#381: Prof. Chris Packard – LDL Cholesterol, ApoB & Atherosclerosis

In Podcasts by Danny Lennon5 Comments

Guest Information

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Professor Chris Packard

Prof. Chris Packard holds an Honorary Professorship of Vascular Biochemistry at the University of Glasgow. Over his career, Professor Packard has focussed on two aspects of atherosclerosis research, lipoprotein metabolism and how it is affected by diets and drugs, and large-scale clinical trials of lipid lowering agents. He is acknowledged as one of the leading researchers in the world in this field.

Prof Packard has published widely on the kinetics of apolipoprotein B and apolipoprotein A metabolism. Key contributions include evaluation of the role of the LDL receptor in vivo, the discovery of metabolic channelling in the apoB lipoprotein delipidation cascade, and the formulation of models to explain the generation of small, dense LDL.

In this episode we discuss:

  1. Understanding systems biomarkers and independently causal factors
  2. Atherosclerosis development
  3. Markers of risk: LDL-C, ApoB, non-HDL-C, etc.
  4. What do we know about Lp(a) currently?
  5. What is the utility (and limitation) of a CAC score?
  6. Cholesterol transport vs. LDL-receptor upregulation as targets for treatment
  7. Is HDL fading from focus?
  8. The "lower is better" paradigm for LDL-C
  9. The LDL/old age "paradox"

Glossary:

  • LDL: Low-density lipoprotein
  • LDL-C: The cholesterol content of LDL particles.
  • ApoB: ApolipoproteinB - a protein structure found on various lipoproteins including LDL, IDL, VLDL and chylomicrons. But is not found on HDL particles. As one ApoB is found on each of those artherogentic particles, it gives a measure of the concentration of atherogenic lipoproteins in the blood.
  • ApoA: Apolipoprotein A is a protein structure found on high-density lipoproteins (HDL). Chylomicrons secreted from intestinal cells also contain ApoA, but it is quickly transferred to HDL in the bloodstream.
  • Non-HDL-C: The measurement of total cholesterol minus high density lipoprotein cholesterol.
  • CRP: C-reactive protein - a protein that is elevated in the blood in response to inflammation. Used as a marker of inflammation.
  • Troponin I: Cardiac troponin I is presented in cardiac muscle tissue. Cardiac troponin is a specific marker of myocardial injury and an independent predictor of cardiovascular mortality in patients with and without cardiovascular disease
  • WOSCOPS: West of Scotland Coronary Prevention Study - a trial of statin-based low-density lipoprotein (LDL) cholesterol-lowering therapy in men ages 45 to 64 years with raised serum cholesterol concentrations.
  • GWAS: A genome-wide association study (GWAS) is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait.

Links & Resources

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Comments

  1. Reply

    This is a brilliant discussion. Very enlightening and answers many questions that I have wrestled with for some time. Well done to all involved!

  2. Reply

    This hurt my brain at a whole new level. Perhaps include apo(a) in the glossary as well. Will go back and listen to the five previous podcasts again probably and go back to this one afterwards…

    1. Author
      Reply

      Hopefully in a good way! Yes, things got quite dense in this one, so hopefully it will all start fitting together after revisiting the other content.

  3. Reply

    Prof Packard mentioned that the study which showed that low LDL increased all-cause mortality included data from homicides. What that this study? https://www.bmj.com/content/371/bmj.m4266

    Is there anyplace where that issue is documented or discussed? Was it ever addressed by the study authors?

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