Important updates in cardiology from Clyde W. Yancy, MD, MSc

Key takeaways:

• Recent updates include a new disease staging construct, novel biologics, emerging evidence on GLP-1 agonists and more.
• These innovations will change the way physicians practice medicine, an expert said.

BOSTON — A “laundry list of new trials” in cardiovascular medicine has led to “a decided portfolio of new ways of thinking, new interventions and a new potential to modify the natural history of CVD,” an expert said.

“This is an exciting time. We have tools and strategies like we've never had before,” Clyde W. Yancy, MD, MSc, MACP, MACC, FAHA, FHFSA, a professor and chief of cardiology at Northwestern University Feinberg School of Medicine, told Healio.

For the past several years, Yancy has traveled to the ACP Internal Medicine Meeting to update attendees on important topics in cardiology.

Part of this year’s update was an extension of what Yancy discussed during last years’ meeting, including a universal definition of heart failure, revised guidelines on the treatment of heart failure, novel treatments for hypertension — particularly baxdrostat (Cincor Pharma/AstraZeneca), a drug that targets aldosterone synthase — and the role of SGLT2 inhibitors “as specific disease-modifying therapy for heart failure with preserved ejection fraction.”

But Yancy also shared new developments for 2024 that he said will “change the way we think and the way we practice.”

CKM: A new disease staging construct

The first update is the conceptualization of cardiovascular-kidney-metabolic syndrome, or CKM, a new term endorsed by the American Heart Association in October.

The term was created to emphasize the association between obesity, type 2 diabetes, chronic kidney disease (CKD) and the cardiovascular system. It also reflects the development of new medications that improve glycemic control and prevent both worsening kidney disease and CVD.

“It’s a brilliant concept because it captures the importance of this one prevalent phenomenon, medical obesity, and helps us appreciate that the proinflammatory signals, because of adiposity, lead to hepatic changes, renal changes and cardiovascular changes,” Yancy said. “Perhaps the mediator of all of this is a proinflammatory signal associated with oxidative stress and associated with neurohormonal upregulation.”

Physicians can now think about CKD, heart failure, nonalcoholic liver disease and diabetes “as one complete construct that starts with adiposity” and systematically influences multiple organ systems, Yancy said.

There are four stages of CKM:

• stage 0, no risk factors;
• stage 1, excess and/or dysfunctional adiposity;
• stage 2, metabolic and renal risk factors such as hypertension, metabolic syndrome type 2 diabetes or CKD;
• stage 3, subclinical atherosclerosis CVD or subclinical heart failure; and
• stage 4, clinical CVD.

This “new way of thinking” about stages of risk “builds on our enlightened understanding of adiposity,” Yancy said.

“I urge you to read about, think about CKM,” he added.

PREVENT risk scoring algorithm

The next update is the Predicting Risk of Cardiovascular Disease Events (PREVENT) risk scoring algorithm, which Yancy said will enhance the prevention and management of CVD.

PREVENT is an online calculator that evaluates 10- and 30-year absolute risk associated with CKM. It is “race agnostic” and allows physicians to incorporate traditional risk factors as well as social determinants of health, Yancy said.

“When we do that, we then get a very different kind of calculus of what is the likelihood of a CVD event, including stroke,” he said. “When we partner that with the CKM stage, we now have better clarity than we've ever had before on whether it's lifestyle modification, plus medical therapies, plus more aggressive interventions. Really a brand new way to think about things.”

Cardiovascular benefits of GLP-1 agonists

Moving into the pharmacologic space, Yancy discussed “what’s top of mind for all of us,” which is the potential benefits of GLP-1 receptor agonists beyond weight loss.

“Arguably, we might begin to think about these drugs as generational compounds, much like we thought about statins 30 years ago,” he said. “Much like statins changed society, it’s plausible — plausible — that the GLP-1 receptor agonists may do the same thing.”

In the SELECT trial — which included about 17,000 patients with pre-existing heart disease — Wegovy (semaglutide 2.4 mg, Novo Nordisk) was associated with an additional 20% RR reduction in cardiovascular events, including recurrent myocardial infarction, stroke and heart failure events, compared with placebo.

“This is in patients who entered the trial with a previous MI, with heart failure, with hypertension, a prior stroke or peripheral vascular disease,” Yancy said. “These are the patients we see ... The results were absolutely stunning.”

Patients with a BMI of 27.5 kg/m² were eligible to receive semaglutide, Yancy noted. Although the cohort lacked women and underrepresented racial and ethnic groups, Yancy said the results still left “a pretty powerful statement.”

New biologics

Another important update is emerging research on novel treatment approaches using small interfering RNA.

Data show that zilebesiran (Roche, Alnylam), a compound targeting angiotensinogen, has “a profound ability to reduce BP on top of already standard therapy in patients with resistant hypertension,” Yancy said.

“A very important patient population, but the real take-home, administered every 6 months,” he said. “So, not only more effective BP lowering, but improvement in adherence.”

Early research also indicates that lepodisiran (Eli Lilly), another small interfering RNA compound, may substantially lower lipoprotein (a), a genetic risk factor for CVD that currently has no treatment options.

“Now with targeted therapy using the small interfering RNA, recognizing that there's also a project going on using an oligonucleotide, we might soon be able to offer an intervention for patients with this unique risk factor not otherwise modifiable with standard therapies,” Yancy said.

Incidental calcification findings

Shifting the focus to back to CVD risk, Yancy noted that it can be challenging for physicians to approach incidental calcification findings from a nongated CT that was ordered for another reason. He encouraged physicians to use this information to estimate an Agatston score.

“We can, in fact, derive a qualitative representation of a quantitative calcium score and then behave accordingly whether it’s low, intermediate or high risk,” Yancy said. “And so, don't consider those things incidental. Use those as a leverage to have the conversation about modifying disease risk.”

Life’s Essential 8

The last update is the American Heart Association’s transition from Life’s Simple 7 to Life’s Essential 8, which incorporated sleep as a metric for cardiovascular health. The campaign encourages patients to:

• eat better;
• be more active;
• quit tobacco use;
• get enough sleep;
• manage weight;
• control cholesterol;
• control blood sugar; and
• maintain BP.

“That assortment of choices that we all make and interventions we can all follow is associated with much better outcomes,” Yancy said.

*Editor's note: This article is part of a Healio exclusive series in which Yancy recaps his talk at the ACP Internal Medicine Meeting. Check out the videos in this series below:

• VIDEO: Newly defined syndrome is ‘a brilliant concept’ on stages of CVD risk
• VIDEO: New CVD risk algorithm incorporates social determinants of health
• VIDEO: Cardiovascular benefits of GLP-1 agonists ‘absolutely stunning’
• VIDEO: Small interfering RNA holds promise for cardiovascular care
• VIDEO: Use incidental calcification findings to estimate CVD risk
• VIDEO: Following Life’s Essential 8 leads to ‘much better outcomes’

References:

• Lincoff AM, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2307563.
• PREVENT online calculator. https://professional.heart.org/en/guidelines-and-statements/prevent-calculator. Accessed May 3, 2024.
• Yancy CW. Update in cardiology. Presented at: ACP Internal Medicine Meeting; April 18-20, 2024; Boston.