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1. A sleep apnoea questionnaire predicts organ damage in hypertensive patients

Author

Bisogni, V, Pengo, M, Maiolino, G, Cesari, M, Lerco, S, Rossitto, G, Concistrè, A, Petramala, L, Letizia, C, Seccia, T, Rossi, G, Bisogni V, Pengo M, Maiolino G, Cesari M, Lerco S, Rossitto G, Concistrè A, Petramala L, Letizia C, Seccia TM, Rossi GP., Bisogni, V, Pengo, M, Maiolino, G, Cesari, M, Lerco, S, Rossitto, G, Concistrè, A, Petramala, L, Letizia, C, Seccia, T, Rossi, G, Bisogni V, Pengo M, Maiolino G, Cesari M, Lerco S, Rossitto G, Concistrè A, Petramala L, Letizia C, Seccia TM, and Rossi GP.

Abstract

Background: Arterial hypertension is associated with obstructive sleep apnoea, poor quality and duration of sleep, which might contribute to hypertension-mediated organ damage. Methods: We investigated the presence of insomnia, restless legs syndrome, and obstructive sleep apnoea using validated questionnaires (Insomnia Severity Index, Restless Legs Syndrome Rating Scale, and STOP-Bang), and their relationship with hypertension-mediated organ damage, in hypertensive patients. Results: In 159 consecutive consenting hypertensive patients [age 47(11) years, median and (interquartile range), body mass index 25.5(5.9) kg/m 2 , office systolic and diastolic blood pressure 144(23)/92(12) mmHg], the STOP-Bang, but not the other scores, predicted cardiac remodelling: compared to patients with a STOP-Bang score < 3, those at high risk of obstructive sleep apnoea showed higher left ventricular mass index [49.8(11.9) vs. 43.3(11.9) g/m 2.7 , p < 0.0001], left atrium volume [25.7(2.5) vs. 25.0(2.8) ml/m 2 , p = 0.003], and aortic root diameter [33.6(3.0) vs. 33.0(3.7) mm, p < 0.0001]. They did not differ for microalbuminuria and estimated glomerular filtration rate. At multivariate analysis, after adjustment for office systolic blood pressure values, the STOP-Bang score remained a predictor of left ventricular mass index; while the Insomnia Severity Index and restless legs syndrome risk score had no predictive value. However, a significant interaction between STOP-Bang and Restless Legs Syndrome Rating Scale scores in determining left ventricular remodelling was found. Conclusions: In consecutive hypertensive stage I patients the STOP-Bang questionnaire allowed identification of a high-risk cohort featuring a more prominent cardiac damage. Hence, this inexpensive tool can be useful for risk stratification purposes in municipalities with limited access to health care resources.

Published
2019

2. Design of a study to investigate the mechanisms of obstructive sleep apnoea by means of drug-induced sleep endoscopy

Author

Bisogni, V, Maiolino, G, Ceolotto, G, Pengo, M, Marchese Ragona, R, Artusi, C, Brugnolo, L, Lerco, S, Borsetto, D, Gaudioso, P, Martini, A, Plebani, M, Rossi, G, Bisogni V., Maiolino G., Ceolotto G., Pengo M., Marchese Ragona R., Artusi C., Brugnolo L., Lerco S., Borsetto D., Gaudioso P., Martini A., Plebani M., Rossi G. P., Bisogni, V, Maiolino, G, Ceolotto, G, Pengo, M, Marchese Ragona, R, Artusi, C, Brugnolo, L, Lerco, S, Borsetto, D, Gaudioso, P, Martini, A, Plebani, M, Rossi, G, Bisogni V., Maiolino G., Ceolotto G., Pengo M., Marchese Ragona R., Artusi C., Brugnolo L., Lerco S., Borsetto D., Gaudioso P., Martini A., Plebani M., and Rossi G. P.

Abstract

Obstructive sleep apnoea (OSA) is an independent risk factor of hypertension and cardiovascular diseases. Recurrent episodes of upper airways collapse during sleep causing blood oxygen desaturation, hypercapnia, and micro-arousals, are known to activate the sympathetic nervous system (SNS). However, whether changes in the renin-angiotensin-aldosterone system and endothelial activation also occur remains contentious. Based on routine use of drug-induced sleep endoscopy (DISE) for the work-up of OSA patients in our centre, we designed a prospective study to investigate the haemodynamic and humoral changes occurring during the apnoeic episodes reproduced in vivo in the course of DISE. Specifically, plasma aldosterone concentration and renin activity, C-terminal fragment of proendothelin-1, as a marker of endothelial damage, and free plasma catecholamines, will be measured at fixed times during DISE. The activity of catechol-O-methyltransferase (COMT), a key catecholamine-inactivating enzyme that has been scantly investigated thus far owing to the lack of commercially available kits, will be also determined by a newly developed high performance liquid chromatography method, which is herein described. The aim of this study is to provide novel information on the haemodynamic, hormonal, and SNS changes, and also on COMT activity modification concomitantly occurring during apnoea, thus contributing substantively to the understanding of the pathophysiology of OSA.

Published
2019

3. A sleep apnoea questionnaire predicts organ damage in hypertensive patients

Author

Silvia Lerco, Claudio Letizia, Luigi Petramala, Teresa Maria Seccia, Maurizio Cesari, Antonio Concistrè, Giacomo Rossitto, Martino F. Pengo, Gian Paolo Rossi, Valeria Bisogni, Giuseppe Maiolino, Bisogni, V, Pengo, M, Maiolino, G, Cesari, M, Lerco, S, Rossitto, G, Concistrè, A, Petramala, L, Letizia, C, Seccia, T, and Rossi, G

Subjects
Adult, Male, medicine.medical_specialty, Sleep Apnea, hypertension, hypertension-mediated organ damage, insomnia, Obstructive sleep apnoea, restless legs syndrome, Female, Heart, Heart Injuries, Humans, Hypertension, Kidney, Middle Aged, Risk Assessment, Risk Factors, Severity of Illness Index, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Surveys and Questionnaires, 030204 cardiovascular system & hematology, Poor quality, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Insomnia, Internal Medicine, 030212 general & internal medicine, Restless legs syndrome, business.industry, Obstructive, General Medicine, medicine.disease, Sleep in non-human animals, Organ damage, Cardiology, Cardiology and Cardiovascular Medicine, medicine.symptom, business
Abstract

Background: Arterial hypertension is associated with obstructive sleep apnoea, poor quality and duration of sleep, which might contribute to hypertension-mediated organ damage. Methods: We investigated the presence of insomnia, restless legs syndrome, and obstructive sleep apnoea using validated questionnaires (Insomnia Severity Index, Restless Legs Syndrome Rating Scale, and STOP-Bang), and their relationship with hypertension-mediated organ damage, in hypertensive patients. Results: In 159 consecutive consenting hypertensive patients [age 47(11) years, median and (interquartile range), body mass index 25.5(5.9) kg/m 2 , office systolic and diastolic blood pressure 144(23)/92(12) mmHg], the STOP-Bang, but not the other scores, predicted cardiac remodelling: compared to patients with a STOP-Bang score < 3, those at high risk of obstructive sleep apnoea showed higher left ventricular mass index [49.8(11.9) vs. 43.3(11.9) g/m 2.7 , p < 0.0001], left atrium volume [25.7(2.5) vs. 25.0(2.8) ml/m 2 , p = 0.003], and aortic root diameter [33.6(3.0) vs. 33.0(3.7) mm, p < 0.0001]. They did not differ for microalbuminuria and estimated glomerular filtration rate. At multivariate analysis, after adjustment for office systolic blood pressure values, the STOP-Bang score remained a predictor of left ventricular mass index; while the Insomnia Severity Index and restless legs syndrome risk score had no predictive value. However, a significant interaction between STOP-Bang and Restless Legs Syndrome Rating Scale scores in determining left ventricular remodelling was found. Conclusions: In consecutive hypertensive stage I patients the STOP-Bang questionnaire allowed identification of a high-risk cohort featuring a more prominent cardiac damage. Hence, this inexpensive tool can be useful for risk stratification purposes in municipalities with limited access to health care resources.

Published
2020
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4. Design of a study to investigate the mechanisms of obstructive sleep apnoea by means of drug-induced sleep endoscopy

Author

Piergiorgio Gaudioso, Martino F. Pengo, Valeria Bisogni, Mario Plebani, Alessandro Martini, Gian Paolo Rossi, Laura Brugnolo, Silvia Lerco, Giulio Ceolotto, Daniele Borsetto, Carlo Artusi, Rosario Marchese Ragona, Giuseppe Maiolino, Bisogni, V, Maiolino, G, Ceolotto, G, Pengo, M, Marchese Ragona, R, Artusi, C, Brugnolo, L, Lerco, S, Borsetto, D, Gaudioso, P, Martini, A, Plebani, M, and Rossi, G

Subjects
Adult, Male, Sympathetic nervous system, medicine.medical_specialty, obstructive sleep apnoea, catechol-O-methyltransferase, Clinical Biochemistry, Hemodynamics, Pilot Projects, 030204 cardiovascular system & hematology, Catechol O-Methyltransferase, Plasma renin activity, Endothelial activation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Catecholamines, Internal medicine, Renin–angiotensin system, Renin, medicine, Humans, 030212 general & internal medicine, Prospective Studies, drug-induced sleep endoscopy, endothelin-1, renin-angiotensin-aldosterone system, sympathetic nervous system, Protein Precursors, Aldosterone, Sleep Apnea, Obstructive, Catechol-O-methyl transferase, business.industry, Biochemistry (medical), Endoscopy, General Medicine, medicine.anatomical_structure, chemistry, Research Design, Cardiology, medicine.symptom, business, Sleep, Hypercapnia
Abstract

Background Obstructive sleep apnoea (OSA) is an independent risk factor of hypertension and cardiovascular diseases. Recurrent episodes of upper airways collapse during sleep causing blood oxygen desaturation, hypercapnia, and micro-arousals, are known to activate the sympathetic nervous system (SNS). However, whether changes in the renin-angiotensin-aldosterone system and endothelial activation also occur remains contentious. Methods Based on routine use of drug-induced sleep endoscopy (DISE) for the work-up of OSA patients in our centre, we designed a prospective study to investigate the haemodynamic and humoral changes occurring during the apnoeic episodes reproduced in vivo in the course of DISE. Specifically, plasma aldosterone concentration and renin activity, C-terminal fragment of proendothelin-1, as a marker of endothelial damage, and free plasma catecholamines, will be measured at fixed times during DISE. The activity of catechol-O-methyltransferase (COMT), a key catecholamine-inactivating enzyme that has been scantly investigated thus far owing to the lack of commercially available kits, will be also determined by a newly developed high performance liquid chromatography method, which is herein described. Results and conclusions The aim of this study is to provide novel information on the haemodynamic, hormonal, and SNS changes, and also on COMT activity modification concomitantly occurring during apnoea, thus contributing substantively to the understanding of the pathophysiology of OSA.

Published
2019

5. Eryptosis in Peritoneal Dialysis-Related Peritonitis: The Potential Role of Inflammation in Mediating the Increase in Eryptosis in PD.

Author

Virzì GM, Milan Manani S, Marturano D, Clementi A, Lerco S, Tantillo I, Giuliani A, Battaglia GG, Ronco C, and Zanella M

Abstract

Background: Peritonitis and exit site infections are the main complications of patients treated with peritoneal dialysis (PD). Erythrocytes (red blood cells—RBCs) are very sensitive cells, and they are characterized by eryptosis (programmed cell death). The purpose of this research was to assess eryptosis in PD patients with PD-related peritonitis and its connection to inflammatory markers in vivo and in vitro. Material and Methods: In this study, we included 65 PD patients: 34 PD patients without systemic inflammation nor PD-related peritonitis in the previous 3 months, and 31 PD patients with an acute episode of PD-related peritonitis. We measured C-reactive protein (CRP) and cytokine (IL-1β, IL-6, and IL-18) levels as systemic inflammatory markers. Eryptosis was evaluated by flow cytometric analyses in freshly isolated RBCs. The induction of eryptosis due to in vitro exposure to IL-1β, IL-6, and IL-18 was verified. Results: Eryptosis was significantly higher in PD patients with peritonitis (9.6%; IQR 4.2−16.7), compared to the those in the other group (2.7%; IQR 1.6−3.9) (p < 0.0001). Significant positive correlations were noticed between eryptosis and CRP, IL-1β, and IL-6. RBCs, incubated with greater concentrations of all cytokines in vitro, resulted in significantly higher occurrences of eryptosis in comparison with those incubated with lower concentration and with untreated cell (p < 0.05), and for those with extensive exposure (p < 0.05). Conclusion: In conclusion, we investigated a potential relationship between systemic eryptosis and the in vivo and in vitro inflammatory damage of the peritoneal membrane during peritonitis. Thus, the presented results revealed that upregulated inflammatory markers and immune system dysregulation could be the cause of high levels of systemic eryptosis during PD-related peritonitis.

Published
2022
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6. High sodium intake, glomerular hyperfiltration, and protein catabolism in patients with essential hypertension.

Author

Rossitto G, Maiolino G, Lerco S, Ceolotto G, Blackburn G, Mary S, Antonelli G, Berton C, Bisogni V, Cesari M, Seccia TM, Lenzini L, Pinato A, Montezano A, Touyz RM, Petrie MC, Daly R, Welsh P, Plebani M, Rossi GP, and Delles C

Subjects
Adult, Biomarkers blood, Biomarkers urine, Essential Hypertension physiopathology, Female, Fluid Shifts, Humans, Kidney physiopathology, Male, Metabolomics, Middle Aged, Natriuresis, Water-Electrolyte Balance, Blood Pressure, Dietary Proteins metabolism, Essential Hypertension metabolism, Glomerular Filtration Rate, Kidney metabolism, Metabolome, Muscle Proteins metabolism, Sodium, Dietary metabolism
Abstract

Aims: A blood pressure (BP)-independent metabolic shift towards a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures, as surrogates for cardiovascular risk, in hypertensive patients., Methods and Results: We analysed clinical and biochemical data from 766 consecutive patients with essential hypertension, collected at the time of screening for secondary causes. The systematic screening protocol included 24 h urine (24 h-u-) collection on usual diet and avoidance of renin-angiotensin-aldosterone system-confounding medications. Urinary 24 h-Na+ excretion, used to define classes of Na+ intake (low ≤2.3 g/day; medium 2.3-5 g/day; high >5 g/day), was an independent predictor of glomerular filtration rate after correction for age, sex, BP, BMI, aldosterone, and potassium excretion [P = 0.001; low: 94.1 (69.9-118.8) vs. high: 127.5 (108.3-147.8) mL/min/1.73 m2]. Renal Na+ and water handling diverged, with higher fractional excretion of Na+ and lower fractional excretion of water in those with evidence of high Na+ intake [FENa: low 0.39% (0.30-0.47) vs. high 0.81% (0.73-0.98), P < 0.001; FEwater: low 1.13% (0.73-1.72) vs. high 0.89% (0.69-1.12), P = 0.015]. Despite higher FENa, these patients showed higher absolute 24 h Na+ reabsorption and higher associated tubular energy expenditure, estimated by tubular Na+/ATP stoichiometry, accordingly [Δhigh-low = 18 (12-24) kcal/day, P < 0.001]. At non-targeted liquid chromatography/mass spectrometry plasma metabolomics in an unselected subcohort (n = 67), metabolites which were more abundant in high versus low Na+ intake (P < 0.05) mostly entailed intermediates or end products of protein catabolism/urea cycle., Conclusion: When exposed to high Na+ intake, kidneys dissociate Na+ and water handling. In hypertensive patients, this comes at the cost of higher glomerular filtration rate, increased tubular energy expenditure, and protein catabolism from endogenous (muscle) or excess exogenous (dietary) sources. Glomerular hyperfiltration and the metabolic shift may have broad implications on global cardiovascular risk independent of BP., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2021
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