Cardiovascular-Kidney-Metabolic Syndrome Requires a Collaborative Approach to Treatment

There are close connections between obesity, diabetes, chronic kidney disease (CKD), and the cardiovascular system that can be understood through the cardiovascular-kidney-metabolic (CKM) construct, explained Chiadi Ndumele, MD, PhD, FAHA, the Robert E. Meyerhoff assistant professor at Johns Hopkins University, during a session at the American Heart Association (AHA) Scientific Sessions 2023 in Philadelphia, Pennsylvania.

Ndumele explained that the AHA established an initiative to provide guidance to support collaborative practice across disciplines in the treatment of CKM conditions.¹ The AHA CKM Initiative was led by a large interdisciplinary group of physicians, scientists, and nurses, and a result of their collaboration was a scientific statement by AHA published in Circulation on October 9, 2023.^1,2

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The scientific statement focused on the CKM construct, specifically highlighting CKM syndrome, which is a newly described multisystem syndrome that involves the interactions of risk factors—such as obesity, type 2 diabetes and other metabolic abnormalities, CKD, and cardiovascular disease risk—associated with poor health, organ damage, cardiovascular events, and early death. According to the scientific statement, nearly every major organ system is impacted by CKM syndrome and the results of this impact can lead to kidney failure, premature cognitive decline, metabolic dysfunction-associated steatotic liver disease, obstructive sleep apnea, and increased cancer risk.³

Notably, the greatest burden of CKM syndrome on patients is its cardiovascular effects, which are associated with the greatest clinical impact.¹

“The reason we care about [CKM syndrome] is because it's associated with significantly premature mortality, and most of that mortality is due to cardiovascular disease,” Ndumele said during the session. “[Also,] CKM syndrome is disproportionately present among individuals with more adverse social determinants of health.”¹

For this reason, Ndumele explained that the scientific statement provides a socioecological framework for understanding CKM health. The socioecological effects of CKM health can impact health behaviors that can lead to obesity, with downstream consequences strongly influenced by several factors that represent the social context in which we eat, live, work, and play.¹

“Factors at the societal level, at the community level, at the interpersonal level—all of those impact our health behaviors that really influence a given individual's likelihood of developing these consequences in [CKM] syndrome,” Ndumele said. “Then each individual has their own biological predisposition on top of that, and that can be influenced by the social context.”¹

Additionally, Ndumele noted that the scientific statement describes the potential for fragmented patient care for patients with CKM syndrome, as these patients often have multiple conditions and are seeing multiple providers. Further, each of these providers may be following different guidelines for the treatment of each condition, creating unique challenges for care. For this reason, it is important to provide comprehensive, cohesive, and holistic care for patients with CKM syndrome that represents not only the individual biological factors, but also aspects of the social context. Additionally, Ndumele explained that the treatment for CKM syndrome should be based around collaboration between providers spanning across disciplines and specialties.¹

Ndumele explained that the scientific statement helps to address this by providing a staging framework for CKM syndrome.¹

“Obesity is really at the crux [or] at the beginning of most of CKM syndrome for most individuals, so really it's our first stage of CKM syndrome,” Ndumele said. “If you go through our stages, you'll see we start with stage 0, which are individuals with no CKM risk factors. That's what we want to preserve—individuals with ideal cardiovascular health. Stage 1 is individuals who have excess or dysfunctional adiposity that can then pave the way for much of what comes afterwards. Stage 2, we start to develop metabolic risk factors of [CKD]. Then in stage 3, we can develop subclinical, so asymptomatic early heart disease, and that also is represented in stage 3 by higher predicted risk.”¹

For patients at stage 4, Ndumele explained that these individuals have progressed all the way to clinical cardiovascular disease, overlapping with the preceding metabolic risk factors, such as obesity, diabetes, high blood pressure, or CKD. To approach treatment, Ndumele said its best to think about the stage of the patient.¹

“At stage 1, we're really thinking about lifestyle change,” Ndumele said. “Then we also have additional options to support weight management and lifestyle change as needed. The likelihood of using those are going to increase as individuals move along the spectrum, as their risk will also increase as well.”¹

On the other hand, for patients at stage 4 of CKM syndrome who have already had cardiovascular disease and have obesity, there are additional considerations to add to the therapeutic panel.¹

“But it's important to emphasize that those individuals are somewhat at the extreme of this CKM syndrome progression,” Ndumele said. “The other thing I want to emphasize, in addition to that we have treatments that are tied to the different stages, is that this also represents an opportunity for earlier identification and prevention across the life course.”¹

According to Ndumele, the concept of assessing CKD stage progression and stage regression is important to consider for patients in their youth and adulthood.¹

“For those individuals who are in stages 1, 2, and 3, with substantial lifestyle change and weight loss, there's the potential to actually regress and go back in staging,” Ndumele said.¹

References

1. Ndumele CE. AHA Scientific Sessions 2023 Late-Breaking Science. Presented at: AHA Scientific Sessions 2023; November 10, 2023.

2. Ndumele CE, Neeland IJ, Tuttle KR, et al. A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association. Circulation. 2023. doi: 10.1161/CIR.0000000000001186

3. Persaud N. AHA Advisory Focuses on Cardiovascular-Kidney-Metabolic Syndrome. Renal & Urology News. October 17, 2023. Accessed November 11, 2023. https://www.renalandurologynews.com/news/nephrology/chronic-kidney-disease-ckd/aha-advisory-focuses-on-cardiovascular-kidney-metabolic-syndrome/#:~:text=In%20its%20new%20presidential%20advisory,events%2C%20and%20early%20death%2C%20including