Cardiovascular-Kidney-Metabolic Syndrome

SUMMARY:

Cardiovascular-kidney-metabolic (CKM) syndrome is an interconnected health disorder including obesity, type 2 diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) that can lead to poor health outcomes and multiorgan dysfunction. The 2026 AHA/ACC/ADA/ASN practice guideline is a vast multidisciplinary clinical resource for this complex syndrome. It emphasizes the role of social determinants of health (SDOH) and lifestyle factors in the development of this syndrome.

CKM Syndrome Stages

CKM pathology is progressive with absolute risk of CVD increasing along the stages below.

Stage 0: no risk factors
- normal BMI and waist circumference | normal glucose | normal blood pressure | normal lipids | normal kidney function | no evidence of subclinical or clinical CVD
Stage 1: overweight OR obese | prediabetes
Stage 2: metabolic risk factors (listed below) OR CKD OR both
- Hypertension | Hypertriglyceridemia (≥150 mg/dL) | metabolic syndrome | moderate-to-high risk CKD (see categories below) | Type 2 diabetes (T2D)
Stage 3: subclinical CVD (Subclinical ASCVD OR Subclinical heart failure) OR very-high-risk CKD OR ≥20% 10-yaer CVD risk using PREVENT-CVD equation
Stage 4: clinical CVD with stage 2 CKM risk factors
- Congestive heart disease | heart failure | stroke | peripheral artery disease | atrial fibrillation
  - Stage 4a – no kidney failure
  - Stage 4b – kidney failure present (eGFR <15 mL/min or need for chronic kidney replacement therapy)

PREVENT Equations

PREVENT-HF
- Assess risk of heart failure (HF)
- Goal to catch subclinical HF
PREVENT-ASCVD
- Assess risk of coronary heart disease | nonfatal MI | stroke
- Goal to evaluation subclinical atherosclerosis | initiate lipid-lowering therapies
PREVENT-CVD
- Assess total CVD risk using a composite of ASCVD and HF scores
- Goal to define CKM stage and recommend initiation of GLP-1 or SGLT2i or both | recommend therapy for BP management

CKM Preventative Assessment Recommendations

Stage 0
- Annual measurements of weight | waist circumference | blood pressure
- Every 5 years measure lipids | blood sugar | eGFR
- Calculate 10- and 30-year risk with PREVENT-CVD
Stage 1
- Annual measurements of weight | waist circumference | blood pressure
- Every 2 to 3 years measure lipids | blood sugar | eGFR
- Calculate 10- and 30-year risk with PREVENT-CVD
- Calculate Fibrosis-4 (FIB-4) index every 2-3 years to assess risk for liver fibrosis
Stages 2 to 3
- Annual measurements of weight | waist circumference | blood pressure
- Annual measurements of lipids | blood sugar | eGFR | urine albumin-to-creatinine ratio (UACR)
- Calculate 10- and 30-year risk with PREVENT-CVD
- Calculate Fibrosis-4 (FIB-4) index every 1-2 years to assess risk for liver fibrosis
Stage 4
- Annual measurements of weight | waist circumference | blood pressure
- Annual measurements of lipids | blood sugar | eGFR | urine albumin-to-creatinine ratio (UACR)
- Intensive lifestyle modification and drug treatment to prevent recurrence of CVD and progression of CKD to kidney failure

Validated SDOH Tools

Health Leads
Center for Medicare & Medicaid Innovation: Accountable Health Communities Screening Tool
AAFP: The EveryONE Project
PRAPARE Implementation and Action Toolkit
OCHIN: Social Determinants of Health Electronic Health Record Tools in Community Health Centers
HealthBegins Upstream Risks Screening Tool

CKD Classifications

Low risk
- GFR ≥ 60 AND Albuminuria <30 mg/mmol
Moderately increased risk
- GFR ≥ 60 AND albuminuria 30 to 299 mg/mmol | GFR 45 to 59 AND albuminuria <30 mg/mmol
High risk
- GFR ≥ 60 AND albuminuria ≥300mg/mmol | GFR 45 to 59 AND albuminuria 30 to 299 mg/mmol | GFR 30 to 44 AND albuminuria <30 mg/mmol
Very high risk
- GFR <60 AND albuminuria ≥300mg/mmol | GFR <45 AND albuminuria 30 to 299 mg/mmol | GFR <30 AND albuminuria <30 mg/mmol

CKM Management

Patients with obesity
- Non-judgmental weight loss counseling
- Goal to lose 5 to 10% of body weight
- Lifestyle modifications and behavioral interventions are first line
- Consider GLP-1 or bariatric surgery if not reaching weight loss goals
- Phentermine-topiramate can also be helpful, up to 13% of body weight loss
- Assess for OSA annually
Patients with T2D
- Includes patients diagnosed with gestational diabetes mellitus (GDM)
- Lifestyle modifications and weight management for glycemic control
- Address all risk factors as needed
- Use PREVENT-CVD equation to decide on GLP-1 or SGLT2i therapy
- Metformin is indicated if not at glycemic targets
- Combine GLP-1 + SGLT2i if multiple risk factors or ≥7.5% PREVENT-CVD score
Patients with CKD
- Without diabetes
  - UACR <30 mg/g –> No kidney protection needed
  - UACR ≥ 30mg/g –> Start RASi + SGLT2i
- With diabetes
  - START RASi + SGLT2i
  - UACR ≥ 30mg/g –> Add finerenone
  - Check UACR every 3 to 6 months
  - Persistent albuminuria (UACR ≥ 100 mg/g) –> Add GLP-1
Patients with HTN
- HTN contributes to CKD | CKD contributes to worsening of HTN
- Lifestyle modifications are first line
  - DASH diet | sodium reduction | weight loss | increased physical activity
- Blood pressure goal is <130/80
- First line pharmacologic therapies:
  - RASi (preferred in CKD with albuminuria) | thiazide-type diuretics | long-acting dihydropyridine calcium channel blockers
  - Single-pill combination therapy with two first-line agents is preferred
Patients with coronary artery calcium score (CAC) >100
- Initiate lipid lowering therapies
- Address variety of CKM factors
Patients with pre-HF
- Initiate intensive lifestyle interventions and risk factor control
- With T2D or CKD –> start SGLT2i
  - UACR ≥ 30 mg/g –> Consider adding finerenone
  - UACR ≥ 100 mg/g –> Add GLP-1

Stage 4 CKM Management

Manage the individual conditions with goal of improving quality of life and enhancing secondary prevention

ASCVD
- Use aspirin + anti-platelet agent OR anticoagulation OR both
- Initiate maximally tolerated statin therapy + adjunctive agents (ezetimibe, bempedoic acid, PCK9i) when indicated
Peripheral artery disease (PAD) | chronic coronary disease (CCD) | cerebrovascular disease
- Initiate high-intensity or maximally tolerated statin and anti-platelet therapy
- Consider additional lipid lowering therapy as indicated by LDL-C and triglycerides
- Consider addition of aspirin + rivaroxaban for PAD
Obesity
- Treat as in other stages of CKM
- Goal to lose >5 to 10% of body weight
  - DO NOT start naltrexone/bupropion or phentermine-containing medications for weight loss as they can increase BP and heart rate
HF – initiate guideline directed medical therapy (GDMT)
- HFrEF: beta blocker | steroidal MRA | ARNI/ACEi/ARB | SGLT2i | diuretics as needed
- HFpEF: SGLT2i | diuretics as needed
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
- Focus on weight loss with approaches outlined for obesity
- With T2D or metabolic dysfunction associated steatohepatitis (MASH) with clinically significant liver fibrosis
  - GLP-1 can improve MASLD

Learn More – Primary Sources

AHA/ACC/ADA/ASN: Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026)

NEJM: Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes (2020)