Half a century tales of familial hypercholesterolemia (FH) in Japan

Familial hypercholesterolemia (fh) is a disease characterized by a triad: elevated low-density lipoprotein (ldl) cholesterol,tendon xanthomas,and premature coronary heart disease. thus,it can be considered as a model disease for hypercholesterolemia and atherosclerotic cardiovascular disease (ascvd). for the diagnosis of hetero-fh,the detection of achilles tendon xanthomas by palpation or on x-ray is an indispensable diagnostic skill in clinical lipidology. to prevent the under-diagnosis and under-treatment of fh,the diagnostic criteria should be more convenient and user-friendly. for a patient with cutaneous or tendon xanthomas,the probability of fh is very high; however,an absence of xanthoma does not rule out fh. brown and goldstein elucidated the pathogenesis of fh by their work on ldl-receptor (ldl-r),for which they were awarded the nobel prize in 1985. in the 1950s,fh patients were divided into heterozygous (hetero-) and homozygous (homo-) fh,and diagnosing homo- and hetero-fh based on the phenotypic features of ascvd or xanthomas frequently became difficult without the dna analysis of fh genes. it is estimated that heterozygous mutations in the ldl-r or the proprotein convertase subtilisin/kexin type 9 (pcsk9) gene will be found at a combined frequency of 0.005,which corresponds to 1/199 people in the general population in japan. statins and anti-pcsk9 monoclonal antibodies are highly specific and efficient drugs for treating hetero- or homo-fh patients. most clinical studies have reported an amelioration of ascvd using long-term statin therapy. clinical results using anti-pcsk9 monoclonal antibodies will emerge in a few years. in homo-fh patients,mipomersen and lomitapide are expected to yield good results. it is important to sequentially unravel the unrecognized pathogenetic mechanisms of fh to reduce its under-recognition and develop new management strategies for it. © 2017 japan atherosclerosis society.