Predictive Ability of a Clinical-Genetic Risk Score for Venous Thromboembolism in Northern and Southern European Populations.
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SUBMITTER: Salas E
PROVIDER: S-EPMC8266419 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundVenous thromboembolism (VTE) has been associated with a higher risk of developing malignancy and mortality, and patients with VTE may therefore benefit from increased surveillance. We aimed to construct a clinical predictive score that could classify patients with VTE according to their risk for developing these outcomes.MethodsObservational cohort study using an existing clinical registry in a tertiary academic teaching hospital in Buenos Aires, Argentina. 1264 adult patients greater than 17 years of age presented new VTE between June 2006 and December 2011 and were included in the registry. We excluded patients with previous or incident cancer, those who died during the first month, and those with less than one year of follow up (< 5%). 540 patients were included. Primary outcome was new cancer diagnosis during one year of follow-up, secondary composite outcome was any new cancer diagnosis or death. The score was developed using a multivariable logistic regression model to predict cancer or death.ResultsDuring follow-up, one-quarter (26.4%) of patients developed cancer (9.2%) or died (23.7%). Patients with the primary outcome had more comorbidities, were more likely to have previous thromboembolism and less likely to have recent surgery. The final score developed for predicting cancer alone included previous episode of VTE, recent surgery and comorbidity (Charlson comorbidity score), [AUC of 0.75 (95% CI 0.66-0.84) and 0.79 (95% CI 0.63-0.95) in the derivation and validation cohorts, respectively]. The version of this score developed to predict cancer or death included age, albumin level, comorbidity, previous episode of VTE, and recent surgery [AUC = 0.72 (95% CI 0.66-0.78) and 0.71 (95% CI 0.63-0.79) in the derivation and validation cohorts, respectively].ConclusionsA simple clinical predictive score accurately estimates patients' risk of developing cancer or death following newly diagnosed VTE. This tool could be used to help reassure low risk patients, or to identify high-risk patients that might benefit from closer surveillance and additional investigations.Trial registrationClinicalTrials.gov: NCT01372514.
| S-EPMC3723428 | biostudies-literature
Project description:Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between "northern" and "southern" European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the "southern" population; and most northern, western, eastern, and central Europeans have >90% in the "northern" population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the "southern" population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.
| S-EPMC1564423 | biostudies-literature
Project description:IntroductionVTE-BLEED is a validated score for identification of patients at increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE). It is unknown whether VTE-BLEED high-risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score.MethodsThis was a post hoc analysis of the randomized, double-blind, placebo-controlled PADIS-PE trial that randomized patients with a first unprovoked pulmonary embolism (PE) initially treated during 6 months to receive an additional 18-month of warfarin vs. placebo. The primary outcome of this analysis was recurrent VTE during 2-year follow-up after anticoagulant discontinuation, that is, after the initial 6-month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted for study treatment allocation, was compared between patients in the high- vs. low-risk VTE-BLEED group.ResultsIn complete case analysis (n = 308; 82.4% of total population), 89 (28.9%) patients were classified as high risk; 44 VTE events occurred after anticoagulant discontinuation during 668 patient-years. The cumulative incidence of recurrent VTE was 16.4% (95% confidence interval [CI], 10.0%-26.1%; 14 events) and 14.6% (95% CI, 10.4%-20.3%; 30 events) in the high-risk and low-risk VTE-BLEED groups, respectively, for an adjusted hazard ratio of 1.16 (95% CI, 0.62-2.19).ConclusionIn this study, patients with unprovoked PE classified at high risk of major bleeding by VTE-BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.
| S-EPMC6611364 | biostudies-literature
Project description:BackgroundVenous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality and has a known genetic contribution. We tested the performance of a genetic risk score for its ability to predict VTE in 3 cohorts of patients with cardiometabolic disease.MethodsWe included patients from the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) trials (history of a major atherosclerotic cardiovascular event, myocardial infarction, and diabetes, respectively) who consented for genetic testing and were not on baseline anticoagulation. We calculated a VTE genetic risk score based on 297 single nucleotide polymorphisms with established genome-wide significance. Patients were divided into tertiles of genetic risk. Cox proportional hazards models were used to calculate hazard ratios for VTE across genetic risk groups. The polygenic risk score was compared with available clinical risk factors (age, obesity, smoking, history of heart failure, and diabetes) and common monogenic mutations.ResultsA total of 29 663 patients were included in the analysis with a median follow-up of 2.4 years, of whom 174 had a VTE event. There was a significantly increased gradient of risk across VTE genetic risk tertiles (P-trend <0.0001). After adjustment for clinical risk factors, patients in the intermediate and high genetic risk groups had a 1.88-fold (95% CI, 1.23-2.89; P=0.004) and 2.70-fold (95% CI, 1.81-4.06; P<0.0001) higher risk of VTE compared with patients with low genetic risk. In a continuous model adjusted for clinical risk factors, each standard deviation increase in the genetic risk score was associated with a 47% (95% CI, 29-68) increased risk of VTE (P<0.0001).ConclusionsIn a broad spectrum of patients with cardiometabolic disease, a polygenic risk score is a strong, independent predictor of VTE after accounting for available clinical risk factors, identifying 1/3 of patients who have a risk of VTE comparable to that seen with established monogenic thrombophilia.
| S-EPMC7887088 | biostudies-literature
Project description:BackgroundChronic venous disease is common and shares some risk factors with venous thromboembolism (VTE). Several genetic loci have been discovered and well-replicated for VTE in European descent populations. We examined associations of a genetic risk score (GRS), comprising known VTE loci, with chronic venous disease.MethodsThe San Diego Population Study (SDPS) is a multi-ethnic cohort that evaluated 2404 men and women aged 29-91 from 1994 to 1998 for chronic venous disease. The current study includes 1447 participants genotyped for 33 variants in 22 established VTE risk loci. Using these variants, unweighted and weighted GRS were constructed. Logistic regression was used to examine associations with venous disease.ResultsIn non-Hispanic whites, African-Americans, Hispanics, and Asians, each standard deviation increment higher of the unweighted 33-SNP GRS was associated with a 1.45-fold (95% CI (1.26, 1.67)), 1.74-fold (1.18, 2.55), a 1.80-fold (1.30, 2.51), and 1.88-fold (1.30, 2.73) greater odds, respectively, for moderate plus severe disease. The difference in c-statistics was significant between a known venous risk factor model and a model adding the 33-SNP GRS for whites (p=0.008), African-Americans (0.03), and Hispanics (p=0.04), with marginal significance in Asians (p=0.06).ConclusionsGRS comprising variants primarily from VTE findings in European descent populations were associated with chronic venous disease across all race/ethnic groups, and contributed significantly to prediction, indicating some level of generalizability to other race/ethnic groups. Future work should focus on more in depth examination of racial/ethnic group genetic architecture in relation to chronic venous disease.
| S-EPMC4718662 | biostudies-literature
Project description:Background Venous thromboembolism (VTE) is a threat to the prognosis of tumor patients, especially for critically ill patients. No uniform standard model of VTE risk for critically ill patients with tumors was formatted by now. We thus analyzed risk factors of VTE from the perspectives of patient, tumor, and treatment and assessed the predictive value of the ICU-VTE score, which consisted of six independent risk factors (central venous catheterization, 5 points; immobilization ≥ 4 days, 4 points; prior VTE, 4 points; mechanical ventilation, 2 points; lowest hemoglobin during hospitalization ≥ 90 g/L, 2 points; and baseline platelet count > 250,000/μL, 1 points). Methods We evaluated the data of tumor patients admitted to the intensive care unit of the Peking University Cancer Hospital between November 2011 and January 2022; 560 cases who received VTE-related screening during hospitalization were chosen for this retrospective study. Results The inhospital VTE occurrence rate in our cohort was 55.7% (312/560), with a median interval from ICU admission to VTE diagnosis of 8.0 days. After the multivariate logistic regression analysis, several factors were proved to be significantly associated with inhospital VTE: age ≥ 65 years, high tumor grade (G3–4), medical diseases, fresh frozen plasma transfusion, and anticoagulant prophylaxis. The medium-high risk group according to the ICU-VTE score was positively correlated with VTE when compared with the low-risk group (9–18 points vs. 0–8 points; OR, 3.13; 95% CI, 2.01–4.85, P < 0.001). The AUC of the ICU-VTE scores according to the ROC curve was 0.714 (95% CI, 0.67–0.75, P < 0.001). Conclusions The ICU-VTE score, as well as tumor grade, might assist in the assessment of inhospital VTE risk for critically ill patients with tumors. The predictive accuracy might be improved when combining two of them; further follow-up researches are needed to confirm it. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02705-z.
| S-EPMC9442986 | biostudies-literature
Project description:ESSENTIALS: There is little prospective information on genetic risk scores to predict venous thromboembolism (VT). Community based cohort followed a median of 22.6 years for VT occurrence. A 5-SNP risk score identified whites at risk of VT, but not African Americans. The utility of genetic risk scores for VT is yet to be established.Case-control studies have created genetic risk scores of single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) and documented their ability to predict VTE, but prospective data are lacking.To test the ability of a genetic risk score to predict VTE incidence in a prospective study, particularly in African Americans.We computed a previously proposed genetic risk score, based on five established VTE SNPs in the F5, F2, ABO, FGG, and F11 genes, in 9520 whites and 3049 African Americans initially free of VTE. We followed them a median of 22.6 years for VTE occurrence (n = 380 events in whites and n = 187 in African Americans).In whites, the five-SNP weighted genetic risk score ranged from 0 to 5.8, and VTE risk increased 1.41-fold (95% confidence interval [CI] 1.27-fold to 1.56-fold) per allele increment. In African Americans, the weighted genetic risk score ranged from 0 to 4.6 and the hazard ratio per risk allele was 1.14 (95% CI 0.94-1.38), with adjustment for 10 principal components of ancestry. The area under the receiver operating characteristic curve for 20-year prediction of VTE from the weighted genetic risk score was 0.59 (95% CI 0.56-0.63) in whites and 0.56 (95% CI 0.51-0.61) in African Americans. Adding non-genetic factors increased the area under the curve to 0.67 in whites and to 0.66 in African Americans.Higher values for a five-SNP genetic risk score helped identify white adults at risk of VTE. The genetic risk score did not identify future VTE occurrence in African Americans.
| S-EPMC4715510 | biostudies-literature
Project description:ObjectiveHospital-acquired venous thromboembolism (VTE, including pulmonary embolism [PE] and deep vein thrombosis [DVT]) is a preventable cause of hospital death. The Caprini risk assessment model (RAM) is one of the most commonly used tools to assess VTE risk. The RAM is operationalized in clinical practice by grouping several risk scores into VTE risk categories that drive decisions on prophylaxis. A correlation between increasing Caprini scores and rising VTE risk is well-established. We assessed whether the increasing VTE risk categories assigned on the basis of recommended score ranges also correlate with increasing VTE risk.MethodsWe conducted a systematic review of articles that used the Caprini RAM to assign VTE risk categories and that reported corresponding VTE rates. A Medline and EMBASE search retrieved 895 articles, of which 57 fulfilled inclusion criteria.ResultsForty-eight (84%) of the articles were cohort studies, 7 (12%) were case-control studies, and 2 (4%) were cross-sectional studies. The populations varied from postsurgical to medical patients. There was variability in the number of VTE risk categories assigned by individual studies (6 used 5 risk categories, 37 used 4, 11 used 3, and 3 used 2), and in the cutoff scores defining the risk categories (scores from 0 alone to 0-10 for the low-risk category; from ≥5 to ≥10 for high risk). The VTE rates reported for similar risk categories also varied across studies (0%-12.3% in the low-risk category; 0%-40% for high risk). The Caprini RAM is designed to assess composite VTE risk; however, two studies reported PE or DVT rates alone, and many of the other studies did not specify the types of DVTs analyzed. The Caprini RAM predicts VTE at 30 days after assessment; however, only 17 studies measured outcomes at 30 days; the remaining studies had either shorter or longer follow-ups (0-180 days).ConclusionsThe usefulness of the Caprini RAM is limited by heterogeneity in its implementation across centers. The score-derived VTE risk categorization has significant variability in the number of risk categories being used, the cutpoints used to define the risk categories, the outcome being measured, and the follow-up duration. This factor leads to similar risk categories being associated with different VTE rates, which impacts the clinical and research implications of the results. To enhance generalizability, there is a need for studies that validate the RAM in a broad population of medical and surgical patients, identify standardized risk categories, define risk of DVT and PE as distinct end points, and measure outcomes at standardized follow-up time points.
| S-EPMC9783939 | biostudies-literature
Project description:Multiple genetic and environmental risk factors contribute to venous thromboembolism (VTE) risk. Understanding how genes and environmental risk factors interact may provide key insight into the pathophysiology of VTE and may identify opportunities for targeted prevention and treatment. It was our aim to examine the main effects and the potential effect-modification between single nucleotide polymorphisms (SNPs) at established loci and lifestyle risk factors for VTE. We performed a nested case-control study using data on 1,040 incident VTE cases and 16,936 controls from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study cohorts, who gave blood, were selected as participants in a previous genome-wide association study (GWAS), and completed a biennial questionnaire at time of blood draw. We selected SNPs that were associated with VTE risk in previous GWAS studies. A genetic risk score (GRS) was constructed to evaluate the combined effect of the 16 SNPs that have reached genome-wide significance in previous GWAS of VTE. Interactions between SNPs and VTE risk factors (BMI and smoking) were also assessed. We found a significant association between our GRS and VTE risk. The risk of VTE among individuals in the highest GRS tertile was 2.02 times that of individuals in the lowest GRS tertile (p-trend = 9.69×10(-19)). The OR was 1.52 (p=1.03×10(-8)) for participants in the highest GRS tertile compared to those in the medium GRS tertile. However, while BMI and smoking were associated with VTE, and their effects were additive to each other we did not observe any significant multiplicative gene-environment interactions.
| S-EPMC5177985 | biostudies-literature
Project description:Age-related hearing impairment (ARHI) affects 25-40% of individuals over the age of 65. Despite the high prevalence of this complex trait, ARHI is still poorly understood. We hypothesized that variance in hearing ability with age is largely determined by genetic factors. We collected audiologic data on females of Northern European ancestry and compared different audiogram representations. A web-based speech-to-noise ratio (SNR) hearing test was compared with pure-tone thresholds to see if we could determine accurately hearing ability on people at home and the genetic contribution to each trait compared. Volunteers were recruited from the TwinsUK cohort. Hearing ability was determined using pure-tone audiometry and a web-based hearing test. Different audiogram presentations were compared for age-correlation and reflection of audiogram shape. Using structural equation modelling based on the classical twin model the heritability of ARHI, as measured by the different phenotypes, was estimated and shared variance between the web-based SNR test and pure-tone audiometry determined using bivariate modelling. Pure-tone audiometric data was collected on 1033 older females (age: 41-86). 1970 volunteers (males and females, age: 18-85) participated in the SNR. In the comparison between different ARHI phenotypes the difference between the first two principle components (PC1-PC2) best represented ARHI. The SNR test showed a sensitivity and specificity of 89% and 80%, respectively, in comparison with pure-tone audiogram data. Univariate heritability estimates ranged from 0.70 (95% CI: 0.63-0.76) for (PC1-PC2) to 0.56 (95% CI: 0.48-0.63) for PC2. The genetic correlation of PC1-PC2 and SNR was -0.67 showing that the 2 traits share variances attributed to additive genetic factors. Hearing ability showed considerable heritability in our sample. We have shown that the SNR test provides a useful surrogate marker of hearing. This will enable a much larger sample to be collected at a fraction of the cost, facilitating future genetic association studies.
| S-EPMC3340381 | biostudies-literature