Inflammation Test Developed Predicts Cardiovascular Disease

Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear.

An assessment blending several measures of immune-cell responsiveness predicted cardiovascular problems in individuals who likely would have slipped under the radar. A blood test produces a single number that strongly predicts the development of the world’s most prevalent medical disorder: cardiovascular disease.

An international team of scientists led by those at Stanford University School of Medicine (Stanford, CA, USA) longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. Testing for levels of C-reactive protein (CRP), a circulating protein linked to inflammation, has been shown to further enhance the prediction of cardiovascular risk, even among patients with normal cholesterol levels. A CRP reading is relatively simple to get, requiring only a blood draw and relatively straightforward laboratory tests.

The new test developed is more complicated but appears to have superior diagnostic value to either the cholesterol or CRP test. Rather than testing circulating inflammatory proteins, it tests for the response of immune cells themselves to inflammation, a signal that appears to be more stable and hence a more robust diagnostic. In the study, it was able to detect early cardiovascular irregularities in otherwise asymptomatic individuals. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ.

When immune cells from young people were stimulated with certain cytokines, the activation levels of STAT proteins skyrocketed. When the same thing was done to immune cells from old people, STAT-protein activity increased a lot less. The investigators blended 15 separate cytokine-responsiveness measurements to generate a single number called a cytokine response score (CRS). This measure, which varied considerably among different older adults, was quite stable from year to year for any given individual.

A higher CRS is better, as it indicates a more-responsive immune system and lower background inflammation. The team found that cytokine response scores were inversely correlated with clinical signs of atherosclerosis and with two measures associated with the heart’s ability to relax between beats. Importantly, the borderline subjects also had low cytokine response scores.

Mark M Davis, PhD, professor of microbiology and immunology and the senior author of the study, said, “For too many men experiencing a heart attack or stroke, the first observed hint of cardiovascular risk is their death. The CRS may be a useful proxy for healthy aging and its predictive accuracy in cardiovascular disease further substantiates the inflammatory underpinnings of that prevalent, age-related condition.” The study was published on October 13, 2016, in the Cell Systems.

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Stanford University School of Medicine