Trends in the Prevalence of Cardiovascular-Kidney-Metabolic (CKM) Syndrome

Prevalence of cardiovascular-kidney-metabolic (CKM) syndrome among U.S. adults.

National Health and Nutrition Examination Survey (NHANES).

Noninstitutionalized U.S. adults aged ≥20 years. Pregnant women and adults with BMI <18.5 excluded.

2001–March 2020.

U.S. adults aged ≥20 years with CKM stages 1–4.

U.S. adults aged ≥20 years with data on serum creatinine, urine albumin-to-creatinine ratio, and variables for CKM stage.

CKM stages are progressive and defined as:

Stage 1: BMI ≥ 25 kg/m², or waist circumference ≥88 cm in females and ≥102 cm in males, or HbA1c between 5.7% and 6.4%.

Stage 2: Moderate-high chronic kidney disease (CKD) risk (Kidney Disease: Improving Global Outcomes [KDIGO]), diabetes, hypertension, triglycerides ≥ 135 mg/dL, or metabolic syndrome.

Stage 3: High predicted 10-year cardiovascular disease (CVD) risk (≥20% Predicting Risk of CVD EVENTs [PREVENT] CVD risk equation) or very high CKD risk (KDIGO).

Stage 4: Self-reported congestive heart failure, coronary heart disease, angina, heart attack, or stroke.

[See Reference 1 for more information.]

Based on the CKD Epidemiology Collaboration (CKD-EPI) (2021) equation for calibrated creatinine: eGFR = 142 x [min(serum creatinine in mg/dL) /κ, 1)]**α x [max(serum creatinine/κ, 1)]**-1.20 x 0.9938**age x (1.012 if female).
κ = 0.7 if female and 0.9 if male
α = -0.241 if female and -0.302 if male
** = raise to the power

Urine albumin-to-creatinine ratio (UACR) was calculated as urine albumin divided by urine creatinine. Albuminuria is defined as UACR ≥ 30 mg/g. Urine albumin is measured in random urine collection by fluorescent immunoassay.

Serum creatinine values used for eGFR calculation are standardized against isotope dilution mass spectrometry (IDMS).

Low risk: eGFR ≥ 90 or 60–89 mL/min/1.73m² and albuminuria < 30 mg/g

Moderate risk: eGFR 45–59 mL/min/1.73m² and albuminuria < 30 mg/g, or eGFR ≥60 mL/min/1.73m² and albuminuria 30–299 mg/g

High risk: eGFR 30–44 mL/min/1.73m² and albuminuria < 30 mg/g, or eGFR 45–59 mL/min/1.73m² and albuminuria 30–299 mg/g, or eGFR ≥ 60 mL/min/1.73m² and albuminuria ≥ 300 mg/g.

Very high risk: eGFR < 30 mL/min/1.73m² regardless of albuminuria level, or eGFR 30–44 mL/min/1.73m² and albuminuria ≥30 mg/g, or eGFR 45–59 mL/min/1.73m² and albuminuria ≥300 mg/g

[See Reference 2 for more information.]

Any three of the following: waist circumference ≥88 cm in females and ≥102 cm in males; HDL < 40 mg/dL in males and < 50 mg/dL in females; triglycerides ≥ 150 mg/dL; hypertension; HbA1c ≥ 5.7%.

Self-reported diabetes or HbA1c ≥6.5%.

Self-reported hypertension or measured blood pressure ≥130/80.

Females: log_Odds_CVD = -3.307728 + (0.7939329 * Age_cent /10) + (0.0305239 * non_HDL_SI_cent) - (0.1606857 * HDL_SI_cent /0.3) - (0.2394003 * min_SBP_110_cent /20) + (0.360078 *  max_SBP_110_cent /20) + (0.8667604 * diabetes) + (0.5360739 * Smoke_now) + (0.6045917 * min_GFR_60 / -15) + (0.0433769 * max_GFR_60 / -15) + (0.3151672 * Rx_HTN) - (0.1477655 * Statin) - (0.0663612 * Rx_HTN * max_SBP_110_cent /20) + (0.1197879 * Statin * non_HDL_SI_cent) - (0.0819715 * Age_cent /10 * non_HDL_SI_cent) + (0.0306769 * Age_cent /10 * HDL_SI_cent /0.3) -     (0.0946348 * Age_cent /10 * max_SBP_110_cent /20) - (0.27057 * Age_cent /10 * diabetes) - (0.078715 * Age_cent /10 * Smoke_now) - (0.1637806 * Age_cent /10 * min_GFR_60 / -15)

Males: log_Odds_CVD = - 3.031168 + (0.7688528 * Age_cent /10) + (0.0736174 * non_HDL_SI_cent) - (0.0954431 * (HDL_SI_cent /0.3)) - (0.4347345 * min_SBP_110_cent /20) + (0.3362658 * max_SBP_110_cent /20) + (0.7692857 * diabetes) + (0.4386871 * Smoke_now) + (0.5378979 * min_GFR_60 / -15) + (0.0164827 * max_GFR_60 / -15) + (0.288879 * Rx_HTN) - (0.1337349 * Statin) - (0.0475924 * Rx_HTN * max_SBP_110_cent /20) + (0.150273 * Statin * non_HDL_SI_cent) - (0.0517874 * Age_cent /10 * non_HDL_SI_cent) + (0.0191169 * Age_cent /10 * HDL_SI_cent /0.3) - (0.1049477 * Age_cent /10 * max_SBP_110_cent /20) - (0.2251948 * Age_cent /10 * diabetes) - (0.0895067 * Age_cent /10 * Smoke_now) - (0.1543702 * Age_cent /10 * min_GFR_60 / -15)

Where:

SBP = Systolic blood pressure

HDL = High-density lipoprotein

Non_HDL = Total cholesterol – HDL

Risk_CVD=exp(log_Odds_CVD)/(1+exp(log_Odds_CVD))

All laboratory values are in SI units, and centered as follows:

Age_cent = age_years-55

non_HDL_SI_cent = non_HDL_SI-3.5

HDL_SI_cent = HDL_SI-1.3

min_SBP_110_cent=(min(SBP, 110) - 110)

max_SBP_110_cent=(max(SBP, 110) - 130)

min_GFR_60=(min(eGFR_2021, 60) - 60)

max_GFR_60=(max(eGFR_2021, 60) - 90)

Smoke_now = 0/1 indicator for current smoking (daily or occasional)

Diabetes = 0/1 indicator for individuals with diabetes

Rx_HTN = 0/1 indicator for individual taking a medication for hypertension

Statin = 0/1 indicator for individual taking a statin medication

Values were Winsorized if they fell outside of the range used for equation development:

SBP <90 or >200 mm Hg

TC <130 or >320 mg/dL

HDL-C <20 or >100 mg/dL)

[See Reference 3 for more information.]

Estimates were standardized to the 2010 U.S. Census population for adults: 20–39 years: 36.7%, 40–59 years: 37.9%, 60–69 years: 13.0%, and 70+ years: 12.4%.

Albuminuria and kidney function were assessed from one-time cross-sectional measurements, possibly overestimating CKD prevalence. Some data recommended to define CKM stage 3–4, including cardiac biomarkers, echocardiographic parameters, coronary calcification, peripheral artery disease, or atrial fibrillation, were unavailable, possibly underestimating CKM stages 3–4.

Appropriate NHANES survey weights were used for all analyses; if relative standard error was greater than 30%, the estimates were not shown. Serum creatinine measurements were assay corrected for NHANES years 2005 and 2006 and prior to be combined with later years.