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
- 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.
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.
PosterUtility of proteomic trajectories of cardiovascular risk and cardiorespiratory fitness to monitor adverse health states throughout post-COVID-19 illness
Cardiovascular involvement is a prominent observation in patients during the acute phase of COVID-19 infection, as well as in convalescence. However, the etiology, trajectory, and underlying biology of cardiac dysfunction across the spectrum of COVID-19 illness is not fully understood. To address this, the CISCO-19 study (NCT04403607) was formed to investigate the multisystem effects of COVID-19 from hospitalized patients
PosterIdentifying genetic and environmental influences on proteins associated with age, cardiovascular risk, and other endpoints using the SomaScan® Assay
Protein quantitative trait locus pQTL studies identify genetic variants that are statistically associated with protein levels Results from the growing number of pQTL studies can be combined with genome wide association studies to identify proteins that underlie the genetic risk of disease, thus revealing the mechanisms of disease and potential drug targets.
PosterSomaScan® Platform confirmation and performance validation
The SomaScan® Platform for proteomic profiling uses 7288 (7K) SOMAmer® reagents, single stranded DNA aptamers, to 6596 unique Human Protein Targets. The modified aptamer binding reagents1, SomaScan assay2, its performance characteristic for 5k3 and 7k4 content sets, and specificity5,6,7 to human targets have been previously described. We combine profiles of validation and performance metrics with orthogonal confirmation of specificity from published literature to provide a comprehensive view of the specificity and utility of the SomaScan Platform.