The current understanding of cardiovascular disease (CVD) is largely centered on dyslipidemia, where certain lipoproteins are considered atherogenic and can be targeted through lifestyle, diet, or pharmaceuticals. Complex metabolic changes associated with metabolic syndrome and diabetes has further broadened the perspective to also include lipoprotein particle number and size, with certain lipoprotein characteristics showing stronger atherogenic potential. Notably, ratios such as LDL-C/apoB and TAG/HDL-C, surrogate markers of LDL particle size, are robust predictors of metabolic syndrome and type 2 diabetes. Dietary intervention studies have shown that specific dietary compositions can modulate both concentration and size of lipoprotein, though the clinical implication of these broader lipid profile changes remain unclear. Beyond dyslipidemia, CVD is also increasingly recognized as an inflammatory disorder, where heightened immune activation and circulating inflammatory markers are proposed to play a central role at all stages of disease development. It is well known that the metabolic changes occurring during development of metabolic syndrome and type 2 diabetes involves systemic inflammation. Interestingly, recent UK Biobank findings using NMR biomarkers revealed that some lipid fractions traditionally considered atherogenic were, somewhat surprisingly, associated with favorable health outcomes, including increased longevity, while reinforcing the negative impact of inflammatory biomarkers on overall health. The UK biobank dataset presents a unique opportunity to investigate how a broad range of lipoprotein-lipid markers relate to inflammatory markers, measures of blood glucose, and dietary factors. By examining how these factors interact, in males and females and in the context of insulin resistance, we aim to evaluate the prognostic value of lipoprotein-lipid markers in predicting CVD risk and mortality, and their relative importance at different disease stages.
