OC 16.4 - Thrombin Generation Is Associated with Stroke in a General Adult Population: Prospective Findings from the Moli-sani Study

Sunday, June 25, 2023

11:30 – 11:45 ET

Room: 510

Session Available As: On-Demand

Co-Author(s)

SC

Simona Costanzo

Senior Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy
Pozzilli, Molise, Italy

Presenting Author(s)

Romy De Laat-Kremers, PhD

Post-doctoral Research Project Leader
Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Co-Author(s)

AD

Augusto Di Castelnuovo

Senior Researcher
Mediterranea Cardiocentro, Napoli, Italy
Napoli, Campania, Italy
AD

Amalia De Curtis

Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy
Pozzilli, Molise, Italy
TP

Teresa Panzera

Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy
Pozzilli, Molise, Italy
Marisa Ninivaggi, PhD

Research Project Leader
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
CC

Chiara Cerletti

Senior Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy
Pozzilli, Molise, Italy
Gd

Giovanni de Gaetano

Senior Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy
Pozzilli, Molise, Italy
LI

Licia Iacoviello

Full Professor
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy
Pozzilli, Molise, Italy
MD

Maria Benedetta Donati

Senior Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Pozzilli, Molise, Italy
Bd

Bas de Laat, MD, PhD

General Director
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Background: The thrombin generation (TG) assay evaluates the potential of plasma to form thrombin, and is used to detect a hypo- or hypercoagulability tendency at the individual level. To date epidemiological findings on relationship of TG measures with stroke are inconsistent.

Aims: To evaluate whether variation in TG parameters is associated with stroke in an Italian adult population.

Methods: We analysed data on 20,109 individuals (53.3% women, age 54.8 ±11.5 years) enrolled in the Moli-sani study (2005-2010), without a history of cardiovascular disease or use of vitamin K antagonists at baseline. TG was determined by Calibrated Automated Thrombinography using PPP-reagent. The association of the TG parameter endogenous thrombin potential (ETP) with stroke was assessed by multivariable Cox-proportional hazard models.

Results: Over a median follow-up of 8.2 years, N=183 (0.9%) fatal and not-fatal stroke events were ascertained. Individuals in the lowest or the highest ETP quintiles showed a higher rate of stroke compared to individuals in the third one: hazard ratio (HR):1.63 (95% confidence interval (CI):1.03-2.58) and HR:1.75 (95%CI:1.06-2.89), respectively (Figure 1). Dose-response analyses by restricted cubic spline functions confirmed the U-shaped relationship between ETP and risk of stroke (P overall association 0.032, P non-linear association 0.013; Figure 2). Preliminary, underpowered analyses by stroke subtypes showed U-shaped association with ischemic (N=95), but a negative linear link with haemorrhagic (N=50) events.

Conclusion(s): In comparison with median values, both lower and higher levels of ETP, corresponding to the total amount of thrombin formed during the assay, are associated with a higher risk of stroke. The dual role of thrombin in the coagulation cascade could be explain the U-shaped relationship with total (particularly ischemic) stroke. Further confirmation of a relationship between TG and stroke would not only contribute to the knowledge on the physio-pathological processes leading to thrombosis, but also suggest new preventive approaches.

Learning Objectives:

Upon completion, participant will be able to improve his/her knowledge on the association between TG parameters and stroke.
Upon completion, participant will be able to acquire the U-shaped relationship between TG parameters and total (particularly ischemic) stroke risk, possibly explained by the dual role of thrombin in the coagulation cascade.
Upon completion, participant will be able to acquire that the relationship between TG and stroke would not only contribute to the knowledge on the physio-pathological processes leading to thrombosis, but also suggest new preventive approaches