Objective: This study aimed to conduct a systematic review and meta-analysis of associations between loneliness, social isolation, and living alone and risk of mortality among individuals with established cardiovascular disease. Methods: Five electronic databases were searched (MEDLINE [Ovid], PsycINFO, EMBASE, PubMed, and SCOPUS) from inception to November 25, 2021. In all, 35 studies were included in a narrative synthesis and, where appropriate, a meta-analytic evaluation using a random-effects model. Results: Living alone was associated with increased risk of all-cause mortality (k = 15, n = 80,243, hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.20-1.83, I 2 = 83%), and meta-regressions found that the effects were stronger in studies from Europe and with longer follow-up. However, there was evidence of publication bias. Social isolation was associated with increased risk of all-cause mortality, measured both as a dichotomous variable (k = 3, n = 2648, HR = 1.46, 95% CI = 1.08-2.04, I 2 = 31%) and as a continuous variable (k = 5, n = 2388, HR = 1.11, 95% CI = 1.02-1.24, I 2 = 51%). Meta-analysis was not feasible for loneliness as exposure, but narrative synthesis of four studies suggested a tentative association between loneliness and increased risk of all-cause mortality. Conclusions: Supporting public health concerns, our review finds that loneliness, social isolation, and living alone are associated with premature mortality among individuals with established cardiovascular disease. However, evidence of publication bias and large methodological differences across studies point to the need for more rigorous research.
