For years, it was assumed that ‘bad’ LDL cholesterol enters the arterial wall, where it might form a clot and eventually block it, resulting in heart attacks and strokes. Approximately 35 million Americans currently take cholesterol-lowering statins.
However, substantial trials are currently underway to investigate the role of inflammation in heart disease, despite the fact that this is a danger that few people are aware of.
If you have heart problems, you may soon be prescribed a powerful anti-inflammatory.
Patients who were given colchicine — an anti-inflammatory medicine traditionally used to treat gout — within a few days of a heart attack were less likely to have another heart attack than those who were given a placebo, according to a recent study from the Montreal Heart Institute in Canada.
For years, people have believed that inflammation promotes heart disease. Nearly 30,000 seemingly healthy women in the United States had their cholesterol and C-reactive protein (CRP), an inflammation marker, assessed in 1997 and again eight years later in a landmark trial.
It turned out that at the end of the study, the women who had more inflammation were more likely to have a heart problem than the women who had more cholesterol.
Decade later, study leader Paul Ridker, a cardiologist at Brigham and Women’s Hospital in Boston and a professor of medicine at Harvard University, conducted the JUPITER trial, which randomized participants with elevated CRP but low cholesterol to either a statin or a placebo. Those who took the statin had a 44% lower risk of a cardiovascular event like a heart attack than those who took the placebo.
However, because statins treat both cholesterol and inflammation, the study didn’t say which was more important.
Additional evidence supporting the role of inflammation in heart disease comes from trials involving individuals with diabetes, who are known to be at an increased risk of cardiovascular disease.
What’s intriguing is that, while high blood sugar levels increase the risk of heart attack, “only treating blood glucose does not reduce that risk”, according to Professor Robin Choudhury, an expert on inflammation and a cardiologist at Oxford University.
Something else is going on, in other words. Professor Choudhury and his colleagues want to modify people’s perceptions of diabetes as solely a high-glucose condition.
“The goal is to identify opportunities to provide new treatment options to reduce the burden of heart disease,” he adds.
One theory is that high glucose levels in diabetes stimulate immune cells engaged in inflammation, which leads to inflammation.
Separately, cholesterol’s impact in heart disease is understood to be more than merely obstructing arteries: it also plays a role in inflammation. The plaques that lead to clots or blockages are formed by ‘bad’ cholesterol in the arterial wall, but new research suggests that it has a much more active chemical role that involves inflammation.
“We now know that if you lower cholesterol, markers of inflammation come down as well,” says Dr. Choudhury.
“The problem starts because cholesterol shouldn’t be in the artery walls. There is a process for removing it but if that doesn’t work, then the immune system gets called in.”
This causes molecules known as interleukins to be released, which attract immune system, “and the scene is set for inflammation to damage the heart”, he adds.
So taking drugs to reduce inflammation, in addition to statins, makes a lot of sense.
However, researchers such as Professor Choudhury have discovered that using any old anti-inflammatory is ineffective.
“You need ones that target the interleukins involved,” he says.
This was demonstrated in a 2019 experiment led by Professor Ridker that included 4,500 participants with heart disease and type 2 diabetes and was financed by the National Heart, Lung, and Blood Institute in the United States. Methotrexate, a well-known anti-inflammatory medicine, was given to patients to test if it reduced heart attacks or fatalities. It didn’t work. The explanation was that it had no effect on the key interleukins, notably IL-1-beta and IL-6.
However, the anti-inflammatory medicine colchicine, which has been used for 100 years, does target them, and some cardiologists have started prescribing it, according to Nature magazine.
While large-scale trials support the use of anti-inflammatory medications to prevent heart disease, the question of whether these powerful drugs should be administered for prevention remains unanswered.
Patients may take them for years with little or no apparent benefit on a daily basis, and potential side effects vary from headaches and vomiting to liver and lung illness.
This worries Ziad Mallat, a cardiovascular medicine professor at the University of Cambridge. “The risk is that the patient becomes more vulnerable to infections,” he says.
This is due to the fact that these anti-inflammatory medicines work by decreasing the efficacy of the immune system.
“Colchicine does lower inflammation affecting the heart but patients have more infections,” says Professor Mallat, who recently published research on a medication called Aldesleukin that can reduce inflammation while also keeping the immune system’s defensive side active.
Now, he and his colleagues are considering developing an mRNA vaccine similar to the one used for Covid-19, identifying the protein that causes the cholesterol-driven inflammation, and using the vaccine to stop it.
But is the new approach correct — does heart disease start first, followed by inflammation?
That’s the suggestion of Dr. James DiNicolantonio of Saint Luke’s Mid America Heart Institute in the United States, a senior cardiovascular research scientist.
“Rather than being the cause of heart disease, inflammation is the body’s response to poor diet, lifestyle and environmental factors,” he says.
“We should be aiming for optimum amounts of micronutrients: deficiencies of vitamins and minerals are key factors in heart disease, as is a diet high in refined carbohydrates and sugar.”
Professor Ridker, on the other hand, does not feel we must choose between the two. On the opposite.
“The likes of diet, exercise and smoking cessation not only all lower systemic inflammation, they also reduce cardiovascular event rates,” he told Good Health.
“So nutrition and lifestyle factors matter more than ever for prevention.”
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