PB0884 - Platelet hyperaggregability in Framingham Heart Study participants living with obesity

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

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

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
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
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
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
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
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
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: Obesity is an independent risk factor for non-communicable disease and the most prevalent comorbidity associated with poor prognosis in thrombotic disorders. Persistent platelet activation and chronic immune activation contribute to a hypercoagulable state in obesity

Aims: To assess platelet function in Framingham Heart Study (FHS) participants living with obesity.

Methods: We included 3,429 participants from the Framingham Heart Study (FHS) Third Generation cohort, New Offspring Spouse (NOS) and OMNI cohort. We excluded participants (n=24) who were classified as underweight (BMI < 18.5) and (n=2) who had missing data. A total of 3,403 Eligible participants were categorized into four subgroups based on the WHO body mass index (BMI) classification. We assessed the levels of adenosine diphosphate (ADP)-induced platelet degranulation (%CD62P expression) and integrin activation (%PAC-1 binding) using flow cytometry. In addition, we assessed agonist-induced aggregation (3.19µM ADP, 0.061 mg/mL, collagen, 4.48µM TRAP-6 amide) using whole blood impedance aggregometry.

Results: The included FHS participants comprised of 28.8% lean individuals (BMI < 25; n=979); 36.9% participants classified as overweight (BMI=25.0-29.9; n=1255); 29.4% participants living with Class 1 obesity (BMI>30.0; n=1001), and 4.9% Class 2 or 3 obesity (BMI≥35.0, n=168). In participants with class 1 obesity, the levels of ADP-induced %PAC-1 binding were decreased (ß=-0.11, SE=0.05, P=3.23E-02) when compared to lean participants. In addition, participants who were classified as overweight, had hyper-aggregable platelets in response ADP (ß=0.16, SE=0.16, P=1.74E-04); collagen (ß=0.11, SE=0.04, P=5.46E-03); TRAP-6 (ß=0.17, SE=0.04, P=8.73E-05) compared to lean individuals. Lastly, in participants with class 1 obesity, platelets were hyperreactive to ADP (ß=0.17, SE=0.047, P=2.8E-04) and TRAP-6 (ß=0.29, SE=0.05, P=1.33E-09).

Conclusion(s): In individuals with obesity, platelets are hypo-responsive to ADP-induced integrin activation and hyper-responsive to ADP, and TRAP-6 induced aggregation.