Familial Hypercholesterolaemia Patients with LDLR Mutation Among Asian Population in Southeast Asian Countries: Systematic Review

Familial hypercholesterolaemia (FH) is a genetic disorder associated with premature cardiovascular diseases; however, the majority of patients remain undertreated. This systematic review aimed to determine the prevalence of FH patients with low-density lipoprotein receptor (LDLR) gene pathogenic variants (PV) among the Asian population in Southeast Asian countries. Our search yielded 1,120 citations, with 28 deemed possibly suitable based on title and abstract screening. However, only six studies that utilised the Dutch Lipid Clinic Network (DLCN) or Simon Broome (SB) criteria were eligible to be included. These studies provided prevalence figures for clinically diagnosed FH patients, with a total of 17.1% (n=1,005/5,874); this rate was represented by three Malaysian studies, which estimated that 36–76% of clinically diagnosed FH patients had LDLR PV. Most patients reported having pre-existing cardiovascular disease, a family history of premature coronary artery disease and tendon xanthomata. This study found that the prevalence of LDLR PV among genetically confirmed FH patients in Southeast Asia is 20.5% (n=286/5,874). Genetically confirmed FH patients are at a higher risk of developing premature coronary artery disease, requiring more aggressive lipid-lowering treatment. Therefore, identifying LDLR PV among the population is essential for early FH diagnosis and treatment. KEYWORDS Arterial disease, autosomal dominant, LDL receptor, LDLR prevalence, pathogenic variants, premature CAD, Undertreated