• Figure 1

    Key steps for management of patients with or at risk for CRM

  • 1.

    Ahmad FB, Anderson RN. The leading causes of death in the US for 2020. JAMA 2021; 325:18291830. doi: 10.1001/jama.2021.5469

  • 2.

    Rahimi K, et al. Cardiovascular disease and multimorbidity: A call for interdisciplinary research and personalized cardiovascular care. PLoS Med 2018; 15:e1002545. doi: 10.1371/journal.pmed.1002545

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Sarafidis P, 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; 34:208230. doi: 10.1093/ndt/gfy407

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Diabetes mellitus: A major risk factor for cardiovascular disease. A joint editorial statement by the American Diabetes Association; The National Heart, Lung, and Blood Institute; The Juvenile Diabetes Foundation International; The National Institute of Diabetes and Digestive and Kidney Diseases; and The American Heart Association. Circulation 1999; 100:11321133. doi: 10.1161/01.cir.100.10.1132

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Hebert SA, Ibrahim HN. Hypertension management in patients with chronic kidney disease. Methodist Debakey Cardiovasc J 2022; 18:4149. doi: 10.14797/mdcvj.1119

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Ostrominski JW, et al. Prevalence and overlap of cardiac, renal, and metabolic conditions in US adults, 1999-2020. JAMA Cardiol 2023; 8:10501060. doi: 10.1001/jamacardio.2023.3241

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Eberly LA, et al. Racial, ethnic, and socioeconomic inequities in glucagon-like peptide-1 receptor agonist use among patients with diabetes in the US. JAMA Health Forum 2021; 2:e214182. doi: 10.1001/jamahealthforum.2021.4182

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Das SR, et al. 2020 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2020; 76:11171145. doi: 10.1016/j.jacc.2020.05.037

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    • Search Google Scholar
    • Export Citation
  • 9.

    Cusick MM, et al. Population-wide screening for chronic kidney disease: A cost-effectiveness analysis. Ann Intern Med 2023; 176:788797. doi: 10.7326/M22-3228

Cardiac, Renal, and Metabolic Overlap: A Public Health Crisis?

Waseem Farooq Waseem Farooq, MD, is a cardiology fellow, and Agnes S. Kim, MD, PhD, is an associate professor of medicine at the Pat and Jim Calhoun Cardiology Center, University of Connecticut Health, Farmington.

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Agnes S. Kim Waseem Farooq, MD, is a cardiology fellow, and Agnes S. Kim, MD, PhD, is an associate professor of medicine at the Pat and Jim Calhoun Cardiology Center, University of Connecticut Health, Farmington.

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Cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM), which form the cardiac, renal, and metabolic (CRM) triad, are the leading causes of death, disability, and rising health care costs in the United States (1, 2). CRM conditions share overlapping risk factors and common pathophysiological mechanisms, including impaired glucose metabolism, dyslipidemia, hypertension, and obesity (3). T2DM, obesity, and metabolic syndrome contribute to endothelial dysfunction, inflammation, and oxidative stress, setting the stage for atherogenesis (4). CKD contributes to salt and volume retention, overactivation of the sympathetic and renin-angiotensin-aldosterone system, and generalized endothelial dysfunction, leading to hypertension and heart failure (5). Conversely, uncontrolled hypertension and heart failure (i.e., CVD) can deteriorate renal function. Although it has been known that CRM conditions are deeply interconnected, the prevalence and overlap of CRM multi-morbidity among US adults had not been known until a recent study published in JAMA Cardiology (6).

Using the National Health and Nutrition Examination Survey (NHANES) database, Ostrominski et al. (6) found a high and increasing prevalence of CRM multi-morbidity in the last 2 decades. Between 1999 and 2020, the proportion of US adults with at least one CRM condition increased from 21.2% to 26.3%; with two conditions, from 5.3% to 8.0%; and with all three conditions, from 0.7% to 1.5%. Older (aged > 65 years) and male participants had a higher CRM comorbidity burden, as did self-reported non-Hispanic Black participants and those with low socioeconomic status, those who were unemployed, and participants without a high school degree. Among those aged 65 years or older, one-third had one CRM condition, 17.1% had two conditions, and 5.0% had all three conditions. In particular, CKD had been historically underreported and underdiagnosed, and the current study highlights the growing recognition of the predominance of CKD. The prevalence of key CRM risk factors (hypertension, obesity, and prediabetes) is also increasing.

The CRM public health crisis is exacerbated by the undertreatment of CRM and its risk factors. Common medications, such as statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), and relatively newer agents like sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), for which abundant data have now been presented on their cardiovascular and nephroprotective effects, were shown to be severely underutilized (6). Despite strong guideline recommendations, almost one-third of participants with three CRM conditions were not treated with a statin. Only 46.8% of patients with CVD plus CKD and 60.7% of those with CKD plus T2DM reported use of an ACE inhibitor or ARB. Utilization of GLP-1 RAs and SGLT2 inhibitors was rare even among patients with CVD plus CKD and CKD plus T2DM, only 4.8% and 3.0%, respectively (6). Furthermore, previous research has shown that low socioeconomic status and racial inequalities are associated with undertreatment (7). Given recent data on the role of novel therapies and the significant reduction in the risk of major adverse cardiovascular events in patients with T2DM and CVD, more patients with CRM overlap should be treated with these medications (8).

Figure 1 proposes key steps for the comprehensive and collaborative management of patients with, or at risk for, CRM conditions. First, we assess the patient's risk profile and use guideline-directed therapy for CV prevention, including lifestyle changes as well as using anti-hypertensive, anti-hyperlipidemic, anti-platelet, and anti-hyperglycemic medications as needed. Next, we perform a comprehensive evaluation using history, physical, and laboratory data, along with a detailed evaluation of social determinants of health. There is increasing evidence that generalized screening for CKD with at least annual assessment of urinary albumin (e.g., spot urinary albumin-to-creatinine ratio) and estimated glomerular filtration rate is worthwhile, especially in patients with T2DM and hypertension (9). For CRM management, a team-based, multi-disciplinary approach should be taken with an emphasis on the use of SGLT2 inhibitors and GLP-1 RAs, which have promising results from CV outcome trials (8). The interdisciplinary care would involve primary care physicians working together with cardiovascular, nephrology, and endocrine colleagues to deliver optimal results. Patients with T2DM and concurrent atherosclerotic CVD (ASCVD), heart failure, or kidney disease or who are at high risk for ASCVD should be strongly considered for either SGLT2 inhibitors or GLP-1 RAs for cardiovascular and renal benefits (3). Treatment of obesity, which lies at the crux of the CRM overlap, is critically important (3). Finally, population-based interventions that promote health equity, such as improved access to care and affordability of the newer therapies, will be important. These strategies should ideally be incorporated into national guidelines.

Figure 1
Figure 1

Key steps for management of patients with or at risk for CRM

Citation: Kidney News 16, 3

Footnotes

The authors report no conflicts of interest.

References

  • 1.

    Ahmad FB, Anderson RN. The leading causes of death in the US for 2020. JAMA 2021; 325:18291830. doi: 10.1001/jama.2021.5469

  • 2.

    Rahimi K, et al. Cardiovascular disease and multimorbidity: A call for interdisciplinary research and personalized cardiovascular care. PLoS Med 2018; 15:e1002545. doi: 10.1371/journal.pmed.1002545

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Sarafidis P, 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; 34:208230. doi: 10.1093/ndt/gfy407

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Diabetes mellitus: A major risk factor for cardiovascular disease. A joint editorial statement by the American Diabetes Association; The National Heart, Lung, and Blood Institute; The Juvenile Diabetes Foundation International; The National Institute of Diabetes and Digestive and Kidney Diseases; and The American Heart Association. Circulation 1999; 100:11321133. doi: 10.1161/01.cir.100.10.1132

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Hebert SA, Ibrahim HN. Hypertension management in patients with chronic kidney disease. Methodist Debakey Cardiovasc J 2022; 18:4149. doi: 10.14797/mdcvj.1119

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Ostrominski JW, et al. Prevalence and overlap of cardiac, renal, and metabolic conditions in US adults, 1999-2020. JAMA Cardiol 2023; 8:10501060. doi: 10.1001/jamacardio.2023.3241

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Eberly LA, et al. Racial, ethnic, and socioeconomic inequities in glucagon-like peptide-1 receptor agonist use among patients with diabetes in the US. JAMA Health Forum 2021; 2:e214182. doi: 10.1001/jamahealthforum.2021.4182

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Das SR, et al. 2020 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2020; 76:11171145. doi: 10.1016/j.jacc.2020.05.037

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Cusick MM, et al. Population-wide screening for chronic kidney disease: A cost-effectiveness analysis. Ann Intern Med 2023; 176:788797. doi: 10.7326/M22-3228

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