Independent and joint effects of body mass index and metabolic health in mid- and late-life on all-cause mortality: a cohort study from the Swedish Twin Registry with a mean follow-up of 13 Years

Abstract

Background: There is robust evidence that in midlife, higher body mass index (BMI) and metabolic syndrome (MetS), which often co-exist, are associated with increased mortality risk. However, late-life findings are inconclusive, and few studies have examined how metabolic health status (MHS) affects the BMI-mortality association in different age categories. We, therefore, aimed to investigate how mid- and late-life BMI and MHS interact to affect the risk of mortality.

Methods: This cohort study included 12,467 participants from the Swedish Twin Registry, with height, weight, and MHS measures from 1958-2008 and mortality data linked through 2020. We applied Cox proportional hazard regression with age as a timescale to examine how BMI categories (normal weight, overweight, obesity) and MHS (identification of MetS determined by presence/absence of hypertension, hyperglycemia, low HDL, hypertriglyceridemia), independently and in interaction, are associated with the risk of all-cause mortality. Models were adjusted for sex, education, smoking, and cardiovascular disease.

Results: The midlife group included 6,252 participants with a mean age of 59.6 years (range = 44.9-65.0) and 44.1% women. The late-life group included 6,215 participants with mean age 73.1 years (65.1-95.3) and 46.6% women. In independent effect models, metabolically unhealthy status in midlife increased mortality risks by 31% [hazard ratio 1.31; 95% confidence interval 1.12-1.53] and in late-life, by 18% (1.18;1.10-1.26) relative to metabolically healthy individuals. Midlife obesity increased the mortality risks by 30% (1.30;1.06-1.60) and late-life obesity by 15% (1.15; 1.04-1.27) relative to normal weight. In joint models, the BMI estimates were attenuated while those of MHS were less affected. Models including BMI-MHS categories revealed that, compared to metabolically healthy normal weight, the metabolically unhealthy obesity group had increased mortality risks by 53% (1.53;1.19-1.96) in midlife, and across all BMI categories in late-life (normal weight 1.12; 1.01-1.25, overweight 1.10;1.01-1.21, obesity 1.31;1.15-1.49). Mortality risk was decreased by 9% (0.91; 0.83-0.99) among those with metabolically healthy overweight in late-life.

Conclusions: MHS strongly influenced the BMI-mortality association, such that individuals who were metabolically healthy with overweight or obesity in mid- or late-life did not carry excess risks of mortality. Being metabolically unhealthy had a higher risk of mortality independent of their BMI.

Keywords: Body weight; Metabolic syndrome; Metabolically benign obesity; Metabolically healthy obesity; Mortality; Obesity.