Summary
Paul Saladino and Mike Fave unpack their views on lipids, true cardiovascular disease risk, and when elevated LDL cholesterol actually warrants concern. They discuss primary versus secondary prevention, lipid-lowering drugs, blood markers, imaging techniques for metabolic function, and gene mutations related to cholesterol metabolism.
Key Points
- When elevated LDL cholesterol is truly concerning vs. benign
- Primary vs. secondary prevention for cardiovascular disease
- Blood markers and imaging for assessing metabolic function
- Gene mutations affecting cholesterol metabolism
- Nuanced view on lipid-lowering drugs and statins
Key Moments
12 blood markers beyond LDL that actually show cardiovascular risk
Mike Fave enumerates the blood markers that provide a complete cardiovascular risk profile beyond a basic lipid panel. These include high-sensitivity CRP, homocysteine, oxidized LDL, myeloperoxidase, lipoprotein phospholipase A2, parathyroid hormone, D3, fasting insulin, glucose, hemoglobin A1C, and C-peptide. The lipid panel alone gives marginal information. LDL values are indirect risk factors that must be interpreted alongside direct vascular markers and metabolic health indicators.
"high sensitivity CRP, homocysteine, oxidized LDL, myeloperoxidase, lipoprotein, phospholipase A2, parathyroid hormone D3, insulin, glucose, hemoglobin A1C, and possibly C-peptide if you're diabetic."
Feldman study: LDL of 272 average with zero plaque correlation on CCTA
Saladino and Fave discuss the Dave Feldman CCTA study where 80 lean mass hyperresponders with a mean LDL of 272 mg/dL and a maximum of 591 showed no correlation between LDL elevation and plaque formation. The same incidence of cardiovascular disease was found in people with average LDL levels at a comparison site. Additionally, a study of nearly 1,200 people with genetic familial hypercholesterolemia found that 45% had a CAC score of zero despite average on-treatment LDL of 158.
"the average LDLC was 272 milligrams per deciliter and a max of 591."
Doctors never check fasting insulin but want to prescribe statins
Saladino is frustrated that 99.9% of patients he asks in DMs or in person report their doctor never checked fasting insulin before recommending a statin. He argues this is an antiquated medical paradigm. The association between LDL and atherosclerosis breaks down in metabolically healthy individuals as shown by the Framingham study when stratified by HDL, CAC scores of zero, and HDL-to-triglyceride ratios. Yet mainstream medicine, promoted by figures like Peter Attia, continues to insist LDL causes atherosclerosis without contextual analysis.
"did your doctor do any other blood work to look at your cardiovascular risk? And they say, no, they just basically do a lipid panel."
