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Updated: Sep 27, 2025
Author Spotlight: Assessing the Cardiovascular Profile of Patients with Metabolic Syndrome
Published on: September 27, 2024
Different Metabolic Phenotypes of Obesity and Risk of Coronary Artery Calcium Progression and Incident Cardiovascular
Jing-Wei Gao1, Si You1, Zhao-Yu Liu2
1Department of Cardiology (J.-W.G., S.Y., Q.-Y.H., J.-F.W., P.-M.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Insights
Metabolically healthy obesity (MHO) increases the risk of coronary artery calcium (CAC) progression. Many with MHO develop unhealthy metabolic profiles, highlighting distinct obesity risks for cardiovascular disease events.
Area of Science:
- Cardiovascular disease research
- Obesity and metabolic health studies
- Public health and preventative medicine
Background:
- Obesity is a growing public health concern.
- Metabolic syndrome is a cluster of conditions that increase the risk of heart disease, stroke, and diabetes.
- Understanding the long-term cardiovascular implications of different obesity phenotypes is crucial for preventative strategies.
Purpose of the Study:
- To determine if obesity, with or without metabolic syndrome, is associated with the progression of coronary artery calcium (CAC).
- To investigate the prospective association between obesity phenotypes and the occurrence of cardiovascular disease events.
- To analyze the distinct risks posed by different metabolic phenotypes of obesity starting in young adulthood.
Main Methods:
- Utilized data from 1730 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
- Assessed coronary artery calcium (CAC) progression using computed tomography at baseline (year 15) and follow-up (year 20 or 25).
- Defined metabolically healthy obesity (MHO) as a body mass index ≥30 kg/m² without metabolic syndrome components, with sensitivity analyses for various metabolic phenotypes.
Main Results:
- Over 9.1 years of follow-up, 439 participants showed CAC progression.
- Metabolically healthy obesity (MHO) was linked to a significantly higher risk of CAC progression compared to metabolically healthy normal weight individuals.
- Obesity with an unhealthy metabolic profile consistently showed the highest risk for CAC progression and cardiovascular disease events; up to 60% of MHO participants transitioned to metabolically unhealthy obesity.
Conclusions:
- Different metabolic obesity phenotypes emerging in young adulthood have varying risks for CAC progression and cardiovascular disease events later in life.
- Metabolically healthy obesity (MHO) is an intermediate phenotype, carrying distinct risks compared to both metabolically healthy normal weight and metabolically unhealthy obese individuals.
- Longitudinal tracking of metabolic health in obese individuals is essential for accurate cardiovascular risk assessment.
Background:
To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events.
Methods:
A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes.
Results:
During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369-2.264] to 2.047 [1.380-3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout.
Conclusions:
Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals.
Registration:
URL: https://www.
Clinicaltrials:
gov; Unique identifier: NCT00005130.
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