Key result
ApoB outperforms estimated LDL-C as a more precise cardiovascular risk marker across target levels.
Why the study?
The ACC/AHA Multisociety guidelines rank apoB as superior to LDL-C for residual cardiovascular risk but state minimal discordance at LDL-C targets, based on apoB values differing from guideline choices.
Is apoB a more precise marker of cardiovascular risk than estimated LDL-C at guideline target levels?
Observational
Yes
Is apoB a more precise marker of cardiovascular risk than estimated LDL-C at guideline target levels?
ApoB is a more precise marker of cardiovascular risk than estimated LDL-C at guideline target levels, challenging current ACC/AHA recommendations.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“In 2026, the American College of Cardiology/American Heart Association/Multisociety dyslipidemia guideline followed virtually the same course. Based on the evidence, apoB was ranked above both LDL-C and HDL-C for assessment of risk and the effectiveness of therapy. However, the actual recommendations ranked apoB below both and, as written, make it unlikely that apoB will be commonly used in clinical care for either purpose.”
ApoB may refine residual risk assessment at LDL-C targets; challenges guideline minimal-discordance assumptions but leaves practice change open pending trials.
Background The ACC/AHA Multisociety guidelines rank apoB as superior to LDL-C to identify residual cardiovascular risk but also state that discordance between apoB and Martin-Hopkins (MH) LDL-C, is minimal at LDL-C targets of 100 and 70 mg/dL. However, these results are based on different values of apoB than those chosen by the guidelines. Methods Variance between LDL-C estimated by MH, modified-Sampson (mS) or Friedwald (F) and apoB was examined in the NHANES database. Differences between achieving guideline target levels of MH LDL-C, mS LDL-C and F LDL-C versus guideline target levels of apoB (90, 70, and 55 mg/dL) or the percentile equivalent values of apoB in the untreated NHANES-based population (79, 58 and 46 mg/dL) were calculated. Clinical significance of discordance of MH-LDL-C was determined in UK Biobank overall and at the 3 target levels of MH LDL-C. Results Significant discordance was present between LDL-C, however estimated, and apoB in the NHANES participants. Substantial differences between apoB and LDL-C at target levels was evident using guideline target values of apoB and even greater using population equivalent values of apoB. In UK Biobank, residual discordance analysis demonstrated apoB was a more precise marker of cardiovascular risk than MH LDL-C overall and at MH LDL-C target levels of LDL-C of 100 and 70 mg/dl. Conclusions This report identifies an apparent consequential error in the ACC/AHA Multisociety guidelines and further supports the view that apoB should have at least equal priority to LDL-C and non-HDL-C in routine clinical care.
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Cole et al. (2026) conducted an observational in Cardiovascular risk. apoB vs. estimated LDL-C (Martin-Hopkins, modified-Sampson, Friedewald) was evaluated on Discordance between estimated LDL-C and apoB, and precision as a marker of cardiovascular risk. ApoB was a more precise marker of cardiovascular risk than Martin-Hopkins estimated LDL-C overall and at target levels of 100 and 70 mg/dL, highlighting significant discordance between the markers.
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