Time. Is it on My Side?
Time. There never seems to be enough of it. With our hectic lives, even the simplest of inconveniences, such as a car breaking down or a heart attack, can totally sour the afternoon and derail our well-laid plans. Wouldn’t it be nice to have advance warning for when we might expect to encounter an interruption to those plans? In part to gain us such a portent, several groups recently assessed a new technology for determining an individual’s cardiovascular disease risk, and the development of a warning test. Their combined efforts may indeed allow us to better plan our lives, or at least serve as a wake-up call that we need to change something in order to have more time to live.
The new technology that could play a crucial role in granting us more time is the SOMAscan® assay, which currently measures changes in over 1,130 proteins. To assess the practicality of SOMAscan in cardiovascular disease research, a research group led by Rob Gerszten at Beth Israel Deaconess Medical Center looked at “controlled heart attacks” to identify protein differences between pre- and post-heart attack in patients’ blood. Aside from identifying biomarkers that are well-established for heart injuries, the researchers also found several not previously seen. They also looked for biomarkers related to other traits that are known to elevate a person’s risk for cardiovascular disease (e.g. age, smoking, cholesterol levels, etc.). They noted the candidate biomarkers they discovered using SOMAscan may shed light into novel pathways that could in some way relate back to the development of cardiovascular disease. The researchers also noted that the SOMAscan assay was faster compared to mass spectrometry, an important consideration when assaying a large number of participants.
In addition to evaluating the SOMAscan assay for biomarker discovery, the research group also evaluated the accuracy of the individual SOMAmer® reagents in identifying their intended target proteins. Using mass spectrometry, the researchers found that all the SOMAmers tested did indeed hit the right targets.
In related work, a research group led by Peter Ganz at University of California San Francisco used the SOMAscan assay to identify a potential prognostic test for true cardiovascular risk in patients with stable coronary heart disease (CHD). The researchers initially analyzed plasma samples from CHD patients who took part in the Heart and Soul study (a study initially intended to assess how mental health affects heart disease patients) for biomarkers that could stratify risk, a measurement that has proved challenging when using traditional or even genetic methods. From the initial phase, the group identified nine proteins that passed the statistical rigors.
To further assess the accuracy of the nine-protein panel, Ganz and his group conducted another round of SOMAscan testing on samples from a completely different set of individuals (participants in the HUNT3 study whose medical data and samples were collected and could be used for further medical or social science research), they verified their findings from the Heart and Soul samples. The researches also evaluated paired samples from the Heart and Soul study participants to determine if the individuals’ risk change as a cardiovascular event approached. They found that indeed that the closer an individual came to a cardiovascular event, the greater the change for the nine-protein panel results when compared to baseline values. These changes were, in turn, shown to be a more reliable and accurate measure than the current clinical standards for assessing cardiovascular risk.
The related findings of these two research groups underline the ability of the SOMAscan assay to benefit cardiovascular disease research, and suggest that we are inching closer to being able to fine-tune our prediction of when a cardiovascular event may happen. Which in turn, may grant us the time we need to accomplish all our well-laid plans.
Ngo, D., Sinha, S., Shen, D., Kuhn, E. W., Keyes, M. J., Shi, X., . . . Gerszten, R. E. (2016) Aptamer-Based Proteomic Profiling Reveals Novel Candidate Biomarkers and Pathways in Cardiovascular Disease. Circulation, 134(4), 270-285. doi:10.1161/CIRCULATIONAHA.116.021803
Ganz, P., Heidecker, B., Hveem, K., Jonasson, C., Kato, S., Segal, M. R., . . . Williams, S. A. (2016) Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease. JAMA, 315(23), 2532-2541. doi:10.1001/jama.2016.5951