#24 - Tom Dayspring, M.D., FACP, FNLA – Part V of V: Lp(a), inflammation, oxLDL, remnants, and more

1. Get Checked for Preventable Diseases

Do not ignore preventable and treatable diseases like cardiovascular disease; get regularly checked and seek accurate advice based on correct metrics to avoid needless early deaths.

2. Focus on ApoB Particle Number

Prioritize lowering ApoB particle number (LDL-P) as it is the primary driver forcing particles into the arterial wall, leading to oxidation and plaque formation.

3. Utilize Biomarkers for Personalized Therapy

Employ a comprehensive panel of biomarkers to identify existing pathologies and individualize therapeutic suggestions, combining nutritional and pharmacological approaches as needed to normalize identified issues.

4. Address Insulin Resistance for Remnants

If you suspect remnants, address insulin resistance through nutritional therapy, including some degree of carbohydrate restriction and incorporating fasting, especially if not in a high-risk category requiring immediate pharmacology.

5. Measure ApoC3 Content of ApoBs

Seek a blood test for ApoC3 content of ApoB particles, as ApoC3-enriched LDLs are not effectively cleared and are a significant biomarker for cardiovascular risk, especially in those with high triglycerides.

6. Optimize ApoC3 Function for Longevity

Understand that hypofunctioning ApoC3 is a strong predictor of longevity, suggesting that optimizing ApoC3 function is crucial for long-term cardiovascular health.

7. Consider DHA to Lower ApoC3

If aiming to lower ApoC3, consider supplementing with DHA (docosahexaenoic acid), as it has been shown to lower ApoC3, unlike EPA.

8. Use High-Dose EPA to Lower ApoB

Consider high-dose, prescription-strength EPA as an adjunctive therapy to statins, as it can lower ApoB by an additional 8-10% and has other physiological benefits.

9. Assess Omega-3 Index via Red Blood Cells

To accurately assess your omega-3 status, measure red blood cell omega-3s (omega-3 index) which reflect long-term intake (30-90 day half-life), rather than transient plasma levels.

10. Measure LP(a) Particle Count

To accurately quantify dangerous LP little a particles, seek an LP little a particle count (LP(a)-P) assay, which uses electrophoresis and immunostaining, as traditional NMR assays lipid content, not protein content.

11. Measure ADMA/SDMA for Endothelial Function

Measure asymmetric (ADMA) and symmetric (SDMA) dimethyl arginine levels to assess endothelial function, as elevated levels indicate impaired nitric oxide synthesis due to reduced arginine availability.

12. Address Hyperhomocysteinemia

If you have hyperhomocysteinemia, address it (e.g., with methylated B vitamins for MTHFR mutations) as it inhibits the clearance of ADMA and SDMA, thereby impairing nitric oxide production and contributing to vascular pathology.

13. Prioritize Cystatin C for Renal Function

Use cystatin C instead of or in addition to creatinine for assessing renal function, especially in muscular individuals, as it is not influenced by muscle mass and provides a more accurate measure.

14. Utilize Dual EGFR for Best Renal Assessment

Seek a dual estimated glomerular filtration rate (eGFR) calculation based on both creatinine and cystatin C for the most comprehensive and accurate assessment of renal clearance.

15. Investigate Albuminuria

If albumin is present in your urine, investigate further as it signals a serious vasculopathy or kidney disease, indicating membrane problems in glomeruli or blood vessels.

16. Use ADMA/SDMA to Drive Lifestyle Change

In primary prevention, if ADMA/SDMA markers are elevated, use this as a signal of endothelial dysfunction to become super aggressive nutritionally and consider pharmacological interventions if lifestyle changes are insufficient.

17. Target Non-LP(a) LDL-P with Statins

If you have high LP little a, statins will primarily lower LDL particles that do not have ApoA attached, providing benefit even if your total LDL-P remains higher than desired due to the LP little a component.

18. Consider PCSK9 Inhibitors for LP(a)

If LP little a is high and affordable/covered, PCSK9 inhibitors can lower LP little a particle count by 30-50%, offering a more significant reduction than niacin.

19. Use Oxidative Markers for Nutritional Guidance

Measure oxidative markers like OXLDL, myeloperoxidase, or F2 isoprostanes to identify a pro-oxidative state and encourage nutritional therapies to combat it, as specific drugs or supplements for this are not yet definitively proven.

20. Assess Oxidized ApoB Phospholipids with High LP(a)

If you have high LP little a, consider assessing oxidized ApoB phospholipids (if available) as this indicates a ‘double whammy’ of risk, potentially guiding more aggressive interventions.

21. Investigate Omega-3 Supplement Form

Inquire about the specific esterification vehicle of your omega-3 supplement (e.g., mono-, di-, or triacylglyceride, or phospholipid) as this affects bioavailability and the presence of other fatty acids.

22. Ensure Adequate Pancreatic Enzyme Function

If taking esterified omega-3 supplements (most common forms), ensure healthy pancreatic enzyme function, as these enzymes are necessary to de-esterify the fatty acids for absorption.

23. Commit to Lifelong Learning

Continuously study and learn, especially in complex fields like medicine, as deep understanding requires sustained effort and is not acquired quickly.

24. Consult Experts for Complex Topics

For complex topics, seek guidance from recognized experts rather than relying solely on general internet information, as experts can provide nuanced and accurate insights.

25. Ground First Principles in Biology

While first principles thinking is valuable, in biology, always ground your theoretical conclusions in established facts and experimental data, as biological systems often defy simple derivations.

26. Exercise Caution with Niacin for LP(a)

While some lipidologists use niacin to lower LP little a by about 20% and lower ApoB, it does not improve HDL particle count and may even worsen HDL function by making HDLs bigger.

27. Exercise Caution with IL-1 Inhibitors

Be aware that IL-1 inhibitors, while effective in reducing inflammation and improving outcomes, are expensive and carry a risk of increased cancers due to serious inhibition of the immune system.

28. Limit LPPLA-2 Testing

LPPLA-2 is not a reliable pro-oxidative biomarker for predicting outcomes or guiding therapy, and its inhibitors have shown no outcome reduction; it may only be useful as a one-time screening in primary prevention.

29. Understand OXLDL Limitations

When measuring OXLDL in plasma, recognize it reflects ‘minimally oxidized’ ApoB (aldehydes on ApoB) and indicates a pro-oxidative state, rather than truly oxidized LDL particles which occur in the arterial wall.

30. Consider F2 Isoprostanes for Oxidation

To assess a pro-oxidative state, consider measuring F2 isoprostanes via a small urine sample, as this biomarker is clearly linked to oxidative stress.

31. Monitor SDMA for Renal Function

Use SDMA as an additional marker for renal function, as elevated levels can indicate renal disease and contribute to pathology by decreasing nitric oxide production.

32. Recognize VLDL Cholesterol as Poor Remnant Estimate

Understand that VLDL cholesterol (estimated by triglycerides/5 or non-HDL minus LDL cholesterol) is a poor and often inaccurate estimate of pathological VLDL remnants.

33. Use Correct Lipid Terminology

Use ‘LP little a’ (small case ‘a’) to refer to the potentially pathogenic, atherogenic LDL particle, and ’lipoprotein A’ or ‘apoprotein A1’ for the main apoprotein on an HDL particle, to avoid confusion.