New heart disease test

Researchers have developed a blood test that may help detect heart disease in asymptomatic individuals by measuring the immune system’s response to inflammation, a symptom tied to various age-related diseases like dementia and arthritis. In a nine-year-long study of 90 people without heart disease, the test, which spits out a number indicating risk, was better at predicting the condition than a CRP test or cholesterol testing, which is accurate only about half the time. Heart disease remains the leading cause of death worldwide, accounting for about 610,000— or one in four— deaths each year in the United States alone, according to the Centers for Disease Control and Prevention (CDC).

“There hasn’t been much immunology in cardiology, and almost any cardiology in immunology,” senior author Mark M. Davis, director of the Institute for Immunity, Transplantation and Infection at Stanford University, told “So these are fields that need to talk to each other more … [so that] cardiologists can feel comfortable looking at immunological data and deciding what might work best for their patients.”

Davis and his team began by administering an annual flu shot to 29 people — 19 older and 10 younger — to study how their cells responded to the vaccine.  They determined this response by studying how much of the vaccine ran through the participants’ blood. Over the course of nine years, this participant group would expand to 90 people— 60 people over age 60 and 30 people under age 40— all of who were given the vaccine, and assessed annually with various tests to study their immune function and markers of inflammation.

It’s well known that as an individual ages, his or her immune system falters. That’s why older patients don’t respond as well to the flu vaccine as younger people. But researchers drew a correlation between the participants’ vaccine response and levels of chronic inflammation. Inflammation is also tied to heart disease.

The immune system consists of specialized white blood cells, which fight infection and talk to each other with small, secreted molecules called cytokines, said Davis, who is also a microbiology and immunology professor at Stanford. Cytokines are known to kick the immune system into high gear and are essentially the hormones of the immune system, while the blood is the highway of the immune system.

Separately in a lab dish, Davis and his team analyzed how participants’ immune cells responded to cytokine stimulation. This stimulation triggers chemical changes in intracellular substances called STAT proteins, which in turn stimulates more immunological activity.

In the young patients, cytokine stimulation led to high activation of STAT proteins, but in the older group, STAT protein activity rose significantly less.

However, in the older patients, pre-stimulation levels of STAT protein activation were significantly higher than in those from young people, suggesting their immune systems are constantly in an overstimulated state.

“That suggests [the older patients are] already getting some kind of stimulation even if you’re not doing anything to them,” Davis said. “So they have a low level of cytokines in blood that is chronically stimulating white blood cells— that would be chronic inflammation, and it doesn’t suggest good things about how well your immune system might be functioning.”

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Using those observations and mixing 15 cytokine-responsive measurements, researchers devised a cytokine response score. Higher scores signaled lower inflammation and greater immune response.

Researchers gathered the cytokine response scores of 40 older subjects and cross-referenced results from their cardiovascular health assessments, which they took up to two years later. They drew correlations between the cytokine response scores and the participants’ clinical signs of atherosclerosis, a disease wherein plaque accumulates in the arteries, as well as two other tests that measure the heart’s ability to relax between beats. The scores were better at predicting signs of inflammation-based cardiovascular risk than the standard CRP test.

Next, Davis and his team are collaborating with scientists at other universities to better understand how immune system changes may correlate to clinical health outcomes— and not just heart disease but other age-related diseases, too.

“We’re putting that data together and trying to create a profile of healthy people with different ages to say, ‘What’s normal?’ ‘What’s the normal range of someone who is reasonably healthy?’” Davis said. “And of course people are not always healthy, and in a long-range study they die of different things—cardiovascular disease and cancer—and ‘Can we see anything leading up to that that could be a signal of someone that’s in danger?’”

As for the cytokine response score, the test is too complex to be rolled out in a clinical setting just yet, but Davis said it could be easily simplified and commercialized.

“I hope it will attract interest and that other people will confirm it with other studies,” he said, “and hopefully a company would license it and develop a practical test.”

Study results were published online Thursday in the journal Cell Systems.

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