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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