OBJECTIVES: Advancements in analytical technologies and increasing use of Machine Learning make available a wide set of new possible biomarkers from lipidomics as possible predictors of cardiometabolic disease risk. However, from a cost-effectiveness point of view, decisions on which tests to order should consider the improvement over the existing knowledge brought by these new biomarkers in predicting the outcome of interest. By state-of-the-art statistical methods we evaluated whether and which of a set of lipids, derived from targeted plasma lipidomics profile of stable CAD patients (H2020-689068-SMARTool project clinical trial), can significantly contribute to improve the performances of the Minimal Risk Tool (MRT), a pre-test model developed in a secondary analysis of the PROMISE trial to identify patients with chest pain but normal coronary arteries and no clinical events during follow-up hence deriving minimal benefit from diagnostic tests.

METHODS: The association between a set of triglycerides, ceramides and sphyngomielines and the minimal risk endpoint was checked by the Mann–Whitney test. The MRT was validated by regression methods considering calibration in-the-large, overall and specific effect of predictors. The re-estimated model (reMRT) was used as a baseline model in a Likelihood Ratio Test to assess the added predictive value of each associated lipid. A sensitivity analysis was carried out by considering two alternative baseline models developed on the cohort.

RESULTS: Triglycerides did not bring any significant improving contribution. The reMRT predictive capability was significantly improved by Cer(d18:1/16:0) and SM(40:2) (p ≤ 0.01), and weakly by SM(41:1) (p = 0.052). Other sphingolipids bringing significant predictive improvement to the alternative models were SM(34:1), SM(41:2), SM(38:2) and SM(42:4).

CONCLUSIONS: Patient-specific plasma lipidomics is a promising source of diagnostic biomarkers, exploitable not only to assess the risk of obstructive CAD but also to rule-out subjects without coronary atherosclerosis, then meeting the need of a more appropriate use of imaging diagnostic testing.