Use ApoB as the primary marker for atherogenic lipoproteins because it is a more standardized immunoassay, is referenced in all contemporary guidelines, and may have fewer false positives compared to other LDL particle count methods.
Strive to achieve ApoB concentrations under 50 milligrams per deciliter, as this level is associated with the most significant risk reduction in clinical trials and is comparable to newborn levels.
Even after optimizing ApoB levels, thoroughly examine and treat all other factors that might be injuring the endothelium or arterial wall, as atherosclerosis is a multi-factorial disease.
Get an LP(a) test once as an adult, as it is a genetically determined marker that does not change significantly over time and helps in thorough cardiovascular risk assessment.
For elevated and problematic LP(a), maximally lower all other ApoB, optimize metabolic parameters (glucose, insulin, blood pressure), and control factors like uric acid and homocysteine.
Do not waste money, time, or brain energy on commercial HDL function panels (e.g., HDL size, ApoA1, ceramides) as they are not useful bedside metrics and lack proven clinical relevance.
Focus on VLDL cholesterol (as a proxy for remnants), ApoB, LP(a), and metabolic markers such as glucose, insulin, homocysteine, uric acid, and aggressive blood pressure management for comprehensive risk assessment.
To accurately track health biomarkers like ApoB, consistently use the same metric and assay, ideally from the same lab, to ensure results are comparable over time.
When deliberating statin therapy, especially with patient hesitancy, utilize adjunctive diagnostics like coronary artery calcium (CAC) scoring and LP(a) testing, alongside family history and other risk factors, to inform the decision.
For statin therapy, consider starting with a lower dose and optimizing ApoB lowering with a second drug like ezetimibe or bempedoic acid, rather than immediately using maximum statin doses, unless in acute high-risk scenarios.
Consider bempedoic acid as an ApoB-lowering option, especially for individuals with statin intolerance or muscle aches, as it is hepatoselective and does not have uptake in muscle cells.
For high-risk individuals seeking evidence-based omega-3 therapy, consider using 4 grams per day of EPA-only to reduce macrovascular outcomes, especially when combined with a statin.
Fibrates, particularly fenofibric acid, are underused and should be considered for individuals with triglyceride-rich lipoproteins and clear signs of insulin resistance or diabetes, as they show benefits for both macrovascular and microvascular endpoints.
If a fibric acid is indicated, prefer fenofibric acid (e.g., Trilipix) as it is considered the purest fibric acid and is not a pro-drug.
Niacin is no longer recommended in any major lipid guidelines for general lipid management due to lack of proven cardiovascular benefit and is considered a ‘dead drug’ by most lipidologists.
Do not be concerned about very low plasma LDL cholesterol levels (e.g., 30 mg/dL) as cells can synthesize their own cholesterol and are not deprived, given that plasma cholesterol is a tiny fraction of total body cholesterol.
Given the low cost of ApoB assays (e.g., $3-4), patients should advocate for this test as there is no economic excuse for physicians to avoid ordering it over more expensive or less standardized lipid metrics.
If LP(a) is elevated, consider measuring oxidized phospholipids on ApoB (OxPL-ApoB) to determine if the LP(a) particles are carrying injurious oxidized lipids, indicating a higher risk.
While LP(a) is a critical risk factor, it is not currently an acceptable direct goal of therapy because there is no trial data supporting its direct modulation as a primary treatment target.
To obtain an accurate VLDL cholesterol measurement, subtract directly measured LDL cholesterol and HDL cholesterol from total cholesterol; do not use a calculated LDL cholesterol for this purpose.
While 4 grams/day of EPA is evidence-based for high triglycerides, for individuals with triglycerides below 150 mg/dL but still having residual ApoB risk, using EPA-DHA combinations is still a reasonable consideration.
If taking 4 grams of EPA daily and the omega-3 index still indicates DHA deficiency, consider supplementing with additional DHA to ensure adequate levels.
When assessing atherosclerosis risk, individualize the approach by considering multiple factors beyond just particle number, such as endothelial function and particle quality, as it is a multi-factorial disease.