Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide. Despite the proven benefit of statins, many patients fail to achieve guideline-recommended LDL-C goals. Contributing factors include poor adherence, statin intolerance, and high baseline LDL-C levels. This gap leaves patients vulnerable to residual cardiovascular risk—driven not only by LDL-C but also by other atherogenic lipoproteins, including non-HDL-C, apoB, triglyceride-rich lipoproteins, and Lp(a).

Mechanistic insights underscore LDL-C’s central role in atherosclerosis and plaque vulnerability. The PCSK9 pathway regulates LDL receptor recycling, directly influencing LDL-C levels. Inhibiting this pathway—through currently available therapeutic strategies—has been associated with enhanced LDL clearance. Imaging studies link intensive LDL-C reduction to plaque stabilization and regression. These findings support the potential benefit of earlier, more profound LDL-C lowering in high-risk populations.

Recent guideline revisions advocate for lower LDL-C thresholds and emphasize identifying patients who may benefit from more intensive lipid-lowering approaches. Systematic risk assessment, EHR tools, and shared decision-making may help clinicians address barriers to care. Multidisciplinary collaboration remains key in optimizing adherence, education, and access.

How can healthcare professionals better identify and manage ASCVD patients with high residual cardiovascular risk despite statin therapy? What changes to clinical workflows or patient engagement strategies could support timely and intensive LDL-C management?

Dr. Joanna Chikwui, Chief of Cardiac Surgery at Cedars-Sinai and Chair of AHA Scientific Sessions, spotlighted significant breakthroughs across cardiology. Updates included novel therapies for hyperlipidemia, gene-editing tools for inherited cardiovascular risk, innovations in atrial fibrillation management, and compelling lifestyle findings—including a surprising inverse relationship between moderate coffee intake and AF incidence.

Dr. Heidi May, Epidemiologist at Intermountain Health, presented results from the Target-D randomized trial, which found that personalized vitamin D dosing after myocardial infarction significantly reduced the risk of recurrent heart attack. These findings underscore the importance of individualized supplementation strategies and signal a broader shift toward precision prevention and risk stratification in cardiovascular care.

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