A prospective cohort study to identify and evaluate endotypes of venous thromboembolism: Rationale and design of the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism project (GMP-VTE).

Several clinical, genetic and acquired risk factors for venous thromboembolism (VTE) have been identified. However, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. This is reflected by uncertainties regarding the primary and secondary prevention of VTE and the optimal duration of antithrombotic therapy. A growing body of literature points to clinically relevant differences between VTE phenotypes (e.g. deep vein thrombosis (DVT) versus pulmonary embolism (PE), unprovoked versus provoked VTE). Extensive links to cardiovascular, inflammatory and immune-related morbidities are testament to the complexity of the disease. The GMP-VTE project is a prospective, multi-center cohort study on individuals with objectively confirmed VTE. Sequential data sampling was performed at the time of the acute event and during serial follow-up investigations. Various data levels (e.g. clinical, genetic, proteomic and platelet data) are available for multi-dimensional data analyses by means of advanced statistical, bioinformatic and machine learning methods. The GMP-VTE project comprises n = 663 individuals with acute VTE (mean age: 60.3 ±â€¯15.9 years; female sex: 42.8%). In detail, 28.4% individuals (n = 188) had acute isolated DVT, whereas 71.6% subjects (n = 475) had PE with or without concomitant DVT. In the study sample, 28.9% (n = 129) of individuals with PE and 30.1% (n = 55) of individuals with isolated DVT had a recurrent VTE event at the time of study enrolment. The systems-oriented approach for the comprehensive dataset of the GMP-VTE project may generate new biological insights into the pathophysiology of VTE and refine our current understanding and management of VTE.

Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study.

Aims: The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results: In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German population-based cohorts. Using log-binomial regression models, an increased risk for occurrence of arterial hypertension [relative risk (RR) 1.38, 95% confidence interval (95% CI 1.21-1.57)] and dyslipidaemia [RR 1.26 (95% CI 1.12-1.42)] was found. This indicates a premature occurrence compared to the general population of approximately 6 and 8 years, respectively [rate advancement period estimator, RAPhypertension 5.75 (95% CI 3.5-8.0) and RAPdyslipidaemia 8.16 (95% CI 4.4-11.9)]. Overall, no differences were observed for obesity and diabetes. Overt CVD was present in 4.5% (95% CI 3.0-6.6%) of CCS [RR 1.89 (95% CI 1.34-2.66), RAPCVD 7.9 (95% CI 4.1-11.7)], of which the most frequent entities were congestive heart failure and venous thromboembolism. Prevalences of CVRF and CVD increased with age without reaching a plateau over time. Conclusion: This large CCS screening examination revealed consistently in comparison to three population samples a considerably increased risk for premature CVD. The findings in these young adult CCS indicate a high burden of cardiovascular morbidity and mortality in the long term. Clinicaltrials. gov-Nr: NCT02181049.

Coagulation and inflammation in long-term cancer survivors: results from the adult population.

Essentials The increase of cancer survival remains curtailed by cardiovascular mortality. We studied a large range of inflammatory and coagulation biomarkers in long-term cancer survivors. Cancer history has an important impact on mortality independent of cardiovascular risk factors. Fibrinogen and von Willebrand factor are potential biomarkers in survivors of increased mortality. SUMMARY: Background The advances in cancer treatment and detection of early cancer have resulted in a steady increase in the number of of cancer survivors over the years. However, because of the long-term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular disease (CVD) is increasing in survivors. Objectives To investigate traditional cardiovascular risk factors (CVRFs), inflammation and the coagulation profile in long-term cancer survivors (cancer diagnosis ≥ 5 years) from a large adult population-based study sample. Methods The presence of cardiovascular risk factors (CVRFs) and laboratory markers were compared in individuals with (n = 723) and without (n = 13626) a long-term history of cancer from the Gutenberg Health Study. Data on coagulation factors, D-dimer and von Willebrand factor (VWF) activity were available for 4974 individuals (n = 244 cancer survivors). Results In multivariable regression models, a history of cancer was, independently of CVRFs and CVD, associated with higher fibrinogen levels (ß 6.99, 95% confidence interval [CI] 1.16-12.8), VWF activity (ß 5.08, 95% CI 0.02-10.1), and antithrombin activity (ß 1.85, 95% CI 0.44-3.27). Cancer survivors with CVD showed notably higher VWF activity than individuals with CVD without a history of cancer, with a difference in the means of 23.0 (7.9-38.1). Multivariate Cox regression analysis, adjusted for CVRFs, confirmed that a long-term history of cancer is associated with a 72% higher mortality. Increased mortality in cancer survivors was dependent on fibrinogen level and VWF activity level. Conclusion Cancer survivors showed a worse inflammation and coagulation profile than individuals without a history of cancer. Overall mortality in long-term cancer survivors was increased independently of traditional CVRFs. These results underline the need to further investigate plasma biomarkers as complementary cardiovascular risk predictors in cancer survivors.

PO-58 - Cardiovascular risk profile in survivors of adult cancer - results from the general population study.

INTRODUCTION: The advancements in cancer treatment and detection of early cancer have resulted in steady increase of adult cancer survivors over the years. However, due to the long term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular diseases (CVD) is increasing in survivors. Identifying risk factors and interventions to reduce the excess burden of CVD in this vulnerable population is urgently needed. AIM: To investigate the cardiovascular risk factors (CVRFs), inflammation and coagulation profile in cancer survivors from a large population-based study. MATERIALS AND METHODS: Presence of CVRFs and laboratory markers have been compared in individuals with (n=1,359) and without (n=13,626) history of cancer. Standard laboratory profile, including blood glucose and lipid profile, has been evaluated in 15,010 individuals from the Gutenberg Health Study (GHS). Coagulation factors, D-dimer and von Willebrand factor (vWF) activity were available in N=4,993. RESULTS: The individuals with history of cancer were older compared to no history of cancer with mean age of 61,5years and 54.4years, respectively (p<0.001). Traditional CVRFs as diabetes (14% vs 8.8%), dyslipidemia (49.6% vs 43.7%) and hypertension (60.3 vs 48.7%) were more frequent whereas smoking was less frequent (14.5% vs 19.9%) in cancer survivors (p<0.001). The standard laboratory profile showed cancer survivors with lower erythrocyte, platelet and white blood cell counts and higher C-reactive protein (CRP), glucose, HbA1c and triglycerides levels (p<0.001). Multivariable logistic regression analysis adjusted for age, sex and CVRFs demonstrated an independent association with diabetes (odds ratio, OR: 1.24, 1.02-1.50; p=0.027) and higher CRP (OR: 1.01, 1.01-1.02; p=0.00071). Fibrinogen, FV, FVII, FVIII and FXI, D-dimer and vWF activity were higher in cancer survivors (p<0.001). Multivariable logistic regression confirmed an independent association with higher fibrinogen (OR: 1.002, 1.000-1.003) and vWF activity (OR: 1.005, 1.001-1.008). CONCLUSIONS: This is the first study investigating CVRFs, inflammation and coagulation profile in individuals with history of cancer from a well characterized population-representative adult sample. It gives evidence for higher prevalence of CVRFs, particularly diabetes in this vulnerable population. Markers of inflammation as CRP and fibrinogen and vWF activity were higher in cancer survivors independent of the cardiovascular risk profile. These results underline the increased risk of CVD and need for development of cardio-oncology programs offering cardiovascular prevention.