PCSK9 inhibitors in real life-Cardiometabolic risk management in dyslipidemic patients in Vienna.

BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have emerged as important therapeutic options for patients unable to achieve the low-density lipoprotein cholesterol (LDL­C) target or to tolerate alternative lipid-lowering agents. The aim of this study was to investigate the efficacy of PCSK9 inhibitor treatment in tertiary routine care, by determining the percentage of patients reaching individual LDL­C target levels 1 year after treatment initiation. PATIENTS AND METHODS: Patients routinely started on PCSK9 inhibitors at our lipid clinic between 2017 and 2020 were retrospectively analyzed. Attainment of the LDL­C target, utilization of follow-ups, cardiovascular events and effects on laboratory parameters were investigated. RESULTS: In this study 347 patients were included, with the majority managed in secondary prevention (94.5%). The LDL­C target was achieved by 44.9% after ca. 14 months, with differences between statin users and non-users (51.0% vs. 22.7%; p < 0.001). The median LDL­C decreased from 126.00 mg/dL at baseline to 48 mg/dL (-61.6%; -77.00 mg/dL; p < 0.001) after ~2 months and to 60 mg/dL (-52.9%; -59.00 mg/dL; p < 0.001) after ~14 months. Median lipoprotein(a) levels decreased significantly from 184.0 nmol/L to 165.5 nmol/L (-25.9%; -25.5 nmol/L; p = 0.001) after ~2 months, whereas no effects on creatine kinase, amylase and lipase were detectable. Of the patients 15% utilized 4 follow-ups. The PCSK9 inhibitor intolerance occurred in 3.5% of patients. CONCLUSION: With the effect of LDL-lowering remaining constant over 14 months, PCSK9 inhibitor treatment showed effective and sustainable LDL­C lowering in a majority of patients in secondary prevention, bringing them closer to the recommended LDL­C goal, particularly those under concomitant statin medication. Treatment with PCSK9 inhibitors appears to be well-tolerated, confirming data from clinical trials in real life.

Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.

The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model. FSL and control rats of both genders were assessed over 8 months, characterizing their performance at different time points on motor, sensorimotor and complex learning/memory based tasks. Changes over time in physiological parameters, such as corticosterone and blood glucose levels, were monitored. Regional glucose metabolism, used as a marker of neuronal activity, was assessed at different time points using F18-FDG Positron Emission Tomography (PET). Results show that certain deficits at 2-3 months--on tests such as the Elevated Plus Maze, Object Recognition, and the Forced Swim Test--were transitory and the phenotype was no longer present when re-testing at 6-7 months of age. However, a stable impairment was detected on a learning and memory task, particularly indicating dysfunction in retention of spatial information. Furthermore, at multiple time points, the PET scan indicated a significate bilateral, hypo-metabolism in the temporal lobes in the FSL rats compared to healthy controls. The data suggests possible alterations of entorhinal cortex metabolism concomitant with specific behavioral changes and supports the importance of understanding the dynamics and the time and gender dependence of the phenotypes present.