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Risk factors

Lipoprotein(a) in coronary artery disease

Nature Reviews Cardiology volume 22, page 702 (2025)Cite this article

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High plasma LDL-cholesterol (LDL-C) levels have long been recognized as a major driver of coronary artery disease (CAD), owing to the well-established role of LDL in promoting atherosclerotic plaque formation and progression. Over time, this understanding has led to the development of several effective LDL-lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type-9 inhibitors, all of which significantly improve cardiovascular outcomes. However, a substantial number of patients continue to experience adverse cardiovascular events and remain at high risk despite achieving optimal plasma LDL-C levels. This residual risk has driven efforts to identify additional contributors to CAD that are not fully addressed by traditional lipid-lowering strategies.

In 1974, a study by Kåre Berg, Gösta Dahlen and Heikki Frick, published in Clinical Genetics, resurfaced a long-overlooked idea into clinical focus by identifying lipoprotein(a) (Lp(a)) as a novel contributor to CAD. Berg and colleagues had initially identified the Lp(a) antigen in 1963, but the clinical relevance of this lipoprotein remained unclear. The 1974 study provided the first direct evidence linking Lp(a) to CAD in humans. In a cohort of 46 Finnish patients with suspected or angiographically confirmed coronary heart disease, 59% of these individuals were found to have the Lp(a) antigen in the serum, compared with 31% of individuals in the healthy control group. Moreover, a distinct fraction in lipoprotein electrophoresis analyses, known as pre-β1-lipoprotein, was observed in 17 patients, 16 of whom were also Lp(a)-positive. This near-complete overlap between the presence of pre-β1-lipoprotein and a Lp(a)-positive phenotype suggested that pre-β1-lipoprotein was the particle that carried the Lp(a) antigen. Furthermore, the study also observed that Lp(a) and pre-β1-lipoprotein were more prevalent among patients with visible coronary lesions and among individuals who smoked, which suggested a possible interaction between genetic predisposition and environmental exposure.

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References

Original article

  • Berg, K. et al. Lp(a) lipoprotein and pre-β1-lipoprotein in patients with coronary heart disease. Clin. Genet. 6, 230–235 (1974)

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Authors and Affiliations

  1. Vascular Health Unit, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada

    Jae Hyun Byun & Stella S. Daskalopoulou

  2. Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada

    Jae Hyun Byun & Stella S. Daskalopoulou

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  1. Jae Hyun Byun
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  2. Stella S. Daskalopoulou
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Correspondence to Jae Hyun Byun.

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The authors declare no competing interests.

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Byun, J.H., Daskalopoulou, S.S. Lipoprotein(a) in coronary artery disease. Nat Rev Cardiol 22, 702 (2025). https://doi.org/10.1038/s41569-025-01194-3

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