Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers
Open accessAbstract
A new cardiometabolic-based chronic disease (CMBCD) model is presented that provides a basis for early and sustainable, evidence-based therapeutic targeting to promote cardiometabolic health and mitigate the development and ravages of cardiovascular disease. In the first part of this JACC State-of-the-Art Review, a framework is presented for CMBCD, focusing on 3 primary drivers (genetics, environment, and behavior) and 2 metabolic drivers (adiposity and dysglycemia) with applications to 3 cardiovascular endpoints (coronary heart disease, heart failure, and atrial fibrillation). Specific mechanistic pathways are presented configuring early primary drivers with subsequent adiposity, insulin resistance, β-cell dysfunction, and metabolic syndrome, leading to cardiovascular disease. The context for building this CMBCD model is to expose actionable targets for prevention to achieve optimal cardiovascular outcomes. The tactical implementation of this CMBCD model is the subject of second part of this JACC State-of-the-Art Review.
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Obesity can exacerbate insulin resistance, which worsens low-grade chronic inflammation, dyslipidaemia, and hypertension, placing people with obesity at increased risk of developing cardiovascular disease and type 2 diabetes.
“Obesity can exacerbate insulin resistance, which further worsens low-grade chronic inflammation, dyslipidaemia, and hypertension, thus placing people with obesity at increased risk of developing cardiovascular disease and type 2 diabetes.1”
Low muscle mass is often unrecognized and is independently associated with increased risk of mortality and morbidity, reduced quality of life, increased risk of type 2 diabetes, and other adverse health outcomes.
“Low muscle mass is often unrecognized and is independently associated with increased risk of mortality and morbidity, reduced quality of life, increased risk of T2D, and other adverse health outcomes.”
From Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity (2025) · cites this paper as [8]
The Adiposity-Based Chronic Disease section discusses adiposity and insulin resistance, not the consequences of low muscle mass. A References entry mentions skeletal muscle mass in a study of cardiac structure and function, but our copy does not address whether low muscle mass is often unrecognized or independently associated with the listed outcomes (searched: low muscle mass, sarcopenia, quality of life). (LLM, conf=0.76)
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References 183 · Cited by 243
- Authors
- Mechanick, J. I., Farkouh, M. E., Newman, J. D., & Garvey, W. T.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University of Toronto (CA)
- NYU Langone Health (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Mechanick, Jeffrey I.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 75
- Issue
- 5
- Pages
- 525-538
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC7187687
- OpenAlex
- W3004369106
- Cited by
- 243
- References
- 183
- Citations by year
- 2026: 43 · 2025: 45 · 2024: 32 · 2023: 40 · 2022: 33 · 2021: 29 · 2020: 21
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Amgen
- Gilead Sciences
- Pfizer
- American Medical Association
- AstraZeneca
- University of Alabama
- Merck
- Novo Nordisk
- Boehringer Ingelheim
- Sanofi
- Novartis
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- cardiometabolic health, adiposity, dysglycemia, insulin resistance, beta-cell dysfunction, metabolic syndrome, coronary artery disease, heart failure, atrial fibrillation, cardiovascular disease prevention, genetic and environmental risk factors, therapeutic targeting
- MeSH terms
- Cardiovascular Diseases, Chronic Disease, Humans, Glucose Metabolism Disorders, Adiposity
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