Achilles tendon thickness assessed by X-ray predicting a pathogenic mutation in familial hypercholesterolemia gene

Abstract

Abstract Background The 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria adopts a cut off value of ≥9 mm of Achilles tendon thickness (ATT) detected by X-ray as one of the three key items. This threshold was determined based on an old data assessing ATT of 36 non-FH individuals published in 1977. Although the specificity of this clinical criteria is extremely high due to a strict threshold, there are substantial number of patients with FH whose ATT <9 mm. We aimed to determine a cut off value of ATT detected by X-ray to differentiate FH and non-FH based on genetic diagnosis. Methods The individuals (male/female = 486/501) with full assessments of genetic analyses for FH-genes (LDLR, and PCSK9), serum lipids, and ATT detected by X-ray at Kanazawa University Hospital and National Cerebral and Cardiovascular Center Research Institute were included in this study. Receiver operating characteristic (ROC) analyses were performed to determine a better cut off point of ATT predicting a pathogenic mutation of FH. Results ROC analyses revealed the best cut off values of ATT as 7.6 mm for male, and 7.0 mm for female with the sensitivities and specificities of 0.83 and 0.83 for male and 0.86 and 0.85 for female, respectively. If the thresholds of ATT of 8.0/7.5 mm and 7.5/7.0 mm were applied to diagnose of male/female FH, the sensitivities/specificities predicting a pathogenic mutation of FH by the 2017 JAS FH clinical criteria would be 0.82/0.90 and 0.85/0.88, respectively. Conclusions These results suggest that the cut-off value of ATT detected by X-ray is obviously lower than 9.0 mm adopted by the 2017 JAS FH clinical criteria. Funding Acknowledgement Type of funding sources: None.