Urinary proteome

Introduction

Factors that lead to atherosclerosis can exert systemic effects, including impaired kidney function, potentially creating distinct urine protein signatures prognostic of cardiovascular disease (CVD) risk. Urine possesses several attractive features for biomarker discovery and assessment of disease, including CVD, as it is readily available, can be collected non-invasively, and enables monitoring of a wide range of physiological processes.

The aims of this project were as follows:

• To determine the number of proteins detectable in urine
• To explore the relationship between the urinary proteome and risk of secondary CVD events in individuals with stable coronary heart disease (CHD)
• To identify proteins in urine that may reveal new biological pathways and systems underlying CVD risk
• To compare the prognostic performance of protein biomarkers in urine and in plasma in predicting CVD events

Methods Overview

• 24 h urine samples were assayed for proteins from 818 participants in the observational Heart & Soul cohort of outpatients with stable CHD, collected at study baseline (Beatty et al. J Am Heart Assoc: 4(7): e001646).
• Follow-up > 11-y.
• Kidney function ranged from normal to moderately impaired.
• A total of 4,316 proteins were measured using SomaScan®, a high-throughput assay that uses modified aptamers as binding reagents.
• A protein-based normalization was performed.
• Urine proteins were analyzed for their association with the CVD outcome (defined as myocardial infarction, stroke, heart failure or death) and CVD risk prediction models were constructed using the LASSO method and backwards selection.

Conclusion

A 4-y CVD risk prediction model based on urinary proteins performs similarly to a model based on plasma, suggesting the potential clinical utility of urine as a matrix for early CVD detection.