Familial Hypercholesterolemia: Use of Registries, Biobanks, and Cohort Studies To Improve its Diagnosis and Management in Non-Western Populations

Abstract

Familial hypercholesterolemia (FH) is the most common monogenic disorder in humans, with an estimated prevalence of 1:200-1:250, based on unbiased genetic screening in Western populations. The vast majority of FH can be explained by mutations in three key genes; LDLR (receptor not synthesized or not functional), APOB (ligand not properly recognizing LDLR), and PCSK9 (gain of function mutations causing excessive elimination of LDLR). Causal mutations in these genes lead to lifelong elevations in low-density lipoprotein-cholesterol, xanthomatosis, and premature atherosclerotic cardiovascular disease. Several large scale patient registries have proliferated around the world and provide real-world data on prevalence and current treatment patterns. In this way, they have highlighted major gaps in the identification, treatment, and follow-up of patients with FH. Regrettably, these registries reveal a consistent and sobering message - patients with FH either remain undiagnosed or receive delayed diagnosis, there are low rates of LDL-C goal attainment even with combination lipid-lowering therapy, and rates of atherosclerotic cardiovascular disease are remarkably higher than the general population. Currently, there are well-developed FH registries in the Netherlands, United Kingdom, Spain, France, Norway, Brazil, Canada, and the United States. Notably absent from this list is the entirety of the Asian continent. As collaborating U.S. investigators who have clinical and research experience with FH and FH registries, we encourage the clinical research leadership of Thailand to design and launch a national FH Registry and genetic biorepository. Besides serving as a tool to advance the science of FH, particularly as it relates to the Thai population, this effort will undoubtedly raise awareness and lead to more efficient diagnosis and treatment, the true role of a registry. The opportunity for Thailand is enormous.