Review of the American Heart Association PREVENT guidelines: how non-high-density lipoprotein cholesterol and apolipoprotein B fit in.

INTRODUCTION: A remarkable new American Heart Association calculator for estimating risk of cardiovascular disease was released in 2024, with guidelines following in 2026. These guidelines now use non-high-density lipoprotein cholesterol (HDL-C) along with low-density lipoprotein cholesterol to guide and escalate therapy. Moreover, the calculator uses non-HDL-C as the primary screening lipoprotein marker to fully capture the hidden cholesterol burden. METHODS: For its Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) calculator, the American Heart Association compiled an immense, diverse dataset comprising more than 6.5 million US adults. The PREVENT equations not only use the conventional nonlipid risk markers but also reframe how cardiovascular disease is assessed by embedding it into a cardiovascular-kidney-metabolic syndrome framework. RESULTS: Why did PREVENT not use apolipoprotein B (apo B) for the primary marker? In head-to-head comparisons, apo B has consistently been shown to outperform non-HDL-C, especially in high-risk syndromes. Here, using receiver operating characteristic curve analysis and C statistics, I show that after adjustment for conventional risk factors, apo B and non-HDL-C are equivalent for screening. DISCUSSION: The guidelines suggest that apo B be used for risk reclassification and as needed for targeting of statin and ezetimibe therapy. Here, I clarify the reasons for this suggestion.