PURPOSE OF REVIEW The global burden of atherosclerotic cardiovascular disease (ASCVD) drives lipid-lowering strategies, now undergoing their biggest transformation since statins. In 2025 and 2026, the two most influential guideline bodies, the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) and the American College of Cardiology/American Heart Association (ACC/AHA), both released updated guidance that reflects evolving clinical evidence. This review provides a detailed, head-to-head examination of their recommendations, highlighting areas of convergence, divergence, and the clinical implications for practitioners on both sides of the Atlantic. RECENT FINDINGS The 2025 Focused Update of the 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias builds incrementally on an established framework, incorporating new trial data within its existing risk-stratified, target-driven model. In contrast, the 2026 ACC/AHA Guideline on the Management of Dyslipidaemia represents a comprehensive rewrite, introducing a novel risk calculator, reinstating explicit LDL-C targets for all risk categories, and endorsing a more flexible, individualized selection of nonstatin therapies. SUMMARY Both documents embrace the 'lower is better' and 'strike early and strong' paradigms, yet they differ profoundly in how they apply these principles. The review distinguishes the ESC/EAS's structured, stepwise approach from the ACC/AHA's flexible, individualized paradigm (Graphical abstract).
PURPOSE OF REVIEW Familial hypercholesterolemia is a prevalent genetic disorder characterized by lifelong elevated LDL-cholesterol (LDL-C), resulting in increased risk of premature atherosclerosis and cardiovascular events. General and familial hypercholesterolemia-specific risk scores (SAFEHEART-RE, Montreal-FH, and FH risk score) are insufficient to capture the interindividual variability in cardiovascular risk. Current guidelines and consensus statements recognize the potential value of coronary computed tomography in familial hypercholesterolemia, although specific guidance on timing and modality remains limited. This review evaluates the evidence and role of coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA) for improved cardiovascular risk stratification and therapeutic guidance. RECENT FINDINGS Although elevated CACS is highly prevalent among patients with heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), younger familial hypercholesterolemia patients may exhibit exclusively noncalcified plaque, and because most are treated with statins, which may increase coronary calcification, CACS should be interpreted with caution. CCTA provides comprehensive assessment of plaque burden, stenosis, and high-risk features, which are associated with adverse cardiovascular outcomes. CCTA may support therapy intensification by identifying patients with substantial coronary plaque burden, while the absence of detectable atherosclerosis should not justify withholding guideline-recommended lipid-lowering therapy (LLT). SUMMARY CCTA may provide additional information on atherosclerotic burden in familial hypercholesterolemia. In HeFH, evidence is currently insufficient to support routine CCTA screening at specific ages or intervals. CCTA at approximately 30 years of age in men and 40 years of age in women may represent a proposed strategy requiring prospective evaluation. In children with HoFH, screening is recommended at least once after the age of 3. Follow-up imaging should be individualized according to clinical indication, imaging findings, treatment response and radiation-associated risks.
PURPOSE OF REVIEW:Despite aggressive cholesterol lowering, many patients continue to experience cardiovascular events ("residual risk"), emphasizing the need for novel risk reduction strategies. This review highlights recent advances in studying atherosclerosis resolution, with a focus on the key role played by plaque inflammation. RECENT FINDINGS:Preclinical studies demonstrate that while atherosclerosis resolution can involve plaque size reductions, more important are changes in plaque remodeling, as measured by necrotic core, CD68 area, and collagen content. Resolution can be partially achieved with cholesterol lowering, inflammation resolution alone, or better yet, combination approaches. This review evaluates lipid-lowering strategies, as well as inflammation-targeting pathways involving efferocytosis, pro-resolving macrophages, platelets, and caloric restriction. Translational studies and clinical trials targeting inflammatory pathways, including interleukin (IL)-1β, IL-6, NLRP3, and pro-resolving mediators further support inflammation modulation as a therapeutic strategy. SUMMARY:Many preclinical models of atherosclerosis resolution promote significant plaque remodeling by lipid-lowering, inflammation resolution, or combination approaches. Many recent and currently recruiting clinical trials are testing the benefits of inflammation resolution to further reduce cardiovascular risk in at-risk patients.
PURPOSE OF REVIEW:Endothelial-to-mesenchymal transition (EndMT) has been implicated in the development of cardiovascular disease, including atherosclerosis. EndMT is a complex continuum with multiple involved pathways, each with different pathophysiologic implications depending on the driving regulators. RECENT FINDINGS:In this brief review, we will focus on the latest studies that have helped elucidate the role of lipids and related factors in the initiation of EndMT in the setting of atherosclerosis, with particular attention to atherosclerotic plaque stability and sex specific differences of disease. SUMMARY:We explore potential therapeutic strategies, including the impact that lipid modulation has on EndMT and the effects of EndMT-specific approaches on lipid deposition. Overall, this will inform future areas of research on EndMT modulation.
