#012 Dr. Ronald Krauss on LDL Cholesterol, Particle Size, Heart Disease & Atherogenic Dyslipidemia
Aug 27, 2015
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Dr. Ronald Krauss discusses cholesterol, LDL vs HDL, dietary impact on heart health, misconceptions about cholesterol & CVD risk, statins, and refining risk assessment through cholesterol particle size measurement in an enlightening and informative episode.
LDL particle size impacts heart disease risk, with small dense particles posing greater danger due to artery wall accumulation.
Dietary factors like saturated fats and carbohydrates influence lipoprotein metabolism and heart disease risk differently.
Statins primarily target larger LDL particles, with limited efficacy in reducing small LDL particles, emphasizing the need for precision medicine.
Deep dives
Understanding LDL and HDL Cholesterol
LDL and HDL cholesterol play critical roles in heart disease risk. LDL cholesterol encompasses different particle sizes ranging from small and dense to large and buoyant, with smaller particles associated with higher heart disease risk. Despite higher LDL cholesterol being linked to heart disease, the smaller dense particles pose more danger due to their tendency to accumulate in artery walls and cause damage. On the other hand, HDL cholesterol, known as 'good' cholesterol, plays a role in removing excess cholesterol from tissues, lowering heart disease risk. Atherogenic dyslipidemia, characterized by high small LDL, low HDL, and high triglycerides, is a crucial measure of heart disease risk.
Formation and Impact of Small Dense LDL Particles
The formation of small dense LDL particles primarily originates in the liver, where triglycerides are packaged into VLDL particles that give rise to LDL particles. As these particles travel in the bloodstream, they shrink due to triglyceride breakdown, leading to the creation of small dense LDL particles. These smaller particles have reduced affinity for LDL receptors, causing them to circulate longer and potentially contribute to atherosclerosis. The binding of lipopolysaccharides (LPS) to these particles, derived from gut bacteria, might aid in endotoxin sequestration, affecting cardiovascular health.
Impact of Dietary Factors on Lipoprotein Metabolism
Dietary factors, including saturated fats and carbohydrates, influence lipoprotein metabolism and heart disease risk. While saturated fats can increase large LDL particles, high-carbohydrate diets, especially those rich in simple sugars like fructose, promote the production of small LDL particles. Processed starches have a higher glycemic index, potentially affecting lipoprotein metabolism. Understanding the interplay between different dietary components, such as saturated fats and added sugars, is crucial for deciphering their combined impact on heart health.
Phenomenon of Parallel Research on Dairy Fats and Metabolic Benefits
There has been a significant focus on exploring the potential metabolic benefits of consuming dairy fats, deviating from conventional recommendations. While acknowledging the importance of research funding, particularly from philanthropic sources, there remains a necessity for robust and comprehensive studies in this area. Notable advancements in understanding the impact of foods on cholesterol levels have reshaped public perspectives, shifting away from the assumption that saturated fats are solely responsible for heart disease.
Statins' Effects on LDL Cholesterol and Small LDL Particles
Research has delved extensively into the effects of statins on LDL cholesterol, with a particular emphasis on the differential impact on small LDL particles. While statins primarily target larger LDL particles for reduction, their efficacy in lowering small LDL particles is comparatively limited. Despite this, the overall cardiovascular benefits of statins, notably in reducing heart disease risk, remain firmly established. However, concerns regarding potential adverse effects, including the development of type 2 diabetes, underscore the importance of precision medicine approaches to optimize statin therapy and patient selection.
Dr. 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. He developed an assay that allows the quantification of low density lipoprotein particle size and concentration (known to the wider world as LDL cholesterol) based on a technique which determines the size of the particle based on physics...meaning the speed at which it flies through the air.
In this episode, we discuss...
(00:00) Introduction
(03:58) An overview of lipoproteins – HDL, LDL, and VLDL
(09:32) Cholesterol is a “passenger” on a train
(12:09) LDL vs HDL - why one is dangerous and the other isn’t
(17:42) Raising HDL doesn’t reduce heart disease risk the same way as lowering LDL
(19:13) Leaky gut and inflammation increase VLDL production to protect the body
(30:38) The misconception that dietary cholesterol significantly raises blood cholesterol
(40:56) Saturated fats vs carbohydrates in raising cholesterol and CVD risk
(53:08) Statins are a reliable, but imperfect, therapy for lowering CVD risk
(01:08:20) Measuring cholesterol particle size refines risk assessment and informs medication use