Summary
Cardiovascular-kidney-metabolic (CKM) syndrome is a disorder characterized by the interaction between metabolic risk factors (e.g., obesity, diabetes, hypertension, hypertriglyceridemia), chronic kidney disease (CKD), and cardiovascular disease (CVD). Poor CKM health, especially among populations affected by negative social determinants of health (SDOH), can lead to cardiovascular events and premature deaths. Screening for metabolic risk factors and addressing adverse SDOH, with components varying based on the patient's age and health status, is recommended from early life to prevent the onset of atherosclerotic cardiovascular disease (ASCVD) and/or CKD. CKM syndrome is divided into 5 stages to outline the progression from having no risk factors (CKM stage 0) to having CVD with or without renal failure (CKM stage 4). Management is based on the CKM stage and focuses on the prevention of disease development and progression while taking the patient's SDOH into account. Metabolic risk factors are managed according to current guidelines.
Definitions
Cardiovascular-kidney-metabolic syndrome: a systemic health disorder that involves complex interactions between metabolic risk factors (e.g., obesity, diabetes), chronic kidney disease, and cardiovascular disease, resulting in multiorgan dysfunction and poor cardiovascular outcomes [1]
Pathophysiology
Biological and environmental risk factors and SDOH → dysfunctional adipose tissue → inflammation and insulin resistance → CKM risk factors (e.g., dyslipidemia, diabetes) and/or CKD → subclinical atherosclerosis, subclinical myocardial dysfunction, and/or progressive decline of renal function → poor health outcomes (e.g., stroke, heart failure, atrial fibrillation, coronary artery disease, ESRD) → disability and death [1]
CKM syndrome starts early in life and progresses over time. [1]
Screening
In addition to the factors listed below, screen children and adults routinely for SDOH.
Age < 21 years [1]
- Overweight and obesity: Screen annually using CDC growth charts for age and sex.
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Hypertension: Start assessing at 3 years of age.
- No risk factors: Screen annually.
- Risk factors present: Screen at every health care visit.
-
Hypercholesterolemia
- Obtain a fasting lipid panel once between 9 and 11 years of age; start at 2 years of age in patients with additional risk factors.
- Repeat a fasting lipid panel once between 17 and 21 years of age.
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Diabetes and MASLD [1]
- Obtain hyperglycemia tests and ALT once between 9 and 11 years of age.
- If results are normal, repeat every 2–3 years in patients with obesity, or who are overweight with one additional risk factor
-
Mental and behavioral health
- Screen at least annually for all children. See “Mental and social health screening” in "Well-child visits" for details.
Age ≥ 21 years [1]
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Metabolic syndrome components
- BMI and waist circumference: Measure annually.
-
Blood pressure measurement, hyperglycemia tests, and lipid panel :
- CKM stage 0: obtain every 3–5 years
- CKM stage 1 (or history of gestational diabetes): obtain every 2–3 years
- CKM stage 2: obtain annually
- MASLD-related advanced fibrosis: Obtain a FIB-4 score every 1–2 years in individuals with diabetes, prediabetes, or ≥ 2 metabolic risk factors.
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Kidney disease: UACR, serum creatinine, and serum cystatin C
- CKM stage 2 or higher: obtain annually
- Very high risk of progression of CKD: obtain more frequently according to current guidelines
-
ASCVD [2][3]
- See “ASCVD risk assessment” for details on screening frequency and tools, e.g., PREVENTTM equations.
- Consider coronary artery calcium score for patients with borderline or intermediate 10-year ASCVD risk.
-
Heart failure
- There is no strong recommendation for screening to detect preclinical heart failure.
- Consider echocardiogram and/or cardiac biomarkers on a case-by-case basis according to age, comorbidities, and ASCVD risk score.
Subsequent screening intervals are based on the CKM stage.
Staging
CKM risk factors
-
Excess and/or dysfunctional adiposity
- Overweight or obesity (elevated BMI)
- Abdominal obesity
- Prediabetes
- Other metabolic CKM risk factors
Risk-enhancing factors
Risk-enhancing factors are elements that heighten the chances of advancing through stages of CKM syndrome and raise the risk of developing CVD and kidney failure. [1]
- ASCVD risk-enhancing factors
- Adverse SDOH, e.g., low socioeconomic status
- Mental health disorders, e.g., anxiety and depression
- Other sex-specific factors, e.g., early menopause, pregnancy complications, erectile dysfunction, and PCOS
CKM staging
The CKM staging framework illustrates the interactions between CKM components and the risk of progression into clinical CVD with or without renal failure.
| CKM staging [1] | |||
|---|---|---|---|
| Stage | Definition | ||
| CKM stage 0 |
| ||
| CKM stage 1 |
| ||
| CKM stage 2 |
| ||
| CKM stage 3 |
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| CKM stage 4 |
| ||
Management
Approach
- Promote overall health for patients with all stages of CKM syndrome, e.g.:
- Provide education about life's essential 8.
- Encourage lifestyle modifications for ASCVD prevention.
- Address relevant CKM syndrome components, e.g.:
CKM stage 2 or higher should be managed by a multidisciplinary care team.
Life's Essential 8 framework
- Definition: a framework designed by the American Heart Association to promote and quantify cardiovascular health (CVH) by focusing on eight key areas [4]
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Components and ideal values
- Nutrition: DASH diet most of the time
- Physical activity: 150 minutes/week of at least moderate-intensity activity
- Avoidance of nicotine
- Sleep: 7 to < 9 hours
- Normal weight
- Cholesterol: non-HDL cholesterol < 130 mg/dL
- Blood glucose: normal levels, i.e., fasting glucose < 100 mg/dL, HbA1c < 5.7%
- Blood pressure: < 120/80 mm Hg
Optimal CVH is further determined by SDOH and psychological health, i.e., the presence of positive factors such as a sense of purpose, happiness, and optimism, and the absence of negative factors, such as depression, anxiety, and stress.