The role of inflammation in heart disease is overlooked

Doctors are in the midst of a major overhaul of the causes of heart attacks and strokes – among the most common causes of death worldwide.

For decades, much of the focus has been on cholesterol: statins, prescribed to lower cholesterol, are the most commonly prescribed drugs to prevent cardiovascular disease in the UK. But a growing number of researchers say this overlooks another key factor: inflammation, or the background activity of the immune system.

This week, research showed that in people taking statins to lower their cholesterol, inflammation is a bigger risk factor for heart attack or stroke than whether they still have cholesterol. pupil. “It’s clear that if you don’t start tackling the inflammatory response, you’ll never beat this disease,” says Paul Ridker of Brigham and Women’s Hospital in Boston, who participated in the research. “It is no longer a hypothesis; it is a proven fact.

The cholesterol theory is primarily based on large studies that have found higher levels of “bad cholesterol” to correlate with higher rates of heart attacks.

The other clue was that cholesterol is one of the main components of fatty plaques in artery walls that can restrict blood flow to major organs. Heart attacks and strokes usually occur because such plaque ruptures, with pieces breaking off and blocking small blood vessels downstream.

With this understood, cholesterol-lowering statins became one of the most commonly used drugs. More than 200 million people worldwide take a statin, either because they have survived a heart attack or stroke, or because they are at risk of having one. Numerous large-scale trials have shown that statins are very effective in reducing heart attacks, further supporting the cholesterol theory of heart disease.

So where does inflammation come from? The revised idea is that these plaques are not just inert blockages, but are alive with immune cell activity. Animal studies have shown that plaques that are more inflamed are more likely to burst and spread the deadly fragments into the bloodstream. And recent evidence suggests that statins may work by mitigating inflammation as well as lowering cholesterol.

Despite growing evidence of the importance of inflammation, it has yet to translate into new ways to prevent or treat cardiovascular disease. But that may be about to change.

Ridker’s team analyzed the numbers from three large trials that each tested a different therapy aimed at reducing heart attacks and strokes in people taking statins.

The results of these therapies are not what is relevant here. At the start of the trials, participants’ blood was subjected to a battery of tests, including for cholesterol and a characteristic compound of inflammation, called C-reactive protein (CRP).

All three trials showed that high CRP was linked to more deaths from cardiovascular disease than from high cholesterol. People in the quarter of participants with the highest CRP had a 268% higher risk than the quarter with the lowest. By comparison, having high cholesterol only increases the risk by 27%.

Knowing that inflammation is part of the disease process is useless unless we can do something about it. But in recent years, several drugs designed to do just that have been tested.

One of the most promising is a plant-derived compound called colchicine, which is already used to reduce inflammation in gout sufferers. Two recent randomized trials have shown that colchicine also reduces strokes and heart attacks by about 30%, a similar amount to statins.

Colchicine is not approved for the prevention of cardiovascular disease outside of Canada, although in 2021 it was considered an option in the guidelines of the European Society of Cardiology. If it were to be recommended by a similar body in the UK, doctors could prescribe it “off label”, says Nilesh Samani of the University of Leicester, who was not involved in the latest study.

One caveat is that people who have had a heart attack or stroke may already be on many pills, and the more drugs a person takes, the more likely they are to interact with each other and cause side effects, not to mention inconveniences for patients.

Nevertheless, there is growing evidence that to prevent heart disease and stroke, doctors must place the same importance on fighting inflammation as they do on cholesterol. “It’s not one or the other – it’s both,” says Jean-Claude Tardif of the Montreal Heart Institute in Canada, who participated in one of the colchicine trials.

“Often in science it’s a series of incremental steps that eventually lead to radical change. This document has highlighted that.