The DOI matches its Crossref record; 208 of the 208 references it cites were found in a registry or an index.
A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association
Open accessAbstract
A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.
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The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Assessments for prediabetes or diabetes with fasting blood glucose, HbA1c, or oral glucose tolerance tests are critical because of the strong association of hyperglycemia with cardiovascular and kidney disease.39,40”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Successful interventions included frequent feedback and support, which have been shown to positively impact program adherence.24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both classes of agents reduce major adverse cardiovascular events (MACE) and CVD mortality across multiple clinical trials,39,40 with SGLT2i having a particular impact on HF hospitalizations and GLP-1–based therapy having a more substantial impact than SGLT2i on incident ASCVD events.”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both classes of agents reduce major adverse cardiovascular events (MACE) and CVD mortality across multiple clinical trials,39,40 with SGLT2i having a particular impact on HF hospitalizations and GLP-1–based therapy having a more substantial impact than SGLT2i on incident ASCVD events.”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Incidentally identified moderate-to-severe coronary calcifications on a nongated chest computed tomography scan typically correlates with CAC ≥100, carries similar prognostic value, and can also identify patients with CKM syndrome most likely to benefit from preventive therapies.21–24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In adults across the CKM stages, intensive lifestyle interventions and intensive risk factor control with coordinated care and pharmacotherapies have robust evidence of improving CKM health.22–24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GLP-1–based therapy often causes significant weight loss and improvements in CKM risk profiles and MASLD, while SGLT2i has a marked impact on CKD.19–30”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“MBS causes substantial weight loss (up to 30% to 35% body weight) and improvements in multiple CKM risk factors.23–25”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both SGLT2i and GLP-1–based therapy improve kidney outcomes,49–51 with GLP-1–based therapy additionally promoting significant weight reduction and glycemic control (especially semaglutide and tirzepatide)19–25 and reducing liver fibrosis in MASH”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The risk-benefit and appropriate strategies for treating obesity in patients with HFrEF remain undefined.24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“RASi, with ARNI having superior HF benefits over ACEi/ARB; and 2) SGLT2i.13,21–25”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Among these 4 medication classes (6 classes if the patient also self-identifies as Black race), 2 are kidney-protective; namely, 1) RASi, with ARNI having superior HF benefits over ACEi/ARB; and 2) SGLT2i.13,21–25”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“MBS is associated with a lower risk of incident major adverse liver outcomes and MACE in large cohort studies.6,24,25”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In patients with BMI ≥30 kg/m2, pooled DOAC use was linked to a 20% reduction in stroke/systemic embolism/MI/all-cause mortality and a 44% reduction in major bleeding versus VKA, with similar VTE prevention.24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The early postpartum period representing the 12 weeks following delivery, sometimes referred to as the fourth trimester, is a critical window to optimize women's CKM health, particularly for women with APOs.40”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The largest HbA1c reductions are achieved by treatment plans that include GLP-1–based treatments, particularly semaglutide and tirzepatide, in addition to insulin.24,25”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“APOs are also associated with higher subsequent risk for developing CKM risk factors (hypertension, diabetes, dyslipidemia) and CVD (including HF, coronary heart disease, PAD, and vascular dementia).12,23–27”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The AHA and ACOG recommend frequent CVD risk factor screening and lifestyle counseling among postpartum women who experience APOs.40,41”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Both classes of agents reduce major adverse cardiovascular events (MACE) and CVD mortality across multiple clinical trials,39,40 with SGLT2i having a particular impact on HF hospitalizations and GLP-1–based therapy having a more substantial impact than SGLT2i on incident ASCVD events.”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
The cited source says what the claim attributes to it.
In the citing paper
“SGLT2i appear to primarily reduce incident and worsening HF.17,37–44”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
The cited source says what the claim attributes to it.
In the citing paper
“As such, the current study supports IPE as a potential therapeutic strategy for CKM patients beyond traditional standard of care measures as outlined in the recent AHA Scientific Statement [3]”
From Icosapent ethyl reduces CVD risk in cardiovascular-kidney-metabolic syndrome: REDUCE-IT CKM (2026) · cites this paper as [3]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Another small RCT showed that a social work–led care coordination intervention reduced 30-day readmission rates by 22% among older inpatients with high risk of readmission.24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“A systematic review of registry data reported several strategies for successful weight loss maintenance, including regular breakfast intake and having healthy food at home.40”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“A recently published modeling study suggested that GLP-1-based therapies, at an annual cost of $19 881, would not be cost-effective compared with RYGB surgery.24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Lactation also reduces pancreatic oxidative stress and risks for T2D in women with GDM and should be discussed with them before, during, and after pregnancy.22–24”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“This benefit was consistent with or without background SGLT2i40 or GLP-1 RA use.41”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“numerous observational studies support a positive, linear association of glycemia with HF incidence and events.23–25”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In adults with CKM syndrome stage 4 syndrome with CKD and symptomatic HFpEF, the cost-effectiveness of adding a SGLT2i prior to GDMT at 2025 US prices is indeterminate.”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“However, these analyses pooled individuals without, and with, CKD and did not directly incorporate the benefit of SGLT2i therapy on kidney outcomes.”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Metabolic and bariatric surgery causes remission of MASLD, even in advanced stages.6,24,25”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [24]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“One analysis based on the results of the EMPEROR-PRESERVED trial found that empagliflozin therapy, at an annual cost of $3920, would have an incremental cost-effectiveness ratio $437 400 per QALY gained.40”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In 2 high-quality simulation model–based cost-effectiveness analyses that evaluated the economic value of adding SGLT2i therapy to prior GDMT in adults with symptomatic HFpEF using a US health care sector perspective and a lifetime analytic horizon, addition of SGLT2i therapy to GDMT was projected to be not cost-effective, but the incremental cost-effectiveness ratio was sensitive to the effect on”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Taken together, these analyses suggest that SGLT2i therapy is not cost-effective at current drug prices (incremental cost-effectiveness ratio ≥$120 000 per QALY gained).”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The effects of RASi, SGLT2i, and nsMRA on albuminuria are evident within weeks of initiation,40–42”
From 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome (2026) · cites this paper as [40]
Experimental — accuracy not yet measured
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Citations
Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
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2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab368 · Cited by 13,344
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KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease
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Self-citationDapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
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Self-citation
Research works printed but not linked: 1
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Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association
Ndumele, C. E., Rangaswami, J., Chow, S. L., Neeland, I. J., Tuttle, K. R., Khan, S. S., Coresh, J., Mathew, R. O., Baker-Smith, C. M., Carnethon, M. R., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001184 · Cited by 2,208
Self-citationDevelopment and validation of the American Heart Association’s PREVENT equations
Khan, S. S., Matsushita, K., Sang, Y., Ballew, S. H., Grams, M. E., Surapaneni, A., Blaha, M. J., Carson, A. P., Chang, A. R., Ciemins, E., et al. (2024) · Circulation · doi:10.1161/circulationaha.123.067626 · Cited by 1,234
Self-citationKhan, S. S., Coresh, J., Pencina, M. J., Ndumele, C. E., Rangaswami, J., Chow, S. L., Palaniappan, L. P., Sperling, L. S., Virani, S. S., Ho, J. E., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001191 · Cited by 797
Self-citationBadve, S. V., Bilal, A., Lee, M. M. Y., Sattar, N., Gerstein, H. C., Ruff, C. T., McMurray, J. J. V., Rossing, P., Bakris, G., Mahaffey, K. W., et al. (2025) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00271-7 · Cited by 359
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Self-citation
Metadata
- Authors
- Ndumele, C. E., Neeland, I. J., Tuttle, K. R., Chow, S. L., Mathew, R. O., Khan, S. S., Coresh, J., Baker-Smith, C. M., Carnethon, M. R., Després, J.-P., Ho, J. E., Joseph, J. J., Kernan, W. N., Khera, A., Kosiborod, M. N., Lekavich, C. L., Lewis, E. F., Lo, K. B., Ozkan, B., Palaniappan, L. P., Patel, S. S., Pencina, M. J., Powell-Wiley, T. M., Sperling, L. S., Virani, S. S., Wright, J. T., Rajgopal Singh, R., Elkind, M. S. V., Rangaswami, J., & on behalf of the American Heart Association
- ORCID
- Ndumele, Chiadi E.
- Neeland, Ian J.
- Tuttle, Katherine R.
- Chow, Sheryl L.
- Mathew, Roy O.
- Khan, Sadiya S.
- Coresh, Josef
- Baker-Smith, Carissa M.
- Carnethon, Mercedes R.
- Després, Jean-Pierre
- Ho, Jennifer E.
- Joseph, Joshua J.
- Kernan, Walter N.
- Khera, Amit
- Kosiborod, Mikhail N.
- Lekavich, Carolyn L.
- Lewis, Eldrin F.
- Lo, Kevin B.
- Palaniappan, Latha P.
- Patel, Sonali S.
- Pencina, Michael J.
- Sperling, Laurence S.
- Virani, Salim S.
- Wright, Jackson T.
- Elkind, Mitchell S.V.
- Rangaswami, Janani
- Venue
- Circulation
- Published
- 2023-11-14
- Volume
- 148
- Issue
- 20
- Pages
- 1636-1664
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W4387435427
- Semantic Scholar
- 6defeae42f8fd0ab65e2d773c4ac2548dcdcbb45
- Cited by
- 1,405
- References
- 208
- Citations by year
- 2026: 694 · 2025: 569 · 2024: 134 · 2023: 8
- FWCI
- 50.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- eCommons - AKU (Aga Khan University) (submittedVersion)
- Funders
- American Heart Association
- Public Health Agency of Canada
- National Heart, Lung, and Blood Institute (R01HL140224)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- cardiovascular-kidney-metabolic syndrome, chronic kidney disease, cardiovascular disease, obesity, diabetes mellitus, metabolic risk factors, cardiovascular risk, renal outcomes, prevention, screening, lifestyle modification, weight loss, cardioprotective therapy, social determinants of health, competing risks, multidisciplinary care
- MeSH terms
- American Heart Association, Cardiovascular Diseases, Humans, Kidney, Risk Factors, United States, Metabolic Syndrome, Renal Insufficiency, Chronic
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