Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement

Area of Science:

• Cardiovascular Medicine
• Biomarker Discovery
• Proteomics

Background:

• Aortic valve stenosis (AS) is a leading cause of cardiac valve surgery with high mortality if untreated.
• The underlying causes of AS remain largely unknown, necessitating research beyond traditional case-control studies.
• Prospective studies identifying novel biomarkers could illuminate AS pathogenesis.

Purpose of the Study:

• To identify potential protein biomarkers associated with the development of aortic valve stenosis (AS).
• To investigate the relationship between cardiovascular proteins and AS in a large population cohort.
• To explore whether identified associations are influenced by concurrent atherosclerotic disease.

Main Methods:

• A prospective population survey with baseline blood samples identified 334 AS cases and matched controls.
• Plasma samples were analyzed using a proximity extension assay for 92 cardiovascular proteins.
• Conditional logistic regression and validation cohorts were used to assess protein associations with AS.

Main Results:

• Six proteins (GDF-15, galectin-4, vWF, IL-17RA, TFRC, PCSK9) were associated with AS in the discovery cohort.
• Associations were robust even after adjusting for cardiovascular risk factors.
• In patients with concurrent coronary artery disease, five proteins showed robust associations in validation, suggesting a link to atherosclerosis.

Conclusions:

• Five proteins were identified as altered years before AS surgery.
• The observed protein associations with AS appear to be significantly influenced by concurrent atherosclerotic disease.
• These findings may provide new mechanistic insights into AS, particularly in the context of atherosclerosis.