Cardiologist examines the latest breakthroughs in coronary inflammation research

One recent analysis published in the Lancet by Paul Ridker et al. involved pooling data from three big trials looking at lowering triglycerides. They compared LDL cholesterol to high sensitivity C-reactive protein (hs-CRP) in terms of predicting risk.

"It turned out that hs-CRP as a marker of inflammation was a much more potent predictor of cardiovascular death than even LDL cholesterol. If the LDL is pretty well controlled, maybe inflammation is more important in terms of residual cardiovascular risk, and maybe we should be targeting it with specific therapeutics," Bhatt explained.

Breakthroughs in coronary inflammation detection and therapy

While a patient's residual risk from inflammation could be identified in the past, there was not much anyone could do about it until the 2023 U.S. Food and Drug Administration (FDA) approval of colchicine to treat coronary inflammation. This marked a turning point, spurring a wave of interest in anti-inflammatory strategies at cardiology meetings over the past year. Bhatt highlighted the mixed results of colchicine trials, some being positive, some being negative, and suggested that future research should focus on patients with residual inflammatory risk—those with controlled cholesterol, but elevated levels of hs-CRP.

Bhatt said colchicine has shown promise in some studies, but has not performed well in others, including the recent CLEAR SYNERGY (OASIS 9) trial presented at TCT 2024.

However, he said the drug has opened the door to cardiologists thinking about how to test and treat for inflammation. He said there is a lot of interest in targeted approaches like interleukin-6 (IL-6) inhibition, and pointed to the ongoing Artemis trial, involving approximately 10,000 patients, as a key study investigating the efficacy of IL-6 inhibitors administered once monthly as a subcutaneous injection to reduce the risk of major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI).

"We definitely need more randomized data, but nonetheless, I think this whole area of inflammation, there's no question that if you have a bunch of cholesterol, you're forming plaques in your coronary or other arteries. It's really inflammation that incites the plaque rupture and leads to ischemic events," Bhatt explained.

He said the question is, if you get the LDL super low, is there still a role of inflammation? Bhatt said the target for future trials needs to be on patients who do have well controlled LDL but have residual cardiovascular risks and elevated hs-CRP.

"I think that there could be a role of inflammation or therapies targeting inflammation, even if the cholesterol is brought down to very, very low levels, say with PCSK-9 inhibitors or other therapies that are on the horizon. But all of this needs to be tested in randomized clinical trials," Bhatt said.

He said there are a lot of drug companies now looking at targeted anti-inflammatories to treat coronary disease that will be seen in studies presented at future cardiology meetings.

Using hs-CRP and CT imaging as a markers of coronary inflammation

High-sensitivity CRP has emerged as a potent marker of systemic inflammation and cardiovascular risk. While rheumatologists have long used CRP in diagnosing and monitoring inflammatory conditions, cardiologists are increasingly leveraging hs-CRP to guide preventive care. However, Bhatt said hs-CRP is a marker of systemic inflammation and will show elevation for a variety of reasons, including cancer, infections and chronic inflammatory conditions, such as rheumatoid arthritis. So it is not specific to the coronary arteries.

"In primary prevention, hs-CRP can help decide whether to start a statin when LDL levels are borderline," Bhatt explained. However, he cautioned against an over-reliance on biomarkers, emphasizing the need for cardiovascular outcome trials to validate therapeutic strategies.

More targeted tests are currently being tested in trials. One such test uses noninvasive coronary computed tomography angiography (CCTA) to image the arteries and then uses an artificial intelligence algorithm to identify its perivascular fat attenuation index around the vessels as a surrogate for visualizing inflamed vessels. CT also can show areas of plaque and the types of plaques inside the vessels, which can pinpoint vulnerable plaques. The technology has also been shown in studies to show reversal of coronary inflammation when anti-inflammatory drugs are taken.

With recent advances and reimbursements now available for FDA-cleared CT coronary AI plaque analysis and CT fractional flow reserve (CT-FFR), patients can be screened non invasively using CCTA. This technology is already eliminating the need for the vast amount of diagnostic invasive angiograms. The addition of perivascular fat attenuation on these scans would offer a much more targeted test for coronary inflammation and help cardiologists assess the need for additional therapy.

Expanding horizons with cardio-rheumatology clinics

The intersection of cardiology and rheumatology represents another promising frontier. Chronic inflammatory conditions, such as rheumatoid arthritis, significantly increase cardiovascular risk. A growing number of academic centers are now establishing cardio-rheumatology clinics to address this overlap, optimizing care for patients with systemic inflammation.

"Patients with rheumatologic illnesses often face dual risks—from their underlying inflammation and the medications used to treat it," Bhatt noted. By aggressively managing cardiovascular risk factors, these specialized clinics could significantly reduce adverse outcomes.

Some of these clinics also are already serving as a testing ground with studies to assess the new CT inflammation imaging technology and the ability to observe clinical efficacy of anti-inflammatories on the coronaries.