Impact of Lipoprotein(a) on Residual Cardiovascular Risk After an Acute Coronary Syndrome

TL;DR

This paper reviews how lipoprotein(a) contributes to ongoing heart disease risk after a heart attack, despite existing treatments.

Contribution

The paper synthesizes current evidence on Lp(a)'s role in residual cardiovascular risk after acute coronary syndrome.

Findings

Lp(a) is a significant contributor to residual cardiovascular risk after acute coronary syndrome.

Current therapies targeting Lp(a) are limited, but RNA-based treatments show promise in reducing Lp(a) levels.

Ongoing clinical trials are evaluating whether Lp(a) reduction translates to improved clinical outcomes.

Abstract

Reducing residual cardiovascular risk following acute coronary syndrome (ACS) remains a major unmet clinical need. Despite substantial advances in lipid-lowering therapies, the risk of recurrent major adverse cardiovascular events (MACEs) after ACS remains high, with an estimated incidence of approximately 33.4% at 5 years. Residual cardiovascular risk is driven by multiple mechanisms, including persistent inflammation, a prothrombotic status, metabolic disturbances, and the presence of atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C). Lipoprotein(a) (Lp(a)) is a pro-inflammatory, prothrombotic, and pro-atherosclerotic lipoprotein that appears to play a major role in residual risk after ACS or ischemic stroke. Elevated Lp(a) is a well-established independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Nevertheless, evidence regarding its prognostic value specifically after ACS remains limited, with marked heterogeneity across studies, which complicates direct comparisons and interpretation. In addition, while Lp(a) levels are predominantly genetically determined, recent studies have reported intra-individual variability, although their clinical significance remains uncertain. Finally, current therapeutic options specifically targeting Lp(a) are limited. Novel RNA-based therapies, including antisense oligonucleotides, small interfering RNAs, and emerging gene-editing approaches, have demonstrated profound and sustained reductions in circulating Lp(a) levels. Yet, whether this biological effect translates into reductions in hard clinical endpoints is under evaluation in ongoing clinical trials. This review aims to synthesize current evidence on the role of Lp(a) as a major contributor to residual cardiovascular risk following ACS.

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