Establishing reference intervals for triglyceride-containing lipoprotein subfraction metabolites measured using nuclear magnetic resonance spectroscopy in a UK population

Abstract

Background: Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. Methods: Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (<55, 55–65, >65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. Results: The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. Conclusion: This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.