Applying proteomics to one of the world’s longest-running heart studies

Applying proteomics to one of the world’s longest-running heart studies

Imagine the limitations of owning a computer that’s unable to connect to the internet. The same applies for large amounts of epidemiological data from which potential insights can’t be harnessed due to limited technology. With the development of large-scale proteomics, researchers are now analyzing data from the 30+ year-old Atherosclerosis Risk in Communities (ARIC) study to investigate patterns in cardiovascular, kidney disease, Alzheimer’s, and more. Early discoveries, including novel protein targets and pathways, are paving the way for new therapeutic interventions.

 

The ARIC study is the largest heart health community surveillance study designed to investigate causes of atherosclerosis, cardiovascular risk factors, and stroke. The study, which began in 1987 with nearly 16,000 participants, has now been running for over 33 years. Participants attend regular clinical examinations alongside periodic telephone follow-ups. The ARIC study is a treasure trove of longitudinal clinical data and has led to discoveries that have shaped clinical practice guidelines for cardiovascular-related diseases.

 

With the right tools, population studies like the ARIC study can provide deep insight into causal and risk factors for various diseases. Proteomics provides real-time measurements of changes in protein profiles that correlate with current health status – basically assessing biological changes in real time. 

 

The SomaScan® Assay is a multiplexed platform that makes high-throughput, deep proteomic analysis of large clinical studies a reality. The SomaScan Assay measures 7,000 proteins in a single blood sample, allowing users to identify protein signatures of disease progression or improvement, predictive biomarkers, and the impact of interventions. Over time, protein signatures reveal patterns in clinical metrics that provide insight into changes in major biological pathways that corelate with healthy or disease states.

 

Dr. Joseph Coresh and a group of scientists at Johns Hopkins applied the power of the SomaScan Assay to the ARIC study data from frozen plasma obtained on three visits spanning 1990 to 2013. The group successfully developed discovery and validation methods for cardiovascular disease, chronic kidney disease, and dementia. Their studies identified biomarkers for these conditions and revealed proteins and pathways that can serve as targets for therapeutic intervention.

 

Briefly, here are highlights of early findings from these studies that are relevant to dementia, cardiovascular and kidney disease.

  • SomaScan analyses of blood samples of over 10,000 middle-aged and elderly people showed abnormally high levels of 38 proteins associated with a risk of developing dementia1. A specific protein, SVEP1, was found to have direct causal relationship with Alzheimer’s. The data suggests that although dementia (which often develops from Alzheimer’s disease) develops late in life, dozens of proteins predicting the disease are already in the blood stream up to five years prior1.
  • In a population of older adult cancer survivors, inflammatory proteins associated with dementia were identified. These risk-related biomarkers can be used in dementia risk screening and might even serve as preventive or therapeutic targets in cancer survivors2.
  • A study focused on cardiopathies found that levels of triglyceride-rich lipoproteins could independently predict cardiovascular disease risks in middle-aged adults3.
  • Another study found that a cytokine growth factor, GDF-15, can predict bleeding risk in people who do not have a history of cardiovascular disease, improving risk prediction beyond conventional risk factors4.

The SomaScan Assay is a powerful proteomics platform for comprehensive analysis that provides tremendous insight for research and healthcare. Discovering new protein signatures opens doors to novel therapeutic targets and/or prevention therapies.

 

The findings from Dr. Coresh and his team are a typical example of knowledge that can be gleaned when proteomic analysis is applied to longitudinal data. Other large epidemiological studies, like the Cardiovascular Health Study (CHS), Cleveland Family Study (CFS),  Multi-Ethnic Study of Atherosclerosis (MESA), and Coronary Artery Risk Development in Young Adults (CARDIA) all hold data for which proteomic analysis using groundbreaking technology like the SomaScan Assay would be impactful, producing novel discoveries and clinical insights.

 

References

  1. Walker, K. A. et al. Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk. Nat. Aging 2021 15 1, 473–489 (2021).
  2. Ugoji, C. et al. Circulating Inflammatory Proteins Associated with Dementia Risk in Older Adult Cancer Survivors in the Atherosclerosis Risk in Communities (ARIC) Study. Cancer Epidemiol. Prev. Biomarkers 30, 802–802 (2021).
  3. Hussain, A. et al. Association of low-density lipoprotein triglycerides (LDL-TG) and remnant-like protein cholesterol (RLP-C) with cardiovascular events in the elderly: the atherosclerosis risk in communities (ARIC) study. (2020) doi:10.1016/S0735-1097.
  4. Mathews, L. et al. Abstract 13846: Growth Differentiation Factor 15 and Risk of Clinical Bleeding Events in the Atherosclerosis in Communities (ARIC) Study. Circulation 142, (2020).
  5. Yu, Z. et al. Polygenic Risk Scores for Kidney Function to the Circulating Proteome, and Incident Kidney Diseases: the Atherosclerosis Risk in Communities Study. bioRxiv 2020.09.05.284265 (2020) doi:10.1101/2020.09.05.284265.

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