What does this research mean for the field?

Elevated Lipoprotein(a) levels and specific LPA gene variants are significantly associated with the initiation, faster progression, and worse clinical outcomes of calcific aortic valve disease. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

April 20, 2023Open Access

Lipoprotein(a) and calcific aortic valve disease initiation and progression: a systematic review and meta-analysis

PPPanteleimon PantelidisElectrophysiology EOEvangelos OikonomouCardiac Imaging SLStamatios LampsasNational and Kapodistrian University of Athens

Structured PICO

Does elevated Lipoprotein(a) increase the risk of calcific aortic valve disease initiation, progression, and adverse outcomes?

Population

163,139 subjects from 44 studies (16 of which were meta-analysed)

Intervention

Elevated Lipoprotein(a) [Lp(a)] levels and LPA gene minor alleles (rs10455872 and rs3798220)

Comparator

Lower Lipoprotein(a) levels or absence of LPA gene minor alleles

Outcome

Aortic valve calcification and stenosis (AVS) initiation, progression, and serious adverse outcomes including death

Elevated Lipoprotein(a) and its genetic variants are significantly associated with the initiation and faster progression of calcific aortic valve disease, as well as an increased risk of adverse outcomes including death.

Abstract

Although evidence indicates the association of lipoprotein(a) Lp(a) with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This systematic review and meta-analysis explores the connection between Lp(a) and aortic valve calcification and stenosis (AVS). We included all relevant studies, indexed in eight databases, up to February 2023. A total of 44 studies (163 139 subjects) were included, with 16 of them being further meta-analysed. Despite considerable heterogeneity, most studies support the relationship between Lp(a) and CAVD, especially in younger populations, with evidence of early aortic valve micro-calcification in elevated-Lp(a) populations. The quantitative synthesis showed higher Lp(a) levels, by 22.63 nmol/L (95% CI: 9.98-35.27), for patients with AVS, while meta-regressing the data revealed smaller Lp(a) differences for older populations with a higher proportion of females. The meta-analysis of eight studies providing genetic data, revealed that the minor alleles of both rs10455872 and rs3798220 LPA gene loci were associated with higher risk for AVS (pooled odds ratio 1.42; 95% CI: 1.34-1.50 and 1.27; 95% CI: 1.09-1.48, respectively). Importantly, high-Lp(a) individuals displayed not only faster AVS progression, by a mean difference of 0.09 m/s/year (95% CI: 0.09-0.09), but also a higher risk of serious adverse outcomes, including death (pooled hazard ratio 1.39; 95% CI: 1.01-1.90). These summary findings highlight the effect of Lp(a) on CAVD initiation, progression and outcomes, and support the early onset of Lp(a)-related subclinical lesions before clinical evidence.

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