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Polygenic Determinants of Arterial Stiffness: Implications for Hypertension

Adam D Gepner1,2, Ryan J Pewowaruk1,2,3, Claudia E Korcarz1,2

  • 1William S. Middleton Memorial Veteran's Hospital, Department of Medicine - Division of Cardiovascular Medicine, Madison, WI, USA.

Medrxiv : the Preprint Server for Health Sciences
|November 24, 2025
PubMed

Insights

Genetic risk for high blood pressure is linked to load-dependent arterial stiffness, not structural stiffness. Polygenic risk scores for blood pressure predict arterial stiffness components, highlighting distinct genetic influences.

Area of Science:

  • Cardiovascular genetics
  • Vascular biology
  • Biostatistics

Background:

  • Arterial stiffness, encompassing structural and load-dependent components, is a key cardiovascular disease risk marker.
  • High blood pressure is a significant contributor to load-dependent arterial stiffness.

Purpose of the Study:

  • To investigate the genetic associations between polygenic risk scores (PRS) for blood pressure (BP) and distinct components of arterial stiffness.
  • To differentiate the genetic underpinnings of structural versus load-dependent arterial stiffness.

Main Methods:

  • Utilized data from 5,942 participants in the Multi-Ethnic Study of Atherosclerosis.
  • Calculated total, structural, and load-dependent carotid arterial stiffness from ultrasound data.
  • Employed multivariable regression and Mendelian Randomization (MR) to assess associations between BP PRS and arterial stiffness components.

Main Results:

  • Polygenic risk scores for systolic and diastolic blood pressure were significantly associated with total and load-dependent arterial stiffness.
  • No significant association was found between blood pressure PRS and structural arterial stiffness.
  • Mendelian Randomization confirmed that BP PRS predict mean arterial pressure (MAP), and elevated MAP increased load-dependent stiffness.

Conclusions:

  • Genetic factors influencing blood pressure have a differential impact on the components of arterial stiffness.
  • Load-dependent arterial stiffness is genetically linked to blood pressure, while structural stiffness is not.
  • These findings underscore the distinct genetic etiologies of arterial stiffness mechanisms.
Abstract

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