CKM Syndrome Affects the Vast Majority of Adults in the United States

Nearly 90% of adults in the United States meet criteria for cardiovascular, kidney, and metabolic (CKM) syndrome, and 14.6% meet criteria for advanced stages 3 to 4. Older, Black, and male adults are at particularly high risk. These high rates have not improved in the last decade.

The latest findings are based on nationally representative data from 10,762 adults in the 2011-2020 National Health and Nutrition Examination Survey (NHANES). Over the period, 25.9% had stage 1, 49.0% had stage 2, 5.4% had stage 3, and 9.2% had stage 4 CKM syndrome. Data were lacking for subclinical atherosclerotic cardiovascular disease (CVD), subclinical heart failure, peripheral arterial disease, and atrial fibrillation, so the prevalence of stages 3 and 4 may be underestimated.

“The lack of progress, in part, may reflect concomitant improvement and worsening of different risk factors over time,” Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues wrote in JAMA.¹ “Equitable health care approaches prioritizing CKM health are urgently needed.”

Variation by Age, Sex, and Race

Adults 65 years or older had a significant 27-fold increased prevalence of advanced CKM syndrome (stages 3 or 4) compared with those aged 20 to 44 years. Men had a 1.4-fold increased prevalence of advanced CKM syndrome compared with women. Black adults had a 1.4-fold increased prevalence compared with White adults.

The American Heart Association (AHA) proposed the concept of CKM syndrome in 2023 in Circulation, stating that “[m]ore guidance is needed on definitions, staging, prediction strategies, and algorithms for the prevention and treatment of cardiovascular-kidney-metabolic syndrome to optimize cardiovascular-kidney-metabolic health across diverse clinical and community settings.”²

Dr Vaduganathan and colleagues defined stage 0 as the absence of CKM risk factors, such as hypertension. Individuals with stage 1 had excess or dysfunctional adiposity, and those with stage 2 had additional metabolic risk factors or moderate- or high-risk chronic kidney disease (CKD). Adults with stage 3 had very high-risk CKD or high predicted 10-year CVD risk. Those with stage 4 had established CVD, such as coronary artery disease.

Dmitry Abramov, MD, of Loma Linda University Medical Center in Redlands, California, and colleagues conducted a similar analysis using NHANES data from 2011 to 2018 and reached similar conclusions when they examined the prevalence of CKM syndrome according to age groups.

Among cohorts aged 20 to 44, 45 to 64, and 65 years or older, 17.35%, 5.45%, and 1.80% had stage 0 CKM, respectively, whereas 80.94%, 85.95%, and 72.03%, respectively, had risk factors and subclinical CKM (stages 1-3), the investigators reported.

“These results highlight the high burden of risk factors for CVD, including among individuals who have not yet developed clinical CVD, and the low prevalence of individuals without CKM syndrome even among young adults,” the authors wrote in the Journal of the American College of Cardiology.³

The authors also commented: “Understanding the burden of interrelated comorbidities and convergence of risk factors is important for public health efforts behind the identification and management of the CKM syndrome, particularly given the increasing number of therapeutic management options for these conditions. Such efforts may include targeted screening and prevention efforts among individuals with early stages of the CKM syndrome to prevent progression to higher stages and symptomatic CVD.”

Nephrology Implications

In a perspective piece published in the Journal of the American Society of Nephrology,⁴ Nisha Bansal, MD, MS, of the University of Washington in Seattle, and colleagues discussed the implications of CKM syndrome staging for nephrologists.

“This is an important advance for the nephrology community and provides a new opportunity to forge strong partnerships with other clinicians to advance the care of patients with or at risk of CKD by integrating care for kidney disease, cardiovascular disease, diabetes, obesity, and other metabolic risk factors,” they wrote.

Patients with or at risk for CKM syndrome can be seen and referred by primary care physicians, cardiologists, and endocrinologists, and attended by pharmacists, nursing staff, care navigators, social workers, and community health workers, they noted.

The National Kidney Foundation in partnership with Phreesia recently conducted a survey of 4445 US patients with diabetes or hypertension, who are at risk for CKD and cardiovascular diseases. Two in 3 of these high-risk patients were not aware of their risk for kidney disease, investigators reported in The American Journal of Accountable Care. A Patient Activation Measure® comprised of 40 questions evaluated patients’ knowledge, skills and confidence in managing their own health. Scores, ranging from 0 to 100, reflect patients who are “overwhelmed and disengaged” to “proactive and goal oriented.”

Results showed that 70% and 51% of highly activated patients with diabetes or hypertension, respectively, have discussed kidney health with their healthcare provider, compared to just 38% and 7% of low-activation patients, respectively.

“This research illustrates that the frequency of patient-provider conversations and patient activation influence patient awareness of their risk for CKD,” said Elizabeth Montgomery, National Vice President of Learning Strategies and Population Health Programs at the National Kidney Foundation and co-author of the research in a news release. “Strategies to improve patient initiation of conversations with their clinicians regarding kidney disease risk is one pathway to improve the low rates of CKD testing and diagnosis in the US.”

Clinicians and patients can use the AHA’s PREVENT™ online risk calculator to determine an individual’s risk for CKM syndrome, according to Dr Bansal’s team.

Broader screening for CKD is currently under consideration by the US Preventative Services Task Force, and the CKM framework may further encourage screening including in children and young adults. The framework proposes starting screening at ages younger than 21 years in children and adolescents with risk factors such as obesity, hypertriglyceridemia, diabetes, or hypertension.

For preventing or delaying progression, the CKM treatment approach encourages initiation, titration, and continuation of therapies in patients with CKD, such as renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists.

To the extent the CKM framework promotes greater inclusion of patients with CKD in clinical trials for cardiovascular disease and other diseases, nephrology may see progress, according to Dr Bansal’s team.

Patients with CKD or its risk factors meet criteria for at least stage 2 CKM syndrome. Having stage G4 or G5 CKD is considered a risk equivalent for subclinical cardiovascular disease and automatically places a patient in stage 3 of the syndrome, Dr Bansal and coauthors explained. Patients with clinical cardiovascular disease (coronary heart disease, heart failure, stroke, peripheral artery disease, atrial fibrillation) and CKD, metabolic risk factors, or adiposity, automatically meet criteria for stage 4 CKM syndrome.

“In stage 4 CKM, patients with kidney failure treated with dialysis are separated from those without kidney failure because of the substantial cardiovascular risk and the unique approaches to risk factor management and treatment (in the context of a lack of quality data to guide treatment decisions),” Dr Bansal’s team wrote.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of authors’ disclosures.