Cardiovascular and genetic determinants of platelet ADP- and epinephrine-induced hyperreactivity – Results from the Gutenberg Health Study

G. Baidildinova; V. ten Cate; M. Panova-Noeva; B. Dahlen; A. Gieswinkel; S. Rapp; K. Strauch; M. Beutel; N. Pfeiffer; K. L. Lackner; T. Münzel; H. ten Cate; P. S. Wild; K. Jurk

doi:10.1055/s-0044-1779058

Hämostaseologie, Table of Contents

Hamostaseologie 2024; 44(S 01): S2-S3
DOI: 10.1055/s-0044-1779058

Abstracts

Topics

T-01. Venous and arterial thrombosis

Cardiovascular and genetic determinants of platelet ADP- and epinephrine-induced hyperreactivity – Results from the Gutenberg Health Study

G. Baidildinova

¹University Medical Center of the Johannes Gutenberg University Mainz, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany

²Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands

,

V. ten Cate

¹University Medical Center of the Johannes Gutenberg University Mainz, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany

³University Medical Center of the Johannes Gutenberg University Mainz, Preventive Cardiology and Preventive Medicine, Department of Cardiology, Mainz, Germany

,

M. Panova-Noeva

¹University Medical Center of the Johannes Gutenberg University Mainz, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany

,

B. Dahlen

¹University Medical Center of the Johannes Gutenberg University Mainz, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany

³University Medical Center of the Johannes Gutenberg University Mainz, Preventive Cardiology and Preventive Medicine, Department of Cardiology, Mainz, Germany

,

A. Gieswinkel

³University Medical Center of the Johannes Gutenberg University Mainz, Preventive Cardiology and Preventive Medicine, Department of Cardiology, Mainz, Germany

,

S. Rapp

³University Medical Center of the Johannes Gutenberg University Mainz, Preventive Cardiology and Preventive Medicine, Department of Cardiology, Mainz, Germany

,

K. Strauch

⁴University Medical Center of the Johannes Gutenberg University Mainz, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Mainz, Germany

,

M. Beutel

⁵University Medical Center of the Johannes Gutenberg University Mainz, Department of Psychosomatic Medicine and Psychotherapy, Mainz, Germany

,

N. Pfeiffer

⁶University Medical Center of the Johannes Gutenberg University Mainz, Department of Ophthalmology, Mainz, Germany

,

K. L. Lackner

⁷University Medical Center of the Johannes Gutenberg University Mainz, Institute for Clinical Chemistry and Laboratory Medicine, Mainz, Germany

,

T. Münzel

⁸University Medical Center of the Johannes Gutenberg University Mainz, Department of Cardiology, Cardiology I, Mainz, Germany

,

H. ten Cate

²Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands

⁹Maastricht University Medical Center, Maastricht, Thrombosis Expertise Center, Heart and Vascular Center, Maastricht, Netherlands

,

P. S. Wild

¹University Medical Center of the Johannes Gutenberg University Mainz, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany

³University Medical Center of the Johannes Gutenberg University Mainz, Preventive Cardiology and Preventive Medicine, Department of Cardiology, Mainz, Germany

,

K. Jurk

¹University Medical Center of the Johannes Gutenberg University Mainz, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany

³University Medical Center of the Johannes Gutenberg University Mainz, Preventive Cardiology and Preventive Medicine, Department of Cardiology, Mainz, Germany

› Author Affiliations

Abstract

Full Text

Introduction Platelets contribute to the development of cardiovascular diseases with arterial or venous origin. This study aimed to compare platelet ADP and epinephrine hyperaggregability to other platelet function tests and to determine the predictive value of clinical factors and common genetic variants.

Method Normal- vs. high-responsive platelets to 0.5 µM of ADP and epinephrine in the light transmission aggregometry (LTA) were discriminated by the intersection of two distributions in a Gaussian mixture model from 903 population-based Gutenberg Health Study participants. Utilizing robust Poisson regression analysis, prevalence ratios (PR) were estimated between four platelet hyperaggregability comparison groups and 1) additional platelet parameters assessed by LTA, flow cytometry, platelet function analyzer, and calibrated automated thrombinography, 2) clinical characteristics, and 3) platelet-related common genetic variants.

Results Platelet hyperaggregability in response to ADP and/or epinephrine was associated with maximum aggregation for all tested agonists and tissue factor exposure in vivo after adjustment for age, sex, platelet count and platelet function-interfering medications (PR>1, all group comparisons). Increased platelet aggregation induced by ADP and epinephrine was strongly related to atrial fibrillation (PR>1, all group comparisons), whereas dyslipidemia was associated with ADP high-responsive platelets and venous thromboembolism with epinephrine high-responsive platelets in the LTA (p<0.05). Common variants in GPVI (rs1613662, rs1671152) demonstrated predictive impact on platelet ADP hyperaggregability and rs3737224 (PEAR1) and rs11575845 (MPIG6B) on platelet epinephrine hyperaggregability (p<0.05).

Conclusion This study identifies common and specific cardiovascular and genetic determinants of platelet ADP and epinephrine hyperresponsiveness independent of established confounders. Evaluation of platelet ADP/epinephrine hyperaggregability may provide 1) diagnostic value for platelet hyperactivity in atrial fibrillation, dyslipidemia, and VTE and 2) benefits for personalized antiplatelet treatment.