Proteomics and heart failure: Improving risk stratification and treatment
New research suggests that proteomics could improve – or even replace – current techniques for assessing the risk of heart failure progression and mortality while also promoting access to individualized treatment.
The prevalence of heart failure in the United States
Heart failure is a major public health burden associated with high morbidity and mortality, as well as rising costs of healthcare. Approximately six million adults in the United States are currently experiencing heart failure, and the prevalence is anticipated to increase over time to impact an estimated nine million by 2030. Because heart failure progression has a high level of variability across patients, it can be difficult for healthcare providers to adequately assess the risk level of patients with this condition.
Current risk stratification misses the mark
Currently, risk stratification for patients with heart failure generally involves a combination of clinical risk scores and the measurement of previously established biomarkers (e.g., natriuretic peptides: NTproBNP). Two widely accepted clinical risk scores include the Seattle HF model score and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score, both of which utilize commonly available input data (e.g., age, sex, blood pressure) to determine a continuous risk score. However, there is room for improvement, as both leave unanswered questions regarding other biological pathways involved with the progression of heart failure and the recognition of pathophysiological subgroups within all heart failure patients.
Examining the potential for proteomics in heart failure risk stratification
Proteomics has the potential to offer early insight into the status and progression of diseases, providing crucial information even before symptoms are experienced or observed, which allows for better informed treatment and proactive medicine. A recent study, led by Dr. David Lanfear at Henry Ford Hospital, aimed to determine whether the plasma proteome could provide insight beyond the currently established risk stratification methods for patients experiencing heart failure.
Tool of choice: The SomaScan® Assay by SomaLogic
Dr. Lanfear’s study utilized impressive technology created by SomaLogic to create and validate a plasma proteomic risk score (PRS). The SomaScan® Assay is an aptamer-based proteomics platform capable of capturing nearly 5,000* proteins at once, and it was used to examine the plasma of 1,017 patients experiencing heart failure with reduced ejection fraction (HFrEF).
*Note: The current version of the SomaScan Assay is capable of measuring 7,000 proteins.
The plasma proteome provides strong predictions for heart failure progression
Using the SomaScan Assay, researchers identified 128 proteins that were significantly associated with patient mortality. This list was refined using LASSO-penalized Cox regression and concurrent stepwise forward and backward selection. This proteomic analysis was performed independently of SomaLogic. The following eight proteins were retained to build the proteomic risk score:
- Pseudocholinesterase
- Stanniocalcin-1
- Renin
- ERBB1
- ASM
- UGT 1A6
- Carbonic anhydrase 6
- APBB3
The higher bins of HFrEF proteomic risk score were associated with a lower quality of life, heart failure preconditions (e.g., coronary artery disease and type II diabetes mellitus), a shorter six-minute walk distance, and a greater reduction in ejection fraction over time. Overall, results indicated that the circulating proteome in HFrEF patients showed considerable changes as the risk of death increased. Additionally, the proteome risk score not only significantly improved predictions on top of the standard risk stratification methods, but the results suggest that utilizing the SomaScan Assay to measure the plasma proteome has the potential to be used as an independent indicator of the risk of death in patients with HFrEF, because its standalone performance is comparable to that of MAGGIC or NT-proBNP. This means that the proteomic risk score could potentially be utilized within clinical trials as an indicator of whether novel therapeutics are working to decrease heart failure risk.
It should also be noted that many of the proteins included within the score were novel within the HFrEF context and have not previously been associated with the canonical pathways linked to heart failure. Further studies of these proteins could investigate how they contribute to the development and progression of heart failure and whether they are prospective drug targets.
To learn more about this innovative research, you can register to attend the free GEN webinar where Dr. David Lanfear will discuss using the SomaScan Assay to interrogate the circulating proteome for heart failure risk stratification.
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