Abstract
Introduction: Metabolomic biomarker profiling by Nuclear Magnetic Resonance (NMR) is a powerful technique to examine molecular signatures for heart failure risk and clarify pathological differences to cardiovascular outcomes. Hypothesis: Blood lipids and metabolite biomarkers may differ in how they relate to prediction of heart failure vs coronary and stroke outcomes. Methods: We measured detailed plasma lipids and metabolites by NMR metabolomics in ~250,000 individuals from UK Biobank. We assessed shared and discordant biomarkers for heart failure hospitalisation in relation to myocardial infarction, ischemic stroke, peripheral artery disease, cardiac arrest and cardiovascular death. During 10 years of follow-up, 7.800 incident heart failure hospitalisation events occurred and 5-10.000 incident events for cardiovascular outcomes. Results: The overall pattern of biomarker associations differed for heart failure compared to for example, myocardial infarction, with biomarkers of LDL metabolism and apolipoprotein being especially discordant (Figure). In contrast, biomarkers of chronic inflammation and circulating fatty acids were concordant for the risk of heart failure and myocardial infarction. There were also prominent differences in the metabolic biomarker signatures for the risk of different types of cardiovascular diseases, such as between chronic ischemic heart disease, and different types of stroke. The biomarker association magnitudes were strongest for cardiovascular mortality and especially strong for short time to event onset. Conclusions: Heart failure and different cardiovascular endpoints have partly different metabolic biomarkers signatures. These may represent pathophysiological differences and have relevance for cardiovascular risk prediction, especially if using the five-point major adverse cardiovascular event definition.
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