Abstract

Background: HDL cholesterol, together with LDL-c and triglycerides, are biomarkers widely used to assess risk of myocardial infarction (MI). Thereafter, apoA1 and HDL particle number (HDL-P) were identified as biomarkers inversely associated with risk of MI. State-of-the-art nuclear magnetic resonance spectroscopy allows for profiling of lipidomic markers within HDL, providing an unprecedented opportunity to identify novel biomarkers of MI. Methods: We examined associations between HDL lipid components and risk of MI in the UK Biobank. We leveraged the most up to date lipidomic data measured by NMR. A total of 8229 MI incidents were documented among 249,140 participants over a median 17.7 years of follow-up. Results: Independent of existing risk factors including LDL-c, triglycerides, apo-A1, HDL-P, the percentage of cholesterol over total lipids in HDL was inversely associated with the risk of MI with Hazard Ratio (HR) of 0.85 (0.76, 0.95), when comparing the highest quintile to the lowest. The percentage of triglycerides in HDL was positively associated with 1.13 (1.01, 1.26). We created the ratio of cholesterol to triglyceride within HDL and found it to be inversely associated with risk of MI (HR=0.89 [0.79, 0.99]). This finding is robust and consistently supported across subclasses of HDL. Conclusions: The ratio of cholesterol to triglycerides within HDL particles may be a new marker of risk for MI, independent of existing biomarkers. Table 1 . Hazard Ratios for Myocardial Infarction (MI) across Percentages of Lipids in HDL. Model 1: Cox model adjusted for conventional covariates: Age, Sex, Race, Body Mass Index, Hypertension status, Statin Use, Type 2 Diabetes status, Smoking, Education, Alcohol intake, and Townsend Deprivation Index, LDL-C, and TriglyceridesModel 2: Cox model adjusted for Model 1 covariates plus Apolipoprotein A1 and HDL particle number.

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