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Updated: Oct 3, 2025

Author Spotlight: Assessing the Cardiovascular Profile of Patients with Metabolic Syndrome
Published on: September 27, 2024
Impaired Metabolic Health and Low Cardiorespiratory Fitness Independently Associate With Subclinical Atherosclerosis
Angela Lehn-Stefan1,2, Andreas Peter1,2,3, Jürgen Machann1,2,4
1Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich, 72076 Tübingen, Germany.
Insights
Impaired metabolic health and low cardiorespiratory fitness independently predict cardiovascular disease risk in obese individuals. Low fitness may explain increased risk in metabolically healthy obesity compared to normal weight individuals.
Area of Science:
- Cardiovascular disease research
- Metabolic health studies
- Fitness and health outcomes
Background:
- Metabolic health (MH) and cardiorespiratory fitness (CRF) are linked to cardiovascular disease (CVD) risk.
- The independent contributions of MH and CRF to CVD risk, and their interplay across different body mass index (BMI) categories, remain unclear.
Purpose of the Study:
- To investigate whether impaired MH and reduced CRF independently predict CVD risk.
- To examine if these relationships differ between normal weight, overweight, and obese individuals.
Main Methods:
- Analysis of data from 421 participants in the Tübingen Diabetes Family Study.
- Assessment of anthropometrics, metabolic parameters, maximal aerobic capacity (VO2max) for CRF, and carotid intima-media thickness (cIMT) as an atherosclerosis marker.
- Categorization of subjects into 6 phenotypes based on BMI and MH status.
Main Results:
- In obese subjects, older age, male sex, lower VO2max, and impaired MH were independent predictors of increased cIMT.
- Metabolically healthy obesity (MHO) was associated with higher cIMT than metabolically healthy normal weight (MHNW).
- This difference in cIMT between MHO and MHNW became non-significant after accounting for VO2max.
Conclusions:
- Impaired MH and low CRF are independent determinants of increased cIMT in obese individuals.
- Low CRF may partially explain the elevated CVD risk observed in MHO compared to MHNW individuals.
Context:
For a given body mass index (BMI), both impaired metabolic health (MH) and reduced cardiorespiratory fitness (CRF) associate with increased risk of cardiovascular disease (CVD).
Objective:
It remains unknown whether both risk phenotypes relate to CVD independently of each other, and whether these relationships differ in normal weight, overweight, and obese subjects.
Methods:
Data from 421 participants from the Tübingen Diabetes Family Study, who had measurements of anthropometrics, metabolic parameters, CRF (maximal aerobic capacity [VO2max]) and carotid intima-media thickness (cIMT), an early marker of atherosclerosis, were analyzed. Subjects were divided by BMI and MH status into 6 phenotypes.
Results:
In univariate analyses, older age, increased BMI, and a metabolic risk profile correlated positively, while insulin sensitivity and VO2max negatively with cIMT. In multivariable analyses in obese subjects, older age, male sex, lower VO2max (std. ß -0.21, P = 0.002) and impaired MH (std. ß 0.13, P = 0.02) were independent determinants of increased cIMT. After adjustment for age and sex, subjects with metabolically healthy obesity (MHO) had higher cIMT than subjects with metabolically healthy normal weight (MHNW; 0.59 ± 0.009 vs 0.52 ± 0.01 mm; P < 0.05). When VO2max was additionally included in this model, the difference in cIMT between MHO and MHNW groups became statistically nonsignificant (0.58 ± 0.009 vs 0.56 ± 0.02 mm; P > 0.05).
Conclusion:
These data suggest that impaired MH and low CRF independently determine increased cIMT in obese subjects and that low CRF may explain part of the increased CVD risk observed in MHO compared with MHNW.
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