It turns out that cholesterol isn’t the only thing you have to worry about to keep your heart healthy. In recent years, doctors have started to focus on inflammation — the same process that makes cuts red and painful — as an important contributor to a heart attack. It’s the reason doctors recommend low-dose aspirin…
It turns out that cholesterol isn’t the only thing you have to worry about to keep your heart healthy. In recent years, doctors have started to focus on inflammation — the same process that makes cuts red and painful — as an important contributor to a heart attack. It’s the reason doctors recommend low-dose aspirin to prevent recurrent heart attacks in people who have already had them, why they also prescribe statins, which lower both cholesterol and inflammation, and why they have started to measure inflammation levels in the blood.
But it’s never been clear exactly how much inflammation adds to heart disease risk. Since statins lower both, it’s hard to tell whether inflammation or cholesterol has the bigger impact on heart problems.
But in a new paper published in the New England Journal of Medicine and presented at the European Society of Cardiology meeting, scientists say they now have proof that lowering inflammation alone, without affecting cholesterol, also reduces the risk of a heart attack.
In the study, 10,000 people who have already had a heart attack were randomly assigned to get injected with a placebo or different doses of a drug called canakinumab. Canakinumab, made by Novartis, is currently approved to treat rare immune-related conditions and works to reduce inflammation but does not affect cholesterol levels. After four years, the people who received the drug had a 15% lower chance of having a heart attack or stroke compared to people who didn’t get the drug. The medication also reduced the need for angioplasty or bypass surgery by 30%.
“Even I am pinching myself,” says Dr. Paul Ridker, who led the study and is director of the center for cardiovascular disease prevention at Brigham and Women’s Hospital and is a pioneer in exposing the role inflammation plays in heart disease. “This outcome is more than we hoped for. The bottom line is we now have clear evidence that lowering inflammation through this pathway lowers rates of heart attack and stroke with no change at all in cholesterol.”
About a quarter of people who have heart attacks will have another heart event even if they keep their cholesterol at recommended levels. For them, it may not be cholesterol so much as inflammation that is driving their heart disease. So the study further solidifies the fact that heart doctors should be measure inflammation as well as cholesterol in their heart patients. An inexpensive blood test that looks for a protein that rises in the blood with inflammation, called C-reactive protein (CRP), can tell doctors how much inflammation their patients have. Beginning in 2003, the American Heart Association started to provide guidelines on how doctors should use CRP testing; for patients like those in the current trial, the group did not see any additional benefit to CRP testing since those patients should already be treated with statins, which can lower both cholesterol and inflammation.
But with the new results, those guidelines may change. Ridker says the findings should clarify how doctors can optimize the way they treat their heart patients — about half of people who have had a heart attack tend to have high levels of inflammatory factors, while half have high cholesterol levels. The inexpensive CRP test could identify those with higher inflammation, who might be candidates for taking a drug like canakinumab.
The drug is not currently approved for any heart conditions, but Novartis will likely look at doing more studies to confirm its effectiveness in treating heart disease.
Perhaps more intriguing are additional results that Ridker reported, related to cancer. In a separate study published in the Lancet using data from the same study, he found that people taking canakinumab lowered their risk of dying from any cancer over four years by 50%, and their risk of fatal lung cancer by 75%.
While the connection between heart disease and cancer may not seem obvious, Ridker says that many people who have had heart problems, like those in the study, are former or current smokers, since smoking is a risk factor for heart attacks. And smoking increases inflammation. “People who smoke a pack of cigarettes a day are chronically inflaming their lungs,” he says. That’s why he decided to look at cancer deaths as well as heart events in his study population.
The cancer data is still preliminary, and needs to be confirmed with additional studies, but it’s encouraging, says Dr. Otis Bradley, chief medical officer for the American Cancer Society, who was not involved in the study. “We know that free oxygen radicals and inflammation can damage DNA and can cause cancer,” he says. “This all makes sense to me.” Studies have already shown, for example, that inflammation may be a factor in prostate cancer and colon cancer.
But whether anti-inflammatory agents, like canakinumab, or even over-the-counter drugs like aspirin, should be part of standard cancer treatment isn’t clear yet. There are a number of different inflammatory pathways, and canakinumab targets just one. Other pathways, along with new anti-inflammatory drugs, may emerge with more research.
When it comes to heart disease, however, it’s clear that inflammation-fighting medications like canakinumb may represent the next generation of treatment. “Ten years from now we will be doing more personalized medicine,” says Ridker. “Some people will get more cholesterol lowering. Some will get more inflammation-lowering drugs. Some will get other agents that we haven’t considered yet. It’s a wonderful new era in heart disease treatment.”