Abstract 18914: Metabolomic Biomarker Profiling Improves Cardiovascular Risk Assessment for Patients on Statins: Evidence From 35000 Individuals From the United Kingdom

Introduction: Identification of individuals at high cardiovascular risk even when using statins can guide second line therapy for primary prevention.

Hypothesis: We addressed whether metabolomic biomarker profiling has utility in predicting onset of major adverse cardiovascular events (MACE) and heart failure among individuals already on statin therapy.

Methods: Circulating lipids, fatty acids, amino acids, glycolysis metabolites and inflammation markers were measured by NMR metabolomics in ~275,000 individuals from UK Biobank. The study population was filtered to people using statins at blood sampling, comprising 34,971 individuals. During 10-year follow-up, 2156 first occurrence MACE events and 1753 heart failure hospitalisation events occured. Using multivariable regression modelling, we derived separate 10-year residual risk scores for the first onset of MACE and heart failure. We assessed the predictive improvements of adding the metabolomic biomarkers to established risk factors and routine cholesterol measurements.

Results: Adding the metabolomic biomarkers to established risk factors and cholesterol measures improved AUC from 0.67 to 0.70 for 3-point MACE and from 0.68 to 0.71 for heart failure. Using only the metabolomic biomarkers from the low-cost NMR assay, along with age and sex, yielded a performance close to that of the full model, achieving AUC of 0.69 for 3-point MACE and 0.70 for heart failure. Substantial improvements were observed when looking at the high-risk tails of the risk scores. When comparing the highest risk decile to the remaining 90% of study population, adding the metabolomic biomarkers to established risk factors and cholesterols increased the hazard ratio from 2.2 (95% CI 1.9-2.6) to 2.8 (95% CI 2.4-3.3) for 3-point MACE and from 2.7 (95% CI 2.3-3.3) to 3.4 (95% CI 2.8-4.0) for heart failure, i.e. reaching comparable risk elevation as seen in familial hypercholesterolemia.

Conclusions: Metabolomic biomarker profiling by a low-cost NMR assay enhanced prediction of incident MACE and heart failure beyond established risk factors for individuals already on statin therapy. This may complement the residual risk assessment in primary prevention settings and guide second line therapy to those with most benefit.