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Feliciano LD, Freire JPC, Lopes CF, Lima PHM, Costa JMC, de Melo FF. Lipoprotein(a) in clinical practice: From genetic risk assessment to therapeutic silencing. World J Transl Med 2026; 12(4): 124606 [DOI: 10.5528/wjtm.124606]
World J Transl Med. Nov 28, 2026; 12(4): 124606 Published online Nov 28, 2026. doi: 10.5528/wjtm.124606
Lipoprotein(a) in clinical practice: From genetic risk assessment to therapeutic silencing
Lucas D Feliciano, João P C Freire, Caio F Lopes, Pedro H M Lima, Juan M C Costa, Fabrício Freire de Melo
Lucas D Feliciano, João P C Freire, Caio F Lopes, Pedro H M Lima, Juan M C Costa, Fabrício Freire de Melo, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
Author contributions: Feliciano LD contributed to the conceptualization of the manuscript; Feliciano LD, Freire JPC, Lopes CF and Lima PHM contributed to the investigation and wrote the original draft; Feliciano LD and Lima PHM developed the tables; Feliciano LD and de Melo FF were responsible for manuscript editing and review; Costa JMC developed the figures; de Melo FF supervised the writing of the original draft; all authors read and approved the final manuscript.
AI contribution statement: The authors acknowledge the use of the Gemini (Google) language model as an assistive technology during the preparation of this manuscript, specifically for language editing and formatting assistance. The tool was not used to generate data, perform analyses, or draw scientific conclusions. The authors agree to take full responsibility for the entire content of this manuscript, including any parts for which AI tools were used as assistive technology. The authors confirm that all AI-assisted outputs were carefully reviewed, verified, and validated. The authors assume full responsibility for the accuracy, integrity, and originality of the manuscript.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Fabrício Freire de Melo, PhD, Professor, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Rua Hormindo Barros 58, Quadra 17, Lote 58, Vitória da Conquista 45029-094, Bahia, Brazil. freiremeloufba@gmail.com
Received: June 22, 2026 Revised: July 27, 2026 Accepted: September 11, 2026 Published online: November 28, 2026 Processing time: 138 Days and 7.1 Hours
Abstract
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle increasingly recognized as an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Its unique structure, composed of a low-density lipoprotein-like particle bound to apolipoprotein(a), confers both atherogenic and proinflammatory properties that distinguish it from other circulating lipoproteins. This review examines the molecular structure of Lp(a), its genetic determinants, and the mechanisms linking elevated Lp(a) levels to atherogenesis and vascular inflammation. We critically discuss the role of apolipoprotein(a) isoform variability, kringle domain polymorphisms, oxidized phospholipid transport, endothelial dysfunction, inflammatory signaling pathways, and thrombogenic pathways in mediating cardiovascular risk. In addition, we review current approaches for laboratory assessment and summarize emerging therapeutic strategies aimed at selectively lowering Lp(a), including antisense oligonucleotides and small interfering RNA-based therapies. Recent advances in molecular therapeutics have demonstrated substantial reductions in circulating Lp(a) concentrations, although definitive evidence regarding cardiovascular outcome benefits is still under investigation. A better understanding of Lp(a) biology and its inflammatory and atherogenic mechanisms may improve risk stratification and support the development of personalized preventive and therapeutic strategies in cardiovascular medicine.
Core Tip: Lipoprotein(a) [Lp(a)] is increasingly recognized as an important genetically determined cardiovascular risk factor with proatherogenic, proinflammatory, and prothrombotic properties that contribute to atherosclerotic cardiovascular disease and calcific aortic valve disease. This review discusses the molecular structure, genetic determinants, pathogenic mechanisms, and clinical relevance of Lp(a), as well as current challenges in laboratory assessment and emerging targeted therapies. Advances in understanding and treating elevated Lp(a) may improve cardiovascular risk stratification and open new perspectives for personalized preventive cardiology.
