Abstract
Background and Objectives: Familial hypercholesterolemia (FH) is the most common genetic cause of cardiovascular disease. This study was aimed to examine the Achilles tendon thickness using plain radiograph of lateral heels in FH subjects (diagnosed using the Dutch Lipid Clinic Network [DLCN] score above 3 [possible, probable or definite FH]), non-FH subjects with elevated LDL-cholesterol (LDL-C) >130 mg/dL and subjects with LDL-C below 130 mg/dL. The sensitivity, specificity, and optimal cutoff values with the highest diagnostic accuracy for diagnosis of FH were determined. In addition, the coronary calcium score (CAC) using computed tomography was investigated in FH and non-FH subjects. Finally, genetic variation in FH subjects was also explored. Results: Analysis was performed among 221 FH subjects, 58 non-FH subjects with high LDL-C and 55 subjects with LDL-C<130 mg/dL. The Achilles tendons in FH subjects were significantly thicker than those in the other 2 groups. No significant difference in Achilles tendon thickness between men and women was observed. The thickness cutoff values ≥6.9 mm gave the highest diagnostic accuracy of 77% with 87% sensitivity and 63% specificity. Age, presence of corneal arcus, history of CAD and LDL-C level showed significant relationship with Achilles tendon thickness. For CAC scores among 209 FH subjects and 58 non-FH subjects, the proportion of FH subjects who had CAC>0 was not significantly different than that of non-FH subjects. CAC scores were significantly associated with age. Among 272 FH subjects, genetic variations in the LDLR, APOB and PCSK9 genes were observed in 76, 3 and 2 subjects, respectively (27.9, 1.1 and 0.7%). Achilles tendon in FH subjects who had genetic variations in the involved genes was significantly thicker than those who did not have genetic variations, but the CAC scores were not significantly different between these two groups. Conclusions: Measurements of Achilles tendon thickness by plain radiographs showed that cutoff values of ≥6.9 mm gave 77% accuracy for FH diagnosis with 87% sensitivity and 63% specificity. The proportion of FH subjects with CAC >0 was not significantly different than that of non-FH subjects. Genetic variations in the involved genes were found in 32%, the majority of which was in the LDLR gene. FH subjects who had genetic variations had significantly thicker Achilles tendon than those who did not, but the CAC scores were not significantly different. Key words: Cardiovascular disease, familial hypercholesterolemia, cholesterol, LDL, coronary artery calcium score, genetic variation
