Cardiometabolic risk factor burden associates with an immature platelet profile.

Cardiometabolic risk factors, obesity, diabetes and hyperlipidemia contribute to cardiovascular disease (CVD). While platelets are involved in CVD pathogenesis, the relationship between risk factor burden on platelet indices and the platelet transcriptome remains uncertain. Blood was collected from CVD-free adults, measuring platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and absolute immature platelet fraction (AIPF) by hemogram. Platelets were isolated and analyzed via RNA sequencing. Participants were stratified by number of cardiometabolic risk factors (diabetes, obesity, hyperlipidemia). We calculated median (IQR) values of platelet indices and p-for-trend via linear regression across risk factor burden. To evaluate the association between risk factor burden and platelet transcripts, we performed multivariable linear regression adjusting for age, sex, and race/ethnicity. Among 141 participants, (50.5 ± 14.8 years, 42% male, 26% Black) risk factor burden was associated with increasing platelet size, IPF, and AIPF but not platelet count. Platelet RNA sequencing identified 100 differentially expressed transcripts ( < .01; 66 upregulated, 34 downregulated). Gene ontology enrichment analysis demonstrated upregulated pathways of secondary metabolic processes (NES = 1.96,  < .01), and hematopoietic stem cell proliferation (NES = 1.95,  < .01). Greater cardiometabolic risk factor burden is associated with increased platelet size and immaturity and suggesting novel platelet-mediated mechanisms linking risk factor burden with CVD.