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Updated: Jan 7, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

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Multisystem comorbidities and shared genetic pathways in calcific aortic stenosis: a phenome-wide and Mendelian

Zihao Zhou1, Yidan Zheng1, Shiyan Hu1

  • 1Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Heart (British Cardiac Society)
|December 29, 2025
PubMed

Insights

Calcific aortic stenosis (CAS) is linked to many systemic conditions, primarily due to genetic factors involving LPA and lipoprotein(a). Targeting LPA may reduce the broad health burden of CAS.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Epidemiology

Background:

  • Calcific aortic stenosis (CAS) often co-occurs with systemic diseases, but their links and genetic basis are unclear.
  • Understanding these relationships is crucial for managing CAS patients comprehensively.

Purpose of the Study:

  • To map the network of CAS comorbidities across multiple body systems.
  • To identify shared genetic mechanisms underlying CAS and its associated conditions.

Main Methods:

  • Utilized UK Biobank data (467,484 participants) for observational and polygenic phenome-wide association studies.
  • Employed disease-trajectory analyses and two-sample Mendelian randomization (MR) with FinnGen data.
  • Assessed the role of LPA variants and plasma lipoprotein(a) (Lp(a)) using polygenic risk score (PRS) analyses.

Main Results:

  • CAS showed associations with 42 cardiovascular and non-cardiovascular conditions, notably metabolic, endocrine, hematologic, and respiratory disorders.
  • Circulatory and metabolic diseases often preceded other comorbidities in CAS trajectories.
  • MR supported causal links from CAS to cardiovascular diseases, iron-deficiency anemia, mental disorders, and pleural effusion, largely mediated by LPA/Lp(a).

Conclusions:

  • CAS is part of a wide multisystem comorbidity network, significantly influenced by genetic variation at LPA and elevated Lp(a).
  • These findings reveal pleiotropic effects linking valvular calcification to systemic diseases.
  • Targeting LPA presents a potential therapeutic strategy to alleviate the systemic burden of CAS.
Abstract

Keywords:
Aortic Valve StenosisBiostatisticsCohort StudiesGenetics

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