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. 2023 Sep 5;6(9):e2334836.
doi: 10.1001/jamanetworkopen.2023.34836.

Surrogate Adiposity Markers and Mortality

Irfan Khan  1   2   3   4   5 , Michael Chong  1   2   3 , Ann Le  1   2   3 , Pedrum Mohammadi-Shemirani  1   2   3 , Robert Morton  1   2   3 , Christina Brinza  1   2   3   6 , Michel Kiflen  1   2   3   7 , Sukrit Narula  1   2   3   4   8 , Loubna Akhabir  1   2   3 , Shihong Mao  1   2   3 , Katherine Morrison  1   9   10 , Marie Pigeyre  1   2   3 , Guillaume Paré  1   2   3   4
Affiliations

Surrogate Adiposity Markers and Mortality

Irfan Khan et al. JAMA Netw Open. .

Erratum in

  • Error in Methods.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Feb 3;8(2):e250472. doi: 10.1001/jamanetworkopen.2025.0472. JAMA Netw Open. 2025. PMID: 39903470 Free PMC article. No abstract available.

Abstract

Importance: Body mass index (BMI) is an easily obtained adiposity surrogate. However, there is variability in body composition and adipose tissue distribution between individuals with the same BMI, and there is controversy regarding the BMI associated with the lowest mortality risk.

Objective: To evaluate which of BMI, fat mass index (FMI), and waist-to-hip (WHR) has the strongest and most consistent association with mortality.

Design, setting, and participant: This cohort study used incident deaths from the UK Biobank (UKB; 2006-2022), which includes data from 22 clinical assessment centers across the United Kingdom. UKB British participants of British White ancestry (N = 387 672) were partitioned into a discovery cohort (n = 337 078) and validation cohort (n = 50 594), with the latter consisting of 25 297 deaths and 25 297 controls. The discovery cohort was used to derive genetically determined adiposity measures while the validation cohort was used for analyses. Exposure-outcome associations were analyzed through observational and mendelian randomization (MR) analyses.

Exposures: BMI, FMI, and WHR.

Main outcomes and measures: All-cause and cause-specific (cancer, cardiovascular disease [CVD], respiratory disease, or other causes) mortality.

Results: There were 387 672 and 50 594 participants in our observational (mean [SD] age, 56.9 [8.0] years; 177 340 [45.9%] male, 210 332 [54.2%], female), and MR (mean [SD] age, 61.6 [6.2] years; 30 031 [59.3%] male, 20 563 [40.6%], female) analyses, respectively. Associations between measured BMI and FMI with all-cause mortality were J-shaped, whereas the association of WHR with all-cause mortality was linear using the hazard ratio (HR) scale (HR per SD increase of WHR, 1.41 [95% CI, 1.38-1.43]). Genetically determined WHR had a stronger association with all-cause mortality than BMI (odds ratio [OR] per SD increase of WHR, 1.51 [95% CI, 1.32-1.72]; OR per SD increase of BMI, 1.29 [95% CI, 1.20-1.38]; P for heterogeneity = .02). This association was stronger in male than female participants (OR, 1.89 [95% CI, 1.54-2.32]; P for heterogeneity = .01). Unlike BMI or FMI, the genetically determined WHR-all-cause mortality association was consistent irrespective of observed BMI.

Conclusions and relevance: In this cohort study, WHR had the strongest and most consistent association with mortality irrespective of BMI. Clinical recommendations should consider focusing on adiposity distribution compared with mass.

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Conflict of interest statement

Conflict of Interest Disclosures: Mr Khan reported receiving support from Ontario Graduate Scholarship–Masters Scholarship, awarded by the Government of Ontario. Dr Mohammadi-Shemirani reported being employed by Deep Genomics Inc during the study. Dr Morton reported now being an employee at the Novo Nordisk Foundation. Dr Morrison reported receiving personal fees from Novo Nordisk for serving on the advisory board outside the submitted work. Dr Paré reported receiving grants from Bayer and receiving personal fees from Amgen, Novartis, and Illumina outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of Body Mass Index (BMI), Fat Mass Index (FMI), and Waist-to-Hip Ratio (WHR) With All-Cause Mortality Among 387 672 Participants from the UK Biobank
BMI calculated as weight in kilograms divided by height in meters squared.
Figure 2.
Figure 2.. Linear Mendelian Randomization Analyses Comparing Genetically Determined Adiposity Measures in Their Association With All-Cause Mortality
BMI indicates body mass index; FMI, fat mass index; OR, odds ratio; and WHR, waist-to-hip ratio.
See this image and copyright information in PMC

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