Cardiovascular-Kidney-Metabolic (CKM) Syndrome

Cardiovascular-Kidney-Metabolic (CKM) syndrome is a systemic disorder characterized by the interconnected pathophysiology of obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). It encompasses individuals at risk for CVD as well as those with existing CVD.  Due to the heavy burden of poor cardiovascular-kidney-metabolic health in the population, the American Heart Association created a presidential advisory discussing current knowledge and future needs.

CKM Syndrome Definition and Staging

“Cardiovascular-kidney-metabolic (CKM) syndrome is defined as a health disorder attributable to connections among obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD), including heart failure, atrial fibrillation, coronary heart disease, stroke, and peripheral artery disease. CKM syndrome includes those at risk for CVD and those with existing CVD”

A staging system for CKM syndrome has been proposed to guide prevention and treatment:

• Stage 0: No CKM risk factors
• Stage 1: Excess or dysfunctional adiposity (e.g., obesity)
• Stage 2: Presence of metabolic risk factors like Hypertension | Diabetes | Hypertriglyceridemia| Metabolic syndrome| moderate-to-high risk CKD
• Stage 3: Subclinical CVD or risk equivalents (high predicted CVD risk or very high-risk CKD)
• Stage 4: Clinical CVD in CKM syndrome

Risk-enhancing factors influence progression through these stages, emphasizing the importance of early identification and intervention

Screening and Risk Prediction

• Screening for CKM risk factors should occur across the lifespan, with frequency and intensity tailored to the CKM stage
• New risk prediction tools i.e., AHA PREVENT Calculator (See ‘Learn More’ below) incorporate assessments starting at age 30, evaluating risks for both atherosclerotic CVD and heart failure, facilitating earlier and more precise risk stratification

Clinical Management and Therapeutic Strategies

• Lifestyle Modification: Addressing excess or dysfunctional adiposity through weight loss and behavioral changes is fundamental to preventing progression and enabling regression of CKM stages
• Pharmacotherapy: Use of cardioprotective antihyperglycemic agents is prioritized based on patient profile:
  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors are favored for patients with CKD, heart failure, or high heart failure risk.
  • Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended for those with uncontrolled hyperglycemia (HbA1c ≥9 %) | high insulin requirements | severe obesity (BMI ≥35 kg/m²).
  • Combined use of SGLT2 inhibitors and GLP-1RAs may be considered for patients with multiple CKM risk factors and high CVD risk.

Kidney Function Monitoring

• Measurement of urine albumin-creatinine ratio and eGFR or cystatin-C is essential in patients with CKD | Diabetes | Hypertension | Metabolic syndrome to characterize risk and guide kidney-protective therapies e.g., ACE-Inh | ARBs | SGLT2 inhibitors |  finerenone

Social Determinants of Health (SDOH)

• Given the disproportionate burden of CKM syndrome among populations with adverse SDOH, systematic screening for these factors is recommended.
• Community partnerships to promote cardiovascular health equity

KEY POINTS:

• CKM syndrome represents a critical public health challenge marked by the interplay of metabolic, kidney, and cardiovascular disorders.
• Early identification through staging and risk assessment, combined with targeted lifestyle and pharmacologic interventions, offers the potential to improve outcomes and reduce cardiovascular morbidity and mortality.
• Addressing social determinants and adopting integrated care approaches are essential to advancing CKM health on a population level
• Advisory highlights the need for integrated and interdisciplinary care models | enhanced education on CKM health and investment in research | improved access to obesity lifestyle and pharmacotherapy treatments

Learn More-Primary Sources

Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association

The American Heart Association PREVENT Calculator