Polygenic Determinants of Arterial Stiffness: Implications for Hypertension
7 affiliations
- 1William S. Middleton Memorial Veteran's Hospital
- 2University of Wisconsin School of Medicine and Public Health
- 3Ryan Pewowaruk Research Consulting
- 4Nashville VA, Tennessee Valley Healthcare System
- 5Vanderbilt University
- 6The Lundquist Institute for Biomedical Innovation at Harbor‐UCLA Medical Center
- 7USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine
Abstract
Background Components of arterial stiffness (structural stiffness from aging and load-dependent stiffness from high blood pressure) are markers for cardiovascular disease risk. We evaluated relationships between polygenic risk scores (PRS) for blood pressure (BP) and arterial stiffness. Methods Participants (n=5942) are from the Multi-Ethnic Study of Atherosclerosis with measures of carotid ultrasound and genomic DNA. Pulse wave velocity (PWV) was calculated from carotid ultrasound representing total stiffness. Structural stiffness was calculated by adjusting PWV to a 120/80 mmHg blood pressure with participant-specific models. Load-dependent stiffness was the difference of total and structural stiffness. Blood pressure PRSs were previously derived from a genome-wide association study. Associations between BP PRSs and components of carotid arterial stiffness were assessed with multivariable-adjusted regression models. Mendelian Randomization (MR) was performed with two-stage least squares to 1) confirm that BP PRSs strongly predict MAP and 2) estimate the effect of MAP on arterial stiffness. Results Participants (n=5,942) were mean (standard deviation) age of 62.8 (10.3) years (52% female; 39% White, 25% African-American, 13% Asian, 23% Hispanic). Systolic BP (SBP) was 133.5 (20.5) mmHg, diastolic BP (DBP) was 74.27 (10.28) mmHg and pulse pressure (PP) was 59.22 (16.17) mmHg. Total carotid stiffness was associated with the SBP PRS ( β =0.10 +/-0.02, p=5.25E-08) and the DBP PRS ( β : 0.08 +/-0.02, p=7.26E-07) but not PP PRS ( β =0.04 +/-0.02, P=0.05). Load dependent carotid stiffness was associated with the SBP PRS β =0.09 +/-0.01, p=7.93*10 -30 ) the DBP PRS ( β =0.09 +/-0.01, p= 4.92*10 -34 ) and the PP PRS ( β =0.03 +/-0.01, p= 8.18* 10-5 ). Structural carotid stiffness was not associated with any BP PRSs. MR showed that SBP and DPB PRS strongly predict MAP (p<0.001) and each 1-mmHg increase in MAP raised load dependent stiffness by 0.0494 m/s (p<0.001). Conclusion There are key differences in the genetic underpinnings of the mechanistic components of arterial stiffness.
Related
- Office blood pressure measurement versus ambulatory blood pressure monitoring for detecting undiagnosed hypertension in an apparently healthy Mexican adult cohort: complementary central hemodynamic and arterial stiffness assessment
- Pulmonary arterial hypertension before closure of a persistent arterial duct (PDA) in children <12 months: clinical implications and outcome
- Endothelial Redox Dysregulation in Pulmonary Arterial Hypertension: Compartmentalized Mechanisms and Therapeutic Implications
- Dose–effect relationship of an acute isometric exercise session with different durations on blood pressure and arterial stiffness in prehypertensive substance use disorder individuals
- Arterial Stiffness Is Higher in People With Multiple Sclerosis Than in Control Group
BibTeX
@article{gepner2026polygenic,
title = {{Polygenic Determinants of Arterial Stiffness: Implications for Hypertension}},
author = {Adam D. Gepner and Ryan J. Pewowaruk and Claudia E. Korcarz and Adriana Hung and Kent D. Taylor and Y.‐D. I. Chen and Alexis C. Wood and Jie Yao and Xiuqing Guo and Jerome I. Rotter},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.125.047424},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.125.047424},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Polygenic Determinants of Arterial Stiffness: Implications for Hypertension
AU - Adam D. Gepner
AU - Ryan J. Pewowaruk
AU - Claudia E. Korcarz
AU - Adriana Hung
AU - Kent D. Taylor
AU - Y.‐D. I. Chen
AU - Alexis C. Wood
AU - Jie Yao
AU - Xiuqing Guo
AU - Jerome I. Rotter
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.125.047424
UR - https://www.ahajournals.org/doi/10.1161/JAHA.125.047424
AB - Background Components of arterial stiffness (structural stiffness from aging and load-dependent stiffness from high blood pressure) are markers for cardiovascular disease risk. We evaluated relationships between polygenic risk scores (PRS) for blood pressure (BP) and arterial stiffness. Methods Participants (n=5942) are from the Multi-Ethnic Study of Atherosclerosis with measures of carotid ultrasound and genomic DNA. Pulse wave velocity (PWV) was calculated from carotid ultrasound representing total stiffness. Structural stiffness was calculated by adjusting PWV to a 120/80 mmHg blood pressure with participant-specific models. Load-dependent stiffness was the difference of total and structural stiffness. Blood pressure PRSs were previously derived from a genome-wide association study. Associations between BP PRSs and components of carotid arterial stiffness were assessed with multivariable-adjusted regression models. Mendelian Randomization (MR) was performed with two-stage least squares to 1) confirm that BP PRSs strongly predict MAP and 2) estimate the effect of MAP on arterial stiffness. Results Participants (n=5,942) were mean (standard deviation) age of 62.8 (10.3) years (52% female; 39% White, 25% African-American, 13% Asian, 23% Hispanic). Systolic BP (SBP) was 133.5 (20.5) mmHg, diastolic BP (DBP) was 74.27 (10.28) mmHg and pulse pressure (PP) was 59.22 (16.17) mmHg. Total carotid stiffness was associated with the SBP PRS ( β =0.10 +/-0.02, p=5.25E-08) and the DBP PRS ( β : 0.08 +/-0.02, p=7.26E-07) but not PP PRS ( β =0.04 +/-0.02, P=0.05). Load dependent carotid stiffness was associated with the SBP PRS β =0.09 +/-0.01, p=7.93*10 -30 ) the DBP PRS ( β =0.09 +/-0.01, p= 4.92*10 -34 ) and the PP PRS ( β =0.03 +/-0.01, p= 8.18* 10-5 ). Structural carotid stiffness was not associated with any BP PRSs. MR showed that SBP and DPB PRS strongly predict MAP (p<0.001) and each 1-mmHg increase in MAP raised load dependent stiffness by 0.0494 m/s (p<0.001). Conclusion There are key differences in the genetic underpinnings of the mechanistic components of arterial stiffness.
SN - 2047-9980
ER -