{
  "abstract": "Calcific aortic stenosis (CAVS) is the most prevalent valvular heart disease affecting older adults, yet no validated pharmacological intervention can halt its progressive deterioration. Lipoprotein(a) [Lp(a)] denotes a genetically regulated low-density lipoprotein (LDL)-like particle, in which apolipoprotein(a) forms a covalent bond with apolipoprotein B-100. Cumulative genetic, epidemiological, imaging and mechanistic research supports a causal role for elevated circulating Lp(a) in the initiation, and suggests a contribution to the advancement, of calcific aortic valve lesions. Lp(a) mediates valve injury mainly via preferentially transporting oxidized phospholipids (OxPL), anchoring within aortic valve leaflets, triggering endothelial activation and inflammatory cascades, as well as stimulating the autotaxin–lysophosphatidic acid (ATX–LPA) axis; collectively these signals drive osteogenic differentiation and mineralization of valve interstitial cells (VICs). Higher Lp(a) levels correlate with incident aortic valve calcification, accelerated hemodynamic deterioration, augmented calcium deposition quantified by computed tomography (CT), and elevated risks of aortic valve replacement (AVR) or all-cause cardiac death. Conventional lipid-lowering agents fail to reverse disease trajectory in patients with established CAVS. Though proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors only modestly cut Lp(a) concentrations, exploratory analyses have delivered preliminary suggestive signals for cardiovascular protection. RNA-targeted therapeutics and oral agents blocking Lp(a) assembly can reduce circulating Lp(a) by 70% up to over 95%, as demonstrated in early- and mid-phase clinical trials. Most notably, the ongoing Lp(a)FRONTIERS CAVS randomized trial is directly testing whether pelacarsen can decelerate CAVS progression, and no completed trial has yet demonstrated that Lp(a) lowering modifies CAVS disease. This narrative review summarizes Lp(a) biological characteristics, causal evidence linking Lp(a) to CAVS, together with opportunities and unresolved uncertainties surrounding Lp(a)-targeted therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, Qilu Hospital (Qingdao), Shandong University"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Shao Yun Shuang"
    },
    {
      "affs": [
        0
      ],
      "name": "You Bei An"
    },
    {
      "affs": [
        0
      ],
      "name": "Xu Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Wang Hao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xu Xing Sheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Pang Xue Lian"
    },
    {
      "affs": [
        0
      ],
      "name": "Meng Qing Feng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4z0p69zq3byz7.bib",
  "cited_by": 0,
  "doi": "10.3389/fcvm.2026.1963618",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732744/",
  "id": "4z0p69zq3byz7",
  "issns": [
    "2297-055X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1963618/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2705|Cardiac Valve Diseases and Treatments"
    ]
  ],
  "openalex": "W7223103803",
  "pdf_url": "https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2026.1963618/pdf",
  "pmcid": "PMC13732744",
  "pmid": "42985599",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4z0p69zq3byz7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "10.3389/fcvm.2026.1963618",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1963618/full"
    },
    {
      "first_seen": "2026-11-08T12:22:40Z",
      "native_id": "PMC13732744",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcvm.2026.1963618"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiac Valve Diseases and Treatments",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Lipoprotein(a) in calcific aortic stenosis: mechanistic insights, clinical evidence, and emerging therapies",
  "title_text": "Lipoprotein(a) in calcific aortic stenosis: mechanistic insights, clinical evidence, and emerging therapies",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:40Z",
  "url": "https://research.draconitic.com/paper/4z0p69zq3byz7",
  "venue": "Frontiers in Cardiovascular Medicine",
  "versions": []
}