Front Cardiovasc Med. 2025 Dec 16;12:1659228. doi: 10.3389/fcvm.2025.1659228. eCollection 2025.
ABSTRACT
Atherosclerosis, driven primarily by cumulative exposure to low-density lipoprotein cholesterol (LDL-C), is the major cause of atherosclerotic cardiovascular disease (ASCVD). This narrative review examines the pathogenesis of atherosclerosis, linking risk factors, inflammatory pathways, and lipid abnormalities to the formation and progression of atheromatous plaques. Plaque characteristics such as volume, lipid content, fibrous cap thickness, and minimum lumen area are closely associated with cardiovascular outcomes, particularly the risk of major adverse cardiac events (MACEs). Intensive LDL-C lowering through statins, ezetimibe, PCSK9 inhibitors, and emerging agents like bempedoic acid has demonstrated clear benefits in regressing plaques, stabilizing their morphology, and significantly reducing cardiovascular risks. Despite guideline recommendations advocating intensive lipid-lowering strategies, real-world practice reveals considerable gaps, with many high- and very-high-risk patients failing to achieve LDL-C targets. Contributing factors include poor adherence, underuse of combination therapies, and treatment inertia. Early detection and preemptive management of subclinical atherosclerosis, particularly among younger individuals, are gaining attention as strategies to intercept the progression of disease before clinical events occur. Moreover, elevated lipoprotein(a) levels are increasingly recognized as an independent causal factor for ASCVD, and ongoing trials are evaluating specific Lp(a)-lowering therapies. Overall, optimizing lipid management through intensive, early intervention, patient adherence, and personalized treatment approaches holds the key to reducing the global burden of ASCVD. Addressing residual risks and refining early detection strategies will further advance the prevention and management of this chronic, progressive vascular disease.
PMID:41477645 | PMC:PMC12750773 | DOI:10.3389/fcvm.2025.1659228