Apolipoprotein B (Apo B)

Please find below main recommendations and rationales on apolipoprotein B (Apo B) as a useful tool in assessing and monitoring dyslipidemia.

Apo B is becoming an important factor in evaluating complex lipid disorders. I anticipate greater use in the future.

Text has been slightly modified for easier and succinct reading. Part 1 of guidelines were published by National Lipids Association in April 2015.

GT


Excerpts from the Guidelines

Apo B is considered an optional, secondary target for treatment. Epidemiologic studies have generally shown that both apo B and non–HDL are better predictors of ASCVD risk than LDL-C. Because each potentially atherogenic lipoprotein particle contains a single molecule of apo B, the apo B concentration is a direct indicator of the number of circulating particles with atherogenic potential. Apo B and non–HDL share the advantage that neither requires fasting for accurate assessment. Non–HDL is favored over apo B by the NLA Expert Panel because it is universally available, requiring no additional expense compared with the standard lipid profile, and because apo B has not been consistently superior to non–HDL in predicting ASCVD event risk.

Cholesterol-lowering drug therapies, especially statins, alter the relationship between atherogenic cholesterol and apo B, often lowering the cholesterol concentration more than the apo B level. Apo B is a potential contributor to residual ASCVD risk because it may remain elevated in some individuals who have attained their treatment goals for non–HDL and LDL-C, particularly in patients with high triglycerides and low HDL levels. A clinical trial assessing the ability of more aggressive lipid management to lower residual risk in patients on statin therapy, but with residual elevation in apo B (and/or LDL particle concentration), is needed.

An examination of LDL-C, non–HDL-C, apo B, and LDL-particle concentrations among 27,533 apparently healthy women in the Women’s Health Study demonstrated reasonably high correlations between LDL-C and each of the alternate measures (non–HDL-C, apo B, and LDL particle concentration), but substantial discordance between measurements in some individuals. For those with concordant levels of LDL-C and non–HDL-C, apo B, or LDL particle concentration, the clinical utility of these measures for estimating coronary risk was similar. However, among the subgroups of subjects with discordance of LDL-C with another atherogenic lipoprotein-related measure such as non–HDL-C, apo B, or LDL particle concentration (11%-24% depending on the measure used), ASCVD risk was either over- or under-estimated by 20-50% compared with LDL-C alone. Discordance has been defined variably in research conducted to date (eg, median cut points or guideline cut points). Additional research will be needed to further elucidate the clinical importance of discordance between measures of atherogenic lipoprotein burden.

If apo B is used as an optional target for treatment, goals are <90 mg/dL for primary prevention and <80 mg/dL for those with very high risk, although measurement of apo B is generally not necessary until the patient has been treated to his or her goal levels for atherogenic cholesterol. The thresholds for these cut points represent the panel’s consensus based on an evaluation of the available evidence and are consistent with those recommended previously by the American Diabetes Association/ ACC Foundation. Treatment with statins and other cholesterol-lowering drug therapies appears to alter the relationship between atherogenic cholesterol and apo B concentrations.

In an analysis of data from the Limiting Undertreatment of Lipids in ACS with Rosuvastatin (LUNAR) trial, authors reported that during statin therapy, an apo B concentration of 90 mg/dL was associated with mean LDL-C and non–HDL concentrations of 85 and 105 mg/dL, respectively. The corresponding mean values associated with an apo B concentration of 80 mg/dL were 74 mg/dL for LDL-C and 92 mg/dL for non–HDL-C. As discussed previously, patients who remain above the apo B goals, despite having reached their atherogenic cholesterol goals, are discordant and may therefore have residual risk related to an elevated concentration of circulating particles with atherogenic potential.

Clinicians may consider measuring LDL-particle concentration as an alternative to apo B. Apo B and LDL-particle concentration have been reported to perform similarly with regard to the prediction of increased ASCVD risk. The NLA Expert Panel acknowledges that measurement of LDL particle concentration can be useful clinically, particularly once non–HDL and LDL-C goals have been attained, as another potential indicator of residual risk for ASCVD. The Centers for Disease Control–National Heart, Lung, and Blood Institute has standardization programs for LDL-C, non–HDL-C, and apo B measurements. A similar standardization program for LDL particle concentration has not yet been established. Most studies of LDL particle concentration published to date have used a proprietary nuclear magnetic resonance method, but other proprietary methodologies for LDL particle concentration quantification are also available. These various methods appear to have variable agreement in terms of LDL particle size, and their performance for predicting ASCVD risk has not been directly compared.

Accordingly, the NLA Expert Panel did not recommend treatment goals for LDL particle concentration. Additional information about the clinical use of LDL particle concentration may be found in a report issued by another panel of NLA experts: Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing: Advice from an Expert Panel of Lipid Specialists.

NLA Guidelines, Part 1

Journal of Clinical Lipidology

April 2015