Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK

Abstract

Background: BMI is known to be strongly associated with all-cause mortality, but few studies have been large enough to reliably examine associations between BMI and a comprehensive range of cause-specific mortality outcomes.

Methods: In this population-based cohort study, we used UK primary care data from the Clinical Practice Research Datalink (CPRD) linked to national mortality registration data and fitted adjusted Cox regression models to examine associations between BMI and all-cause mortality, and between BMI and a comprehensive range of cause-specific mortality outcomes (recorded by International Classification of Diseases, 10th revision [ICD-10] codes). We included all individuals with BMI data collected at age 16 years and older and with subsequent follow-up time available. Follow-up began at whichever was the latest of: start of CPRD research-standard follow up, the 5-year anniversary of the first BMI record, or on Jan 1, 1998 (start date for death registration data); follow-up ended at death or on March 8, 2016. Fully adjusted models were stratified by sex and adjusted for baseline age, smoking, alcohol use, diabetes, index of multiple deprivation, and calendar period. Models were fitted in both never-smokers only and the full study population. We also did an extensive range of sensitivity analyses. The expected age of death for men and women aged 40 years at baseline, by BMI category, was estimated from a Poisson model including BMI, age, and sex.

Findings: 3 632 674 people were included in the full study population; the following results are from the analysis of never-smokers, which comprised 1 969 648 people and 188 057 deaths. BMI had a J-shaped association with overall mortality; the estimated hazard ratio per 5 kg/m² increase in BMI was 0·81 (95% CI 0·80-0·82) below 25 kg/m² and 1·21 (1·20-1·22) above this point. BMI was associated with all cause of death categories except for transport-related accidents, but the shape of the association varied. Most causes, including cancer, cardiovascular diseases, and respiratory diseases, had a J-shaped association with BMI, with lowest risk occurring in the range 21-25 kg/m². For mental and behavioural, neurological, and accidental (non-transport-related) causes, BMI was inversely associated with mortality up to 24-27 kg/m², with little association at higher BMIs; for deaths from self-harm or interpersonal violence, an inverse linear association was observed. Associations between BMI and mortality were stronger at younger ages than at older ages, and the BMI associated with lowest mortality risk was higher in older individuals than in younger individuals. Compared with individuals of healthy weight (BMI 18·5-24·9 kg/m²), life expectancy from age 40 years was 4·2 years shorter in obese (BMI ≥30·0 kg/m²) men and 3·5 years shorter in obese women, and 4·3 years shorter in underweight (BMI <18·5 kg/m²) men and 4·5 years shorter in underweight women. When smokers were included in analyses, results for most causes of death were broadly similar, although marginally stronger associations were seen among people with lower BMI, suggesting slight residual confounding by smoking.

Interpretation: BMI had J-shaped associations with overall mortality and most specific causes of death; for mental and behavioural, neurological, and external causes, lower BMI was associated with increased mortality risk.

Funding: Wellcome Trust.

Figure 1

All-cause mortality and Level 1 cause-specific mortality outcomes in total study population (A) and in never-smokers only (B) We used a three-level hierarchical classification of causes of death as used by the Global Burden of Diseases, Injuries, and Risk Factors Study. All Level 1 outcomes (communicable diseases, non-communicable diseases, and injuries and external causes) were studied. 5-year exclusion period applied for person-time and events after a BMI record. Dashed vertical lines represent WHO BMI category thresholds of 18·5 kg/m² (underweight to healthy), 25 kg/m² (healthy weight to overweight), and 30 kg/m² (overweight to obese). Estimates adjusted for age at BMI record, deprivation, calendar year, diabetes, alcohol status, and smoking (all as defined at date of BMI measure) and stratified for sex. The p values for overall association and p values for non-linearity were less than 0·0001 for all outcomes, in both full and never-smoker populations. HR=hazard ratio.

Figure 2

Association between BMI and Level 2 and Level 3 cause-specific mortality outcomes among never-smokers (organised by ICD-10 code) We used a three-level hierarchical classification of causes of death as used by the Global Burden of Diseases, Injuries, and Risk Factors Study. We studied all Level 2 non-communicable disease outcomes and selected Level 3 outcomes that were either common causes of death in the UK or were a priori expected to have important associations with BMI. 5-year exclusion period applied for person-time and events after a BMI record; estimates adjusted for age, deprivation, calendar year, diabetes, alcohol status (all as defined at date of BMI measure) and stratified for sex. HR=hazard ratio. ICD-10=International Classification of Diseases, 10th revision.

Figure 3

Association between BMI and all-cause mortality among never-smokers, by sex (A) and age (B) 5-year exclusion period applied for person-time and events after a BMI record; estimates adjusted for age, deprivation, calendar year, diabetes, and alcohol status (all as defined at date of BMI measure) and stratified by sex. HR=hazard ratio.