Aortic stenosis
Systematic review of 153,192 participants confirms a dose-dependent Lp(a)-aortic valve disease link, strongest above 50 mg/dL (Front Cardiovasc Med 2025)
Original title: The role of elevated lipoprotein(a) in aortic valve disease: a systematic review
This PRISMA-guided, PROSPERO-registered systematic review pooled 18 studies, six case-control, six cohort and six cross-sectional, covering 153,192 participants, to assess Lp(a)'s relationship with calcific aortic valve stenosis (CAVS) and aortic valve calcification. No randomised trials were identified. Elevated Lp(a) was consistently associated with increased risk of aortic stenosis and calcification in a dose-dependent manner, with the highest risk at Lp(a) 50 mg/dL or above, though some studies showed risk from 30 mg/dL. The rs10455872 risk allele showed a consistent association while rs3798220 was inconsistent, and Afro-Caribbean individuals had higher baseline Lp(a) but paradoxically lower valve calcification prevalence than Caucasians. The authors conclude Lp(a) is an independent CAVS risk factor shaped by both concentration and genotype, and call for randomised trials of emerging Lp(a)-lowering therapies to establish whether reduction improves valvular outcomes.
Original abstract
Background: Calcific aortic valve stenosis (CAVS) is the most prevalent valvular heart disease and a growing global health concern. Aortic sclerosis (ASc) and aortic stenosis (AS) represent a continuum of progressive disease characterized by leaflet thickening, inflammation, lipid deposition, and calcification. Lipoprotein(a) [Lp(a)], with its pro-atherogenic, pro-inflammatory, and pro-calcific properties, has emerged as a key contributor to this process. While its role in atherosclerotic cardiovascular disease is well established, the relationship between Lp(a) and CAVS has been demonstrated in several key studies; however, the available evidence remains limited in volume, and important gaps persist in understanding mechanisms, risk stratification, and therapeutic implications.
Methods: A systematic literature search was conducted in PubMed, Cochrane Library, ScienceDirect, Medline, ResearchGate, Embase, and Google Scholar in accordance with PRISMA guidelines. Eligible studies included observational designs (cross-sectional, cohort, case-control) and randomized trials evaluating associations between Lp(a) levels, genetic variants, and CAVS. Study quality was assessed using the Newcastle-Ottawa Scale (NOS).
Results: Eighteen studies met the inclusion criteria, comprising six case-control, six cohort, and six cross-sectional studies with a total of 153,192 participants. No randomized controlled trials were identified. Elevated Lp(a) levels were consistently associated with an increased risk of AS and aortic valve calcification (AVC), with a dose-dependent effect. The risk was highest at levels ≥50 mg/dl, though some evidence supported risk at ≥30 mg/dl. Genetic analyses identified rs10455872 as a significant risk allele, while rs3798220 showed inconsistent associations. Multi-ethnic cohorts highlighted racial variability: Afro-Caribbean individuals had higher baseline Lp(a) levels but lower AVC prevalence than Caucasians.
Conclusion: Lp(a) is an independent risk factor for CAVS, influenced by both concentration and genetic variation. Early screening and emerging Lp(a)-lowering therapies, including antisense oligonucleotides, small interfering RNA, and PCSK9 inhibitors, may help mitigate disease progression. Further randomized trials are needed to determine whether Lp(a) reduction translates into cardiovascular and valvular benefit.
Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024533835, PROSPERO CRD42024533835.
ancestryaortic stenosisgenetics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.