Worldwide Prevalence of Familial Hypercholesterolemia

ISS Fro Co Co Ak No Th ins vis Ma BACKGROUND Despite the greater prevalence of familial hypercholesterolemia (FH) in subjects with ischemic heart disease (IHD), premature IHD, and severe hypercholesterolemia (low-density lipoprotein $190 mg/dl), overall prevalence estimates are not available. OBJECTIVES The aim of this study was to provide worldwide estimates of FH prevalence in subjects with IHD, premature IHD, and severe hypercholesterolemia compared with those in the general population. METHODS In this systematic review and meta-analyses, Embase, PubMed, and the Web of Science were searched until June 3, 2019, for peer-reviewed papers and conference abstracts reporting heterozygous FH prevalence in nonfounder populations, revealing 104 studies eligible for inclusion. RESULTS Estimates of FH prevalence were pooled using random-effects meta-analyses and were 0.32% (95% confidence interval [CI]: 0.26% to 0.39% [corresponding to 1:313]) among 10,921,310 unique subjects in the general population (33,036 patients with FH) on the basis of 44 studies, 3.2% (95% CI: 2.2% to 4.3% [1:31]) among 84,479 unique subjects with IHD (2,103 patients with FH) on the basis of 28 studies, 6.7% (95% CI: 4.9% to 8.7% [1:15]) among 31,316 unique subjects with premature IHD (1,471 patients with FH) on the basis of 32 studies, and 7.2% (95% CI: 4.6% to 10.8% [1:14]) among 17,728 unique subjects with severe hypercholesterolemia (920 patients with FH) on the basis of 7 studies. FH prevalence in the general population was similar using genetic versus clinical diagnoses. Seventeen of 195 countries (9%) in the world have reported FH prevalence for the general population, leaving 178 (91%) countries in the world with unknown prevalence. CONCLUSIONS Compared with 1:313 among subjects in the general population, FH prevalence is 10-fold higher among those with IHD, 20-fold higher among those with premature IHD, and 23-fold higher among those with severe hypercholesterolemia. The prevalence of FH is unknown in 90% of countries in the world. (J Am Coll Cardiol 2020;75:2553–66) © 2020 by the American College of Cardiology Foundation. F amilial hypercholesterolemia (FH) is the most common autosomal-dominant genetic disorder, affecting about 30 million subjects worldwide, and is characterized by lifelong highly elevated low-density lipoprotein (LDL) cholesterol levels and thus an increased risk for ischemic heart disease N 0735-1097/$36.00 m the Department of Clinical Biochemistry and the Copenhagen Gener penhagen University Hospital, Herlev, Denmark; and the Faculty of Heal penhagen, Denmark. Dr. Nordestgaard has undertaken consultancies or cea, Amgen, Kowa, Denka Seiken, Amarin, Novartis, Novo Nordisk, and vo Nordisk. All other authors have reported that they have no relationshi e authors attest they are in compliance with human studies committe titutions and Food and Drug Administration guidelines, including patien it the JACC author instructions page. nuscript received November 4, 2019; revised manuscript received Februa (IHD) (1). FH is caused by mutations in LDLR, APOB, and PCSK9 genes, encoding the LDL receptor, its ligand apolipoprotein B, and proprotein convertase subtilisin/kexin type 9, which marks the LDL receptor for degradation, respectively. In addition, elevated lipoprotein(a) may explain 25% of clinical FH https://doi.org/10.1016/j.jacc. 2020.03. 057 al Population Study, Herlev and Gentofte Hospital, th and Medical Sciences, University of Copenhagen, talks sponsored by AstraZeneca, Sanofi, Regeneron, Silence Therapeutics. Dr. Madsen is an employee of ps relevant to the contents of this paper to disclose. es and animal welfare regulations of the authors’ t consent where appropriate. For more information, ry 18, 2020, accepted March 23, 2020. ABBR EV I A T I ON S AND ACRONYMS CI = confidence interval FH = familial hypercholesterolemia IHD = ischemic heart disease LDL = low-density lipoprotein Beheshti et al. J A C C V O L . 7 5 , N O . 2 0 , 2 0 2 0 Worldwide FH Prevalence in Different Subpopulations M A Y 2 6 , 2 0 2 0 : 2 5 5 3 – 6 6 2554 diagnoses (2). Subjects with FH are identified using various diagnostic criteria in either primary care by a positive family history of premature IHD and personal hypercholesterolemia or in hospital settings among patients with premature IHD. European and U.S. guidelines recommend identifying subjects with FH in order to start LDL cholesterol– lowering therapy early in life to prevent IHD and early death (3–5).