Key result
Elevated Lp(a) linked to ~52% higher odds of aortic valve replacement and CV mortality.
Why the study?
Elevated Lp(a) is hypothesized to be associated with the pathophysiology of calcific aortic stenosis, but the extent to which it influences disease progression and clinical outcomes has not been fully elucidated.
Does elevated Lipoprotein(a) (≥35 mg/dL or ≥125 nmol/L) increase the risk of MACE, cardiovascular mortality, aortic valve replacement, and hemodynamic progression in adults with existing calcific aortic stenosis?
Meta-Analysis (n=2,107)
Does elevated Lipoprotein(a) (≥35 mg/dL or ≥125 nmol/L) increase the risk of MACE, cardiovascular mortality, aortic valve replacement, and hemodynamic progression in adults with existing calcific aortic stenosis?
In patients with calcific aortic stenosis, elevated lipoprotein(a) is significantly associated with faster hemodynamic progression and higher rates of aortic valve replacement and cardiovascular mortality.
Elevated Lp(a) may refine risk stratification in calcific aortic stenosis; confirms association with accelerated progression and higher AVR/CV mortality.
Background Elevated Lipoprotein(a) [Lp(a)] is hypothesized to be associated with the pathophysiology of calcific aortic stenosis (AS), but the extent to which it influences disease progression and clinical outcomes has not been fully elucidated. Purpose The purpose of this meta-analysis is to analyse the association between elevated Lp(a) levels and haemodynamic progression of calcific aortic stenosis, rate of aortic valve replacement (AVR), major adverse cardiovascular events (MACE), and cardiovascular mortality in adults with existing calcific AS. Methods A literature search was performed to identify randomised controlled trials that analysed the association of elevated Lp(a) and haemodynamic progression of AS in adults with calcific AS, consistent with the enrolment criteria of the included randomised controlled studies. The primary endpoints of interest included MACE and cardiovascular mortality. The secondary endpoints included annualised change in peak aortic jet velocity and rate of AVR. Calcific AS was defined as peak aortic jet velocity greater than 2.0 m/s and non-rheumatic aortic valve calcification on echocardiography. Elevated Lp(a) was defined as ≥35 mg/dL or ≥125 nmol/L. The search engine included the following databases: PubMed, Embase, and Web of Science. TriNetX, registry, and post hoc analysis studies were excluded. Results A total of 2 randomised controlled studies were selected as there were not enough studies available in the current literature to perform analysis for our primary endpoints. However, there were 2 studies identified that allowed analysis of secondary endpoints and they included 2,107 patients (521 of which had elevated Lp(a) and 1,586 had normal Lp(a)). The median follow-up duration was between 30-60 months; mean age was 68.2 years and 53.8% were men. Patients with elevated Lp(a) demonstrated a significantly higher rate of AVR and cardiovascular mortality (OR 1.52, 95% CI 1.16-1.98; p=0.002). Heterogeneity regarding rate of AVR, cardiovascular mortality analysis was low (I² = 23%). Compared to patients with normal Lp(a), rate of increase in aortic valve peak velocity was faster in patients with elevated Lp(a) (mean difference 0.09, 95% CI 0.04-0.14; p=0.0002). Heterogeneity regarding rate of aortic valve peak velocity analysis was low (I² = 0%). Conclusions Elevated Lp(a) is associated with accelerated AS progression and worse clinical outcomes, supporting its role as a prognostic biomarker and possible therapeutic target in calcific AS.
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Pelletier et al. (2026) conducted a meta-analysis in Calcific aortic stenosis (n=2,107). Elevated lipoprotein(a) (≥35 mg/dL or ≥125 nmol/L) vs. Normal lipoprotein(a) was evaluated on Aortic valve replacement and cardiovascular mortality (OR 1.52, 95% CI 1.16-1.98, p=0.002). Elevated lipoprotein(a) was associated with a higher rate of aortic valve replacement and cardiovascular mortality compared to normal levels (OR 1.52; 95% CI 1.16-1.98; P=0.002).
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