Comparative impact of social isolation on mortality in adults aged 40 years and above with versus without metabolic syndrome: evidence from two large cohorts in the U.S. and U.K.

Abstract

Introduction: Social isolation is increasingly recognized as a significant public health concern associated with mortality risk. However, whether the impact of social isolation on mortality differs between individuals with and without metabolic syndrome (MetS) remains unclear. This study aimed to investigate the associations of social isolation with all-cause mortality, cardiovascular mortality (CVDM), cancer mortality (CAM), other cause mortality (OTM), and premature mortality in MetS and non-MetS populations using data from large cohorts in the UK and the US.

Methods: This study analyzed data from 75,190 participants with metabolic syndrome (MetS) and 229,388 participants without MetS in the UK Biobank, as well as 5758 MetS participants and 7448 non-MetS participants from the U.S. National Health and Nutrition Examination Survey (NHANES). All participants included in the study were aged 40 years or above. The identification of MetS was based on a comprehensive assessment of multiple biochemical indicators, including waist circumference, blood glucose, blood pressure, and blood lipid levels. Social isolation was evaluated using information on marital status, household size, frequency of contact with family and friends, and engagement in social activities. The primary outcomes included all-cause mortality, cardiovascular mortality, cancer mortality, other-cause mortality, and premature mortality, defined as death before the age of 70. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between social isolation and various mortality outcomes. In addition, interaction and subgroup analyses were conducted to explore the potential modifying effects of MetS status, as well as lifestyle and other risk factors, on the relationship between social isolation and mortality.

Results: In the UK Biobank, the rates of all-cause mortality, CVDM, CAM, OTM, and premature mortality among participants with MetS were 9.07%, 1.48%, 4.22%, 3.36%, and 1.98%, respectively; the corresponding rates among participants without MetS were 4.81%, 0.51%, 2.61%, 1.68%, and 2.47%. In NHANES, the respective mortality rates among individuals with MetS were 26.20%, 9.24%, 6.15%, 10.85%, and 13.90%, and among those without MetS were 25.80%, 8.13%, 6.31%, 11.30%, and 14.10%. Cox regression analyses showed that, in the fully adjusted models, social isolation was significantly associated with increased risks of all-cause mortality, CVDM, CAM, OTM, and premature mortality in both individuals with and without MetS. In the UK Biobank, the HRs for participants with MetS were 1.30, 1.21, 1.12, 1.38, and 1.39, respectively; for those without MetS, the HRs were 1.51, 1.75, 1.30, 1.76, and 1.54, respectively. In the U.S. NHANES, the HRs for the MetS group were 1.14, 1.54, 1.48, 1.71, and 1.09, respectively; while for the non-MetS group, the HRs were 1.60, 1.75, 1.47, 1.56, and 1.39, respectively. The results of the interaction and sensitivity analyses were consistent.

Conclusions: Compared to individuals without MetS, those with MetS have higher mortality rates. Moreover, social isolation is associated with increased mortality regardless of MetS status. It is a risk factor for all-cause mortality, CVDM, CAM, OTM, and premature mortality in both MetS and non-MetS populations. Notably, the impact of social isolation on all-cause, cardiovascular, and premature mortality is more pronounced in individuals without MetS. Public health strategies should focus on population-wide interventions to reduce social isolation, enhance social engagement, and improve overall health and longevity, rather than targeting only high-risk groups.