In an interview with Pharmacy Times, Chiadi Ndumele, MD, PhD, MHS, chair of the American Heart Association (AHA)/American College of Cardiology (ACC) cardiovascular-kidney-metabolic (CKM) syndrome guideline writing committee and the director of Obesity and Cardiometabolic Research at Johns Hopkins University, discussed the rationale behind the first-ever guideline to address cardiovascular disease (CVD), metabolic risk factors, and kidney disease as a single, interrelated syndrome. Ndumele explained that excess or dysfunctional adipose tissue often drives metabolic risk factors, which in turn are leading contributors to chronic kidney disease (CKD) and CVD, making a holistic approach essential, particularly as obesity and diabetes increasingly drive cardiovascular risk.1
Ndumele also walked through the guideline's new 4-stage CKM classification system, from Stage 1 (excess or dysfunctional adipose tissue) through Stage 4 (clinical CVD), noting that earlier identification allows clinicians to deploy therapies sooner and gives patients the opportunity for stage regression through lifestyle changes and weight loss. The staging framework, Ndumele said, is intended to guide life-course prevention for both youth and adults.
Pharmacy Times: Can you please introduce yourself?
Chiadi Ndumele, MD, PhD, MHS: My name is Chiadi Ndumele. I am an associate professor of medicine and epidemiology at Johns Hopkins in the Division of Cardiology, and I'm also the director of obesity and cardiometabolic research.
Pharmacy Times: This is the first-ever guideline to address CKM syndrome as a single unified condition. What was the driving force behind developing this guidance now, and what gap in clinical care does it fill that prior specialty-specific guidelines couldn't?
Key Takeaways
- The new AHA/ACC guideline treats cardiovascular disease, metabolic risk factors, and kidney disease as a single, interrelated CKM syndrome rather than separate conditions.
- A new 4-stage classification—from excess/dysfunctional adipose tissue (Stage 1) to clinical cardiovascular disease (Stage 4)—is designed to support earlier detection and intervention.
- Earlier-stage CKM syndrome can potentially be reversed through lifestyle change and weight loss, underscoring the value of identifying at-risk patients before disease progresses.
Ndumele: The CKM syndrome construct really comes from the fact that the conditions that are represented in its name—cardiovascular disease, metabolic risk factors, and kidney disease—are really all very closely interrelated. We now know that a lot of multisystem consequences start because of excess and dysfunctional adipose tissue. This commonly leads to the development of several metabolic risk factors. We also know that metabolic risk factors, particularly hypertension and diabetes, are the largest determinants of CKD, and together these interacting factors all lead to pretty much all forms of cardiovascular disease, as well as premature mortality, primarily due to heart disease. As a consequence, CKM syndrome, in light of the obesity and diabetes epidemics, is becoming the predominant form of CVD risk in our population.
Given all of these major changes, there's a need for us to start to address these factors not as isolated conditions but holistically, and that's part of what the CKM syndrome guideline aims to address. Additionally, it's really clear that it's often the case that many of these conditions, particularly obesity, diabetes, and CKD, either go unrecognized or go unaddressed in our current clinical practice. We want to call attention to these underrecognized and underaddressed factors, make sure we're treating them holistically, and employ the growing array of cardiovascular- and kidney-protective therapies that can really improve outcomes for this population.
Pharmacy Times: The guideline introduces a 4-stage CKM classification system. Can you walk us through what that staging framework looks like in practice and how it should change the way clinicians are screening and risk-stratifying their patients today?
Ndumele: The staging framework for CKM syndrome is really meant to reflect the fact that there is a typical pathophysiologic progression to CKM syndrome that follows the pathophysiology that we now have a much better understanding of. First of all, Stage 1 is excess and/or dysfunctional adipose tissue, which is usually the starting point for most individuals with CKM syndrome. This leads to Stage 2, which is the development of more metabolic risk factors, as well as CKD, either or both, that leads to Stage 3, which is the development of subclinical cardiovascular changes, or the presence of risk equivalents, like very-high-risk CKD or very high predicted risk using the PREVENT risk calculators that include all of the CKM syndrome components, and that is the precursor to Stage 4, which is clinical CVD overlapping with metabolic risk factors and/or CKD.
Now, the challenge is, as a cardiologist, we often meet patients at these later stages when they already have CVD and kidney disease or overlapping metabolic risk factors, and at that point things are very difficult to manage. There's a lot of morbidity, frequent hospitalizations, and high health care costs, and a much higher chance for mortality. It will be wonderful if we can start to leverage this known pathophysiologic progression and identify individuals much earlier in the stages of CKM syndrome, where we know that not only can we deploy therapies that have much more benefit when we give those in the earlier stages, but there's also the opportunity with lifestyle change and weight loss for CKM stage regression, where we can actually go backward and lose the criteria for a given stage. The focus for the staging framework is for life-course prevention, and it's meant for both youth and for adults, and it guides our testing strategies as well as some of our therapeutic strategies for CKM syndrome.
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