ACC: It’s Time for Clinicians to Address Inflammation in CVD

Evidence supporting inflammation’s ties to cardiovascular disease is “no longer exploratory but is compelling and clinically actionable,” according to a new scientific statement released by the American College of Cardiology (ACC).

The document, led by writing group chair George A. Mensah, MD (National Institutes of Health, Bethesda, MD), and published online September 29, 2025, in JACC, sums up the role of chronic, low-grade inflammation in CVD as well as more-recent data specific to the areas of heart failure and pericarditis. It also offers consensus recommendations for practitioners who wish to apply this knowledge.

As the authors note, the hypothesis that inflammation is a driver of CVD is far from new: back in 2002, the US Centers for Disease Control and Prevention teamed up with the American Heart Association to develop a scientific statement on the topic. That report identified high-sensitivity C-reactive protein (hs-CRP) as the biomarker of choice “in specific clinical settings, such as in persons at intermediate CVD risk, where hs-CRP might guide further evaluation and therapy,” they write, though it also “discouraged inflammatory marker use in widespread population screening due to insufficient evidence.”

With what’s known today, however, “the time for taking action has now arrived,” Mensah and colleagues say.

Co-author Paul Ridker, MD (Brigham and Women’s Hospital, Boston, MA), who led the CANTOS trial of the monoclonal antibody canakinumab (Novartis) that targets inflammation, told TCTMD that the scientific statement is aimed at general cardiologists who previously may not have known the details of how inflammation affects CVD.

“Those of us in the vascular biology community who have been thinking about this for the last 30 years recognize that it’s now a real clinical issue that has to be dealt with by our clinical colleagues in daily practice—that’s what this is all about,” he said. “It’s a very important document because it’s a sea change in recognizing that the time has come to change how we practice medicine.”

Where Things Stand

Studies have shown that in seemingly healthy people, elevated levels of hs-CRP can be used to pinpoint who among them might benefit from statin therapy even in the absence of high LDL cholesterol, the authors point out. In secondary prevention, they add, hs-CRP levels indicative of residual inflammation are “strongly predictive of recurrent events,” even in statin-treated patients.

The 2019 US primary prevention guidelines consider “persistently elevated inflammatory markers” to be a risk-enhancing factor. Based on positive findings from the LoDoCo2 trial, the US Food and Drug Administration approved colchicine in 2023 as the first anti-inflammatory drug to prevent CV events in patients who have established atherosclerotic cardiovascular disease (ASCVD) or are at risk of developing it. Colchicine’s use is also endorsed by both European and South American CV prevention guidelines and approved by Health Canada.

Yet the field is not without controversy—most recently, results from the CLEAR SYNERGY (OASIS 9) trial, released in late 2024, disappointingly showed that colchicine fails to reduce the risk of major adverse cardiovascular events when used in patients treated with PCI after acute MI.

Sanjit Jolly, MD (Hamilton General Hospital, McMaster University, Canada), lead investigator for CLEAR SYNERGY (OASIS 9), described the trial as “resoundingly neutral.” With the mixed signals on colchicine, he commented to TCTMD, he doesn’t feel the overall data on inflammation justify a shift in practice just yet.

The idea that it’s actionable is much less certain for me at this point. Sanjit Jolly

In research, when “one experiment shows one thing and another experiment shows another thing, what do we do? Do we discount the experiment that didn’t, so [to speak], work out? Or do we continue to do experiments and try to find the truth?  As a scientist, I don’t know that colchicine is really all that effective in acute MI or coronary artery disease,” said Jolly.

“I  think the idea that it’s actionable is much less certain for me at this point,” he added.

Jolly said that future results from trials of colchicine in peripheral artery disease, heart failure, and CAD hopefully will shed light on whether “modifying inflammation is going to make a big difference in the treatment of vascular disease or whether it will not.” He predicted that, “even if there is an effect, it’ll be very modest. We’re probably talking about 10 or 20% reductions in clinical events in patients who do really well as it is,” something that makes it hard to detect differences.

Given that colchicine is the only approved drug aimed at inflammation in CVD, widespread screening doesn’t make sense at this time, according to Jolly.

It’s not unreasonable to want to identify people at higher risk, he acknowledged. “The issue is if you can’t [take action], it may be less useful,” Jolly continued. “And there’s obviously cost associated with it, to the healthcare system. We know that maybe the money may be better spent elsewhere, like [by] covering prescription drugs for high LDL in the first place for people who can’t afford it.”

Put simply, he said: “ We need further data.”

Screening as a First Step

Mensah et al, while acknowledging that “not all trials of anti-inflammatory therapy in secondary prevention have been successful” and that more clarity is needed on agents beyond colchicine, lay out recommendations on what can be done with what’s already known.

This advice spans several topics:

• Use of hs-CRP (and, to a lesser degree, other biomarkers) for evaluation and risk assessment
• Imaging to detect vascular inflammation, an approach the authors specify is currently limited to research settings
• Use of hs-CRP screening and anti-inflammatory approaches, addressed separately for primary and secondary prevention
• The relationship between inflammatory pathways and behavioral/lifestyle factors (diet, physical activity, body weight, smoking, etc)
• A look at how inflammation is related to heart failure and pericarditis

Screening hs-CRP is the key first step, Ridker stressed. “Physicians won’t treat what they don’t measure. . . .  It’s not about research anymore. It’s about making our patients’ lives better.”

He specified that the biomarker does not, in itself, play an active role in causing CVD. “We know that inflammation is causal in atherosclerosis. CRP is not the causal agent: it’s the way you measure it,” much like a patient’s body temperature can be measured when they’re fighting an infection, Ridker explained.

In their discussion of the existing literature, the statement’s authors point to the “substantial progress” that’s occurred in basic, clinical, and population science over the past two decades. “It is now well established that chronic, silent, low-grade inflammation, together with key mediators like cytokines, chemokines, and acute-phase reactants, plays a pivotal role in atherosclerotic plaque formation, progression, rupture, and thrombogenesis that lead to acute coronary syndrome,” Mensah and colleagues write.

“Additionally, inflammatory pathways, driven by immunoregulatory influences, contribute to endothelial dysfunction, leukocyte infiltration of the subendothelial space, foam cell formation, and apoptosis that further contribute to atherogenesis,” they explain.

It’s not about research anymore. It’s about making our patients’ lives better. Paul Ridker

The writing group also explores current challenges and future paths. More research is needed on alternatives to colchicine as well as on the interplay between inflammation and key physiological systems, they say. “Another promising area of research is the role that novel special pro-resolving bioactive lipid molecules play in promoting the resolution of inflammation and CVD risk reduction.”

They conclude: “The time has come for clinical practice guidelines to implement broad screening of primary and secondary prevention patients for hs-CRP, in combination with LDL cholesterol, and to embrace anti-inflammatory interventions in patients with established ASCVD and evidence of residual inflammatory risk, regardless of LDL cholesterol level.”

Ridker cited “overwhelming evidence” that measuring hs-CRP is at least as important as measuring cholesterol in both the primary and secondary prevention settings. While guidelines support universal cholesterol screening, they frame hs-CRP as more of a “tiebreaker,” he added. “It’s very soft.”

Without stronger endorsement in guideline recommendations, “we’re not going to make progress,” Ridker emphasized.