RNA therapeutics
The Lp(a) implementation gap: screening stays below 1% despite affecting 20% of the world, review (Rev Cardiovasc Med 2026)
Original title: The Lipoprotein(a) Implementation Gap: Bridging Evidence and Clinical Practice
Review examining the gap between evidence and practice for Lp(a), which affects an estimated 1.5 billion people worldwide (20% of the global population) yet remains screened in under 1% of patients. Guideline recommendations evolved from selective screening (2018 ACC/AHA) to universal one-time measurement (2024 National Lipid Association Class I), but reimbursement, provider knowledge gaps and laboratory standardisation issues perpetuate underuse. Observational studies show markedly higher cardiovascular risk with elevated Lp(a), and Mendelian randomisation confirms causal associations with coronary heart disease, large-artery stroke, peripheral artery disease and aortic stenosis, with differential effects across stroke subtypes and non-atherosclerotic outcomes. Despite 70-90% heritability, novel RNA-targeted therapies now achieve 80-95% reductions, with phase 3 cardiovascular outcome trials completing 2026-2029. The authors provide a practical management algorithm stratifying patients by Lp(a) level with corresponding interventions, framing Lp(a) as a model for turning genetic insight into a treatable, precision-medicine target.
Original abstract
Lipoprotein(a) [Lp(a)] represents one of cardiovascular medicine's most profound implementation gaps: a genetically determined risk factor affecting 1.5 billion people worldwide, yet historically underutilized in clinical practice despite overwhelming evidence of its importance. This review examines the transformation of Lp(a) from an untreatable genetic burden to a promising therapeutic target through four interconnected perspectives. First, we document the implementation gap, where, despite affecting 20% of the global population, screening remains below 1%. The evolution from selective screening (2018 American College of Cardiology/American Heart Association (ACC/AHA)) to universal measurement (2024 National Lipid Association (NLA) Class I recommendation) reflects growing recognition, yet persistent barriers, including reimbursement challenges, provider knowledge gaps, and laboratory standardization issues, perpetuate underutilization. Second, we synthesize evidence establishing Lp(a)'s dual nature as both a biomarker and a causal factor. Observational studies demonstrate markedly increased cardiovascular risk with elevated Lp(a), while Mendelian randomization confirms causal relationships with coronary heart disease, large-artery stroke, peripheral artery disease, and aortic stenosis, with differential effects on stroke subtypes and non-atherosclerotic outcomes. Third, we examine the transformation from genetic determinism to pharmacological tractability. Despite 70-90% heritability, novel RNA-targeted therapies achieve unprecedented 80-95% reductions, with phase 3 cardiovascular outcome trials (completing 2026-2029) poised to determine whether dramatic Lp(a) lowering translates to clinical benefit. Finally, we provide a practical management algorithm bridging current evidence-based risk stratification with emerging therapies, stratifying patients by Lp(a) levels with corresponding interventions. The Lp(a) story exemplifies how genetic insights and technological innovation can transform immutable disease aspects into treatable conditions, offering a paradigm for precision cardiovascular medicine while highlighting the urgent need to close the gap between scientific knowledge and clinical implementation.
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Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.