Surrogate Adiposity Markers and Mortality

Area of Science:

• Epidemiology
• Public Health
• Genetics

Background:

• Body mass index (BMI) is a common measure of adiposity but has limitations in reflecting body composition and fat distribution.
• There is ongoing debate regarding the BMI threshold associated with the lowest mortality risk.

Purpose of the Study:

• To determine whether waist-to-hip ratio (WHR), fat mass index (FMI), or BMI has the most robust association with mortality.
• To compare the consistency of these adiposity measures in predicting mortality risk.

Main Methods:

• Utilized UK Biobank data (N=387,672) for observational and Mendelian randomization (MR) analyses.
• Included discovery and validation cohorts with incident deaths analyzed for all-cause and cause-specific mortality.
• Assessed associations between measured and genetically determined BMI, FMI, and WHR with mortality outcomes.

Main Results:

• Waist-to-hip ratio (WHR) demonstrated a linear association with all-cause mortality, while BMI and FMI showed J-shaped associations.
• Genetically determined WHR had a stronger association with all-cause mortality than genetically determined BMI.
• The association between genetically determined WHR and mortality was consistent regardless of measured BMI, and stronger in males.

Conclusions:

• Waist-to-hip ratio (WHR) is a superior predictor of mortality compared to BMI and FMI, showing the strongest and most consistent association.
• Clinical guidelines should prioritize assessing adiposity distribution (like WHR) over simple measures of adiposity mass (like BMI).
• These findings highlight the importance of fat distribution in understanding mortality risk.