This article was first published inÂ
Whenever asked about the risk factors for cardiovascular disease, the big players like smoking, high blood pressure, cholesterol and diabetes take up most of the medical community’s time. But go searching on the internet and you will find a huge obsession with the concept of inflammation. What’s fascinating about inflammation is that it does play a significant role in the development of atherosclerosis. Doing something about it has proved to be more problematic.
To grossly oversimplify, inflammation contributes to the formation of plaques in the coronary arteries and is largely driven by the traditional risk factors. Smoking, diabetes and obesity all increase inflammatory markers. The question is: Does inflammation cause heart disease, or is it a consequence of the underlying risk factors?
Support for inflammation’s direct role in cardiovascular disease came from the CANTOS study. This was a randomized controlled trial that tested canakinumab, a medication that targets interleukin-1 beta and consequently suppresses inflammation. Since it has no other effects on blood pressure, blood sugar levels or cholesterol, any benefit seen would be directly mediated by its anti-inflammatory effect.
Canakinumab showed not just a cardiovascular benefit at study completion, but also a reduction in cancer mortality, which should have made it a blockbuster. But it was also associated with an increased risk of fatal infections and it was never used widely in the population.
CANTOS proved an important point: You can suppress inflammatory markers, which will help reduce both cardiac and cancer risk, but suppressing inflammation comes at a price because you also suppress your immune system. Canakinumab is not used to treat cardiovascular disease today — the risk of fatal infections is too high a trade-off — but it does have some use in treating autoimmune conditions like Still’s disease.
Other attempts to find an anti-inflammatory treatment for heart disease have faced similar disappointments. The Cardiovascular Inflammation Reduction Trial (CIRT) tested methotrexate, a medication used to treat both cancer and autoimmune conditions. But in CIRT, it showed no cardiovascular benefit compared to placebo and joined canakinumab in the discard pile.
The most recent attempt at inflammatory suppression in cardiovascular disease came in the form of colchicine, a medication commonly used to treat gout and pericarditis. In the LoDoCo2 study, colchicine was tested in patients with stable cardiovascular disease, and in the COLCOT study it was given to patients after a heart attack. Both showed a cardiovascular benefit, mainly a reduction in angioplasties. COLCOT also showed a reduction in stroke, though neither showed a cardiovascular mortality reduction. As counterweight, the COPS trial also tested colchicine after a heart attack and found no benefit.
Attempts at meta-analysis found an overall cardiovascular benefit, but no reduction in cardiovascular mortality. A recent (still unpublished) study has challenged that benefit. The CLEAR SYNERGY trial results were presented at the TCT 2024 medical conference. The trial randomized patients to colchicine versus placebo after heart attack and found no cardiovascular benefit. There was one major side effect, which is well documented with colchicine use: The medication induces diarrhea in patients, which forces some to abandon treatment.
Attempts to find a way to suppress inflammation in heart disease continue. The ARTEMIS trial is testing an inhibitor of interleukin-6; we will have to wait and see if it can produce more favourable results. Finding an effective medication with tolerable side effects has been challenging, but not for lack of trying or funding.
Many influencers claim the medical community ignores inflammation and promote their own diets or supplements instead. But countless millions have been spent studying the concept without success because either the benefits are too small or the side effects are too dangerous. Researchers are still trying to find a specific monoclonal antibody that will target molecules like interleukin-6 to achieve that specific anti-inflammatory effect. No smoothie is going to accomplish that.
