Interest rising in CKM syndrome as connections become clearer

Staging cardiovascular-kidney-metabolic syndrome

The AHA’s CKM scientific statement and presidential advisory, first released in 2023, formally outlined four stages of the disease.[1] Joseph was one of the co-authors.

"The syndrome starts with extra weight, particularly adipose tissue in the abdominal region. That is stage one of the condition, and we know that extra adipose tissue drives many metabolic disorders including hypertriglyceridemia, diabetes, hypertension, as well as chronic kidney disease. Those disorders actually make up stage two. And so what we're trying to do is prevent that progression from stage one to stage two or CKM syndrome. Stage three is the subclinical cardiovascular disease. So this is where individuals are being made aware they have cardiovascular disease on imaging, for instance from CT scans. That leads to stage four, which is cardio metabolic syndrome," Joseph said.

He noted that stage four of CKM syndrome is what cardiologists know and treat every day, conditions like myocardial infarctions, strokes, peripheral arterial disease and heart failure. But the connections with these earlier stages are now known and can serve as a gateway to greater preventive cardiology efforts. This promise is what is driving rapidly expanding interest in this topic at cardiology meetings.

The AHA’s CKM syndrome scientific statement and presidential advisory, formally outlined these stages and introduced the PREVENT risk calculator to help clinicians better predict and intervene earlier in the disease process. The tool incorporates lab markers like hemoglobin A1C and urine albumin-to-creatinine ratios alongside social determinants of health, including the Social Deprivation Index.

"Stage four is when someone's coming in with that heart attack, that stroke, peripheral arterial disease, known heart failure. What we're trying to think about here is, how do we prevent that?" Joseph said.

Interdisciplinary prevention opportunities

CKM syndrome has major implications for cardiology practices. Patients with hypertension, diabetes and mild renal dysfunction who may not yet show overt heart disease are often under the care of a cardiologist before seeing an endocrinologist or nephrologist. Joseph said this reality makes it critical for cardiologists to broaden their clinical lens.

He cited new data presented at the 2024 AHA Scientific Sessions highlighting advances in treatment that cross traditional specialty boundaries. One study showed that tighter blood pressure control (targeting 120 mmHg vs. 140 mmHg) in patients with diabetes significantly reduced cardiovascular events. Another found that the dual GIP/GLP-1 receptor agonist tirzepatide reduced risk of cardiovascular death and hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF).

"There's a large opportunity to think about these cadre of newer medications and how they may help us to prevent cardiovascular events, or secondary cardiovascular events, among someone who's already had a cardiovascular event," Joseph said.

Women face greater risks

New research also revealed that women with CKM syndrome may be disproportionately affected. Data presented at the AHA meeting showed women had a 38% higher risk of mortality from CKM syndrome-related conditions compared to men, underscoring the need for tailored risk stratification and treatment.

“In the past, we thought women were at lower risk, but CKM is changing that narrative,” Joseph said. “Once women develop diabetes or metabolic dysfunction, their cardiovascular risk rises sharply. We need to be aggressive in prevention and treatment strategies for women.”

A growing public health challenge

Estimates show that 90% of the U.S. population is at stage one or higher on the CKM syndrome spectrum. Approximately 50% are in stage two—already carrying multiple chronic conditions that elevate their risk of cardiovascular disease. As global data emerges, the burden of CKM may number in the billions worldwide, Joseph explained.

Given its scale and complexity, Joseph is advocating for more collaborative care models, including emerging cardiometabolic health centers where cardiologists, endocrinologists and nephrologists co-manage patients with CKM syndrome.

“I think we will see more cardiometabolic clinics. I've traveled a lot around the country and I'm seeing them across the country. I think that that's one of the frontiers that we're moving towards, and you will see more people trained in cardiometabolic disease,” Joseph explained.

Call to action for cardiologists

Joseph emphasized that cardiologists should begin integrating CKM assessments into their practice immediately. That includes screening for early kidney disease using urine albumin-to-creatinine ratios, monitoring A1C levels, and considering medications like SGLT2 inhibitors and GLP-1 agonists that offer multi-organ protection.

He added that embracing this broader perspective is critical as cardiology evolves toward prevention, population health, and more personalized care.