Association Between Genetic Predictors for C-Reactive Protein and Venous Thromboembolism With Severe Adverse Coronavirus Disease 2019 Outcomes.
Ontology highlight
ABSTRACT: Design
Retrospective cohort study.Setting
U.K. Biobank.Patients or subjects
U.K. Biobank participants with European ancestry who were recorded to have a positive polymerase chain reaction test result for severe acute respiratory syndrome coronavirus 2 between March 16, 2020, and August 14, 2020.Interventions
Not applicable.Measurements and main results
We constructed separate genetic risk scores for C-reactive protein and venous thromboembolism consisting of 56 and 37 genetic variants that have been significantly associated with venous thromboembolism and C-reactive protein, respectively. Among 1,126 individuals who were diagnosed with coronavirus disease 2019, 48% had a coronavirus disease 2019-related hospitalization, 16% received critical care support, 10% had critical respiratory support, and 21% died from coronavirus disease 2019. Genetic predisposition to high C-reactive protein concentrations was marginally associated with a lower risk of death from coronavirus disease 2019 (odds ratio, 0.85; 95% CI, 0.73-1.00; p = 0.05). No other associations were significant.Conclusions
Our results do not support associations between polygenic risk for elevated blood C-reactive protein concentrations or venous thromboembolism and severe coronavirus disease 2019 health outcomes. Thus, considering genetic predisposition associated with C-reactive protein concentrations or venous thromboembolism risk is not meaningful for predicting severe coronavirus disease 2019 health outcomes.
SUBMITTER: Guo B
PROVIDER: S-EPMC8691492 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Emerging evidence shows that coronavirus disease 2019 (COVID-19) is commonly complicated by coagulopathy, and venous thromboembolism (VTE) is considered to be a potential cause of unexplained death. Information on the incidence of VTE in COVID-19 patients, however, remains unclear. Method: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platforms were searched to identify studies with data of VTE occurrence in hospitalized COVID-19 patients. Pooled incidence and relative risks (RRs) of VTE were estimated by a random-effects model. Variations were examined based on clinical manifestations of VTE (pulmonary embolism-PE and deep vein thrombosis-DVT), disease severity (severe patients and non-severe patients), and rate of pharmacologic thromboprophylaxis (≥60 and <60%). Sensitivity analyses were conducted to strengthen the robustness of results. Meta-regression was performed to explore the risk factors associated with VTE in COVID-19 patients. Results: A total of 17 studies involving 1,913 hospitalized COVID-19 patients were included. The pooled incidence of VTE was 25% (95% CI, 19-31%; I 2, 95.7%), with a significant difference between the incidence of PE (19%; 95% CI, 13-25%; I 2, 93.2%) and DVT (7%; 95% CI, 4-10%; I 2, 88.3%; P interaction < 0.001). Higher incidence was observed in severe COVID-19 patients (35%; 95 CI%, 25-44%; I 2, 92.4%) than that in non-severe patients (6%; 95 CI%, 3-10%; I 2, 62.2%; P interaction < 0.001). The high rate of pharmacologic thromboprophylaxis in COVID-19 patients (≥60%) was associated with a lower incidence of VTE compared with the low pharmacologic thromboprophylaxis rate (<60%) (19 vs. 40%; P interaction = 0.052). Severe patients had a 3.76-fold increased risk of VTE compared with non-severe patients (RR, 4.76; 95% CI, 2.66-8.50; I 2, 47.0%). Sensitivity analyses confirmed the robustness of the primacy results. Conclusions: This meta-analysis revealed that the estimated VTE incidence was 25% in hospitalized COVID-19 patients. Higher incidence of VTE was observed in COVID-19 patients with a severe condition or with a low rate of pharmacologic thromboprophylaxis. Assessment of VTE risk is strongly recommended in COVID-19 patients, and effective measures of thromboprophylaxis should be taken in a timely manner for patients with high risk of VTE.
| S-EPMC7423832 | biostudies-literature
Project description:BackgroundVenous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources.MethodsWe present new cross-ancestry meta-analyzed GWAS results involving up to 81 669 VTE cases from 30 studies, with replication of novel loci in independent populations and loci characterization through in silico genomic interrogations.ResultsIn our genetic discovery effort that included 55 330 participants with VTE (47 822 European, 6320 African, and 1188 Hispanic ancestry), we identified 48 novel associations, of which 34 were replicated after correction for multiple testing. In our combined discovery-replication analysis (81 669 VTE participants) and ancestry-stratified meta-analyses (European, African, and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. A genetic risk score of the significantly associated loci in Europeans identified a 6-fold increase in risk for those in the top 1% of scores compared with those with average scores. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein quantitative-trait locus Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 GWAS loci provided insights to biological pathways contributing to VTE, with some loci contributing to VTE through well-characterized coagulation pathways and others providing new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis.ConclusionsOur cross-ancestry GWAS meta-analyses identified new loci associated with VTE. These findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.
| S-EPMC10152894 | biostudies-literature
Project description:OBJECTIVE:Most cases of coronavirus disease 2019 (COVID-19) are identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS:All adults with COVID-19 of moderate severity diagnosed using quantitative RT-PCR and hospitalized at the Central Hospital of Wuhan, China, from 1 January to 20 March 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS:Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher neutrophil count: lymphocyte count ratio (NLR) on admission (OR 1.032, 95% CI 1.042-1.230, p 0.004) and higher C-reactive protein (CRP) on admission (OR 3.017, 95% CI 1.941-4.690, p < 0.001) were associated with increased OR of poor prognosis. The area under the receiver operating characteristic curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, p < 0.001) and 0.84 (95% CI 0.780-0.905, p < 0.001), with a cut-off value of 2.79 and 25.95 mg/L, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI 0.732-0.878, p < 0.001) and 0.89 (95% CI 0.825-0.946, p < 0.001), with a cut-off value of 3.19 and 33.4 mg/L, respectively. CONCLUSIONS:Higher levels of NLR and CRP at admission were associated with poor prognosis of individuals with moderate COVID-19. NLR and CRP were good predictors of progression to critical condition and death.
| S-EPMC7331556 | biostudies-literature
Project description:ObjectiveVenous thromboembolism (VTE) is reported to occur in up to 33% of patients undergoing major vascular surgery. Despite this high incidence, patients inconsistently receive timely VTE chemoprophylaxis. The true incidence of VTE among patients receiving delayed VTE chemoprophylaxis is unknown. We sought to identify the association of VTE chemoprophylaxis timing on VTE risk, postoperative transfusion rates, and 30-day mortality and morbidity in patients undergoing major open vascular surgery.MethodsPatients undergoing major open vascular surgery (open abdominal aortic aneurysm [oAAA] repair, aortofemoral bypass, and lower extremity infrainguinal bypass [LEB]) were identified using the Michigan Surgical Quality Collaborative (MSQC) between July 2012 and June 2015. The VTE rate was compared between patients receiving early versus delayed VTE chemoprophylaxis. VTE chemoprophylaxis delay was defined as therapy initiation more than 24 hours after surgery. The risk-adjusted association of the chemoprophylaxis timing and VTE development was determined using multivariable logistic regression. Blood transfusion rates, 30-day mortality, and postoperative complications were compared across groups.ResultsA total of 2421 patients underwent major open vascular surgery, including 196 oAAA repair, 259 aortofemoral bypass, and 1966 LEB. The overall incidence of 30-day VTE was 1.40%, ranging from 1.12% for LEB to 3.57% for oAAA repair. Among patients receiving early VTE chemoprophylaxis, the rate of VTE was 0.78% versus 2.26% among those with a delay in VTE chemoprophylaxis (P = .002). When accounting for the preoperative risk of VTE, delayed chemoprophylaxis was associated with a significantly higher risk of VTE (odds ratio, 2.38; 95% confidence interval, 1.12-5.06; P = .024). The early VTE chemoprophylaxis group was associated with a significantly decreased risk of bleeding compared with those with a delay (14.31% vs 18.90%; P = .002). Overall 30-day mortality and postoperative complications were similar with the exception of an associated higher rate of infectious complications in the delayed VTE chemoprophylaxis group, including superficial surgical site infection (6.00% vs 4.06%; P = .028), pneumonia (3.25% vs 1.85%; P = .028), urinary tract infection (2.95% vs 1.57%; P = .020), and severe sepsis (3.05% vs 1.71%; P = .029).ConclusionsAlthough patients undergoing major open vascular surgery have a low risk of VTE at baseline, there is a significantly greater risk of developing VTE among patients who have a delay in the administration of VTE chemoprophylaxis. Postoperative transfusion rates were significantly lower among patients receiving early chemoprophylaxis. There were no differences in the 30-day mortality and postoperative complications, except for infectious complications. Given these findings, surgeons should consider early chemoprophylaxis in the postoperative setting after major open vascular surgery without contraindication.
| S-EPMC5741504 | biostudies-literature
Project description:Background: The association between anticoagulation outcomes and prior history of venous thromboembolism (VTE) in chronic thromboembolic pulmonary hypertension (CTEPH) has not been established. This study aimed to compare the efficacy and safety of anticoagulation treatment in CTEPH patients with and without prior history of VTE. Methods: A total of 333 CTEPH patients prescribed anticoagulants were retrospectively included from May 2013 to April 2019. The clinical characteristics were collected at their first admission. Incidental recurrent VTE and clinically relevant bleeding were recorded during follow-up. The Cox proportional regression models were used to identify potential factors associated with recurrent VTE and clinically relevant bleeding. Results: Seventy patients (21%) without a prior history of VTE did not experience recurrent VTE during anticoagulation. Compared to CTEPH patients without a prior history of VTE, those with a prior history of VTE had an increased risk of recurrent VTE [2.27/100 person-year vs. 0/100 person-year; hazard ratio (HR), 8.92; 95% confidence interval (CI), 1.18-1142.00; P = 0.029] but a similar risk of clinically relevant bleeding (3.90/100 person-year vs. 4.59/100 person-year; HR, 0.83; 95% CI, 0.38-1.78; P = 0.623). Multivariate Cox analyses suggested that a prior history of VTE and interruption of anticoagulation treatments were significantly associated with an increased risk of recurrent VTE, while anemia and glucocorticoid use were significantly associated with a higher risk of clinically relevant bleeding. Conclusions: This study is the first to reveal that a prior history of VTE significantly increases the risk of recurrent VTE in CTEPH patients during anticoagulation treatment. This finding should be further evaluated in prospective studies.
| S-EPMC8175786 | biostudies-literature
Project description:BackgroundVenous thromboembolism (VTE) is a common source of perioperative morbidity and mortality.ObjectiveThese evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery.MethodsASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.ResultsThe panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2).ConclusionsFor patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.
| S-EPMC6963238 | biostudies-literature
Project description:Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the risk of VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects. Logistic regression was used to estimate the association between genetic variants and VTE risk. Through bioinformatics analysis of the top signals, we identified expression quantitative trait loci (eQTLs) in whole blood and investigated the messenger RNA expression differences in VTE cases and controls. We identified and replicated single-nucleotide polymorphisms on chromosome 20 (rs2144940, rs2567617, and rs1998081) that increased risk of VTE by 2.3-fold (P< 6 × 10(-7)). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (<10%). We demonstrate that SNPs on chromosome 20 are cis-eQTLs for thrombomodulin (THBD), and the expression of THBD is lower among VTE cases compared with controls (P= 9.87 × 10(-6)). We have identified novel polymorphisms associated with increased risk of VTE in AAs. These polymorphisms are predominantly found among populations of African descent and are associated with THBD gene expression. Our findings provide new molecular insight into a mechanism regulating VTE susceptibility and identify common genetic variants that increase the risk of VTE in AAs, a population disproportionately affected by this disease.
| S-EPMC4832509 | biostudies-literature
Project description:BACKGROUND:Patients with unprovoked first venous thromboembolism (VTE) are at a high risk of recurrence. Although circulating microRNAs (miRNAs) have been found to be associated with VTE and are markers of hypercoagulability, this study is the first to examine whether circulating miRNAs are associated with the risk of VTE recurrence. RESULTS:A nested case-control study design was used where plasma samples were obtained from 78 patients with unprovoked VTE from the Malmö Thrombophilia Study (MATS). A total of 39 VTE patients with recurrent VTE (cases) were matched with 39 VTE patients without recurrent VTE (controls) defined by age and sex (MATS population). Plasma levels of 179 different miRNAs were evaluated in the 78 samples (after anticoagulant treatment was stopped) using qPCR. A total of 110 miRNAs were detected in all samples. Among those, 12 miRNAs (miR-15b-5p, miR-106a-5p, miR-197-3p, miR-652-3p, miR-361-5p, miR-222-3p, miR-26b-5p, miR-532-5p, miR-27b-3p, miR-21-5p, miR-103a-3p, and miR-30c-5p) were found to be associated with recurrent VTE after multiple correction test and conditional logistic regression analysis. A further analysis showed that miR-15b-5p, miR-197-3p, miR-27b-3p, and miR-30c-5p exhibited a trend over time, with a larger difference in miRNA levels between cases and controls for earlier recurrence. Of these 12 miRNAs, 8 miRNAs significantly correlated with circulating transforming growth factor β1/2 (TGFβ1/2). Three of them correlated with platelet count. CONCLUSION:We have identified 12 plasma miRNAs that may have the potential to serve as novel, non-invasive predictive biomarkers for VTE recurrence.
| S-EPMC6374897 | biostudies-other
Project description:BackgroundPrevention of recurrent venous thromboembolism (VTE) is considered a main goal of VTE management. However, the extent to which physicians adhere to the recommendations from evidence-based guidelines is unknown.AimFrom a large, prospective clinical cohort, we aimed to (1) quantify the adherence of treatment recommendations to evidence-based guidelines and establish its predictors, and (2) estimate its impact on clinical outcomes and costs in patients with VTE.MethodsWe included 6'243 consecutive patients with VTE treated at the university outpatient unit. Detailed clinical characteristics and treatment recommendations were recorded. Adherence of treatment recommendations to evidence-based guidelines at risk assessment was assessed in terms of duration of anticoagulant treatment. Data on death were obtained from the Swiss Central Compensation Office. Health care claims data recorded between 2014 and 2019 were retrieved from Helsana, one of the largest Swiss health insurance companies.ResultsThe adherence to evidence-based guidelines was 36.1%. Among patients with non-adherence, overtreatment was present in 70.1%. Significant patient-related predictors of guideline adherence were (a) age above 50 years, (b) male sex, (c) pulmonary embolism, (d) unprovoked VTE, (e) multiple VTE, (f) laboratory tests not ordered, and (g) various cardiovascular comorbidities. Non-adherence was not significantly associated with mortality, hospitalization, admission to nursing home, and costs.ConclusionsThe adherence to evidence-based guidelines was low, and several unrelated predictors appeared. Although these results need to be confirmed in other settings, they highlight the need for implementation of evidence-based guidelines in clinical practice.
| S-EPMC9381867 | biostudies-literature
Project description:Venous thromboembolic disease is a major cause of morbidity in cancer patients. The Perspective database was used to identify patients with solid tumors and a diagnosis of VTE from 2006 to 2012. We examined use of IVC filters, thrombolysis, and thrombectomy. Among 32,545 patients, 23.1% received an IVC filter, 1.9% thrombolytic therapy, and 0.4% underwent thrombectomy. Use of IVC filters decreased between 2006 and 2012 (23.4% to 21.2%, p = 0.012). Older patients, uninsured patients, Hispanics, and those with more comorbidities were more likely to undergo filter placement while patients at rural hospitals were less likely to receive an IVC filter (p < 0.05 for all).
| S-EPMC5047731 | biostudies-literature