A novel monocyte-based biomarker of cardiovascular risk: comparison with QRISK3

TEXT ABSTRACTO_ST_ABSBackgroundC_ST_ABSTraditional cardiovascular risk calculators estimate population-level risk but perform less reliably at the individual level and do not capture biological processes that underlie early atherogenesis. Monocyte activation and platelet-monocyte interactions contribute to early atherogenesis, yet their potential as biomarkers of silent disease in asymptomatic adults has not been defined. The aim of this study was to investigate their utility in prediction of early atherosclerosis in asymptomatic subjects, in comparison to traditional cardiovascular risk calculators. MethodsAsymptomatic adults in a discovery cohort (n=39) underwent flow cytometric profiling of monocyte subsets and monocyte-platelet aggregates (MPA), together with carotid ultrasonography to assess carotid intima-media thickness (cIMT) and plaque. From these data, we derived a composite biomarker, the Monocyte Atherosclerotic Risk Score (MARS). Cardiovascular risk was calculated using QRISK3. An independent validation cohort of clinically healthy subjects (n=151) attending the Physical Examination Centre at Drum Tower Hospital, Nanjing, China, underwent identical biomarker and imaging assessments, with cardiovascular risk calculated using China-PAR. ResultsIn the discovery cohort, MARS showed a strong association with cIMT (r{superscript 2}=0.87, P<0.0001), substantially outperforming QRISK3 (r{superscript 2}=0.30, P=0.003). MARS predicted high-risk cIMT (AUC 0.93, P=0.0001) and carotid plaque (AUC 0.94, P=0.0022), whereas QRISK3 did not. In the validation cohort, MARS again discriminated individuals with carotid plaque (AUC 0.81, P<0.0001), while China-PAR showed no significant predictive ability. ConclusionsThe MARS biomarker generated from flow cytometric profiling detects silent atherosclerosis with higher accuracy than QRISK3 or China-PAR in two independent and ethnically different asymptomatic populations. These findings support further evaluation of MARS as a scalable blood-based tool for identifying individuals who may benefit from targeted imaging and preventive strategies.