Incident cardiovascular disease events in metabolically benign obese individuals
Alexandra D Ogorodnikova1, Mimi Kim, Aileen P McGinn
1Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Insights
Metabolically benign obesity may lower cardiovascular disease (CVD) risk, but definitions vary. Different criteria identify distinct obese subgroups, impacting CVD risk assessment and understanding of obesity
Area of Science:
- Cardiology
- Metabolic Health
- Obesity Research
Background:
- Obesity is a major risk factor for cardiovascular disease (CVD).
- A subset of obese individuals, termed 'metabolically benign,' may have a lower CVD risk, but this remains debated.
- Current definitions for metabolically benign obesity are inconsistent.
Purpose of the Study:
- To assess incident CVD risk in metabolically benign obese individuals using three distinct definitions.
- To compare the CVD risk of metabolically benign obese individuals to at-risk obese individuals and metabolically benign normal-weight individuals.
- To evaluate the overlap and differences between various definitions of metabolically benign obesity.
Main Methods:
- Pooled data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies were analyzed.
- Incident CVD (coronary heart disease and stroke) was assessed over an average follow-up of 11.8 years.
- Three definitions of metabolically benign phenotype were used: ATP-III, expanded ATP-III, and insulin resistance (IR)-based.
Main Results:
- Approximately 18-27% of obese participants met criteria for metabolically benign status across the three definitions.
- Metabolically benign obese individuals showed significantly lower CVD incidence compared to at-risk obese individuals (HRs 0.52-0.71).
- However, metabolically benign obese individuals had similar or slightly higher CVD risk compared to metabolically benign normal-weight individuals (HRs 1.16-1.28).
- Only 28.7% of individuals classified as metabolically benign by any definition met all three criteria, indicating substantial definitional heterogeneity.
Conclusions:
- While metabolically benign obesity appears associated with reduced CVD risk compared to at-risk obesity, the specific subgroup identified varies significantly by definition.
- The lack of consensus in defining metabolically benign obesity highlights potential differences in underlying pathophysiological mechanisms.
- Further research is needed to standardize definitions and elucidate the distinct etiologies within metabolically benign obese populations.
Abstract:
Nearly one-third of obese individuals are classified as metabolically benign; however whether this subgroup is at a lower risk of cardiovascular disease (CVD) is unclear. Using pooled data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies, we assessed incident CVD (coronary heart disease and stroke) using three definitions of the metabolically benign phenotype: (i) the ATP-III metabolic syndrome definition (≤2 of the ATP-III components, excluding abdominal obesity (ii) the expanded ATP-III definition (≤1 of: any ATP-III components, insulin resistance (IR), or systemic inflammation), and (iii) the IR-based definition (sex-specific lowest quartile of the HOMA(IR) distribution). The sample included 6,106 normal weight, 7,115 overweight, and 4,323 obese participants. Among obese, 27.0%, 18.1%, and 20.4% were metabolically benign by the three definitions, respectively. The CVD incidence rates (mean follow-up 11.8 years) were 7.1, 5.8, and 8.4 per 1,000 person-years in metabolically benign obese via the three definitions, respectively, compared to 14.3, 13.8, and 13.3 in at-risk obese, and 7.5, 6.7, and 8.2 in metabolically benign normal weight participants. Multivariable-adjusted hazard ratios of incident CVD in metabolically benign obese compared to their at-risk obese counterparts were 0.59 (95% CI 0.47-0.73), 0.52 (0.39-0.68), and 0.71 (0.57-0.90), respectively; and 1.24 (0.99-1.57), 1.16 (0.86-1.56), and 1.28 (1.01-1.62) compared to metabolically benign normal weight individuals. Only 28.7% of obese participants classified as metabolically benign by at least one definition were "metabolically benign" by all three definitions. Despite similar CVD risk estimates, the three definitions identified different subgroups of the obese population, perhaps suggesting distinct etiologies.
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