Serum uric acid and left ventricular geometry pattern in obese children.

Relative importance of traditional and non-traditional components of metabolic syndrome (MetSy) as risk factors for subclinical target organ damage in obese children is still under investigation. Recent studies highlight the role of serum uric acid (SUA) as an emerging non-traditional independent risk factor which correlates with obesity, MetSy, type 2 diabetes, preclinical cardiac and extracardiac organ damage, as well as cardiovascular events. To study the relationship between SUA and left ventricular geometry pattern in obese children with or without MetSy. In this cross-sectional study, a total of 73 obese children, 64.4% male, and 35.6% female, with median age of 15 years (IQR = 12-16) were examined. Body mass index, glycaemia, standard lipid profile, fasting insulin level, HOMA index, serum uric acid level, 24-h average systolic blood pressure, left ventricular mass index (LVMI) and relative wall thickness (RWT) were evaluated in all children. LVMI in our study group was 46 g/m2.7 (IQR = 42-55) while the RWT was 37% (IQR = 31-41). Median SUA level was 341 μmol/L (IQR = 283-387). In the entire sample of children, SUA was independently associated with the RWT (coeff = 0.02, p < 0.01). In a sub-group of metabolically unhealthy children, we found no statistically significant association between SUA and LVMI nor between SUA and RWT (coeff. = 0.002, p = 0.92; coeff. = 0.01, p = 0.20, respectively). Serum uric acid is an important independent non-traditional risk factor for the development of concentric left ventricular geometry in obese children. These findings deserve further investigation to determine whether high SUA in obese children may be a therapeutic target.

被引量：7 发表：2019

Experience with proprotein convertase subtilisin/kexine type 9 inhibitors (PCSK9i) in patients undergoing lipoprotein apheresis.

We analyzed efficacy and safety of PCSK9i in patients undergoing lipoprotein apheresis (LA) and in patients treated at our outpatient department for metabolic disorders. The medical records of 40 LA patients, taking PCSK9i were reviewed with respect to LDL-cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) lowering as well as occurrence of adverse events. Furthermore, we analyzed the data of 152 patients of our outpatient department, undergoing PCSK9i therapy. Mean pre-apheresis LDL-C value was reduced by PCSK9i from 3.71 ± 1.19 to 1.78 ± 0.84 mmol/l (53 ± 12%). The relative lowering of the pre-apheresis Lp(a) was 20 ± 12% (from 191 ± 63.5 to 152 ± 51.9 nmol/l). 25% of LA patients could stop LA after reaching LDL-C target after initiation of PCSK9i. 75% of the patients are continuing the regular LA therapy, showing an insufficient LDL-C lowering following PCSK9i injections or/and additionally elevated Lp(a) or/and adverse effects of PCSK9i, leading to the discontinuation of injections. The number of LA patients has grown from 112 in 2016 to 128 nowadays due to an increasing percentage of patients with elevated Lp(a) (79% and 89% respectively). The mean reduction rate of LDL-C under PCSK9i therapy in outpatients was 53.03%. In 34% of patients the target value could not be reached. 43% of persons suffered from adverse effects. 3/4 of LA patients could not stop extracorporeal treatment after PCSK9i administration. In hypercholesterolemic patients with coexisting elevated Lp(a) and progressive cardiovascular disease the combination of LA and PCSK9i could be beneficial. The total patients' number in LA units increases due to persons with Lp(a)-hyperlipoproteinemia.

被引量：2 发表：2019

The efficacy of anti-PCSK9 antibodies: Results from recent trials.

The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to the lysosome for degradation. This results in decreased numbers of LDLR available on the cell surface to bind LDL particles and remove them from the circulation and a subsequent increase in circulating LDL-cholesterol (LDL-C) concentrations. Since the role PCSK9 plays in LDL-C metabolism has been discovered in 2003, there have been major efforts in finding efficient and safe methods to inhibit it. Amongst those the fully human PCSK9 antibodies evolocumab and alirocumab have been studied in a wide range of patients such as in those with statin intolerance, as add-on to statin therapy, as monotherapy and in patients with familial hypercholesterolemia and they have been shown to decrease LDL-C by ∼50 to 70%. Rates of achieving LDL-C goals are up to 87-98% of treated subjects. Multiple phase 3 studies with these drugs are already completed and cardiovascular endpoint trials are expected to be concluded by the end of 2016. Both, alirocumab and evolocumab have been approved in 2015 for the treatment of hypercholesterolemia in the European Union and in the United States. Preliminary meta-analytic data show an improvement in cardiovascular morbidity and mortality by ∼50%. If the large ongoing endpoint trials confirm the cardiovascular efficacy and overall safety of these drugs, PCSK9 antibodies will revolutionarize lipid-lowering therapy.

被引量：- 发表：1970

Current insights into the German lipoprotein apheresis standard: PCSK9-inhibitors, lipoprotein apheresis or both?

According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. The therapeutic approach for patients with homozygous familial hypercholesterolemia is unambiguous: In addition to LA, in order to improve LDL-C reduction, PCSK9-I could be applied. In patients with heterozygous familial hypercholesterolemia, PCSK9-I is to be applied first. If in addition to a pronounced LDL-C elevation, cardiovascular complications exist or if imaging techniques documented atherosclerotic changes pre-disposing for a cardiovascular event while LDL-C reduction is insufficiently reduced (LDL-C > 100 mg/dl (2.6 mmol/l)), LA treatment should then be applied as last resort. In patients with elevated Lp(a) concentrations (Lp(a) > 60 mg/dl (>120 nmol/l)) and established cardiovascular disease, therapy should rely primarily on LA methods. If in addition to high Lp(a) levels insufficiently treated LDL-C concentrations (LDL-C > 100 mg/dl (2.6 mmol/l)) exist, in rare cases PCSK9-I can supplement the lipid lowering concept.

被引量：1 发表：1970

Lectin-like oxidized low-density lipoprotein receptor-1 promotes endothelial dysfunction in LDL receptor knockout background.

被引量：8 发表：2017