School of Medicine Publications and Presentations

Document Type

Article

Publication Date

4-7-2023

Abstract

Background

A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern.

Methods

This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure < 130 mmHg, no antihypertensive drugs, waist-to-hip ratio < 0.95 for women or 1.03 for men, and the absence of diabetes. BMI categories included normal weight, overweight, and obesity (BMI < 25, 25–30, ≥ 30 kg/m2). Participants were classified into six subgroups according to BMI category and metabolic healthy status. Outcomes were fatal and nonfatal composited cardiovascular events.

Results

Of 2339 participants, the mean age was 51 years, 1161 (49.6%) were women, 434 (18.6%) had obesity, 117 (5.0%) were classified as MHO, and both cohorts had similar characteristics. Over a median of 9.2-year (3.7–13.0) follow-up, 245 cardiovascular events occurred. Compared to those with metabolically healthy normal weight, individuals with metabolic unhealthy status had a higher risk of cardiovascular events, regardless of BMI category (adjusted HR: 3.30 [95% CI: 1.73–6.28] for normal weight, 2.50 [95% CI: 1.34–4.66] for overweight, and 3.42 [95% CI: 1.81–6.44] for obesity), whereas those with MHO were not at increased risk of cardiovascular events (HR: 1.11 [95% CI: 0.36–3.45]). Factor analysis identified a metabolomic factor mainly associated with glucose regulation, which was associated with cardiovascular events (HR: 1.22 [95% CI: 1.10–1.36]). Individuals with MHO tended to present a higher metabolomic factor score than those with metabolically healthy normal weight (0.175 vs. -0.057, P = 0.019), and the score was comparable to metabolically unhealthy obesity (0.175 vs. -0.080, P = 0.91).

Conclusions

Individuals with MHO may not present higher short-term cardiovascular risk but tend to have a metabolomic pattern associated with higher cardiovascular risk, emphasizing a need for early intervention.

Comments

This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

CC0 applies for supplementary material related to this article and attribution is not required.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Cardiovascular Diabetology

DOI

10.1186/s12933-023-01815-6

Academic Level

faculty

Mentor/PI Department

Neuroscience

Included in

Cardiology Commons

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