Atorvastatin downregulates plasma procarboxypeptidase U concentrations and improves fibrinolytic potential dose-dependently in hyperlipidemic individuals.

BACKGROUND: Statins efficiently lower cholesterol and also exert pleiotropic effects that extend beyond lipid lowering. In a recent pilot study, valuable information on the carboxypeptidase U (CPU) system in hyperlipidemia and the effect of statin therapy was collected. It was shown that proCPU levels are increased in hyperlipidemic patients. Statins significantly decreased proCPU levels and improved plasma fibrinolysis. Furthermore, it was suggested that patients with high baseline proCPU levels are most likely to benefit from statin therapy. OBJECTIVES: We aimed to further substantiate the effect of hyperlipidemia and statin therapy on CPU-related parameters in a larger cohort of hyperlipidemic and statin-treated individuals. METHODS: Blood was collected from 141 individuals treated with different dosages of atorvastatin (10-80 mg), 38 normolipidemic, and 37 hyperlipidemic controls. Lipid parameters and markers of fibrinolysis (proCPU and clot lysis time) were determined and compared between the groups. RESULTS: Pilot study results of high proCPU concentrations in hyperlipidemic patients and the proCPU-reducing effect of atorvastatin were confirmed. Accordingly, an improvement in plasma fibrinolytic potential was seen under the influence of atorvastatin. High interindividual variation in proCPU concentrations was observed in the hyperlipidemic cohort, with up to 80% higher proCPU levels compared with normolipidemic controls. Furthermore, proCPU concentration and the dosage of atorvastatin were inversely correlated. CONCLUSIONS: This study clearly shows that plasma proCPU concentrations and its expected effect on the fibrinolytic rate (as measured by clot lysis time) are increased in hyperlipidemic patients and that these effects can be normalized (and even further reduced compared with normolipidemic patients) by atorvastatin treatment.

Testicular asymmetry in healthy adolescent boys.

OBJECTIVES: To assess the presence of testicular asymmetry and the currently used threshold values in varicocoele management in a healthy adolescent population. SUBJECTS AND METHODS: We conducted an observational cross-sectional study from April 2015 until December 2016 in which we recruited 539 adolescent boys aged 11-16 years. A clinical examination including testicular size measurement by ultrasonography was performed. Testicular volume (TV) was calculated using the Lambert formula (length × width × height × 0.71). The Testicular Atrophy Index (TAI) was calculated using the formula [(TV right - TV left)/largest TV] × 100. The data for all statistical analyses were stratified for Tanner stage for genital development (TSG) and pubic hair (TSP). Non-parametric tests were used to assess the difference between right and left TV, and the prevalence of a smaller left testis for the entire population, and between each TSG and TSP. Parametric tests were used to determine the difference in mean TAI between each TSG and TSP, and to compare the mean TAI to a test value of 0. RESULTS: Of the 539 recruited boys, we excluded 194 due to a current or past pathology, including varicocoeles, influencing normal (testicular) growth or due to incomplete data. Most boys were in the second Tanner stage, followed by the third Tanner stage. The mean (sd) age of the entire population was 13.33 (1.25) years. Of the 345 included participants the mean (sd) left TV was 7.67 (5.63) mL and right TV was 7.97 (5.90) mL. The mean (sd) TAI was 2.85 (17.00)%. In all, 203 (58.84%) boys had a smaller left testis and 142 (41.16%) had a smaller right testis. In all, 51 boys (14.78%) had a TAI >20%, 45 (13.04%) had a TV difference (TVD) of >2 mL with a deficit in left TV, and 69 (20.00)% had a TAI >20% or a TVD of >2 mL with a deficit in left TV. Related-samples Wilcoxon signed-rank test showed a significant difference in mean left and right TV for the entire population, and more specifically for TSG3 (P < 0.001) and TSP3 (P = 0.004). A one-sample t-test showed a significant difference in the mean TAI vs the test value of 0 for the entire population (P = 0.002), and more specifically for TSG3 (P < 0.001) and TSP3 (P = 0.003). CONCLUSION: Testicular asymmetry, with a smaller left testis, was seen in a considerable number of healthy adolescents. One out of five adolescents had a smaller left testis and met one of the threshold values currently used in varicocoele management. Therefore, in left-sided unilateral inguinoscrotal pathology, a smaller ipsilateral testis in combination with a TAI of >20% and/or TVD of >2 mL requires careful interpretation and serial measurements of TV should always be performed. Furthermore, this study provides reference values for TV, TVD and TAI according to TSG and TSP for a healthy adolescent population.