Abstract

BackgroundThe mortality of metabolic-obesity phenotypes has been thoroughly studied, but it is not known if or how the association between mortality and body mass index (BMI), waist circumference or a body shape index (ABSI) differ in strata of cardiometabolic health status.MethodsWe linked data on 12,815 men and women aged 36–79 years from the SAMINOR 1 Survey with mortality data from the Norwegian Cause of Death Registry. We defined metabolically healthy and unhealthy as having zero and ≥ 1, respectively, of the following: MetS, pre-existing diabetes or cardiovascular disease (CVD), or prescribed drugs for high blood pressure, hyperglycaemia or dyslipidaemia. We defined general and abdominal obesity as BMI ≥ 30 kg/m2 and waist circumference ≥ 88 cm (women) or 102 cm (men), respectively, and cross-classified these categories with metabolic status to create metabolically healthy non-obese and obese (MHNO and MHO) and metabolically unhealthy non-obese and obese (MUNO and MUO) phenotypes. We used Cox regression to estimate the hazard ratio (HR) for all-cause and CVD mortality for 1) the four phenotypes and 2) BMI, waist circumference and ABSI fitted with restricted cubic splines. We adjusted for age and lifestyle, and tested for interactions with sex and metabolic status (only continuous measures).ResultsThe MHO phenotype was present in 7.8% of women and 5.8% of men. During a median follow-up of 15.3/15.2 years, 596/938 women/men had died, respectively. The MUNO and MUO groups had higher mortality than the MHNO group. Sex and phenotypes interacted with respect to CVD mortality: relative to the MHNO group, the MHO group had an adjusted HR (95% confidence interval) for CVD mortality of 1.05 (0.38–2.88) in women and 2.92 (1.71–5.01) in men. We found curvilinear associations between BMI/waist circumference and all-cause mortality irrespective of metabolic status. Corresponding relationships with CVD mortality were linear and the slope differed by sex and metabolic status. ABSI was linearly and positively associated with all-cause and CVD mortality in men.ConclusionThe relationships between BMI, waist circumference or ABSI and mortality differed by sex, metabolic status and cause of death. Poor metabolic health substantially increases mortality regardless of obesity status.

Highlights

  • The mortality of metabolic-obesity phenotypes has been thoroughly studied, but it is not known if or how the association between mortality and body mass index (BMI), waist circumference or a body shape index (ABSI) differ in strata of cardiometabolic health status

  • The relationships between BMI, waist circumference or ABSI and mortality differed by sex, metabolic status and cause of death

  • In separate models for each pair of outcome and exposure, we modelled the relationships between all-cause mortality and cardiovascular disease (CVD) mortality and metabolic syndrome (MetS), general obesity phenotypes and abdominal obesity phenotypes using Cox proportional hazard regression

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Summary

Introduction

The mortality of metabolic-obesity phenotypes has been thoroughly studied, but it is not known if or how the association between mortality and body mass index (BMI), waist circumference or a body shape index (ABSI) differ in strata of cardiometabolic health status. Obesity is a strong driver of a cluster of risk factors known as metabolic syndrome (MetS). MetS is etiologically linked to insulin resistance and visceral adipose tissue that promotes a proinflammatory and prothrombotic state, making it an antecedent of both cardiovascular disease (CVD) and type 2 diabetes mellitus [2]. At least half of the cardiovascular risk linked to obesity is mediated through metabolic risk factors [3, 4]. In Europe, approximately 7–19% of people with obesity do not have MetS, so-called metabolically healthy obesity (MHO) [5]. Accumulating evidence strongly suggests that, compared to the metabolically healthy normal-weight group, people with MHO are at increased risk of CVD [6,7,8], type 2 diabetes mellitus [9, 10], and mortality [11, 12]

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