PB0852 - Platelet reactivity is associated with arterial tonometry, vessel diameters and calcium burden

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Jason A. Cunha, B.A.

Postbaccalaureate IRTA Fellow
National Heart Lung and Blood Institute, Division of Intramural Research, Bethesda, MD, USA
Framingham, Massachusetts, United States

Co-Author(s)

Melissa V. Chan, PhD

Post-Doctoral Fellow
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States
BN

Bongani B. Nkambule, PhD

Post-Doctoral Fellow
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States
FT

Florian Thibord, PhD

Post-Doctoral researcher
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States
AL

Amber Lachapelle

Research Associate
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States
Robin E. Pashek

NIH IRTA Post-Baccalaureate Fellow
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States
RV

Ramachandran Vasan

Principal Investigator and Director of the FHS, and Director of the FHS fellowship program in cardio
Boston University
Boston, Massachusetts, United States
JR

Jian Rong

RESEARCH ASSISTANT PROFESSOR, NEUROLOGY; Investigator, Framingham Heart Study
Boston University
Framingham, Massachusetts, United States
EB

Emelia Benjamin

Associate Provost for Faculty Development
Boston University
Boston, Massachusetts, United States
NH

Naomi Hamburg

Joseph A Vita, MD Professor, Medicine
Boston University
Boston, Massachusetts, United States
MC

Ming-Huei Chen

Staff Scientist
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, Massachusetts, USA
Framingham, Massachusetts, United States
GM

Gary Mitchell

President
Cardiovascular Engineering Inc
Framingham, Massachusetts, United States
Andrew D. D. Johnson, PhD

Professor
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States

Background: Arterial tonometry and aortic and coronary calcium measures are useful indicators of cardiovascular disease (CVD) risk. Prior studies found positive associations between serum vascular growth factors (angiopoietin-2), tonometry measures (carotid-femoral pulse wave velocity, mean arterial pressure) and CVD risk. Activated platelets release angiopoietin-1, P-selectin and microvesicles, which may provide a link between vascular structure and platelet function.

Aims: We analyzed platelet function, arterial tonometry, aortic and coronary calcium, and aortic diameters measured in the Framingham Heart Study’s Gen3/NOS/Omni-2 cohorts. We hypothesized that higher platelet reactivity would be associated with subclinical CVD measures, including arterial stiffness and higher calcium (Agatston) scores.

Methods: Platelet reactivity data in whole blood or platelet rich plasma was collected by 5 assay platforms in up to 7 agonists in n=3,429 individuals as previously described (Grech et al. PMID 34939182). We used linear mixed effects models with platelet reactivity phenotypes as outcomes adjusting for CVD risk factors (age, sex, aspirin-use, body mass index, height, heart rate, hypertension medication, lipid medication, total cholesterol:HDL, diabetes, smoking) and accounting for family structure. Calcium values were assessed as ln-transformed (Agatston+1).

Results: Higher vessel calcium displayed a pattern of association with higher platelet reactivity (Fig.1), whereas larger vessel diameters were generally associated with lower platelet reactivity. The arterial tonometry measures (niCFPWV, CPP, AI, GRC, Pf, and Zc) had a combination of positive and negative associations with platelet aggregation measures, including regions with opposite relations between niCFPWV and Zc, which are likely mediated by diameter effects.

Conclusion(s): . Vessel diameter associations are consistent with lower shear environments invoking less platelet reactivity, as platelets can be provoked by shear forces alone, and are potentiated by higher shear. The associations with vessel calcium suggest subclinical atherosclerosis may provoke platelet activation through multiple pathways of activation, thereby contributing to increased thrombosis risk.