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High-density lipoprotein and inflammation in cardiovascular disease

Published:January 19, 2016DOI:https://doi.org/10.1016/j.trsl.2016.01.006
      Great advances are being made at the mechanistic level in the understanding of the structural and functional diversity of high-density lipoprotein (HDL). HDL particle subspecies of different sizes are now known to differ in the protein and lipid cargo they transport, conferring on them the ability to perform different functions that in aggregate would be expected to provide protection against the development of atherosclerosis and its downstream clinical consequences. Exacerbating what is already a very complex system is the finding that inflammation, via alteration of the proteomic and lipidomic composition of HDL subspecies, can modulate at least some of their functional activities. In contrast to the progress being made at the mechanistic level, HDL epidemiologic research has lagged behind, largely because the simple HDL biomarkers used (mainly just HDL cholesterol) lack the needed complexity. To address this deficiency, analyses will need to use multiple HDL subspecies and be conducted in such a way as to eliminate potential sources of confounding. To help account for the modulating influence of inflammation, effective use must also be made of inflammatory biomarkers including searching systematically for HDL-inflammation interactions. Using nuclear magnetic resonance (NMR)-measured HDL subclass data and a novel NMR-derived inflammatory biomarker, GlycA, we offer a case study example of the type of analytic approach considered necessary to advance HDL epidemiologic understanding.

      Abbreviations:

      Apo (apolipoprotein), BMI (body mass index), CAD (coronary artery disease), CHD (coronary heart disease), CVD (cardiovascular disease), HDL (high-density lipoprotein), HDL-C (HDL cholesterol), HDL-P (HDL particle concentration), HPS (Heart Protection Study), hsCRP (high-sensitivity C-reactive protein), IRAS (Insulin Resistance Atherosclerosis Study), JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), LDL (low-density lipoprotein), LDL-C (LDL cholesterol), LDL-P (LDL particle concentration), LP-IR (lipoprotein insulin resistance index), MESA (Multi-Ethnic Study of Atherosclerosis), MPO (myeloperoxidase), NMR (nuclear magnetic resonance), PON1 (paraoxonase-1), PREVEND (Prevention of Renal and Vascular End-stage Disease), RA (rheumatoid arthritis), SAA (serum amyloid A), T2D (type 2 diabetes), VLDL (very low-density lipoprotein)
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