Social isolation and mortality from all causes, cardiovascular disease, and cancer: A systematic review and meta-analysis of 50 cohort studies
Authors: wang fan , Gao Yu , Han Zhen , Yu Yue , Long Zhiping , Jiang Xianchen , Wu Yi , Pei Bing , Cao Yukun , Ye Jingyu , Wang Maoqing , Zhao Yashuang 
Published: July 2022

Abstract
Background
We aimed to assess the associations between social isolation (SI) and the risk of mortality from all causes, cardiovascular disease, and cancer.
Methods
This was a systematic review and meta-analysis of prospective cohort studies.We searched electronic databases, including PubMed, Web of Science, and Embase, from inception until October 2021, as well as the references of retrieved articles. Prospective studies reporting risk estimates for the association between SI and mortality from all causes, cardiovascular diseases, and cancer in adults aged 18 or older were included in the analyses. Data were screened and extracted independently by two investigators. The fully adjusted effect sizes in the original studies were analyzed, and summary analyses were performed using a fixed-effects or random-effects model, according to the heterogeneity among studies. Subgroup analyses, meta-regression, and sensitivity analyses were performed to evaluate the heterogeneity and robustness of the findings. Simple linear regression was used to analyze the changing trends in social network index grade and risk of mortality. The risk of publication bias was tested using funnel plots and Egger’s and Begg’s tests (each significant at P < 0.05). The trim-and-fill method was used to adjust for the influence of potentially unpublished studies on pooled effect estimates when statistical tests indicated publication bias. The study protocol was registered with PROSPERO (reg. NO CRD42022299959)
Results
A total of 50 prospective cohort studies with 1,951,661 individuals were included for analysis. The duration of follow-up among included studies ranged from 6 months to 24.4 years. In pooled analyses, SI was significantly associated with an increased risk of mortality from all causes (pooled effect size, 1.22; 95% confidence interval [CI], 1.16 to 1.29; I2 = 77.6%), cardiovascular disease (1.35; 95% CI 1.25 to 1.45, I2 = 65.5%), and cancer (1.23; 95% CI 1.18 to 1.27, I2 = 44.2%) in the general population. Linear regression showed that social network index grade was significantly correlated with the risk of all-cause mortality (P < 0.001). Additionally, the pooled effect estimate for all-cause mortality in patients with breast cancer was 1.51 (95% CI 1.34 to 1.70), and that for cancer-specific mortality was 1.33 (95% CI 1.02 to 1.75). There was a 28% increased risk of all-cause mortality in socially isolated patients with cardiovascular disease (95% CI 1.10 to 1.48). There was no evidence of a positive association between SI and cancer-specific mortality in patients with colorectal cancer (1.07, 95% CI 0.96 to 1.20).
Conclusions
SI was associated with at least a 20% increased risk of all-cause mortality, cardiovascular disease mortality, and cancer mortality. We highlight that social isolation contributes to chronic disease and mortality, with efforts to improve social isolation likely to have benefits in well-being and survival.