← The Peter Attia Drive

#03 - Ron Krauss, M.D.: a deep dive into heart disease

Jul 2, 2018 1h 56m 21 insights
<p>Whenever I'm stumped on a patient case or in my thinking about lipids, Ron is one of the first people I turn to for insight. Ron is recognized globally for his research into lipidology and has worn many hats in his career, including clinician, lipidologist, nutrition, genetics, and drug research.</p> <p>In this episode, we explore heart disease at its origins before diving into the highly discussed, largely misunderstood, role of LDL and inflammation in atherosclerosis. Ron also shares his insights on the evidence for and against statins and other lipid-lowering therapies. My hope is that both the curious patient and the physician can get a lot out of this episode by being more informed about dyslipidemia and the interventions used to reduce the risk of atherosclerotic disease. We covered a lot of ground on this critically important topic.</p> <p> </p> <p>We discuss:</p> <ul> <li>The pathogenesis of atherosclerosis [7:00];</li> <li>How early atherosclerosis begins [12:40];</li> <li>Ron's motivation for getting into lipidology [43:00];</li> <li>How reading an article series in the NEJM in 1967 had a profound impact on him and his career [43:30];</li> <li>How PCSK9 inhibitors work and why they may be under-utilized [47:00];</li> <li>Mendelian randomization: nature's randomized trial [49:15];</li> <li>The "battle" between particle size and particle number [52:00];</li> <li>The use of statins [1:04:45];</li> <li>The role of chronic inflammation in atherosclerosis [1:24:15];</li> <li>Why niacin may have been unjustly dismissed as a therapeutic option [1:40:45];</li> <li>The HDL paradox: why drugs that raise HDL-C seem to raise (or have little impact on) heart disease risk [1:43:00];</li> <li>Lp(a) [1:47:45];</li> <li>And more.</li> </ul> <p> <span> Learn more at <a href="http://www.peterattiamd.com/"><span><u>www.PeterAttiaMD.com</u></span></a></span></p> <p> <span>Connect with Peter on <a href=""> <span> <u>Facebook</u></span></a> | <a href=""> <span> <u>Twitter</u></span></a> | <a href=""> <span> <u>Instagram</u></span></a></span></p>
Actionable Insights

1. Measure LDL Particle Number

Measure LDL particle number (LDL-P or ApoB) instead of just LDL cholesterol (LDL-C) to accurately assess cardiovascular risk, as the particle itself, not just the cholesterol mass, is the causal agent for plaque formation.

2. LDL is a Causal Factor

Recognize that LDL is a causal factor for heart disease, and lowering it is generally beneficial for reducing risk. However, remember that LDL particle number is the true causal agent, and LDL-C alone may not always reflect risk or treatment benefit.

3. Target Very Low LDL

Consider very low LDL levels (e.g., 10-20 mg/dL) as safe and beneficial, based on genetic evidence from individuals with lifelong low LDL due to PCSK9 loss-of-function mutations who do not develop heart disease.

4. Address Metabolic Syndrome

Actively address metabolic syndrome, characterized by high triglycerides, low HDL cholesterol, and a predominance of smaller LDL particles, as it is a significant underlying factor for cardiovascular disease.

5. Reduce Visceral Fat

Focus on reducing visceral fat, especially around internal organs, as it is a prevalent underlying factor contributing to metabolic syndrome and overall cardiovascular disease risk.

6. Monitor Inflammatory Markers (CRP)

Monitor C-reactive protein (CRP) levels as a marker for inflammatory risk, and aim to lower both LDL (or LDL-P/ApoB) and CRP for maximal cardiovascular protection, as they each contribute to risk.

7. Learn Heart Disease Signs

Educate yourself on the first signs of heart disease, as it is often a ‘silent killer’ with no premonitory symptoms, and early recognition can be critical for intervention.

8. Minimize Lipoprotein Residence Time

Be aware that the length of time lipoproteins circulate in the blood (‘residence time’) is critical; longer circulation, especially of smaller or remnant particles, increases their opportunity to cause arterial damage.

9. Monitor Glucose on Statins

If taking statins, monitor glucose levels regularly, as statins can increase the risk of developing diabetes, particularly in women and with higher doses.

10. Consider Pitavastatin for Myalgia

If experiencing statin-induced myalgias or concerned about diabetes risk, discuss trying pitavastatin (Livolo) with your doctor, as it appears to have a lower association with diabetes risk and potentially fewer muscle side effects.

11. Don’t Abandon Statins Prematurely

Do not abandon statins in favor of PCSK9 inhibitors unless truly statin intolerant, as statins provide additional anti-inflammatory and endothelial health benefits not necessarily replicated by PCSK9 inhibitors.

12. Niacin for Specific Lipid Profiles

Consider niacin as a therapeutic option for patients with high Lp(a) and/or a high number of small LDL particles, especially if statin intolerant or if PCSK9 inhibitors are not an option, as it specifically targets these risk factors.

13. Don’t Rely on HDL Raising

Do not rely on simply raising HDL cholesterol levels as a primary strategy for cardiovascular protection, as clinical trials have shown that increasing HDL alone does not consistently translate to reduced event risk.

14. PCSK9 Inhibitors for High Risk

If you have very high LDL and are statin intolerant, or if maximum statin therapy is insufficient, consider PCSK9 inhibitors as a potent option for lowering LDL and Lp(a).

15. Statin Caution: APOE4 Carriers

If you are an APOE4 gene carrier, exercise greater caution and discuss statin use with your doctor, due to theoretical concerns about potential interactions with brain cholesterol transport, though conclusive evidence is lacking.

16. Re-evaluate Elderly Statin Use

For elderly patients (over 75-80) on high-dose statins, discuss with your doctor whether reducing the dose or discontinuing might be appropriate, weighing the benefits against potential long-term risks like sarcopenia.

17. Address VLDL Remnant Cholesterol

Pay attention to VLDL remnant cholesterol levels, as these particles are highly pathogenic and often missed by standard lipid panels, especially in hypertriglyceridemia.

18. Ubiquinol for Statin Myalgias

For statin-induced myalgias, consider trying ubiquinol (CoQ10), potentially a highly absorbable liquid form, although the evidence for its efficacy in reversing symptoms is not conclusive.

19. Atorvastatin and Diabetes Risk

If on atorvastatin (Lipitor) and concerned about diabetes risk, discuss with your doctor if a switch to another statin like pitavastatin or rosuvastatin (Crestor) might be appropriate, as atorvastatin appears to carry a higher risk for diabetes.

20. Niacin for Elevated Triglycerides

For patients with moderately elevated triglycerides (150-400 mg/dL), niacin can be an alternative approach to lowering triglycerides and small LDL.

21. PCSK9 Inhibitors Target Larger LDL

If using PCSK9 inhibitors, be aware that they primarily lower medium and larger LDL particles, and may have less impact on smaller LDL particles, suggesting a potential complementary role for other therapies in some cases.