Unsupervised clustering of venous thromboembolism patients by clinical features at presentation identifies novel endotypes that improve prognostic stratification
Thrombosis Research, 2023
Pallares Robles A., ten Cate V., Lenz M., Schulz A., Prochaska J., Rapp S., Koeck T., Leineweber K., Heitmeier S., Opitz C., Held M., Espinola-Klein C., Lackner K., Münzel T., Konstantinides S., ten Cate-Hoek A., ten Cate H., Wild P.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Background
Individuals with acute venous thromboembolism (VTE) constitute a heterogeneous group of patients with diverse clinical characteristics and outcome.
Objectives
To identify endotypes of individuals with acute VTE based on clinical characteristics at presentation through unsupervised cluster analysis and to evaluate their molecular proteomic profile and clinical outcome.
Methods
Data from 591 individuals from the Genotyping and Molecular phenotyping of Venous thromboembolism (GMP-VTE) project were explored. Hierarchical clustering was applied to 58 variables to define VTE endotypes. Clinical characteristics, three-year incidence of thromboembolic events or death, and acute-phase plasma proteomics were assessed.
Results
Four endotypes were identified, exhibiting different patterns of clinical characteristics and clinical course. Endotype 1 (n = 300), comprising older individuals with comorbidities, had the highest incidence of thromboembolic events or death (HR [95 % CI]: 3.76 [1.96–7.19]), followed by endotype 4 (n = 127) (HR [95 % CI]: 2.55 [1.26–5.16]), characterised by men with history of VTE and provoking risk factors, and endotype 3 (n = 57) (HR [95 % CI]: 1.57 [0.63–3.87]), composed of young women with provoking risk factors, vs. reference endotype 2 (n = 107). The reference endotype was constituted by individuals diagnosed with PE without comorbidities, who had the lowest incidence of the investigated endpoint. Differentially expressed proteins associated with the endotypes were related to distinct biological processes, supporting differences in molecular pathophysiology. The endotypes had superior prognostic ability compared to existing risk stratifications such as provoked vs unprovoked VTE and D-dimer levels.