Artykuł oryginalnyAtorwastatyna zmniejsza aktywność współczulną i poprawia czułość odruchu z baroreceptorów u osób z hipercholesterolemią i nadciśnieniem tętniczym

Background: Increased sympathetic activity might be related to pathogenesis of hypertension as well as to end organ damage. Animal studies suggest that statins decrease sympathetic activity and increase baroreceptor reflex sensitivity (BRS). Aim: To examine whether atorvastatin decreases muscle sympathetic nerve activity (MSNA) and BRS in hypercholesterolaemic and hypertensive patients. Methods: Ten patients with essential hypertension and untreated hypercholesterolaemia (aged 43 &#177; 12 years) and eight healthy subjects (aged 37 &#177; 7 years) were enrolled in the study. In both groups the recordings of microneurography, ECG, blood pressure and BRS were performed twice, before and after 8 weeks during which the patients (but not controls) were treated with atorvastatin. Results: Compared with controls, the patients had higher MSNA values (36.0 &#177; 6.6 vs. 29.8 &#177; 3.7 bursts/minute), mean BP levels (145.1 &#177; 10 vs. 124.1 &#177; 11.1 mmHg) and total cholesterol concentration (252.6 &#177; 22.6 vs. 179.8 &#177; 20.7 mg/dl) baseline values. Statin therapy resulted in a decrease of total cholesterol (252.6 &#177; 22.0 vs. 173.8 &#177; 26.2 mg/dl, p < 0.05) and MSNA (36.0 &#177; 6.6 vs. 28.6 &#177; 4.8 bursts/min, p < 0.05), whereas BRS values were increased (12.6 &#177; 5.6 vs. 18.1 &#177; 5.9 ms/mmHg, p < 0.05). Post-treatment BRS was inversely related to post-treatment MSNA (r = &#8211;0.73, p < 0.05). In the controls there were no changes in MSNA (29.8 &#177; 3.7 vs. 28.9 &#177; 2.9 bursts/min), BRS (11.9 &#177; 5.0 vs. 13.1 &#177; 4.8 ms/mmHg), total cholesterol, BP and heart rate between the first and the second measurement. Conclusion: Atorvastatin reduces MSNA and increases BRS in hypertensive and hypercholesterolaemic patients. Decrease in sympathetic activity may be the result of improvement of baroreceptor function by atorvastatin.Wstęp: Zwiększona aktywność układu współczulnego odgrywa istotną rolę w patogenezie nadciśnienia tętniczego i jego powikłań. Badania na modelu zwierzęcym sugerują, że statyny mogą obniżać aktywność współczulną i zwiększać czułość odruchu z baroreceptorów (ang. baroreceptor reflex sensitivity, BRS). Cel: Ocena, czy atorwastatyna obniża aktywność współczulną rejestrowaną jako aktywność domięśniowych nerwów współczulnych (ang. muscle sympathetic nerve activity, MSNA) metodą mikroneurografii oraz jak wpływa na BRS u osób z nadciśnieniem tętniczym i hipercholesterolemią. Metody: Zbadano 10 mężczyzn chorych na nadciśnienie tętnicze pierwotne z nieleczoną hipercholesterolemią (wiek 43 &#177; 12 lat) i 8 mężczyzn zdrowych (37 &#177; 7 lat). W obu grupach na początku i po 8 tygodniach wykonano badanie MSNA, ocenę BRS, EKG i pomiary ciśnienia tętniczego. W 8-tygodniowym okresie między badaniami statynę podawano tylko w grupie z hipercholesterolemią. Wyniki: U chorych w porównaniu z grupą kontrolną stwierdzano wyższą aktywność współczulną podczas oceny MSNA (36,0 &#177; 6,6 vs 29,8 &#177; 3,7 pobudzeń/min), wyższe średnie ciśnienie tętnicze (145,1 &#177; 10 vs 124,1 &#177; 11,1 mmHg) i stężenie cholesterolu całkowitego (252,6 &#177; 22,6 vs 179,8 &#177; 20,7 mg/dl). Podawanie atorwastatyny spowodowało obniżenie stężenia cholesterolu (252,6 &#177; 22,0 vs 173,8 &#177; 26,2 mg/dl, p < 0,05) i aktywności współczulnej podczas badania MSNA (36,0 &#177; 6,6 vs 28,6 &#177; 4,8 pobudzeń/min, p < 0,05) oraz zwiększenie BRS (12,6 &#177; 5,6 vs 18,1 &#177; 5,9 ms/mmHg, p < 0,05). U chorych leczonych atorwastatyną odruch z baroreceptorów korelował ujemnie z aktywnością współczulną mierzoną podczas MSNA (r = &#8211;0,73, p < 0,05). W grupie kontrolnej między pierwszym a drugim badaniem nie stwierdzono zmian w aktywności współczulnej podczas oceny MSNA (29,8 &#177; 3,7 vs 28,9 &#177; 2,9 pobudzeń/min), w BRS (11,9 &#177; 5,0 vs 13,1 &#177; 4,8 ms/mmHg), stężeniu cholesterolu, ciśnieniu tętniczym i częstotliwości pracy serca. Wnioski: Podanie atorwastatyny zmniejsza aktywność współczulną mierzoną MSNA i zwiększa BRS u osób z nadciśnieniem tętniczym i hipercholesterolemią. Zmniejszenie aktywności współczulnej może wynikać z poprawy BRS

Atorvastatin reduces sympathetic activity and increases baroreceptor reflex sensitivity in patients with hypercholesterolaemia and systemic arterial hypertension

Background: Increased sympathetic activity might be related to pathogenesis of hypertension as well as to end organ damage. Animal studies suggest that statins decrease sympathetic activity and increase baroreceptor reflex sensitivity (BRS). Aim: To examine whether atorvastatin decreases muscle sympathetic nerve activity (MSNA) and BRS in hypercholesterolaemic and hypertensive patients. Methods: Ten patients with essential hypertension and untreated hypercholesterolaemia (aged 43 ± 12 years) and eight healthy subjects (aged 37 ± 7 years) were enrolled in the study. In both groups the recordings of microneurography, ECG, blood pressure and BRS were performed twice, before and after 8 weeks during which the patients (but not controls) were treated with atorvastatin. Results: Compared with controls, the patients had higher MSNA values (36.0 ± 6.6 vs. 29.8 ± 3.7 bursts/minute), mean BP levels (145.1 ± 10 vs. 124.1 ± 11.1 mmHg) and total cholesterol concentration (252.6 ± 22.6 vs. 179.8 ± 20.7 mg/dl) baseline values. Statin therapy resulted in a decrease of total cholesterol (252.6 ± 22.0 vs. 173.8 ± 26.2 mg/dl, p < 0.05) and MSNA (36.0 ± 6.6 vs. 28.6 ± 4.8 bursts/min, p < 0.05), whereas BRS values were increased (12.6 ± 5.6 vs. 18.1 ± 5.9 ms/mmHg, p < 0.05). Post-treatment BRS was inversely related to post-treatment MSNA (r = -0.73, p < 0.05). In the controls there were no changes in MSNA (29.8 ± 3.7 vs. 28.9 ± 2.9 bursts/min), BRS (11.9 ± 5.0 vs. 13.1 ± 4.8 ms/mmHg), total cholesterol, BP and heart rate between the first and the second measurement. Conclusion: Atorvastatin reduces MSNA and increases BRS in hypertensive and hypercholesterolaemic patients. Decrease in sympathetic activity may be the result of improvement of baroreceptor function by atorvastatin.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.[739543]Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (Project ID No. 739543). We are grateful to Hanka Dekker and Caroline van Essen (representing Volwassen Kinderen en Stofwisselingsziekten, the Dutch metabolic patient organization) and Enrique Contreras (representing Asociacion Espanola de Enfermos de Glucogenosis, the Spanish glycogen storage disease patient organization) for co-creation of the webinars and their input during the development of the questionnaire. This research has been supported by Nina Contreras D'Agosto, a little girl living with Glycogen Storage Disease type 1b, and her parents Marta D'Agosto and Enrique Landelino Contreras Lande, through the platform Nina The Warrior and its thousands of followers and donors at www.ninalaguerrera.org.They are members of the Board of Directors of the Global GSD1b Research Alliance CureGSD1b(www.curegsd1b.org), a growing worldwide community with nearly 200 GSD1b patients and families

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia

Beyond their hypolipidemic effect, statins reduce cardiovascular risk in hypertensive subjects via various mechanisms; one suggested mechanism is that they reduce sympathetic activity. We investigated the hypothesis that simvastatin decreased muscle sympathetic nerve activity (MSNA) in 31 hypertensive subjects with hypercholesterolemia (aged 38.7±10 years). In this randomized, placebo-controlled, double-blinded study, patients were treated with simvastatin (40 mg day-1; n=15) or placebo (n=16) for 8 weeks. Before and after treatment, we measured MSNA, blood pressure and heart rate. Baroreceptor control of the heart rate, or baroreceptor sensitivity (BRS), was computed by the sequence method, a cross-analysis of systolic blood pressure and the electrocardiogram R-R interval. Blood samples were tested for plasma levels of catecholamines, neuropeptide Y, aldosterone, endothelin and renin activity. Simvastatin significantly reduced MSNA (from 36.55 to 27.86 bursts per min, P=0.001), heart rate (from 77±6.7 to 71±6.1 beats per min, P=0.01) and both total and low-density lipoprotein cholesterol (from 249±30.6 to 184±28.3 mg dl -1, P=0.001 and from 169±30.6 to 117±31.2 mg dl-1, P=0.01, respectively). Simvastatin also improved BRS (from 10.3±4.1 to 17.1±4.3 ms per mm Hg, P=0.04). No changes were observed in systolic or diastolic blood pressures, or in plasma levels of catecholamines, neuropeptide Y, endothelin, aldosterone and renin activity. After simvastatin therapy, MSNA and BRS were inversely related (r=-0.94, P<0.05). In conclusion, we found that, in patients with hypertension and hypercholesterolemia, simvastatin reduced MSNA, and this was related to increased baroreceptor sensitivity. © 2010 The Japanese Society of Hypertension All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

PURPOSE This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib