dyslipidemia

Allan Sniderman is a highly acclaimed Professor of Cardiology and Medicine at McGill University and a foremost expert in cardiovascular disease (CVD). In this episode, Allan explains the many risk factors used to predict atherosclerosis, including triglycerides, cholesterol, and lipoproteins, and he makes the case for apoB as a superior metric that is currently being underutilized. Allan expresses his frustration with the current scientific climate and its emphasis on consensus and unanimity over encouraging multiple viewpoints, thus holding back the advancement of metrics like apoB for assessing CVD risk, treatment, and prevention strategies. Finally, Allan illuminates his research that led to his 30-year causal model of risk and explains the potentially life-saving advantages of early intervention for the prevention of future disease.

We discuss:

• Problems with the current 10-year risk assessment of cardiovascular disease (CVD) and the implications for prevention [4:30];
  
• A primer on cholesterol, apoB, and plasma lipoproteins [16:30];
  
• Pathophysiology of CVD and the impact of particle cholesterol concentration vs. number of particles [23:45];
  
• Limitations of standard blood panels [29:00];
  
• Remnant type III hyperlipoproteinemia—high cholesterol, low Apo B, high triglyceride [32:15];
  
• Using apoB to estimate risk of CVD [37:30];
  
• How Mendelian randomization is bolstering the case for ApoB as the superior metric for risk prediction [40:45];
  
• Hypertension and CVD risk [49:15];
  
• Factors influencing the decision to begin preventative intervention for CVD [58:30];
  
• Using the coronary artery calcium (CAC) score as a predictive tool [1:03:15];
  
• The challenge of motivating individuals to take early interventions [1:12:30];
  
• How medical advancement is hindered by the lack of critical thinking once a “consensus” is reached [1:15:15];
  
• PSK9 inhibitors and familial hypercholesterolemia: two examples of complex topics with differing interpretations of the science [1:20:45];
  
• Defining risk and uncertainty in the guidelines [1:26:00];
  
• Making clinical decisions in the face of uncertainty [1:31:00];
  
• How the emphasis on consensus and unanimity has become a crucial weakness for science and medicine [1:35:45];
  
• Factors holding back the advancement of apoB for assessing CVD risk, treatment, and prevention strategies [1:41:45];
  
• Advantages of a 30-year risk assessment and early intervention [1:50:30];
  
• More.

In this episode, Dave Feldman, discusses his journey from software engineer to n=1 experimenter, his experience with low-carbohydrate diets, and his hypothesis that cholesterol levels are influenced by energy metabolism.

We discuss:

• Peter’s synthesis of Dave’s energy model [5:00];
• Dave’s journey from software engineer to cholesterol enthusiast [15:00];
• Standard blood panels, sterol panels, and what moves the needle when it comes to particle numbers [18:30];
• Hyper-responders [20:00];
• Lipoprotein transport [33:45];
• The lean mass hyper-responder phenotype [47:30];
• The progression of atherosclerosis, CAC, and CIMT [52:30];
• Testing for oxidized LDL [55:30];
• All-cause mortality and clinical endpoints [1:01:15];
• What does “LDL as causal” mean? [1:05:15];
• Dave’s low carb cholesterol challenge and drug & genetic study qualifications [1:13:15];
• If all other markers are in an healthy range, but LDL-P is high, is the patient at risk? A couple of case studies, and a self-experiment [1:27:30];
• Peter’s three-day exercise and ketosis experiment [1:41:00];
• What are remnant lipoproteins? [1:45:00];
• What might cause lean mass hyper-responders to have higher LDL particle numbers? [1:53:30];
• A case study from Dave of a lean mass hyper-responder [1:56:30];
• Mass balance and cholesterol flux [2:05:30];
• Can a higher degree of cholesterol explain the lean mass hyper-responder phenotype? [2:10:00];
• Peter’s LDL during his keto-fast-keto experiment [2:13:30];
• Does substituting saturated fats with monounsaturated fats lower LDL-P and LDL-C? [2:15:45];
• Dave’s carb-swap experiments [2:22:15];
• Dave’s carotid intima-media thickness tests [2:41:15];
• Looking for studies that stratify for high HDL-C and low TG alongside low and high LDL-C [2:53:00]; and
• More

Learn more at www.PeterAttiaMD.com

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