Measurement of Achilles Tendon Thickness is a Key for International Harmonization in Clinical Diagnosis of Familial Hypercholesterolemia.

Abstract

Familial hypercholesterolemia (FH) is one of the most common genetic diseases, appearing as high as 1 heterozygote in a general population of 300 individuals globally. This is caused by the diversity of the causing mutations in several genes related to LDL metabolism . Accordingly, it substantially impacts public health by causing atherosclerotic vascular illness, such as coronary heart disease (CAD). Screening patients with FH and their families early enough is therefore important to prevent cardiovascular complications, not only for saving their lives and improving their quality of life but also for relieving public health burden and saving social healthcare cost. The Japan Atherosclerosis Society (JAS) proposed the guidelines for the diagnosis of FH (JASG) designed to identify patients with FH in general practice first in 2012 3) and its renewed version in 2017 , where FH is defined by the presence of at least two of the three major symptoms of a high LDL cholesterol (≥ 180 mg/dl), a family history of FH/ premature CAD, and tendon/skin xanthomas defined as Achilles tendon thickness (ATT) ≥ 9 mm . To estimate the contribution of FH to cardiovascular diseases in Japan, Ohmura et al. found 5.7% and 7.8% by JASG in all age and under 60, respectively, among 359 Japanese patients with acute coronary symptom (ACS) from five major urban hospitals. Tanaka and his colleagues also demonstrated that FH by JASG accounted for 4.3% in all and 15.4% in those under 60 among 141 patients with ACS in a single community hospital. Harada-Shiba et al. analyzed 1944 patients with ACS (mean age, 66.0 years; men, 80.3%) and found 52 (2.7%) patients with FH. FH finding by JASG thus seems largely consistent throughout these studies. Accordingly, the estimated overall risk of ACS is 10 times high among FH in comparison to the general Japanese population and even higher among those under 60. The early commencement of their treatment could reduce premature CAD as much as 10% in Japan. The Dutch Lipid Clinic Network Algorithm (DLCNA) is widely used for finding FH in the EU region and other parts of the world, based on scoring system for the level of certainty in diagnosis, by family and clinical history, LDL cholesterol, and the presence of skin/tendon xanthomas by physical examination. Xanthomas are defined left arbitrary for subjective recognition, and this may have caused some inconsistency among the studies by the DLCNA. It identified 1.6% and 4.8% of probable/definite FH among ACS in a Switzerland study and 2.0% and 7.0% among those with first myocardial infarction in a Danish study in all age and those under 60, respectively. The EUROASPIRE study covering 7044 patients with coronary disease from 24 European countries found more definite/probable FH as 8.3% in all ages and 15.4% and 5.1% in those under and above 60 . Similar reports from China demonstrated the contribution of FH to CAD by the DLCNA definite/probable criteria as 3.9% for all ages and 7.1% for those under 60 . The higher prevalence of FH among younger patients with ACS is consistent throughout these reports, whereas diversity and inconsistency may be found in the rate of FH contribution to ACS. The parallel application of the DLCNA to Japanese cohorts tested for JASG yielded uncertain differential diagnosis of FH, except for definite criteria . These findings revealed that the DLNCA-based diagnosis of FH greatly depends on the arbitrary finding of xanthomas to which a high point was given in the scoring system, whereas JASG is based on more objective and quantitative criteria of measuring ATT. Tada and his colleagues reported in this issue of