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.

Effect of Statin Therapy on the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients With Hyperlipidemia: A Proof-of-concept Observational Study.

PURPOSE: Statins are commonly used in patients with hypercholesterolemia to lower their cholesterol levels and to reduce their cardiovascular risk. There is also considerable evidence that statins possess a range of cholesterol-independent effects, including profibrinolytic properties. This pilot study aimed to explore the influence of statins on procarboxypeptidase U (proCPU) biology and to search for possible effects and associations that can be followed up in a larger study. METHODS: Blood was collected from 16 patients with hyperlipidemia, before and after 3 months of statin therapy (simvastatin 20 mg or atorvastatin 20 mg). Fifteen age-matched normolipemic persons served as control subjects. Lipid parameters and markers of inflammation and fibrinolysis (proCPU levels and clot lysis times) were determined in all samples. FINDINGS: Mean (SD) proCPU levels were significantly higher in patients with hypercholesterolemia compared to control subjects (1186 [189] U/L vs 1061 [60] U/L). Treatment of these patients with a statin led to a significant average decrease of 11.6% in proCPU levels and brought the proCPU concentrations to the same level as in the control subjects. On a functional level, enhancement in plasma fibrinolytic potential was observed in the statin group, with the largest improvement in fibrinolysis seen in patients with the highest baseline proCPU levels and largest proCPU decrease upon statin treatment. IMPLICATIONS: Increased proCPU levels are present in patients with hyperlipidemia. Statin treatment significantly decreased proCPU levels and improved plasma fibrinolysis in these patients. Moreover, our study indicates that patients with high baseline proCPU levels are most likely to benefit from statin therapy. The latter should be examined further in a large cohort.

Patient Perceptions of Electronic Prescriptions in Belgium: An Exploratory Policy Analysis.

In today's world, digitalization and automation are ubiquitous and different countries have different strategies for implementing information technology in health care. In Belgium, these plans include the dematerialization of prescriptions, following the implementation of a system of electronic prescribing. In the light of these changes, we studied the attitudes of patients toward a paperless prescription. We collected the opinions of 273 patients by survey. Older people, or people with more complex medical needs, expressed a clear desire to keep receiving a paper version of the prescription. Younger people foresaw practical advantages, and expressed a willingness to buy prescription-only medicines online. Knowledge about the planned changes was, however, limited. Privacy and autonomy issues were expressed by a large fraction of people. The problem of what happens when a third person wants to pick up medicines for a patient, a frequent occurrence, was often mentioned. We conclude that, at present, patients have inadequate knowledge and understanding about the planned changes. In light of these considerations and the recent technical problems encountered by the system, we feel that an updated risk/benefit analysis of the planned policy is urgently needed.

Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections.

PURPOSE: Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families. METHODS: We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed. RESULTS: We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-ß signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture. CONCLUSION: In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-ß signaling.Genet Med 19 4, 386-395.

Where does selective laser trabeculoplasty stand now? A review.

BACKGROUND: Chronic treatment of glaucoma can present a challenge in patients who lack the means and/or the discipline to use daily glaucoma medication. We wondered if selective laser trabeculoplasty (SLT) could be a useful alternative. INCLUSION CRITERIA: controlled trials comparing efficacy of SLT in adult patients with any form of open angle glaucoma or ocular hypertension and case reports on side effects of SLT. Two recent meta-analyses identified eight randomized clinical trials (RCTs) comparing the effect of SLT with medication (prostaglandin analogs) and with argon laser trabeculoplasty (ALT). We took these eight RCTs as reference base and calculated their success rates where they were not given. Other articles were added to elaborate on technique and side effects. RESULTS: Mean intraocular pressure (IOP) reduction after SLT was 3.8-8.0 mmHg after 6 months to 1 year. Mean success rate of SLT at 6 months to 1 year is 55-82 %. Higher IOP before laser predicts a higher IOP-lowering effect. In terms of mean IOP reduction, reduction in number of medications and treatment success, the effect of SLT was found to show no clinically relevant difference from that of contemporary medication (prostaglandin analogs) and from ALT. CONCLUSIONS: The evidence indicates that SLT is an efficacious primary or adjunctive therapy for treating glaucoma.