Year: 2026
Type: review
Abstract: Extensive evidence now confirms Lipoprotein(a) [Lp(a)] as a causal, independent risk factor for atherosclerotic cardiovascular disease. Elevated Lp(a) levels are detected in approximately 20% of the global population, positioning it as a major contributor to residual cardiovascular risk. Circulating Lp(a) levels are determined predominantly by genetic factors, so they are largely unresponsive to lifestyle modifications or conventional lipid-lowering therapies. Therefore, multiple international guidelines now endorse a one-time, lifetime measurement of Lp(a), as lowering Lp(a) concentrations is expected to have a positive impact on the reduction of cardiovascular risk. Currently, the therapeutic landscape of Lp(a) lowering drugs is rapidly evolving. Some RNA-based therapies (antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)) have been demonstrated to reduce plasma Lp(a) concentrations by up to 98% in early-phase clinical trials. The efficacy and safety of these compounds are currently being evaluated in large-scale cardiovascular outcome trials. The results of these studies will be critical in validating the “Lp(a) hypothesis”: specific reduction of Lp(a) levels can lead to a measurable decrease in cardiovascular events. The purpose of this narrative review is to examine and discuss the available evidence on the role of Lp(a) as a risk factor and pharmacological target to provide a practical tool for decision-making in clinical practice.
Source: Therapeutics
Authors: Elisabetta Ricottini, Nicolò Graziano Ciavaroli, Anna Di Cristo, Antonio Emanuele Lentini, Teresa Trunfio, Luca D’Antonio, Fabio Mangiacapra, Annunziata Nusca, Valeria Cammalleri, Rosetta Melfi, Nino Cocco, Paolo Gallo, Raffaele Rinaldi, Annamaria Tavernese, Francesco Piccirillo, Martina Gelfusa, Giorgio Antonelli, Laura Gatto, Saverio Muscoli, Gian Paolo Ussia
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $1,207
OpenAlex ID: W7151369563