Inflammation playing a much bigger role in heart disease evaluations
A new frontier in cardiovascular medicine is emerging with inflammation, not cholesterol, taking center stage as a key component in the prevention of heart disease. Paul Ridker, MD, MPH, the Eugene Braunwald Professor of Medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, spoke with Cardiovascular Business about how coronary inflammation is reshaping how clinicians evaluate and reduce long-term cardiovascular risk.
Ridker emphasized the transformative potential of high-sensitivity C-reactive protein (hs-CRP), a biomarker for inflammation, in predicting and managing cardiovascular disease.
“We've known for 30 years that inflammation and hyperlipidemia conspire with each other to really drive atherosclerotic disease,” Ridker explained. “What’s changed is, we now have both a reliable biomarker and therapeutic proof of principle that we can target inflammation per se and lower cardiovascular event rates just like we target LDL cholesterol and lower cardiovascular event rates."
CRP is a stronger risk predictor than cholesterol
Recent long-term data from the landmark Women's Health Study published in the New England Journal of Medicine validated hs-CRP as a powerful predictor of cardiovascular events, even more so than traditional markers such as LDL cholesterol and lipoprotein(a). Ridker pointed to the study, which which followed 30,000 women for three decades.
“CRP trumped both LDL and Lp(a). CRP was a more powerful predictor of long-term events,” he explained. “That's really important because we think about our guidelines they are like five- and 10-year risk estimates. But if I tell a woman who is 65, 'Hey, you're at increased risk and you should have started preventive therapies 30 years ago,' it's just too late in the game.”
Ridker said the implications are clear. Cardiovascular risk assessments that overlook inflammation may miss a critical component of disease development and an opportunity to intervene with drug therapies much earlier when it can have a better impact.
Cardiologists should be measuring what matters
Ridker advocates for universal screening of hs-CRP, LDL and Lp(a) in both primary and secondary prevention.
“Doctors won’t treat what they don’t measure,” he said. “We don’t manage blood pressure without measuring it, and we shouldn’t ignore inflammation.”
Pharma’s coronary inflammation arms race
Inflammation-targeting treatments are no longer theoretical. The 2023 FDA approval of colchicine as the first drug to treat for coronary inflammation, marking a pivotal moment, and there are other agents in trials.
"We've seen recent data that the GLP-1 receptor agonists, an incredible class of drugs that have lots of clinical benefits, also lower CRP. And that's not by chance. SGLT-2s also lower CRP. The fact that all these drugs that are so effective also have benefits on inflammation is telling us a message about this underappreciated, and I think underassessed, part of this whole disease process," Ridker explained.
He said it is a very exciting time in cardiovascular drug development.
"Every major pharmaceutical company globally now has an inflammation program. It's no longer just in rheumatology, but it's also in cardiovascular medicine. We are running a series of trials that are looking at interleukin-6 inhibitors for chronic atherosclerosis for HFpEF and for acute coronary ischemia. There are other people looking at the same kinds of molecules in the setting of kidney disease. There's some very novel agents, which people will be hearing about over the next several years, targeting this very specific NLRP-3 to IL-1 to IL-6 pathway, which is the nexus of this whole process. All these new drugs are coming and it's a very, very exciting time for the vascular biology community," Ridker explained.
Innovation enables direct imaging of coronary inflammation
Alongside blood biomarker advances, imaging technology is catching up. Ridker pointed to the use of cardiac computed tomography (CT) imaging and the fat attenuation index, a technique for direct visualization of inflammation in perivascular fat of coronary vessels. Right now, CRP is a measure of inflammation that is systemic and could be from anywhere in the body. But this new CT technique can directly correlate inflammation to the coronary vessels.
"The question is, do these imaging tests provide us with more information? I suspect the answer is going to be yes, but we have a lot more research to do to get us there," he said.
A new paradigm for coronary disease prevention
Despite the technological advances such as advanced CT imaging, Ridker cautioned against an over reliance on expensive tools.
“A good history and physical exam, plus three inexpensive blood tests—LDL, CRP, and Lp(a)—can detect much of the hidden risk,” he said. “This should be routine in both primary and secondary prevention.”
He said disease often runs in families, so if someone has an elevated CRP, LDL and Lp(a), a cascade screening for the rest of that family would be in order, and that can be done very cost effective with those three simple tests.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]