (4.2%) hazard periods and in 6 of the 2,828 (0.2%) control periods, resulting in a high risk of VTE, with odds ratios of 20.0 (95% CI: 8.3–48.1). After adjustments for immobilization and infection, odds ratios for VTE conferred by stroke were attenuated to 6.0 (95% CI: 1.6–22.1), and further to 4.0 (95% CI: 1.1–14.2) when other triggers (major surgery, red blood cell transfusion, trauma, and central venous catheter) were added to the regression model. A mediation analysis revealed that 67.8% of the total effect of stroke on VTE risk could be mediated through immobilization and infection. Analyses restricted to ischemic stroke yielded similar results. In conclusion, acute stroke was a trigger for VTE, and the association between stroke and VTE risk appeared to be largely mediated by immobilization and infection.


2019 ◽  
Vol 119 (06) ◽  
pp. 962-970 ◽  
Author(s):  
Magdalena Johansson ◽  
Lars Johansson ◽  
Maria Wennberg ◽  
Marcus Lind

Background The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible association. Objective This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately. Methods We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE. Results The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00–1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06–1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (p for trend 0.02), with a HR of 1.22 (95% CI, 1.01–1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07–1.59). In women, there were no significant associations. Conclusion High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.


Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3911-3917 ◽  
Author(s):  
Grace H. Ku ◽  
Richard H. White ◽  
Helen K. Chew ◽  
Danielle J. Harvey ◽  
Hong Zhou ◽  
...  

Abstract A population-based cohort was used to determine the incidence and risk factors associated with development of venous thromboembolism (VTE) among Californians diagnosed with acute leukemia between 1993 to 1999. Principal outcomes were deep vein thrombosis in both the lower and upper extremities, pulmonary embolism, and mortality. Among 5394 cases with acute myelogenous leukemia (AML), the 2-year cumulative incidence of VTE was 281 (5.2%). Sixty-four percent of the VTE events occurred within 3 months of AML diagnosis. In AML patients, female sex, older age, number of chronic comorbidities, and presence of a catheter were significant predictors of development of VTE within 1 year. A diagnosis of VTE was not associated with reduced survival in AML patients. Among 2482 cases with acute lymphoblastic leukemia (ALL), the 2-year incidence of VTE in ALL was 4.5%. Risk factors for VTE were presence of a central venous catheter, older age, and number of chronic comorbidities. In the patients with ALL, development of VTE was associated with a 40% increase in the risk of dying within 1 year. The incidence of VTE in acute leukemia is appreciable, and is comparable with the incidence in many solid tumors.


TH Open ◽  
2018 ◽  
Vol 02 (04) ◽  
pp. e428-e436 ◽  
Author(s):  
Amaia Iñurrieta ◽  
José Pedrajas ◽  
Manuel Núñez ◽  
Luciano López-Jiménez ◽  
Alba Velo-García ◽  
...  

Background The ideal duration of anticoagulant therapy in elderly patients with unprovoked venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the rate and severity of pulmonary embolism (PE) recurrences versus major bleeding beyond the third month of anticoagulation in patients >75 years with a first episode of unprovoked VTE. Results As of September 2017, 7,830 patients were recruited: 5,058 (65%) presented with PE and 2,772 with proximal deep vein thrombosis (DVT). During anticoagulant therapy beyond the third month (median, 113 days), 44 patients developed PE recurrences, 36 developed DVT recurrences, 101 had major bleeding, and 241 died (3 died of recurrent PE and 19 of bleeding). The rate of major bleeding was twofold higher than the rate of PE recurrences (2.05 [95% confidence interval, CI: 1.68–2.48] vs. 0.90 [95% CI: 0.66–1.19] events per 100 patient-years) and the rate of fatal bleeding exceeded the rate of fatal PE events (0.38 [95% CI: 0.24–0.58] vs. 0.06 [95% CI: 0.02–0.16] deaths per 100 patient-years). On multivariable analysis, patients who had bled during the first 3 months (hazard ratio [HR]: 4.32; 95% CI: 1.58–11.8) or with anemia at baseline (HR: 1.87; 95% CI: 1.24–2.81) were at increased risk for bleeding beyond the third month. Patients initially presenting with PE were at increased risk for PE recurrences (HR: 3.60; 95% CI: 1.28–10.1). Conclusion Prolonging anticoagulation beyond the third month was associated with more bleeds than PE recurrences. Prior bleeding, anemia, and initial VTE presentation may help decide when to stop therapy.


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