New insights about inflammation

Recent research reignited interest in inflammation, a major player in heart disease.

A buildup of cholesterol-rich plaque inside arteries — known as atherosclerosis — is the root cause of most heart attacks and strokes. Researchers have long recognized that chronic inflammation sparks this artery-damaging process (see "Understanding inflammation"). Now, they're zeroing in on better ways to tackle that aspect of the problem.

Addressing inflammation is vital. Even when people take steps to lower their risks for heart disease, such as reducing their cholesterol and blood pressure, they may still face life-threatening cardiovascular events.

"Even if you're on a statin and your LDL cholesterol is quite low, you're not home free. You may still have inflammatory risk," says Dr. Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Harvard-affiliated Brigham and Women's Hospital. A blood test that detects C-reactive protein (CRP), a byproduct of inflammation, is just as good at predicting heart disease as an LDL measurement, he says.

Understanding inflammation

Inflammation refers to the immune system's response to an injury or infection. For example, if you sprain your ankle or scrape your knee, your immune system unleashes an army of white blood cells to engulf and protect the area, causing visible redness and swelling. Infections such as the flu or pneumonia trigger a similar response to eliminate the harmful pathogens.

Chronic inflammation often begins with a similar cellular response but morphs into a lingering state that persists far longer. Toxins such as cigarette smoke or an excess of fat cells (especially around the belly area) can also trigger inflammation. So can the fatty plaque inside arteries, which causes inflammatory cells to cover and wall off the plaque from the flowing blood. But the plaque may rupture, mingle with blood, and form a clot. These clots are responsible for the majority of heart attacks and most strokes.

The hsCRP test

Results from the test — known as a high-sensitivity CRP (hsCRP) test — are categorized into three levels: below 1 milligram of CRP per liter of blood (mg/L) is considered low risk, 1 to 3 mg/L means average risk, and above 3 mg/L signals high risk. So why don't most doctors do this test routinely? One reason is that cholesterol-lowering statins (the mainstay treatment for reducing heart disease risk) also lower CRP. That's also true for recommended lifestyle approaches, such as exercising, eating a diet that includes lots of plants, controlling your weight, and avoiding tobacco. As a result, knowing your CRP level wouldn't necessarily change your doctor's advice. That's directly related to the second reason: aside from statins, there aren't any currently available drugs proven to lower CRP and related cardiovascular problems.

But two large clinical trials led by Dr. Ridker have helped pave the way for some possible new treatments. A 2017 study found that a drug called canakinumab (Ilaris), which targets a specific molecule involved in inflammation known as interleukin-1, cut the risk of heart attacks, strokes, and other cardiovascular events by 17% in people with heart disease who were already taking standard heart drugs. The benefits were even better among people with the biggest drops in their CRP levels. However, in Dr. Ridker's trial, the drug led to far more striking reductions — up to 70% lower — in lung cancer among the participants. As a result, the drug's maker, Novartis, has changed priorities and is now focusing exclusively on that application, Dr. Ridker explains.

The second study, funded by federal grants, also focused on people with heart disease but tested an older drug called methotrexate (Trexall), which is used to treat rheumatoid arthritis and other inflammatory types of arthritis. But methotrexate did not lower inflammatory markers, CRP levels, or cardiovascular events. Despite that somewhat disheartening result, the finding provided important clues for future drug development, says Dr. Ridker. "Putting the two studies together, we have a road map for the future, because we now recognize the inflammation target for heart disease prevention is somewhere along the pathway from interleukin-1 to CRP," he says.

What you can do

In the meantime, if your LDL cholesterol level is in a good range (less than 70 mg/dL if you've had a heart attack or less than 100 mg/dL if you haven't) but you have other risk factors, including a family history of heart disease, ask your doctor whether an hsCRP test would better assess your risk. A high level should give you even more incentive to follow Dr. Ridker's advice: "Throw out your cigarettes, go to the gym, and eat more vegetables." You also might want to ask your physician about increasing your statin dose or switching to a more potent statin, he adds.

Inflammation Image: © 7activestudio/Getty Images

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