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Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

Independent associations between arterial bicarbonate, apnea severity and hypertension in obstructive sleep apnea

Authors: Davoud Eskandari, Ding Zou, Ludger Grote, Hartmut Schneider, Thomas Penzel, Jan Hedner

Published in: Respiratory Research | Issue 1/2017

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Abstract

Background

Obstructive sleep apnea is characterized by intermittent hypoxia and hypercapnia. CO2 production, transport and elimination are influenced by the carbonic anhydrase enzyme. We hypothesized that elevated standard bicarbonate, a proxy for increased carbonic anhydrase activity, is associated with apnea severity and higher blood pressure in patients with obstructive sleep apnea.

Methods

A retrospective analysis of a sleep apnea cohort (n = 830) studied by ambulatory polygraphy. Office systolic/diastolic blood pressure, lung function, and arterial blood gases were assessed during daytime.

Results

Arterial standard bicarbonate was increased with apnea severity (mild/moderate/severe 24.1 ± 1.8, 24.4 ± 1.7 and 24.9 ± 2.9 mmol/l, respectively, Kruskal-Wallis test p < 0.001). Standard bicarbonate was independently associated with apnea hypopnea index after adjustment for sex, age, body mass index, smoking, alcohol, hypertension, pO2 and pCO2 (standard bicarbonate quartile 1 vs. quartile 4, β = 10.6, p < 0.001). Log-transformed standard bicarbonate was associated with a diagnosis of hypertension or diastolic blood pressure but not systolic blood pressure adjusting for cofounders (p = 0.007, 0.048 and 0.45, respectively).

Conclusions

There was an independent association between sleep apnea severity and arterial standard bicarbonate. The link between high standard bicarbonate and daytime hypertension suggests that carbonic anhydrase activity may constitute a novel mechanism for blood pressure regulation in sleep apnea.
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Literature
2.
go back to reference Maren TH. Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol Rev. 1967;47:595–781.PubMed Maren TH. Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol Rev. 1967;47:595–781.PubMed
3.
go back to reference Wang T, Eskandari D, Zou D, Grote L, Hedner J. Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia. Sleep. 2015;38:1067–73.CrossRefPubMedPubMedCentral Wang T, Eskandari D, Zou D, Grote L, Hedner J. Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia. Sleep. 2015;38:1067–73.CrossRefPubMedPubMedCentral
4.
go back to reference McNicholas WT, Bonsigore MR. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J. 2007;29:156–78.CrossRefPubMed McNicholas WT, Bonsigore MR. Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J. 2007;29:156–78.CrossRefPubMed
5.
go back to reference Parati G, Lombardi C, Hedner J, Bonsignore MR, Grote L, Tkacova R, Levy P, Riha R, Bassetti C, Narkiewicz K, et al. Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (COoperation in Scientific and Technological research) ACTION B26 on obstructive sleep apnea. J Hypertens. 2012;30:633–46.CrossRefPubMed Parati G, Lombardi C, Hedner J, Bonsignore MR, Grote L, Tkacova R, Levy P, Riha R, Bassetti C, Narkiewicz K, et al. Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (COoperation in Scientific and Technological research) ACTION B26 on obstructive sleep apnea. J Hypertens. 2012;30:633–46.CrossRefPubMed
6.
go back to reference Cooper VL, Pearson SB, Bowker CM, Elliott MW, Hainsworth R. Interaction of chemoreceptor and baroreceptor reflexes by hypoxia and hypercapnia - a mechanism for promoting hypertension in obstructive sleep apnoea. J Physiol. 2005;568:677–87.CrossRefPubMedPubMedCentral Cooper VL, Pearson SB, Bowker CM, Elliott MW, Hainsworth R. Interaction of chemoreceptor and baroreceptor reflexes by hypoxia and hypercapnia - a mechanism for promoting hypertension in obstructive sleep apnoea. J Physiol. 2005;568:677–87.CrossRefPubMedPubMedCentral
7.
go back to reference Pickkers P, Garcha RS, Schachter M, Smits P, Hughes AD. Inhibition of carbonic anhydrase accounts for the direct vascular effects of hydrochlorothiazide. Hypertension. 1999;33:1043–8.CrossRefPubMed Pickkers P, Garcha RS, Schachter M, Smits P, Hughes AD. Inhibition of carbonic anhydrase accounts for the direct vascular effects of hydrochlorothiazide. Hypertension. 1999;33:1043–8.CrossRefPubMed
8.
go back to reference Parati G, Revera M, Giuliano A, Faini A, Bilo G, Gregorini F, Lisi E, Salerno S, Lombardi C, Ramos Becerra CG, et al. Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure. Eur Heart J. 2013;34:759–66.CrossRefPubMed Parati G, Revera M, Giuliano A, Faini A, Bilo G, Gregorini F, Lisi E, Salerno S, Lombardi C, Ramos Becerra CG, et al. Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure. Eur Heart J. 2013;34:759–66.CrossRefPubMed
9.
go back to reference Eskandari D, Zou D, Karimi M, Stenlof K, Grote L, Hedner J. Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study. Eur Respir J. 2014;44:140–9.CrossRefPubMed Eskandari D, Zou D, Karimi M, Stenlof K, Grote L, Hedner J. Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study. Eur Respir J. 2014;44:140–9.CrossRefPubMed
10.
go back to reference Latshang TD, Nussbaumer-Ochsner Y, Henn RM, Ulrich S, Lo Cascio CM, Ledergerber B, Kohler M, Bloch KE. Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial. JAMA. 2012;308:2390–8.CrossRefPubMed Latshang TD, Nussbaumer-Ochsner Y, Henn RM, Ulrich S, Lo Cascio CM, Ledergerber B, Kohler M, Bloch KE. Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial. JAMA. 2012;308:2390–8.CrossRefPubMed
11.
go back to reference Grote L, Ploch T, Heitmann J, Knaack L, Penzel T, Peter JH. Sleep-related breathing disorder is an independent risk factor for systemic hypertension. Am J Respir Crit Care Med. 1999;160:1875–82.CrossRefPubMed Grote L, Ploch T, Heitmann J, Knaack L, Penzel T, Peter JH. Sleep-related breathing disorder is an independent risk factor for systemic hypertension. Am J Respir Crit Care Med. 1999;160:1875–82.CrossRefPubMed
12.
go back to reference Arterial hypertension. Report of a WHO expert committee. World Health Organization technical report series 1978;628:7–56. Arterial hypertension. Report of a WHO expert committee. World Health Organization technical report series 1978;628:7–56.
13.
go back to reference Stoohs R, Guilleminault C. MESAM 4: an ambulatory device for the detection of patients at risk for obstructive sleep apnea syndrome (OSAS). Chest. 1992;101:1221–7.CrossRefPubMed Stoohs R, Guilleminault C. MESAM 4: an ambulatory device for the detection of patients at risk for obstructive sleep apnea syndrome (OSAS). Chest. 1992;101:1221–7.CrossRefPubMed
14.
go back to reference Bearpark H, Elliott L, Grunstein R, Cullen S, Schneider H, Althaus W, Sullivan C, Snoring and sleep apnea. A population study in Australian men. Am J Respir Crit Care Med. 1995;151:1459–65.CrossRefPubMed Bearpark H, Elliott L, Grunstein R, Cullen S, Schneider H, Althaus W, Sullivan C, Snoring and sleep apnea. A population study in Australian men. Am J Respir Crit Care Med. 1995;151:1459–65.CrossRefPubMed
15.
go back to reference Roos M, Althaus W, Rhiel C, Penzel T, Peter JH, von-Wichert P. Comparative use of MESAM IV and polysomnograph in sleep-related respiratory disorderes. Pneumologie. 1993;47:112–8.PubMed Roos M, Althaus W, Rhiel C, Penzel T, Peter JH, von-Wichert P. Comparative use of MESAM IV and polysomnograph in sleep-related respiratory disorderes. Pneumologie. 1993;47:112–8.PubMed
16.
go back to reference Bingol Z, Pihtili A, Cagatay P, Okumus G, Kiyan E. Clinical predictors of obesity hypoventilation syndrome in obese subjects with obstructive sleep apnea. Respir Care. 2015;60:666–72.CrossRefPubMed Bingol Z, Pihtili A, Cagatay P, Okumus G, Kiyan E. Clinical predictors of obesity hypoventilation syndrome in obese subjects with obstructive sleep apnea. Respir Care. 2015;60:666–72.CrossRefPubMed
17.
go back to reference Manuel AR, Hart N, Stradling JR. Is a raised bicarbonate, without hypercapnia, part of the physiologic spectrum of obesity-related hypoventilation? Chest. 2015;147:362–8.CrossRefPubMed Manuel AR, Hart N, Stradling JR. Is a raised bicarbonate, without hypercapnia, part of the physiologic spectrum of obesity-related hypoventilation? Chest. 2015;147:362–8.CrossRefPubMed
18.
go back to reference Norman RG, Goldring RM, Clain JM, Oppenheimer BW, Charney AN, Rapoport DM, Berger KI. Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model. J Appl Physiol. 2006;100:1733–41.CrossRefPubMed Norman RG, Goldring RM, Clain JM, Oppenheimer BW, Charney AN, Rapoport DM, Berger KI. Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model. J Appl Physiol. 2006;100:1733–41.CrossRefPubMed
19.
go back to reference Kittivoravitkul P, Kaw R, Hatipoglu U, Wang L, Aboussouan LS. Determinants of Wake Pco2 and Increases in Wake Pco2 over Time in Patients with Obstructive Sleep Apnea. Ann Am Thorac Soc. 2016;13:259–64.CrossRefPubMed Kittivoravitkul P, Kaw R, Hatipoglu U, Wang L, Aboussouan LS. Determinants of Wake Pco2 and Increases in Wake Pco2 over Time in Patients with Obstructive Sleep Apnea. Ann Am Thorac Soc. 2016;13:259–64.CrossRefPubMed
20.
go back to reference Chung F, Chau E, Yang Y, Liao P, Hall R, Mokhlesi B. Serum bicarbonate level improves specificity of STOP-Bang screening for obstructive sleep apnea. Chest. 2013;143:1284–93.CrossRefPubMed Chung F, Chau E, Yang Y, Liao P, Hall R, Mokhlesi B. Serum bicarbonate level improves specificity of STOP-Bang screening for obstructive sleep apnea. Chest. 2013;143:1284–93.CrossRefPubMed
21.
go back to reference Juel C, Lundby C, Sander M, Calbet JA, Hall G. Human skeletal muscle and erythrocyte proteins involved in acid-base homeostasis: adaptations to chronic hypoxia. J Physiol. 2003;548:639–48.CrossRefPubMedPubMedCentral Juel C, Lundby C, Sander M, Calbet JA, Hall G. Human skeletal muscle and erythrocyte proteins involved in acid-base homeostasis: adaptations to chronic hypoxia. J Physiol. 2003;548:639–48.CrossRefPubMedPubMedCentral
22.
go back to reference Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006;173:234–7.CrossRefPubMed Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006;173:234–7.CrossRefPubMed
23.
go back to reference Raurich JM, Rialp G, Ibanez J, Llompart-Pou JA, Ayestaran I. Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO(2) response and acetazolamide treatment effects. Respir Care. 2010;55:1442–8.PubMed Raurich JM, Rialp G, Ibanez J, Llompart-Pou JA, Ayestaran I. Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO(2) response and acetazolamide treatment effects. Respir Care. 2010;55:1442–8.PubMed
25.
go back to reference Luft FC, Zemel MB, Sowers JA, Fineberg NS, Weinberger MH. Sodium bicarbonate and sodium chloride: effects on blood pressure and electrolyte homeostasis in normal and hypertensive man. J Hypertens. 1990;8:663–70.CrossRefPubMed Luft FC, Zemel MB, Sowers JA, Fineberg NS, Weinberger MH. Sodium bicarbonate and sodium chloride: effects on blood pressure and electrolyte homeostasis in normal and hypertensive man. J Hypertens. 1990;8:663–70.CrossRefPubMed
26.
go back to reference He FJ, Marciniak M, Carney C, Markandu ND, Anand V, Fraser WD, Dalton RN, Kaski JC, MacGregor GA. Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives. Hypertension. 2010;55:681–8.CrossRefPubMed He FJ, Marciniak M, Carney C, Markandu ND, Anand V, Fraser WD, Dalton RN, Kaski JC, MacGregor GA. Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives. Hypertension. 2010;55:681–8.CrossRefPubMed
27.
go back to reference Santos A, Martins MJ, Guimaraes JT, Severo M, Azevedo I. Sodium-rich carbonated natural mineral water ingestion and blood pressure. Rev Port Cardiol. 2010;29:159–72.PubMed Santos A, Martins MJ, Guimaraes JT, Severo M, Azevedo I. Sodium-rich carbonated natural mineral water ingestion and blood pressure. Rev Port Cardiol. 2010;29:159–72.PubMed
28.
go back to reference Gold AR, Schwartz AR, Wise RA, Smith PL. Pulmonary function and respiratory chemosensitivity in moderately obese patients with sleep apnea. Chest. 1993;103:1325–9.CrossRefPubMed Gold AR, Schwartz AR, Wise RA, Smith PL. Pulmonary function and respiratory chemosensitivity in moderately obese patients with sleep apnea. Chest. 1993;103:1325–9.CrossRefPubMed
29.
go back to reference Pickkers P, Hughes AD, Russel FG, Thien T, Smits P. In vivo evidence for K(Ca) channel opening properties of acetazolamide in the human vasculature. Br J Pharmacol. 2001;132:443–50.CrossRefPubMedPubMedCentral Pickkers P, Hughes AD, Russel FG, Thien T, Smits P. In vivo evidence for K(Ca) channel opening properties of acetazolamide in the human vasculature. Br J Pharmacol. 2001;132:443–50.CrossRefPubMedPubMedCentral
30.
go back to reference Aamand R, Dalsgaard T, Jensen FB, Simonsen U, Roepstorff A, Fago A. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation. Am J Physiol Heart Circ Physiol. 2009;297:H2068–2074.CrossRefPubMed Aamand R, Dalsgaard T, Jensen FB, Simonsen U, Roepstorff A, Fago A. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation. Am J Physiol Heart Circ Physiol. 2009;297:H2068–2074.CrossRefPubMed
31.
go back to reference Lord S, Sawyer B, O’Connell D, King M, Pond D, Eyland A, Mant A, Holland JT, Hensley MJ, Saunders NA. Night-to-night variability of disturbed breathing during sleep in an elderly community sample. Sleep. 1991;14:252–8.PubMed Lord S, Sawyer B, O’Connell D, King M, Pond D, Eyland A, Mant A, Holland JT, Hensley MJ, Saunders NA. Night-to-night variability of disturbed breathing during sleep in an elderly community sample. Sleep. 1991;14:252–8.PubMed
32.
go back to reference Frassetto LA, Nash E, Morris Jr RC, Sebastian A. Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion. Kidney Int. 2000;58:748–52.CrossRefPubMed Frassetto LA, Nash E, Morris Jr RC, Sebastian A. Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion. Kidney Int. 2000;58:748–52.CrossRefPubMed
Metadata
Title
Independent associations between arterial bicarbonate, apnea severity and hypertension in obstructive sleep apnea
Authors
Davoud Eskandari
Ding Zou
Ludger Grote
Hartmut Schneider
Thomas Penzel
Jan Hedner
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0607-9

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