Validation of physical examinations of tendon xanthomas and changes in the cutoff values of Achilles tendon thickness on radiography in the clinical criteria of heterozygous familial hypercholesterolemia in Japan.

BACKGROUND

The 2022 Japan Atherosclerosis Society familial hypercholesterolemia (FH) clinical criteria were modified. In particular, the cutoff value of Achilles tendon thickness (ATT) on radiography was changed from ≥9 mm in both sexes to ≥8.0 mm in men and ≥7.5 mm in women.

METHODS

A total of 872 patients with FH were retrospectively reviewed. Patients were categorized by an ATT of <7.5/8.0 mm (group 1), ≥7.5/8.0 and <9.0 mm (group 2, new group with FH by ATT), and ≥9 mm (group 3).

RESULTS

In total, 492 patients fell into group 1, 102 in group 2, and 263 in group 3, and 14.0%, 55.9%, and 79.8% of patients in groups 1, 2, and 3, respectively, were positive for a FH mutation. Further, among patients with low-density lipoprotein cholesterol >180 mg/dL, 37.3%, 77.3%, and 86.5% of patients had a FH mutation in groups 1, 2, and 3, respectively. The proportion of patients with protein-truncating mutation (3.8%, 16.7%, and 53.2%, respectively) differed significantly across groups 1 through 3, respectively. Interestingly, only a very small proportion of the patients in groups 2 and 3 had palpable xanthomas (3.0% and 14.4% respectively).

CONCLUSIONS

This study validates the new radiographic ATT criteria, since the vast majority of patients in the intermediate ATT category had true FH, as shown by positive genetic testing, whereas the old ATT criteria left them with just a deferred diagnosis of FH. In addition, use of physical examination alone for the presence of tendon xanthoma may lead to underdiagnosis of FH.