Re: Cardiovascular-kidney-metabolic syndrome.. cell metabolism 2023!!

[문형철]

CommentaryVolume 35, Issue 12p2104-2106December 05, 2023Open Archive

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Cardiovascular-kidney-metabolic syndrome: A step toward multidisciplinary and inclusive care

Sophie E. Claudel1 ∙ Ashish Verma2 ashverma@bu.edu

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Abstract

In a recent Presidential Advisory report, the American Heart Association (AHA) defined cardiovascular-kidney-metabolic (CKM) syndrome as a spectrum of pathology associated with dysfunctional or excess adiposity and leading to adverse cardiovascular outcomes. Implementing the guidelines set forth by the AHA has the potential to improve population-wide CKM health.

초록

최근 미국심장협회(AHA)의 대통령 자문 보고서에서

심혈관-신장-대사(CKM) 증후군은

기능 장애 또는 과도한 지방증과 관련된 병리 스펙트럼으로,

심혈관 질환으로 이어질 수 있다고 정의되었습니다.

AHA가 제시한 지침을 구현하면

전 인구의 CKM 건강을 개선할 잠재력이 있습니다.

Main textIntroduction

The American Heart Association (AHA) recently released a Presidential Advisory statement identifying cardiovascular-kidney-metabolic (CKM) syndrome as a spectrum of disease states associated with dysfunctional or excess adiposity.1 The report’s comprehensive eval‎uation of CKM health and focus on integrated disease models represent a needed addition to clinical guidelines in the era of precision medicine and disease-modifying therapeutics. The report is landmark in its recommendation to integrate CKM care in early childhood with an emphasis on screening, prevention, and early intervention that calls attention to social determinants of health (SDOHs) (Figure 1).

본문 서론

미국심장협회(AHA)는 최근 대통령 자문 성명에서

심혈관-신장-대사(CKM) 증후군을

기능 장애 또는 과도한 지방증과 관련된 질환 스펙트럼으로 규정했습니다.1

cardiovascular-kidney-metabolic (CKM) syndrome as a

spectrum of disease states associated with dysfunctional or excess adiposity

이 보고서의 CKM 건강에 대한 포괄적 평가와 통합 질환 모델에 대한 초점은

정밀 의학 시대와 질환 수정 치료제 시대에 필요한 임상 지침의 추가입니다.

이 보고서는

사회적 건강 결정 요인(SDOHs)에 주의를 기울이며,

유아기부터 CKM 치료를 통합하여 선별, 예방, 조기 개입을 강조하는 획기적 내용입니다

Figure 1 Conceptual framework of the clinical trajectory outlined by the AHA Presidential Advisory on cardiovascular-kidney-metabolic health

Show full captionFigure viewer

There are several foundational concepts discussed in the AHA statement.

(1)

CKM syndrome is a progressive, multiorgan disease state that exists on a spectrum.

(2)

Excess or dysfunctional adiposity is hypothesized to be the underpinning of CKM syndrome, and improving integrated obesity care is foundational to preventing progressive CKM disease.

(3)

Risk for CKM syndrome begins with early-life exposures and is exacerbated by adverse SDOHs across the lifespan.

(4)

Regular screenings for albuminuria and impaired kidney function are central elements to predicting incident cardiovascular disease (CVD) in patients with stage 2 CKM and beyond.

(5)

Newer medications that directly target and treat CKM syndrome must be disseminated equitably, with an emphasis on implementation in populations at highest risk for disease progression.

AHA 성명서에서 논의된 몇 가지 기본 개념이 있습니다.

(1) CKM 증후군은 점진적이고 다기관 질환 상태로, 스펙트럼으로 존재합니다.

(2) 과도하거나 기능 장애 지방증이 CKM 증후군의 기저 원인으로 가정되며, 통합 비만 치료 개선이 CKM 질환 진행을 방지하는 데 기본적입니다.

(3) CKM 증후군 위험은 유아기 노출부터 시작되며, 일생 동안 불리한 SDOHs에 의해 악화됩니다.

(4) 알부민뇨와 신장 기능 장애에 대한 정기 선별은 2단계 CKM 이상 환자에서 발병 심혈관 질환(CVD)을 예측하는 핵심 요소입니다.

(5) CKM 증후군을 직접 표적으로 하는 새로운 약물은 공평하게 보급되어야 하며, 질환 진행 위험이 가장 높은 인구에 중점을 둡니다.

Identification and treatment of CKM syndrome

A hallmark feature of the AHA report is the emphasis on viewing CKM syndrome as a systemic, progressive pathophysiological process. The panel proposes an age-based screening approach that centers on identifying early markers of overweight/obesity, elevated blood pressure, dyslipidemia, and dysglycemia. In higher-risk adults with stage 2 CKM and beyond, the authors specify graded screening for albuminuria, impaired kidney function, coronary artery calcium deposition, serologic cardiac biomarkers, and echocardiography. The guideline further defines a four-stage grading system for diagnosing CKM syndrome that ultimately converges on clinical CVD (Table 1). In the model proposed by the AHA, the primary driver of CKM syndrome is excessive or dysfunctional adiposity. This view is supported by decades of research on the role of visceral fat distribution and dynamic relationships between adiposity and vascular dysfunction.2,3

CKM 증후군의 식별과 치료

AHA 보고서의 특징적인 점은 CKM 증후군을 체계적이고 점진적인 병태생리 과정으로 보는 강조입니다.

패널은 연령 기반 선별 접근을 제안하며,

과체중/비만, 고혈압, 이상지질혈증, 이상혈당증의 초기 마커 식별에 중점을 둡니다.

2단계 CKM 이상 고위험 성인에서는 알부민뇨, 신장 기능 장애, 관상동맥 칼슘 침착, 혈청 심장 바이오마커, 심초음파 검사를 위한 등급별 선별을 지정합니다.

지침은 CKM 증후군 진단을 위한 4단계 등급 시스템을 정의하며, 이는 결국 임상 CVD로 수렴됩니다(표 1). AHA가 제안한 모델에서 CKM 증후군의 주요 원인은 과도하거나 기능 장애 지방증입니다. 이는 내장 지방 분포와 지방증과 혈관 기능 장애 간의 동적 관계에 대한 수십 년의 연구에 의해 뒷받침됩니다.2,3

CKM stageStage definitionRecommended screening for adultsa

Stage 0: no CKM risk factors	normal BMI and waist circumference	• screening for SDOHs • BMI and waist circumference: annually • HbA1c or fasting blood glucose: every 3–5 years
	Normoglycemia
	Normotension
	normal lipid profile
	no evidence of CKD or subclinical or clinical CVD
Stage 1: excess or dysfunctional adiposity	presence of overweight/obesity, abdominal obesity, or dysfunctional adipose tissue without metabolic risk factors or CKD	as for stage 0, except:• HbA1c or fasting blood glucose: every 2–3 years
Stage 2: metabolic risk factors and CKD	metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, and diabetes) or CKD	as for stage 1, with additional:• screening for liver fibrosis: every 1–2 years • UACR and serum creatinine or cystatin C: annually • consideration of CAC and HF screeningb
Stage 3: subclinical CVD in CKM	subclinical ASCVD or subclinical HF in the setting of excess or dysfunctional adiposity, other metabolic risk factors, or CKD	as for stage 3, except:• more frequent UACR and kidney function measurement in those with higher KDIGO risk • individualized CAC and HF screening
Stage 4: clinical CVD in CKM	clinical CVD (including coronary heart disease, HF, stroke, peripheral artery disease, and atrial fibrillation) in the setting of excess or dysfunctional adiposity, other metabolic risk factors, or CKD:• stage 4a: without kidney failure • stage 4b: with kidney failure	as for stage 4 CKM

Table 1

Stages of CKM syndrome

Adapted from Tables 1 and 3 of Ndumele et al.1 ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcification; CKD, chronic kidney disease; CKM, cardiovascular-kidney-metabolic; CVD, cardiovascular disease; HbA1c, hemoglobin A1c; HF, heart failure; KDIGO, Kidney Disease Improving Global Outcomes; SDOHs, social determinants of health; UACR, urinary albumin-to-creatinine ratio.

a

Guidelines vary for individuals less than 21 years of age

b

Guidelines for CAC screening and screening echocardiography are not yet defined

• Open table in a new tab

As a result, proposed treatment of CKM syndrome is centered on reducing overweight or obesity and adoption of agents such as angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), sodium-glucose co-transporter 2 inhibitors (SGLT2is), glucagon-like peptide receptor agonists (GLP1-RAs), and mineralocorticoid receptor antagonists (MRAs).4 Given the bidirectional relationships between cardiovascular, kidney, and metabolic diseases, the AHA Presidential Advisory report outlines several algorithms for selecting newer CKM therapeutic agents based on underlying comorbidities.1 The selective approach is based on data demonstrating improved CKM outcomes (e.g., the recommendation for prioritized use of SGLT2is in proteinuric kidney disease or heart failure)4 and, likely, the logistical and financial barriers to recommending widespread adoption of GLP1-RAs or bariatric surgery for adults with overweight or obesity.5

A systematic approach to addressing social, environmental, and economic determinants of health

The CKM health framework not only addresses the metabolic underpinnings of disease but additionally expands the clinician’s role in eval‎uating exposure to adverse SDOHs across the lifespan. The AHA statement provides detailed references for validated screening tools to assess both individual and community-level SDOHs.1 Equally relevant to the discussion of prevention are environmental and economic determinants of health. Environmental determinants include exposure to crime, hazardous pollutants, climate change microenvironments (such as urban heat islands), and other neighborhood-level factors that drive inflammatory and oxidative stress pathways leading to poor CKM health.6 Economic determinants of health affect an individual’s ability to engage in the recommended AHA Life’s Essential 8 preventative measures,7 as well as access subspecialty care and disease-modifying therapies that could slow disease progression.5,6

Implementation of integrated CKM care models

Lack of clinician familiarity with newer CKM therapies, particularly in individuals with kidney disease, results in siloing of care and adverse CKM outcomes.8 The focus on economic incentives for interdisciplinary care and reimbursement reform to facilitate integrated cardio-renal-metabolic care clinics may alleviate some of these factors. The authors appropriately highlight that validated implementation of science approaches is needed to collaboratively and cooperatively treat these metabolic and kidney diseases known to increase risk of CVD. What is less clear from this Presidential Advisory is how to reach the idealized CKM care model within the current landscape of health economics and healthcare delivery systems.

Conclusions

The AHA Presidential Advisory outlines a comprehensive conceptual model of CKM health and advocates for integrated, multidisciplinary care of patients at risk for developing adverse CKM outcomes. The authors emphasize the role of adverse SDOHs in driving intergenerational cycles of poor CKM health, as well as advocate for clinician involvement in SDOH screening. The AHA report challenges a broad community of clinicians and public health professionals to improve treatment of a large population of patients with CKM syndrome and risk for poor CVD outcomes. The goals outlined by the authors are well intentioned and far reaching. Equitably and effectively implementing optimal CKM care in the current healthcare landscape will require concerted, collaborative efforts from policy makers, healthcare leaders, pharmacists, public health innovators, and clinician advocates to advance CKM health.

Acknowledgments

Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R38HL143584 (S.E.C.).

Declaration of interests

The authors declare no competing interests.

References

1.

Ndumele, C.E. ∙ Rangaswami, J. ∙ Chow, S.L. ...

Cardiovascular-kidney-metabolic health: a Presidential Advisory from the American Heart Association

Circulation. 2023;

Crossref

Scopus (103)

Google Scholar

2.

Koenen, M. ∙ Hill, M.A. ∙ Cohen, P. ...

Obesity, adipose tissue and vascular dysfunction

Circ. Res. 2021; 128:951-968

Crossref

Scopus (292)

PubMed

Google Scholar

3.

Jia, G. ∙ Aroor, A.R. ∙ Sowers, J.R.

The role of mineralocorticoid receptor signaling in the cross-talk between adipose tissue and the vascular wall

Cardiovasc. Res. 2017; 113:1055-1063

Crossref

Scopus (49)

PubMed

Google Scholar

4.

Morales, J. ∙ Handelsman, Y.

Cardiovascular outcomes in patients with diabetes and kidney disease: JACC review topic of the week

J. Am. Coll. Cardiol. 2023; 82:161-170

Crossref

Scopus (18)

PubMed

Google Scholar

5.

Karagiannis, T. ∙ Bekiari, E. ∙ Tsapas, A.

Socioeconomic aspects of incretin-based therapy

Diabetologia. 2023; 66:1859-1868

Crossref

Scopus (16)

PubMed

Google Scholar

6.

Powell-Wiley, T.M. ∙ Baumer, Y. ∙ Baah, F.O. ...

Social determinants of cardiovascular disease

Circ. Res. 2022; 130:782-799

Crossref

Scopus (263)

PubMed

Google Scholar

7.

Lloyd-Jones, D.M. ∙ Allen, N.B. ∙ Anderson, C.A.M. ...

Life’s essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a Presidential Advisory from the American Heart Association

Circulation. 2022; 146:E18-E43

Crossref

Scopus (777)

PubMed

Google Scholar

8.

Rangaswami, J. ∙ Tuttle, K. ∙ Vaduganathan, M.

Cardio-renal-metabolic care models: toward achieving effective interdisciplinary care

Circ. Cardiovasc. Qual. Outcomes. 2020; 13:e007264

Crossref

Scopus (38)

PubMed

Google Scholar

CommentaryVolume 35, Issue 12p2104-2106December 05, 2023Open Archive

Download Full Issue

Cardiovascular-kidney-metabolic syndrome: A step toward multidisciplinary and inclusive care

Sophie E. Claudel1 ∙ Ashish Verma2 ashverma@bu.edu

Affiliations & NotesArticle Info

• Download PDF
• Cite
•  
• Set Alert
• Get Rights
• Reprints

Download Full Issue

Previous articleNext article

Show Outline

Abstract

In a recent Presidential Advisory report, the American Heart Association (AHA) defined cardiovascular-kidney-metabolic (CKM) syndrome as a spectrum of pathology associated with dysfunctional or excess adiposity and leading to adverse cardiovascular outcomes. Implementing the guidelines set forth by the AHA has the potential to improve population-wide CKM health.

Main textIntroduction

The American Heart Association (AHA) recently released a Presidential Advisory statement identifying cardiovascular-kidney-metabolic (CKM) syndrome as a spectrum of disease states associated with dysfunctional or excess adiposity.1 The report’s comprehensive eval‎uation of CKM health and focus on integrated disease models represent a needed addition to clinical guidelines in the era of precision medicine and disease-modifying therapeutics. The report is landmark in its recommendation to integrate CKM care in early childhood with an emphasis on screening, prevention, and early intervention that calls attention to social determinants of health (SDOHs) (Figure 1).

Figure 1 Conceptual framework of the clinical trajectory outlined by the AHA Presidential Advisory on cardiovascular-kidney-metabolic health

Show full captionFigure viewer

There are several foundational concepts discussed in the AHA statement.

(1)

CKM syndrome is a progressive, multiorgan disease state that exists on a spectrum.

(2)

Excess or dysfunctional adiposity is hypothesized to be the underpinning of CKM syndrome, and improving integrated obesity care is foundational to preventing progressive CKM disease.

(3)

Risk for CKM syndrome begins with early-life exposures and is exacerbated by adverse SDOHs across the lifespan.

(4)

Regular screenings for albuminuria and impaired kidney function are central elements to predicting incident cardiovascular disease (CVD) in patients with stage 2 CKM and beyond.

(5)

Newer medications that directly target and treat CKM syndrome must be disseminated equitably, with an emphasis on implementation in populations at highest risk for disease progression.

Identification and treatment of CKM syndrome

A hallmark feature of the AHA report is the emphasis on viewing CKM syndrome as a systemic, progressive pathophysiological process. The panel proposes an age-based screening approach that centers on identifying early markers of overweight/obesity, elevated blood pressure, dyslipidemia, and dysglycemia. In higher-risk adults with stage 2 CKM and beyond, the authors specify graded screening for albuminuria, impaired kidney function, coronary artery calcium deposition, serologic cardiac biomarkers, and echocardiography. The guideline further defines a four-stage grading system for diagnosing CKM syndrome that ultimately converges on clinical CVD (Table 1). In the model proposed by the AHA, the primary driver of CKM syndrome is excessive or dysfunctional adiposity. This view is supported by decades of research on the role of visceral fat distribution and dynamic relationships between adiposity and vascular dysfunction.2,3

CKM stageStage definitionRecommended screening for adultsa

Stage 0: no CKM risk factors	normal BMI and waist circumference	• screening for SDOHs • BMI and waist circumference: annually • HbA1c or fasting blood glucose: every 3–5 years
	Normoglycemia
	Normotension
	normal lipid profile
	no evidence of CKD or subclinical or clinical CVD
Stage 1: excess or dysfunctional adiposity	presence of overweight/obesity, abdominal obesity, or dysfunctional adipose tissue without metabolic risk factors or CKD	as for stage 0, except:• HbA1c or fasting blood glucose: every 2–3 years
Stage 2: metabolic risk factors and CKD	metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, and diabetes) or CKD	as for stage 1, with additional:• screening for liver fibrosis: every 1–2 years • UACR and serum creatinine or cystatin C: annually • consideration of CAC and HF screeningb
Stage 3: subclinical CVD in CKM	subclinical ASCVD or subclinical HF in the setting of excess or dysfunctional adiposity, other metabolic risk factors, or CKD	as for stage 3, except:• more frequent UACR and kidney function measurement in those with higher KDIGO risk • individualized CAC and HF screening
Stage 4: clinical CVD in CKM	clinical CVD (including coronary heart disease, HF, stroke, peripheral artery disease, and atrial fibrillation) in the setting of excess or dysfunctional adiposity, other metabolic risk factors, or CKD:• stage 4a: without kidney failure • stage 4b: with kidney failure	as for stage 4 CKM

Table 1

Stages of CKM syndrome

Adapted from Tables 1 and 3 of Ndumele et al.1 ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcification; CKD, chronic kidney disease; CKM, cardiovascular-kidney-metabolic; CVD, cardiovascular disease; HbA1c, hemoglobin A1c; HF, heart failure; KDIGO, Kidney Disease Improving Global Outcomes; SDOHs, social determinants of health; UACR, urinary albumin-to-creatinine ratio.

a

Guidelines vary for individuals less than 21 years of age

b

Guidelines for CAC screening and screening echocardiography are not yet defined

• Open table in a new tab

As a result, proposed treatment of CKM syndrome is centered on reducing overweight or obesity and adoption of agents such as angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), sodium-glucose co-transporter 2 inhibitors (SGLT2is), glucagon-like peptide receptor agonists (GLP1-RAs), and mineralocorticoid receptor antagonists (MRAs).4 Given the bidirectional relationships between cardiovascular, kidney, and metabolic diseases, the AHA Presidential Advisory report outlines several algorithms for selecting newer CKM therapeutic agents based on underlying comorbidities.1 The selective approach is based on data demonstrating improved CKM outcomes (e.g., the recommendation for prioritized use of SGLT2is in proteinuric kidney disease or heart failure)4 and, likely, the logistical and financial barriers to recommending widespread adoption of GLP1-RAs or bariatric surgery for adults with overweight or obesity.5

A systematic approach to addressing social, environmental, and economic determinants of health

The CKM health framework not only addresses the metabolic underpinnings of disease but additionally expands the clinician’s role in eval‎uating exposure to adverse SDOHs across the lifespan. The AHA statement provides detailed references for validated screening tools to assess both individual and community-level SDOHs.1 Equally relevant to the discussion of prevention are environmental and economic determinants of health. Environmental determinants include exposure to crime, hazardous pollutants, climate change microenvironments (such as urban heat islands), and other neighborhood-level factors that drive inflammatory and oxidative stress pathways leading to poor CKM health.6 Economic determinants of health affect an individual’s ability to engage in the recommended AHA Life’s Essential 8 preventative measures,7 as well as access subspecialty care and disease-modifying therapies that could slow disease progression.5,6

Implementation of integrated CKM care models

Lack of clinician familiarity with newer CKM therapies, particularly in individuals with kidney disease, results in siloing of care and adverse CKM outcomes.8 The focus on economic incentives for interdisciplinary care and reimbursement reform to facilitate integrated cardio-renal-metabolic care clinics may alleviate some of these factors. The authors appropriately highlight that validated implementation of science approaches is needed to collaboratively and cooperatively treat these metabolic and kidney diseases known to increase risk of CVD. What is less clear from this Presidential Advisory is how to reach the idealized CKM care model within the current landscape of health economics and healthcare delivery systems.

Conclusions

The AHA Presidential Advisory outlines a comprehensive conceptual model of CKM health and advocates for integrated, multidisciplinary care of patients at risk for developing adverse CKM outcomes. The authors emphasize the role of adverse SDOHs in driving intergenerational cycles of poor CKM health, as well as advocate for clinician involvement in SDOH screening. The AHA report challenges a broad community of clinicians and public health professionals to improve treatment of a large population of patients with CKM syndrome and risk for poor CVD outcomes. The goals outlined by the authors are well intentioned and far reaching. Equitably and effectively implementing optimal CKM care in the current healthcare landscape will require concerted, collaborative efforts from policy makers, healthcare leaders, pharmacists, public health innovators, and clinician advocates to advance CKM health.

Acknowledgments

Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R38HL143584 (S.E.C.).

Declaration of interests

The authors declare no competing interests.

References

1.

Ndumele, C.E. ∙ Rangaswami, J. ∙ Chow, S.L. ...

Cardiovascular-kidney-metabolic health: a Presidential Advisory from the American Heart Association

Circulation. 2023;

Crossref

Scopus (103)

Google Scholar

2.

Koenen, M. ∙ Hill, M.A. ∙ Cohen, P. ...

Obesity, adipose tissue and vascular dysfunction

Circ. Res. 2021; 128:951-968

Crossref

Scopus (292)

PubMed

Google Scholar

3.

Jia, G. ∙ Aroor, A.R. ∙ Sowers, J.R.

The role of mineralocorticoid receptor signaling in the cross-talk between adipose tissue and the vascular wall

Cardiovasc. Res. 2017; 113:1055-1063

Crossref

Scopus (49)

PubMed

Google Scholar

4.

Morales, J. ∙ Handelsman, Y.

Cardiovascular outcomes in patients with diabetes and kidney disease: JACC review topic of the week

J. Am. Coll. Cardiol. 2023; 82:161-170

Crossref

Scopus (18)

PubMed

Google Scholar

5.

Karagiannis, T. ∙ Bekiari, E. ∙ Tsapas, A.

Socioeconomic aspects of incretin-based therapy

Diabetologia. 2023; 66:1859-1868

Crossref

Scopus (16)

PubMed

Google Scholar

6.

Powell-Wiley, T.M. ∙ Baumer, Y. ∙ Baah, F.O. ...

Social determinants of cardiovascular disease

Circ. Res. 2022; 130:782-799

Crossref

Scopus (263)

PubMed

Google Scholar

7.

Lloyd-Jones, D.M. ∙ Allen, N.B. ∙ Anderson, C.A.M. ...

Life’s essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a Presidential Advisory from the American Heart Association

Circulation. 2022; 146:E18-E43

Crossref

Scopus (777)

PubMed

Google Scholar

8.

Rangaswami, J. ∙ Tuttle, K. ∙ Vaduganathan, M.

Cardio-renal-metabolic care models: toward achieving effective interdisciplinary care

Circ. Cardiovasc. Qual. Outcomes. 2020; 13:e007264

Crossref

Scopus (38)

PubMed

Google Scholar