Heart beat: Advanced test of inflammation may be superior predictor of cardiovascular risk

It’s a diagnostic mainstay: You walk into a doctor’s office — or, these days, maybe a drugstore. Somebody pricks your finger. And a day or two later you’ve got the results of a test that spits out four numbers corresponding with your blood levels of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Bing, bang, boom. Now you know all about your risk for cardiovascular bummers like heart attacks or strokes.

Well, not quite. Cholesterol testing flags cardiovascular risk only about half of the time, says celebrated Stanford immunologist Mark Davis, PhD.

“For too many men experiencing a heart attack or stroke, the first observed hint of cardiovascular risk is their death,” he told me when I spoke to him recently about his latest study, published today in Cell Systems.

You can improve cardiovascular-risk prediction by additionally testing for levels of another circulating substance called CRP, a proxy for the degree to which a person’s immune system is in an aroused state called inflammation. This makes sense because, as I wrote in a news release describing the study:

Medical experts are increasingly convinced that this constantly thrumming, systemic, inflammatory activity threatens diverse tissues throughout the body… Testing for levels of CRP… has been shown to further enhance the prediction of cardiovascular risk, even among patients with normal cholesterol levels.

A team supervised by Davis has devised another kind of blood test that spits out a single number better than cholesterol or CRP tests at scouting for cardiovascular disease, the world’s most prevalent medical disorder. In separate lab dishes, Davis and his colleagues mixed several different types of immune cells with different immune-activity-stimulating substances. In each case, they noted the extent to which this triggered the activation of intracellular molecules that, when activated, amp up a cell’s immunological activity.

The researchers found that, first, pre-stimulation activation levels of these intercellular molecules typically runs higher in older than in younger people — consistent with the general truth that the older you get, the more your immune system tends to be stuck in inflammatory overdrive even when there’s nothing to get excited about. Second, the degree of overdrive varies widely among older people, suggesting it’s not inevitable. Third, the higher this pre-stimulation level of intracellular activation, the weaker the response to actual stimulation — in essence, all that wheel-spinning  makes for a tired immune cell that can’t jump very high when it’s actually time to jump.

For each study participant, Davis’s team distilled an extensive set of these measurements down to a single numerical “score”: the more responsive the person’s immune system, the higher the score. Which led to a fourth finding: Low-scoring participants were more likely, on inspection, to show early signs of arterial stiffness and heart stress, even when participants were asymptomatic.

The new test involves tricky lab procedures, but Davis’s group is working to simplify it to the point of commercial viability. A potential bonus: The same test may well identify risk for a growing list of other conditions tied to excessive systemic inflammation.

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