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

Aims Circulating monocyte-platelet aggregates (MPA) and CD14 + /CD16 + monocytes are elevated in symptomatic patients with atherosclerotic cardiovascular disease. The aim of this study was to investigate their utility in prediction of early atherosclerosis in asymptomatic subjects, in comparison to a traditional cardiovascular risk calculator, QRISK3. Methods Asymptomatic patients attending the hypertension clinic at Guy’s & St Thomas’ Hospitals, London, and healthy volunteer subjects recruited by advertisement, were enrolled (n = 39). Blood (30 mL) was processed for flow cytometry to measure CD14 and CD16 expression on monocytes, and CD14 + CD42b + MPA. Using these measurements, a novel index termed the Monocyte Atherosclerotic Risk Score (MARS) was developed. All subjects also underwent carotid artery ultrasonic angiography. Results Both QRISK3 and MARS correlated significantly with carotid intima-media thickness (cIMT); however, the correlation was much closer for MARS (r 2 = 0.8705, P < 0.0001) than for QRISK3 (r 2 = 0.3012, P = 0.0025). ROC analysis revealed MARS to be highly predictive both of cIMT-determined high cardiovascular risk (C-index = 0.9273, P = 0.0001) and presence of carotid plaque (C-index = 0.9385, P = 0.0022), whereas QRISK3 was not. Conclusions MARS appears superior to QRISK3 in predicting both cIMT and carotid plaque disease. This may help to better identify asymptomatic individuals who would benefit from targeted imaging investigations and prophylactic therapies. LAY SUMMARY In healthy people with no clinical evidence of cardiovascular disease, prediction of risk of atherosclerotic disease (including coronary heart disease and stroke) is notoriously unreliable; although traditional cardiovascular risk calculators work well at a population level, they are much less reliable in individuals. We have developed a blood based biomarker, which we term MARS, which is highly predictive of silent atherosclerosis: much more so than the traditional risk calculator QRISK3, currently in use in the UK. This opens the way to develop a blood test which can be applied clinically to more precisely identify healthy individuals who are at high cardiovascular risk, and who would therefore benefit from further imaging investigations and intensive treatment of cardiovascular risk factors.