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All, We had a pretty long thread not too long ago about Total Cholesterol and Heart Attack Risk but as far as I can tell we haven't talked much about the relative value of a standard lipid panel vs. some of the newer tests for various LDL particle sizes, densities etc. I bring it up for two reasons: One is personal. A family member in their early 50s is an APOE4 carrier (single allele) and not surprisingly, has borderline high cholesterol (210 mg/dL total, 120 LDL, 55 HDL). They are otherwise thin, active, healthy with good fasting blood glucose. So it seems they are one of those borderline cases for statins, and I'm wondering whether getting their LDL particle sizes tested might provide some additional useful diagnostic information for making that decision. I would lean against starting statins in their case (due to possible side effects see below), but I'm wondering if the discovery that they have many (or very few) small dense LDL particles might tip the scales one way or the other. The second reason I bring it up is because I just listened to a long (1:20:00) but very interesting interview by Dr. Rhonda Patrick with Dr. Ronald Krauss, who appears to be a pioneer in research into cholesterol and CVD, the effects of diet on CVD risk, statin side effects, particle size testing etc. I found it really educational to learn more about the mechanics of atherosclerosis, e.g. the details of how inflammation is involved and why we might have evolved to work that way. How small LDL particles have the part of their surface structure occluded just where the liver's LDL-receptor tries to attach to them, making the small particles harder to clear from the bloodstream, making them stick around in the bloodstream for longer to get oxidized / glycated and to infiltrate the arterial walls. Lots of good stuff I didn't know before. But a couple caveats. I'm not an expert on the details of how atherosclerosis works, or anything about particle sizes, so while I found it interesting, I can't vouch for the validity of Dr. Krauss's perspective or the information he shared. And I will note that Dr. Krauss co-authored with Dr. Patty Siri-Tarino and several others a pretty poor and misleading meta-analysis which appeared to call into question the link between saturated fat and heart disease. Their meta-analysis has been roundly criticized briefly by Michael in this thread and more thoroughly by PlantPositive here. He also mentioned he's been sponsored by the dairy industry, and has a patent and receives royalties on a new cutting edge LDL particle measurement test called Cardio IQ® Lipoprotein Fractionation, Ion Mobility which is now available from Quest. So all that is to meant to suggest that one should take what Dr. Krauss says in this interview with a pretty grain of salt. I'd be curious to hear what anyone with more knowledge in the area has to say about particle size testing, as well as the information Dr. Krauss shares both about the etiology of atherosclerosis and the significance of "small dense" LDL particle count vs the standard LDL measure on a lipid panel, particularly for people with borderline risk of CVD. To his credit, Dr. Krauss acknowledges that particle testing isn't for everyone. People at either extreme (i.e. very low or very high LDL cholesterol) probably don't need it - for obvious and opposite reasons. It's only in the borderline cases, like my family member, where it might be helpful. He also said the standard heart attack risk calculators, which don't take into account anything about particle size, do a pretty good job, and particle size and counts doesn't add very much to their accuracy / predictive power. But he sticks by idea that mechanistically, it's the small dense LDL particles that matter most for CVD risk. He also talks about how statins do work, but don't work as well as you might think because they upregulate the liver's LDL-receptor, which is pretty ineffective at clearly the most atherogenic particles - the small dense ones. He talks about statin side effects (muscle pain / weakness, but especially increased risk of diabetes, particularly in women). He is very much in favor of diet and lifestyle interventions to manage CVD risk, but as a researcher and clinician, he says there is trouble both proving the benefits of diet/lifestyle on CVD risk in clinical trials, and convincing his patients to adopt diet and lifestyle modifications, due both to compliance issues, and also in terms of getting the funding to do the research to make a convincing case. He says it's much easier to both get funding for, and to conduct, research on statins and other pharmacological interventions, because there is money to be made, and compliance is much less of an issue. Whether or not Dr. Krauss is blowing smoke about the value of particle size testing, it seemed to my (admittedly relatively naive) ears that Rhonda had a good set of questions and Dr. Krauss had clear and well thought out set of answers. For anyone interested in the topic, check out the show notes below and give it a watch/listen and let us know what you think. --Dean Begin Show Notes ============== Dr. Ronald Krauss on LDL Cholesterol, Particle Size, Heart Disease & Atherogenic Dyslipidemia In this podcast, I interview my friend and colleague Dr. Ronald Krauss. Ronald Krauss, M.D. is the director of atherosclerosis research at Children’s Hospital Oakland Research Institute, Adjunct Professor at UCSF and UC Berkeley. Dr. Krauss is really one of the pioneering scientists that changed the way we all think about cholesterol and saturated fat. The work of Dr. Krauss has demonstrated that smaller, denser LDL particles, which he pioneered a test for, known as the "Ion Mobility" test, has special significance when it comes to determining risk of heart disease. Regrettably, this test is not yet universally employed in a clinical setting in the manner in which total LDL cholesterol is, however. This test is called Cardio IQ® Lipoprotein Fractionation, Ion Mobility and is offered by quest diagnostics. Dr. Krauss is responsible for having played a part in the actual guidelines used by the American Heart Association in his role as chairman of the Nutrition Committee. Additionally, Dr. Krauss has also served on both the Committee on Dietary Recommended Intakes for Macronutrients and the Committee on Biomarkers of Chronic Disease of the Institute of Medicine of the National Academy of Sciences. In this podcast, Ron and I discuss what HDL and LDL cholesterol are, what they do in the body and how they play a role in heart disease. We talk about what small, dense LDL particles are, how they form, what effect eating saturated fat versus refined carbohydrates have on LDL particle size and heart disease risk and more generally what the main risk factors for heart disease are. Ron also talks about the good, bad and the ugly of LDL-lowering drugs known as statins and much more. In this conversation, Ron and I discuss... Changes in the availability of funding for good nutritional research."It's a fact that NIH, which is the major funder of biomedical research in the world, has basically pulled the plug on clinical research support as a general area of emphasis. The infrastructure for doing good nutritional studies, in particular, has relied on a mechanism that is now being withdrawn." - Dr. Ronald M Krauss The important difference between consumption of dietary cholesterol, which has a negligible influence on heart disease risk, and cholesterol produced endogenously in the body (which can be a marker of risk, depending on a complete profile). The good, bad and the ugly of LDL-lowering drugs known as statins and much more. What differentiates fructose from fruit versus fructose as an added sugar, namely: speed of absorption, presence or absence of other beneficial compounds (fiber, micronutrients, polyphenols, etc.), and differences in dose. How LDL (low-density lipoprotein), and particularly the ApoB protein inside of LDL, is needed to transport cholesterol, triglycerides, and fatty acids throughout the bloodstream in order to deliver them to other tissues in the body that may need them. What small, dense LDL particles are, how they form, what effect eating saturated fat versus refined carbohydrates have on LDL particle size and heart disease risk and more generally what the main risk factors for heart disease are. The functional difference between large, buoyant LDL particles and small, dense LDL particles and introduces us to the traits of what he terms "atherogenic dyslipidemia." These traits consist of: High levels of small, dense LDL cholesterol. Low levels of HDL cholesterol. High levels of triglyceride-rich lipoproteins (very-low-density lipoproteins or "VLDL") and their remnants. How small, dense LDL particles increase the risk of atherosclerosis. There is only one ApoB protein per LDL particle, which is what enables ApoB to be a surrogate blood biomarker for LDL particle number. How access to the ApoB protein can become obscured due to conformation changes in the small, dense LDL particles. As the size of the particle decreases, this conformation change reduces the ability for the particle to bind to the LDL receptor and be recycled by the liver. How VLDL particles, the precursor to LDL, demonstrate an interaction with LPS (also known as endotoxin, a component of bacterial cell membranes), and how it's possible that some of the negative associations with this particle size may be a result of their simply being in the blood stream longer: this gives them a greater opportunity to undergo inflammatory transformations.This part is especially exciting to me because it may be an interesting link by which gut health (where much of the bacteria and immune cells in the body are located) and the importance of controlling inflammation to cardiovascular health. How saturated fat appears to increase the larger, more buoyant LDL particles, which do not have the same robust correlation to heart disease risk that the smaller, more dense particles do. Dr. Krauss also takes the stance that consumption of saturated fat does not have as strong of a link to heart disease risk as previously suggested by others, and may be less relevant except in the case of what he termed "hyper-responders." These "hyper-responders" have gene polymorphisms that cause them to respond differently to saturated fat. How increased carbohydrate consumption, especially simple sugars may have been an unintended consequence of the push for low-fat diets, and how this increased traits associated with atherogenic dyslipidemia: namely, a shift from the larger, more buoyant LDL particles to the smaller, more dense LDL particles. Broadly, the differences between the various types of lipoprotein particles, including very-low-density lipoproteins (VLDL), and high-density lipoprotein (HDL) and what their roles are in the body. This really is one of the better science-based podcasts I've posted to date. It's often a bit nuanced, but hopefully with the help of some of the annotations in the video you will find it as enriching as I have. Dr. Krauss is a real pioneer in the field and drops huge amounts of knowledge, so go check it out now! ============== End Show Notes