Health-related quality of life in homozygous familial hypercholesterolemia: A systematic review and meta-analysis

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by extreme elevations of low-density lipoprotein cholesterol (LDL-C) and extremely premature atherosclerotic cardiovascular disease. To date, impacts of HoFH and its treatment on the psychosocial wellbeing of patients have been poorly characterized. Objectives: We performed a systematic review of the association between HoFH and health-related quality of life (HRQL). Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) consensus guidelines. We searched MEDLINE, Embase, The Cochrane Controlled Register of Trials (CENTRAL), Pubmed, Scopus, AfricaWide (via EBSCO), and six trial registries and grey-literature databases from inception to May 2021 for published Englishlanguage literature examining HRQL and its determinants in HoFH. Studies were eligible if they included patients with confirmed HoFH and evaluated HRQL using validated tools. We performed a narrative synthesis of qualitative findings from included studies and, where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals (CIs). Results: Our review identified seven eligible studies examining HRQL in HoFH participants. Pooling data from two included studies, we found that relative to the general population, HoFH patients demonstrated significantly poorer HRQL in multiple dimensions of the 36-item Short-Form Health Survey (SF-36) with lower scores in physical functioning (SMD -0.37; 95% CI: -0.60, -0.15), role limitations due to physical health (SMD -0.63; 95% CI: -1.24, -0.02), social functioning (SMD -0.61; 95% CI: -1.19, -0.03), bodily pain (SMD -0.24; 95% CI: -0.46, -0.01), and general health (SMD -1.55; 95% CI: -1.80, -1.31). No differences were observed in domains of energy and vitality, mental health and emotional well-being, or role limitations due to emotional problems. Patients suffered high treatment burdens related to lipoprotein apheresis that compromised educational attainment and employment. However, few patients received psychological support in navigating their treatment challenges. No studies evaluated the association of HoFH with incident anxiety, depression, or other psychopathology. Conclusions: Limited data are available on quality of life for patients with HoFH. The available data suggest that these patients may suffer disease-related impairments in quality of life. Future work should aim to elucidate relationships between HoFH and mental health outcomes and develop interventions to improve quality of life in this population.