Anxiety, depression, and health-related quality of life in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis

Background: Heterozygous familial hypercholesterolemia (FH) is a common genetic disease predisposing affected individuals to a high risk of cardiovascular disease. Yet, considerable uncertainty exists regarding its impact on psychosocial wellbeing. Objectives: We performed a systematic review and meta-analysis of the association between FH and symptoms of anxiety and depression, and health-related quality of life (HRQL). Methods: We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO, and PubMed for peer-reviewed literature published in English between January 1, 1990 and January 1, 2018. Quantitative and qualitative studies were eligible if they included patients with confirmed FH and evaluated its association with symptoms of anxiety or depression, or HRQL. We performed a narrative synthesis of studies, including thematic analysis of qualitative studies, and where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals. Results: We found 10 eligible studies measuring HRQL, depression and anxiety. Random-effects meta-analysis of 4 (n = 4293) and 5 studies (n = 5098), respectively, showed that patients with FH had slightly lower symptoms of anxiety (SMD: 0.29 [95% CI: 0.53, 0.041) and mental HRQL (SMD: 0.10 [95% 0.20, 0.00]) relative to general population controls. No significant differences existed in depressive symptoms (SMD: 0.04 [95% CI: 0.12, 0.19]) or physical HRQL scores (SMD: 0.02 [95% CI: 0.09, 0.12]). Conclusions: Our systematic review suggests that patients with FH may report small but measurable differences in anxiety symptoms and mental HRQL.