Cardiovascular disease, the number one killer: development, biomarkers, apoB, cholesterol, brain health, and more | Tom Dayspring, M.D.
Peter Attia
Feb 3, 2025
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Tom Dayspring is a world-renowned expert in clinical lipidology and a previous guest on The Drive. In this episode, Tom explores the foundations of atherosclerosis and why atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide for both men and women. He examines how the disease develops from a pathological perspective and discusses key risk factors, including often-overlooked contributors such as insulin resistance and chronic kidney disease. He breaks down the complexities of cholesterol and lipoproteins—including LDL, VLDL, IDL, and HDL—with an in-depth discussion on the critical role of apolipoprotein B (apoB) in the development of atherosclerosis. Additionally, he covers the importance of testing various biomarkers, the impact of nutrition on lipid levels, and the vital role of cholesterol in brain health, including how cholesterol is synthesized and managed in the brain, how it differs from cholesterol regulation in the rest of the body, and how pharmacological interventions can influence brain cholesterol metabolism.
We discuss:
Defining atherosclerotic cardiovascular disease (ASCVD): development, risks, and physiological impact [2:45];
The pathogenesis of ASCVD: the silent development over decades, and the importance of early detection for prevention of adverse outcomes [10:45];
Risk factors versus risk markers for ASCVD, and how insulin resistance and chronic kidney disease contribute to atherosclerosis [17:30];
How hyperinsulinemia elevates cardiovascular risk [24:00];
How apoB-containing lipoproteins contribute to atherosclerosis, and why measuring apoB is a superior indicator of cardiovascular risk compared to LDL cholesterol [29:45];
The challenges of detecting early-stage atherosclerosis before calcification appears [46:15];
Lp(a): structure, genetic basis, and significant risks associated with elevated Lp(a) [55:30];
How aging and lifestyle factors contribute to rising apoB and LDL cholesterol levels, and the lifestyle changes that can lower it [59:45];
How elevated triglycerides, driven by insulin resistance, increase apoB particle concentration and promote atherosclerosis [1:08:00];
How LDL particle size, remnant
Mindsip insights from this episode:
Recognize atherosclerosis starts in childhood for early intervention
Autopsy studies reveal that the process of atherosclerosis, the deposition of cholesterol in artery walls, begins as early as childhood and even in the fetal stage.
Identify desmosterol biomarker to address statin brain fog
Cognitive 'brain fog' from statins may be linked to the over-suppression of a brain cholesterol synthesis marker called desmosterol, which can be measured in the blood.
Understand brain's unique cholesterol synthesis for optimal health
The brain synthesizes 100% of its own cholesterol, which has a half-life of five years, and it cannot be supplied by cholesterol from the rest of the body.
Address APOE4 gene impact on brain cholesterol transport
The APOE4 gene, a major risk factor for Alzheimer's, creates a protein that is less efficient at transporting essential cholesterol between brain cells.
Rethink HDL cholesterol levels as potential dysfunction markers
A high HDL cholesterol level does not guarantee protection and can even be a marker of dysfunctional HDL particles that fail to clear cholesterol effectively.
Monitor triglyceride levels below 100 mg/dL to assess cardiovascular risk
The pathological process linking triglycerides to increased cardiovascular risk begins at a level of 100 mg/dL, far below the standard 'high' cutoff of 150 mg/dL.
Reduce triglycerides to lower atherogenic APOB particles
High triglycerides cause LDL particles to become small and dense, which impairs their clearance by the liver and increases the total number of atherogenic APOB particles.
Prioritize APOB measurement over LDL cholesterol for cardiovascular risk assessment
Measuring the concentration of APOB particles is more important for assessing cardiovascular risk than standard LDL cholesterol, as it's the number of particles that drives atherosclerosis.
Recognize LP(a) as a major heart disease risk factor
The genetic lipoprotein(a), or LP(a), is seven to eight times more atherogenic per particle than a normal LDL particle and is a major risk factor for heart disease.
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