0:26 Peter’s background and history with lipid research
Term used: Familial Hypercholesterolemia (“FH”) is a cluster of genetic abnormalities that result in high total or LDL cholesterol. If someone has Heterozygous Familial Hypercholesterolemia it means they got a copy of an FH gene from one parent only. If they have Homozygous Familial Hypercholesterolemia, they have a copy from both parents. Homozygous FH is considered more severe of the two.
6:20 For people who see their cholesterol rise on low carb, can Peter provide information on whether they should be concerned?
7:00 How big of a problem is heart disease in general?[
9:35 The physical progression of atherosclerosis[
11:54 Are the steps of atherosclerosis necessarily progressive? Can they be stopped or reversed?
16:15 The complexity of the lipid system – a long way to go to full understanding.[
17:20 The work of the Russian researcher Nikolai Anitschkow and what his rabbit study showed about the development of atherosclerosis
21:21 What does the research show regarding cholesterol level and heart disease outcomes/risk?
23:47 What does Peter say to the criticism that there can be possible cherry-picking for studies on cholesterol lowering and cardiovascular disease?
25:00 Thoughts on CETP Inhibitor trials – why did they fail? What does it mean?
Term used: CETP stands for Cholesterol Ester Transfer Protein. It is a protein which transfers cholesterol and triglycerides between the lipoproteins. There is a class of drugs which inhibits the actions of this protein, ultimately resulting in higher HDL-C and lower LDL-C.
29:30 Is LDL-C a causal factor in atherosclerosis?
33:05 Could there be other underlying problems with Familial Hypercholesterolemia other than high LDL?
Term used: CIMT stands for Carotid Intima-Media Thickness, it is an ultrasound that looks at the thickness of certain layers of the artery in the neck (the carotid). It is used as a measure of risk of heart disease, with thicker IMT being higher risk.
40:54 Caveat: The problems with CIMT measurements
43:16 Dave’s CIMT results – are they significant, and is there a danger of confirmation bias?
47:45 Comparing risk and context.
50:45 Could Lean Mass Hyper-responders be an example of paradoxical responders?
51:26 Case study – “Miss K.”[
57:04 Comparing treated versus untreated people who have Familial Hypercholesterolemia
1:04:03 Devil’s Advocate Intro
1:04:23 Are LDL particles, like macrophages, a part of the immune response? In addition is it possible that some of the association between LDL and atherosclerosis is due to this immune response?
Study mentioned: Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: prevalence of coronary and hypertensive heart disease and associated risk factors.
1:10:47 As more evidence emerges to stratify for this triad (high LDL-C, high HDL-C, and low triglycerides), do you likewise predict it will show lower risk for cardiovascular disease?
1:23:45 Many studies tout changes in risk for cardiovascular disease mortality, yet show no difference in all-cause mortality. Doesn’t this run the risk of misleading people to assume overall benefit where there is none?
1:32:30 Audience questions
1:32:42 Are there any CAC scan studies on people from before and after statin therapy?
Term used: CAC stands for Coronary Artery Calcification. It is a CT scan which looks for calcium in the arteries, the score is used as a risk marker for things like heart attack or all-cause mortality, with lower scores being better risk.
1:34:37 Does Peter know how to access databases to test the triad?
1:38:47 Does Peter have any thoughts on how young to start statin treatment in children with Familial Hypercholesterolemia? Is there any information on it interfering with growth, or adverse side effects?
1:44:04 Side effects and statins – is there a problem with using run ins?
1:49:42 Is the increase in residence time of LDL due to modification of the LDL (e.g. glycation, oxidation, etc).
1:50:40 Can LDL be present and not cause plaque?
1:51:31 What does Peter think about Vladimir Subbotin’s work, wherein he disputes that lipid deposition is the initiating factor for atherosclerosis, rather he states that excessive intimal hyperplasia is the initiating factor?
1:53:11 What about the impact on heart disease risk of genetic mutations which result in high LDL without affecting the cells ability to uptake lipids/lipoproteins (e.g. glycogen storage disease)?
2:01:18 Credits and Outro