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New multisociety obesity guidelines pivoted to a combined construct of cardiovascular-kidney-metabolic health that emphasizes cohesive care management across the organ systems.

The guidelines are the first to focus on cardiovascular-kidney-metabolic syndrome (CKM), a relatively new term for explicitly bringing specialties together to catch interrelated problems earlier.

“CKM syndrome is becoming the predominant cause of cardiovascular disease risk in the population, but many of its components are often unrecognized for quite some time and this leads to worse outcomes,” said writing group chair Chiadi E. Ndumele, MD, PhD, of Johns Hopkins School of Medicine in Baltimore. “So if we can address things earlier and also address the interrelated components holistically in a whole-person approach, that will improve patient outcomes.”

Alongside the guideline, the American Heart Association (AHA) and the American College of Cardiology (ACC) published a scientific statement in their respective flagship journals, Circulation and JACC. The American Diabetes Association, its Obesity Association, and the American Society of Nephrology also collaborated on the AHA/ACC guideline and endorsed it.

“We are trying to help clinicians from various specialties all speak in a common language and be on the same page, especially when it comes to managing weight and its clinical consequences,” Ndumele said in a statement.

The guideline replaces the 2013 AHA/ACC guideline for the management of overweight and obesity in adults. 

“[O]besity is repositioned from being simply a cardiovascular risk factor to a central driver of multiorgan disease progression,” David D. Berg, MD, MPH, and Erin A. Bohula, MD, DPhil, both of Brigham and Women’s Hospital and Harvard Medical School in Boston, wrote in an accompanying editorial.

The concept that cardiovascular health should no longer be separated from metabolic and kidney health is important, they noted. 

“The innovation of the new CKM guideline is less about any individual therapeutic recommendation and more about the integration of previously disparate clinical and preventive paradigms into a cohesive concept of a disease continuum,” Berg and Bohula wrote.

The European Society of Cardiology is developing its own guideline for management of cardiovascular disease and chronic kidney disease, anticipated to be discussed at its annual meeting in August.

Staging

The AHA/ACC guideline introduces a staging framework for CKM syndrome, a term coined by the AHA in 2023:

• Stage 1: overweight/obesity or prediabetes without other metabolic risk factors, kidney disease, or cardiovascular disease
• Stage 2: at least one metabolic risk factor (such as hypertension, hypertriglyceridemia, type 2 diabetes, or metabolic syndrome), moderate- to high-risk chronic kidney disease, or both, but no overt cardiovascular disease
• Stage 3: subclinical cardiovascular disease and CKM risk factors, PREVENT-CVD 10-year cardiovascular disease risk of ≥ 20%, or very-high-risk kidney disease risk, according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria (stages G3a with A3, G3b with A2-A3, or G4-G5 range).
• Stage 4: diagnosed cardiovascular disease (coronary heart disease, heart failure, stroke, peripheral artery disease, or atrial fibrillation) with overweight or obesity, other metabolic risk factors, or kidney disease

Too often, patients receive clinical attention only in the later stages, once patients are already suffering the end-organ consequences of processes that started much earlier and the risk for adverse outcomes is high, Ndumele said.

“But the reality is there's a very typical pathophysiologic progression to this that starts with excess and dysfunctional adipose tissue that leads to the development of more metabolic risk factors in chronic kidney disease, that leads to subclinical cardiovascular disease, that then leads to clinical cardiovascular disease and early mortality,” he said. 

The goal is to promote identification in early stages with an emphasis on weight management, “because it's at the root of this CKM syndrome and is really the main determinant of progression and also regression,” Ndumele said. “We know that earlier therapy, earlier addressing of risk, leads to much better outcomes.”

Treatment

The guideline outlines escalating management from intensive lifestyle modification plus obesity drug therapies and/or metabolic and bariatric surgery in stage 1 to pharmacotherapies targeted to other components of CKM syndrome as indicated in stages 2-4. 

The document marks the first time that GLP-1 receptor agonist therapies have been recommended for select individuals with obesity, type 2 diabetes, and other risk factors for cardiovascular disease to reduce the risk for cardiac events.

The risk threshold for starting GLP-1-based therapy, SGLT2 inhibitors, or a combination of the two classes for cardioprotection among individuals with type 2 diabetes and stages 2 or 3 CKM syndrome centered on a 10-year PREVENT-CVD risk of at least 7.5%. 

Care Coordination

Seeing multiple specialists across the CKM spectrum can “lead to fairly fragmented care,” Ndumele said, which is why the guideline also called for interdisciplinary care models for overlap among type 2 diabetes, chronic kidney disease, and cardiovascular disease.

“The need for a point person is emphasized, to coordinate efforts of the CKM interdisciplinary team, to facilitate implementation of evidence-based care and guideline-directed medical therapy (GDMT), and to support patients and clinicians,” the guideline noted.

This care coordinator can review health system data at regular intervals and determine opportunities and strategies for improvement in risk-based interventions, according to the guideline.

Editorialists Berg and Bohula agreed that this portion of the guideline could be among the most important of its contributions, as “evidence-based therapies are often implemented incompletely when responsibility is fragmented.”

“The explicit rejection of siloed care models reflects the reality that modern cardiovascular prevention increasingly requires interdisciplinary collaboration among cardiology, nephrology, endocrinology, obesity medicine, primary care, and preventive medicine,” they wrote. “This shift is likely to become even more important as management options continue to expand and patients with CKM syndrome accumulate increasingly complex therapeutic regimens.”

However, they argue that clinicians shouldn’t underestimate the challenge of implementation. Many healthcare systems just don’t have the infrastructure needed for truly integrated CKM care, access to obesity pharmacotherapy remains inconsistent, and reimbursement structures favor fragmented episodic care rather than longitudinal prevention.

“Moreover, the guideline notes that 90-95% of US adults are in CKM Stage 1-4, which not only highlights the sobering scope of the task at hand but also the impracticality of scaling the same integrated CKM care model to all patients categorized under this framework,” the editorial said.

While working to expand access, clinicians might need to exercise caution when considering which patients should be prioritized in dedicated CKM clinics, they suggested.

Virtual care coordination can be a solution as well, Ndumele said. “There are variations to this model that can work across different kinds of clinical settings and for individuals with different kinds of levels of resources for subspecialty referrals as well as generally for clinical care.”

Ndumele reported no relevant conflicts of interest. 

Berg reported receiving consulting fees from AstraZeneca, Pfizer, and Youngene Therapeutics and honoraria from the Metabolic Endocrine Education Foundation, Pri-Med, Radcliffe Cardiology, Translational Medicine Academy, and USV Private Limited, as well as participating on clinical endpoint committees for studies sponsored by Beckman Coulter, CeleCor Therapeutics, Kowa Pharmaceuticals, Novo Nordisk, and Tosoh Bioscience. 

Bohula reported receiving consulting fees from Amgen, Novo Nordisk, Kowa, Medscape, and Esperion. 

Both editorialists are members of the TIMI Study Group, which receives grants from 4TEEN4 Pharmaceuticals GmbH, Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca, Beijing Inno Medicine, Boehringer Ingelheim, Cleerly, Daiichi-Sankyo, Ionis Pharmaceuticals, Janssen Research and Development, Marea Therapeutics, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Saghmos Therapeutics, Softcell Medical Limited, Verve Therapeutics, and Zora Biosciences. 

Crystal Phend is an award-winning medical journalist with decades of experience reporting on clinical research and healthcare developments across specialties. When not walking the halls at a medical conference, she can be found at a keyboard in upstate New York.