Risk Assessment for Cardiovascular Events using Achilles Tendon Thickness and Softness and Intima-Media Thickness in Familial Hypercholesterolemia.

AIMS: This was a retrospective cohort study that aimed to determine cutoff values for major adverse cardiovascular events (MACEs) in patients with heterozygous FH (HeFH) for Achilles tendon (AT) thickness (ATT) measured by ultrasonography (US-ATT) and radiography (Xp-ATT), AT softness, and intima-media thickness of carotid artery (C-IMT), and to examine the effectiveness of these values as well as AT calcification as indexes in assessing risk for MACEs. METHODS: The subjects were 391 clinically diagnosed HeFH patients. Kaplan-Meier curves were drawn based on the threshold values for the individual indexes calculated from ROC curves, and multivariate analysis was used to examine whether they were predictors of the development of MACEs. RESULTS: The median observation period was 1,239 days (700-1,827 days). Twenty-one subjects (5%) had MACEs during the observation period. The cutoff values for MACEs for US-ATT were 9.9 mm in males and 7.1 mm in females, and those for C-IMT were 1.6 mm in males and 1.5 mm in females. Subjects were classified into two groups according to whether they were above or below the cutoff values and presence of calcification, and we compared MACE rates between them. MACE rates were significantly increased in groups with AT thickening determined by ultrasonography (P＜0.001), AT softening (P＜0.001), presence of calcification in AT (P=0.016) and greater C-IMT (P＜0.001). However, classification according to Xp-ATT revealed no significant difference in MACE rate (P=0.112). CONCLUSIONS: These thresholds and examination for AT calcification will help in risk assessment for patients in Japanese FH practice and encourage stricter and more comprehensive management for patients who exceed the thresholds.

The impact of gene variants on the thickness and softness of the Achilles tendon in familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL)-cholesterol, xanthoma of the Achilles tendon (AT), and premature coronary artery disease (CAD). Ultrasonography can assess AT thickness and softness, making it useful for evaluating AT in FH diagnosis. We aimed to clarify whether FH-causative LDLR or PCSK9 variants affect AT thickness or softness. METHODS: In total, 248 FH and 60 non-familial hypercholesterolemia (non-FH) patients (total: 308) aged ≥30 years were enrolled. Patients with FH were classified according to genotype. AT thickness and elasticity index (EI) as softness were measured by ultrasonography. RESULTS: In FH patients with LDLR variants, AT was significantly thicker and softer than it was in FH patients with PCSK9 variants, FH patients without LDLR or PCSK9 variants, and patients with non-FH. The proportion of patients harboring LDLR variants significantly increased with AT thickness (p = 2.0 × 10-31) and softness (p = 1.4 × 10-18). Among those with AT thickness>8.5 mm and EI < 3.9, patients with LDLR variants accounted for 89% and 83%, respectively. The odds of AT thickening, AT softening and CAD increased 13.3-fold, 4.9-fold, and 2.1-fold, adjusted for the LDL-C year score by the presence of LDLR variants compared with those of patients without LDLR or PCSK9 variants. PCSK9 variants did not influence AT thickening or softening or CAD prevalence. CONCLUSIONS: LDLR variants affected AT thickness and softness independent of the LDL-C year score, but PCSK9 variants did not. Evaluating AT is important for identifying FH patients with LDLR variants at high risk for CAD.

Association between Achilles Tendon Softness and Atherosclerotic Cardiovascular Disease in Patients with Familial Hypercholesterolemia.

AIMS: Achilles tendon (AT) xanthomas are a specific physical finding of familial hypercholesterolemia (FH) and AT thickness has been used for its diagnosis and evaluation of its severity. Recently, we reported that the AT of FH patients was softer than that of non-FH patients and the combined use of a cut-off value for AT softness with that for AT thickness improved diagnostic accuracy. However, an association between AT softness and severity of atherosclerosis has not been reported. Accordingly, the present study aimed to investigate whether AT softness was associated with carotid atherosclerosis and presence of atherosclerotic cardiovascular disease (ASCVD) in FH. METHODS: The AT of 176 genetically diagnosed FH patients and 98 non-FH patients was examined to measure AT thickness and the elasticity index (EI) as an indicator for assessing AT softness using ultrasonography. RESULTS: Increased age was associated with AT softness, and overweight was negatively related to AT softness. There were significant inverse correlations between EI and maximum and mean intima-media thickness (IMT) within the common carotid artery only among FH patients. In multiple linear regression analysis, although the relationship between EI and mean IMT was attenuated, the association between EI and maximum IMT remained robust. In logistic regression analysis adjusted for age, sex and traditional cardiovascular risk factors (smoking history, presence of hypertension, presence of diabetes mellitus, overweight, LDL-cholesterol, HDL-cholesterol, and Log triglycerides), EI was associated with presence of ASCVD (Odds ratio per 1-SD increase, 0.37; 95% CI, 0.15 - 0.86; P=0.0252). CONCLUSION: The degree of lipid deposition in the AT of FH patients could be assessed by its thickness as well as its softness. AT softness is not only useful in diagnosing FH but is also associated with the severity of carotid atherosclerosis and presence of ASCVD. In addition, these findings suggest that AT softness would be helpful in risk assessment for FH patients.

Mindfulness augmentation for anxiety through concurrent use of transcranial direct current stimulation: a randomized double-blind study.

Transcranial direct current stimulation (tDCS) have revealed the capability to augment various types of behavioural interventions. We aimed to augment the effects of mindfulness, suggested for reducing anxiety, with concurrent use of tDCS. We conducted a double-blind randomized study with 58 healthy individuals. We introduced treadmill walking for focused meditation and active or sham tDCS on the left dorsolateral prefrontal cortex for 20 min. We evaluated outcomes using State-Trait Anxiety Inventory-State Anxiety (STAI) before the intervention as well as immediately, 60 min, and 1 week after the intervention, and current density from electroencephalograms (EEG) before and after the intervention. The linear mixed-effect models demonstrated that STAI-state anxiety showed a significant interaction effect between 1 week after the intervention and tDCS groups. As for alpha-band EEG activity, the current density in the rostral anterior cingulate cortex (rACC) was significantly reduced in the active compared with the sham stimulation group, and a significant correlation was seen between changes in STAI-trait anxiety and the current density of the rACC in the active stimulation group. Our study provided that despite this being a one-shot and short intervention, the reduction in anxiety lasts for one week, and EEG could potentially help predict its anxiolytic effect.

Achilles Tendon Ultrasonography for Diagnosis of Familial Hypercholesterolemia Among Japanese Subjects.

BACKGROUND: Difficulty in detecting and measuring Achilles tendon (AT) xanthomas may be responsible for underdiagnosis of familial hypercholesterolemia (FH). We aimed to determine a cutoff value for AT thickness (AT-T) using ultrasonography to diagnose FH, and to investigate the relationship between AT-T and atherosclerosis.Methods and Results:Ultrasonographic AT-T and carotid intima-media thickness (IMT) were evaluated in 130 genetically diagnosed FH patients and 155 non-FH patients. The outline and internal properties of the AT could be clearly determined using ultrasonography, and a good correlation in AT-T was observed between ultrasonography and the conventional method of X-ray radiography (r=0.924, P<0.001). Cutoff values for the diagnosis of FH derived from receiver-operating curves were 5.8 mm (sensitivity 71%, specificity 78%) in men, and 5.5 mm (sensitivity 80%, specificity 81%) in women. Importantly, increased AT-T was positively associated with carotid IMT only in the FH group. Additionally, increased AT-T was associated with the presence of coronary artery disease in a logistic regression analysis adjusted for traditional cardiovascular risk factors. CONCLUSIONS: This is the first study to determine a cutoff value for AT-T based on ultrasonography for the diagnosis of FH in Japanese subjects. Clearer detection and easier measurement of AT-T using ultrasonography would encourage clinicians to diagnose FH more actively, and could solve the problem of underdiagnosis of FH.

Age- and Gender-Specific Risk of Thyroid Cancer in Patients With Familial Adenomatous Polyposis.

CONTEXT: The cribriform-morula variant of papillary thyroid carcinoma (CMV-PTC) is a rare variant of PTC and is associated with familial adenomatous polyposis (FAP). However, the incidence and the nature of CMV-PTC among FAP patients have not been well characterized. OBJECTIVE: The aim of this study was to determine the incidence and characteristics of thyroid cancer screened by neck ultrasonography for FAP patients. Design, Patients, and Intervention: A total of 129 FAP patients were included in this study. Neck ultrasonography was performed using a 12.0-MHz transducer probe. Germline APC gene mutation was examined for by the protein truncation test or DNA sequencing methods. DESIGN, PATIENTS, AND INTERVENTION: A total of 129 FAP patients were included in this study. Neck ultrasonography was performed using a 12.0-MHz transducer probe. Germline APC gene mutation was examined for by the protein truncation test or DNA sequencing methods. RESULTS: Twenty-one patients (16.3%) had solid nodules, and 24 patients (18.6%) had benign cystic nodules. In total, PTC was found in 11 patients (16% of the women and 0% of the men), 8 of which were CMV-PTC and the rest were classical PTC. In 17 female patients with thyroid nodules, CMV-PTC occurred in 8 of 9 patients who were 35 years age or younger but in none of the 8 patients who were older than 35 (P = .0004 by Fisher's exact test). The APC germline mutations in 8 patients with CMV-PTC were present at the 5' side of the profuse type of FAP region (codons 1249-1330). CONCLUSIONS: The prevalence of CMV-PTC in FAP patients was higher than previously reported and this type of tumor was found preferentially in younger (under age 35) female patients with FAP in this cohort.