Traditional and novel risk factors for incident aortic stenosis in community-dwelling older adults

Daniele Massera; Traci M Bartz; Mary L Biggs; Nona Sotoodehnia; Alexander P Reiner; Richard D Semba; John S Gottdiener; Bruce M Psaty; David S Owens; Jorge R Kizer

doi:10.1136/heartjnl-2023-322709

Traditional and novel risk factors for incident aortic stenosis in community-dwelling older adults

Heart. 2023 Dec 15;110(1):57-64. doi: 10.1136/heartjnl-2023-322709.

Authors

Daniele Massera¹, Traci M Bartz², Mary L Biggs², Nona Sotoodehnia^{3

4}, Alexander P Reiner⁵, Richard D Semba⁶, John S Gottdiener⁷, Bruce M Psaty⁴, David S Owens³, Jorge R Kizer^{8

9}

Affiliations

¹ Leon H. Charney Division of Cardiology, New York University Grossman School of Medicine, New York, New York, USA.
² Department of Biostatistics, University of Washington, Seattle, Washington, USA.
³ Division of Cardiology, University of Washington, Seattle, Washington, USA.
⁴ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington, USA.
⁵ Department of Epidemiology, University of Washington, Seattle, Washington, USA.
⁶ Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁷ Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁸ Cardiology Section, San Francisco VA Health Care System, San Francisco, California, USA jorge.kizer@ucsf.edu.
⁹ Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

PMID: 37463733
PMCID: PMC10794538 (available on 2024-12-15)
DOI: 10.1136/heartjnl-2023-322709

Abstract

Objectives: Calcific aortic stenosis (AS) is the most common valvular disease in older adults, yet its risk factors remain insufficiently studied in this population. Such studies are necessary to enhance understanding of mechanisms, disease management and therapeutics.

Methods: The Cardiovascular Health Study is a population-based investigation of older adults that completed adjudication of incident AS over long-term follow-up. We evaluated traditional cardiovascular risk factors or disease, as well as novel risk factors from lipid, inflammatory and mineral metabolism pathways, in relation to incident moderate or severe AS (including AS procedures) and clinically significant AS (severe AS, including procedures).

Results: Of 5390 participants (age 72.9±5.6 years, 57.6% female, 12.5% black), 287 developed moderate or severe AS, and 175 clinically significant AS, during median follow-up of 13.1 years. After full adjustment, age (HR=1.66 per SD (95% CI=1.45, 1.91)), male sex (HR=1.41 (1.06, 1.87)), diabetes (HR=1.53 (1.10, 2.13)), coronary heart disease (CHD, HR=1.36 (1.01, 1.84)), lipoprotein-associated phospholipase-A₂ (LpPLA₂) activity (HR=1.21 per SD (1.07, 1.37)) and sCD14 (HR=1.16 per SD (1.01, 1.34)) were associated with incident moderate/severe AS, while black race demonstrated an inverse association (HR=0.40 (0.24, 0.65)), and creatinine-based estimated glomerular filtration rate (eGFR_cr) showed a U-shaped relationship. Findings were similar for clinically significant AS, although CHD and sCD14 fell short of significance, but interleukin-(IL) 6 showed a positive association.

Conclusion: This comprehensive evaluation of risk factors for long-term incidence of AS identified associations for diabetes and prevalent CHD, LpPLA₂ activity, sCD14 and IL-6, and eGFR_cr. These factors may hold clues to biology, preventive efforts and potential therapeutics for those at highest risk.

Keywords: aortic valve stenosis; epidemiology; risk factors.

MeSH terms

Aged
Aortic Valve Stenosis* / diagnosis
Aortic Valve Stenosis* / epidemiology
Diabetes Mellitus*
Female
Humans
Incidence
Independent Living
Lipopolysaccharide Receptors
Male
Risk Factors

Substances

Lipopolysaccharide Receptors

Abstract

MeSH terms

Substances

Grants and funding