High and increasing prevalence of cardio-renal-metabolic multimorbidity

Prevalence and Overlap of Cardiac, Renal, and Metabolic Conditions in US Adults, 1999-2020

Literature - Ostrominski JW, Arnold SV, Butler JV, et al. - JAMA Cardiol. 2023 Sep 27:e233241 [Online ahead of print]. doi: 10.1001/jamacardio.2023.3241

Introduction and methods


Cardio-renal-metabolic (CRM) conditions are leading causes of morbidity and mortality in the US [1]. As the functions of the CRM systems are highly interconnected [2], individual CRM intersections are becoming more relevant, both clinically and therapeutically [3]. While estimated prevalences of individual CRM conditions in the US have been established (ranging from 9% to 15%) [4-6], the frequency with which CRM conditions coexist has not been systematically assessed.

Aim of the study

The authors examined the current and evolving prevalence and overlap of CRM conditions among US adults.


In this observational cohort study, nationally representative data of 11,607 nonpregnant, US adults (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES), a serial cross-sectional survey in the US, were evaluated. To evaluate the contemporary prevalence of CRM conditions, the authors used NHANES data from January 2015 through March 2020, whereas all survey cycles from January 1999 through March 2020 were used to assess trends in the prevalence of CRM conditions over time. To examine temporal trends in CRM overlap, NHANES data for 1999–2002 and 2015–2020 were compared.

CRM conditions were: (1) CVD, defined as ASCVD, HF, or both; (2) renal impairment (CKD), defined according to eGFR and albuminuria; and (3) metabolic disease, defined as the presence of T2D. Prevalences of key CRM risk factors and components of metabolic syndrome, including hypertension, prediabetes, obesity, and hypercholesterolemia, were also examined.

Main results

Prevalence and overlap of CRM conditions

  • From January 2015 through March 2020, 18.2% of US adults (population estimate: 44.9 million) had 1 CRM condition, 6.5% (16.3 million) had 2 CRM conditions, and 1.5% (3.8 million) had 3 CRM conditions.
  • The most prevalent CRM condition was CKD (13.9%), followed by T2D (13.3%) and CVD (8.6%).
  • The most common CRM dyad was CKD plus T2D (3.2%), followed by CVD plus T2D (1.7%) and CVD plus CKD (1.6%).
  • The CRM comorbidity burden was disproportionately high among participants who were older, were male, reported non-Hispanic Black race or ethnicity, were unemployed, had low socioeconomic status, or did not have a high school diploma.

Temporal trends in prevalence and overlap of CRM conditions

  • The proportion of US adults with ≥1 CRM condition increased from 21.2% in 1999–2002 to 26.3% in 2015–2020 (P for test of linear trend<0.001), whereas the proportion of participants with ≥2 CRM conditions increased from 5.3% to 8.0% (P for trend<0.001) and that of participants with all 3 CRM conditions increased from 0.7% to 1.5% (P for trend<0.001).
  • The frequency of participants with no CRM condition decreased from 78.8% in 1999–2002 to 73.7% in 2015–2020 (P for trend<0.001).

Age-stratified analyses

  • Of the participants aged ≥65 years, 33.6% had 1 CRM condition, 17.1% had 2 CRM conditions, and 5.0% had 3 CRM conditions.
  • The most prevalent CRM condition in the oldest age group was CKD (33.1%), followed by T2D (26.0%) and CVD (23.8%).
  • The most common CRM dyad in this age group was CKD plus T2D (7.3%), followed by CVD plus CKD (6.0%) and CVD plus T2D (3.8%).

Self-reported prescription medication use by CRM status

  • Despite strong guideline recommendations, only 44.6% of the participants with concomitant T2D and CKD were receiving statin therapy. Of the participants with 3 CRM conditions, 69.5% reported taking statins.
  • RAASi use was also suboptimal among participants with 3 CRM conditions (68.8%), as was prescription of GLP-1RAs (4.8%) and SGLT2 inhibitors (3.0%).

Prevalence of key CRM risk factors

  • In the entire study population, prediabetes, hypercholesterolemia, hypertension, and obesity were present in 25.9%, 29.0%, 38.5%, and 41.2% of the participants, respectively.
  • However, among individuals with no established CRM condition, hypercholesterolemia (20.6%), prediabetes (27.3%), hypertension (33.6%), and obesity (37.1%) were also common.


This observational population-based cohort study showed that CRM conditions and their overlap were increasingly common among US adults over the last 2 decades. In recent years, more than 25% had 1 CRM condition and nearly 10% had ≥2 CRM conditions. CRM comorbidity burden was especially high in participants who were older, were male, reported non-Hispanic Black race or ethnicity, or who had adverse socioeconomic characteristics.

In addition, key CRM risk factors were prevalent among both participants with and without established CRM conditions. Moreover, across the CRM spectrum, major treatment gaps were observed. “These findings highlight the importance of collaborative and comprehensive management strategies for patients with or at risk for CRM conditions,” according to the authors.


1. Ahmad FB, Anderson RN. The leading causes of death in the US for 2020. JAMA. 2021;325(18):1829-1830. doi:10.1001/jama.2021.5469

2. Sarafidis P, Ferro CJ, Morales E, et al. SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease: a consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA. Nephrol Dial Transplant. 2019;34(2):208-230. doi:10.1093/ndt/gfy407

3. Joseph JJ, Deedwania P, Acharya T, et al; American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Clinical Cardiology; Council on Hypertension. Comprehensive management of cardiovascular risk factors for adults with type 2 diabetes: a scientific statement from the American Heart Association. Circulation. 2022;145(9):e722-e759. doi:10.1161/CIR.0000000000001040

4. Virani SS, Alonso A, Benjamin EJ, et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-e596.

5. United States Renal Data System. 2020 Annual data report. National Institutes of Health. Accessed May 24, 2021. https://usrds-adr.niddk.nih.gov/2020/chronic-kidney-disease/1-ckd-in-the-generalpopulation

6. Centers for Disease Control and Prevention. National diabetes statistics report 2020—estimates of diabetes and its burden in the United States. Accessed May 24, 2021. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetesstatistics-report.pdf

Find this article online at JAMA Cardiol.

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