Newly-Identified ‘CKM Syndrome’ Links Chronic Conditions to Heart Disease

Heart disease is the leading killer of most people in the U.S. However, cardiovascular disease rarely develops or progresses all on its own—it’s often closely connected with a person’s kidney and metabolic health, according to the American Heart Association (AHA).

In an advisory last week, the AHA designated a new disease state called cardiovascular-kidney-metabolic (CKM) syndrome. Screening for and treating conditions like obesity, diabetes, and kidney disease early on could help minimize both children’s and adults’ risk of developing and dying of heart disease, the organization said.

The guidance explains the four stages of the disease progression. More than 90% of U.S. adults fall on that spectrum, said Chiadi Ndumele, MD, PhD, MHS, chair of the expert panel that wrote the advisory and associate professor of medicine at Johns Hopkins University.

The goal of naming the syndrome, Ndumele said, is not merely to label people with new diseases. It’s intended to make it easier to identify people who are susceptible to developing these conditions early on.

“Oftentimes, different specialists treat different parts of this condition separately, and that can lead to very fragmented care because people are not always reading from the same playbook and because patients are trying to navigate across lots of providers,” Ndumele told Verywell. “There was a focus on trying to understand how we can provide holistic care for the patient.”

That’s especially important, he said, for people who face barriers to accessing healthy foods, safe housing, clean water, unbiased medical care, and other social determinants of health. Getting providers on the same page about how to recognize and treat the risk factors for heart disease early on could decrease the number of premature deaths.

Why Link the Conditions Now?

The U.S. has seen declining rates of cardiovascular mortality in the last 50 years, due in part to the decline in smoking rates and improvement in blood pressure and sugar control, Ndumele said.

However, in the last decade, there has been a “very significant change,” Ndumele said, which increases the urgency for addressing the nation’s cardiovascular health. The rates of cardiovascular mortality appear to be plateauing, and there seems to be an uptick in cardiovascular mortality since the pandemic.

In 2008, the Food and Drug Administration (FDA) started requiring diabetes drug manufacturers to test the impact of the medications on cardiovascular outcomes. That led to greater collaboration between cardiologists, endocrinologists, and nephrologists, and a deeper understanding of what is now called CKM syndrome, according to Deepak Bhatt, MD, MPH, director of the Mount Sinai cardiology department, who was not involved with the advisory.

“The knowledge about this overlap has been growing over the past couple of decades, but no document has brought it all together, I think, quite as nicely as this document has done,” Bhatt said.

He believes the AHA guidance will not only improve outcomes but help save lives.

“Many patients with chronic kidney disease or diabetes or obesity develop and die of cardiovascular disease. Linking all these different disease states that, for the most part, doctors think of as separate buckets, is an extremely useful paradigm shift,” Bhatt said.

Breaking Down the Stages of CKM

The AHA created a staging system to explain the typical progression of CKM syndrome. Ndumele said it emphasizes the early stages of the disease, when some people see things like excess body fat accumulation, rising glucose levels, and early signs of kidney disease.

“The goal is to start identifying risks earlier and start applying preventive approaches earlier so that we reduce the pipeline of individuals who are developing heart disease,” Ndumele said.

CKM syndrome often starts because of excess weight, particularly in the belly, which can lead to inflammation and insulin resistance. That can lead to diabetes, high blood pressure, high cholesterol, and kidney disease. Over time, a person may experience heart disease without symptoms, then symptomatic heart disease, and sometimes kidney failure.

The stages of CKM include:

• Stage 0: No risk factors (normal BMI and waist circumference, normal blood sugar, normal blood pressure, normal lipid profile, and no evidence of chronic kidney disease or cardiovascular disease
• Stage 1: Overweight or obesity, excess fat around the waist, or dysfunctional adipose tissue (this usually manifests as impaired glucose tolerance or prediabetes) without other metabolic risk factors or chronic kidney disease.
• Stage 2: Metabolic risk factors (including hypertriglyceridemia, hypertension, and diabetes) or chronic kidney disease
• Stage 3: Subclinical (i.e., without apparent symptoms) atherosclerotic cardiovascular disease or subclinical heart failure in people with excess or dysfunctional body fat, other metabolic risk factors, or chronic kidney disease
• Stage 4: Clinical cardiovascular disease (including coronary heart disease, heart failure, and stroke) in people with excess or dysfunctional body fat, other CKM risk factors, or chronic kidney disease. This stage is broken into two stages: stage 4a for patients with no kidney failure and stage 4b for patients with kidney failure.

Patients in stages 1 and 2 should focus on lifestyle modifications, like getting adequate physical activity, eating a balanced diet, or cutting back on alcohol. In stage 2, patients may start thinking about medication therapies. The AHA recommends people in the later stages of the disease undergo more intensive treatments.

How to Screen for CKM

People who live with a condition or risk factors associated with CKM may already see a subspecialist who can help them understand where they fall on the spectrum and how to seek treatment. People in earlier stages of CKM may be screened by their primary care provider.

Screening for biological risk factors includes testing blood pressure, taking a lipid panel, and measuring fasting blood sugar. People should be assessed for those factors every three to five years in stage 0, every two to three years in stage 1, and yearly in stage 2 and beyond, the guidelines say.

Depending on a person’s health status, they may also be screened for advanced liver fibrosis, markers of kidney disease, and the signs of subclinical heart failure.

Not every patient with a health problem related to CKM necessarily has an overlapping condition, Bhatt said. But each of those patients is at an increased risk for cardiovascular problems.

“The take-home message for patients is that if they have cardiovascular disease, kidney disease, or metabolic disease—meaning diabetes, obesity, or related conditions—that even if they have one of those things, they’re at risk for all of the others,” he said.

Treatment Options for CKM Are Better Than Ever

It’s possible to not only stop people from progressing through the stages of CKM but to reverse disease progression as well, the AHA writes. Treatments and lifestyle modifications that treat one aspect of CKM can improve a patient’s overall health and reduce their risk of premature death.

The AHA advisory comes as new, highly effective medication treatments for obesity and diabetes enter the market. GLP-1 receptor agonist drugs, including Ozempic and Mounjaro, enable some patients to lose upwards of 20% of their body weight and control their blood sugar.

Bhatt said the GLP-1-based drugs seem to be “a real breakthrough in the treatment of cardio-kidney-metabolic diseases.”

He added that he is also excited about another emerging class of medications, called SGLT-2 inhibitors, which reduce glucose reabsorption to treat heart failure, type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors. Researchers are now probing whether pairing GLP-1 agonists with SGLT-2 inhibitors could help people lose weight and improve heart and kidney health at the same time.

In addition to medication treatments, Ndumele emphasized the effectiveness of improving people’s social determinants of health and supporting them through lifestyle approaches.

“The American Heart Association’s core mission is helping individuals live longer, healthier lives. CKM syndrome is a threat to that, but we also have some very real opportunities to address that,” Ndumele said.