Effects of Hydroxychloroquine on endOthelial function in eLDerly with sleep apnea (HOLD): study protocol for a randomized clinical trial

Imagem de Miniatura
Arquivos
art_SILVA_Effects_of_Hydroxychloroquine_on_endOthelial_function_in_eLDerly_2021.PDF (734.5 KB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BMC
Autores
SILVA, Leticia Maria Tedesco
CORTES, Antonio
ROSSI, Beatriz
BOLL, Liliana
WACLAWOSKY, Gustavo
EIBEL, Bruna
GONCALVES, Sandro Cadaval
MARTINEZ, Denis
Citação
TRIALS, v.22, n.1, article ID 638, 11p, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Sleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardioprotective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses. Objective: In this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea. Methods: We will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for 8 weeks. Discussion: Our study aims to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings.
Palavras-chave
Hydroxychloroquine, Endothelial function, Sleep apnea
URI
https://observatorio.fm.usp.br/handle/OPI/49582
Referências
  1. Achuthan S, 2015, J CARDIOVASC PHARM T, V20, P174, DOI 10.1177/1074248414546324
  2. AUGUSTIN HG, 1994, BIOESSAYS, V16, P901, DOI 10.1002/bies.950161208
  3. Avci AY, 2017, SLEEP BREATH, V21, P703, DOI 10.1007/s11325-017-1486-5
  4. Bili A, 2011, JCR-J CLIN RHEUMATOL, V17, P115, DOI 10.1097/RHU.0b013e318214b6b5
  5. Bonetti PO, 2004, J AM COLL CARDIOL, V44, P2137, DOI 10.1016/j.jacc.2004.08.062
  6. Brant LCC, 2013, J HYPERTENS, V31, P1984, DOI 10.1097/HJH.0b013e328362d913
  7. Bruno RM, 2014, VASC HEALTH RISK MAN, V10, P577, DOI 10.2147/VHRM.S44471
  8. Camici GG, 2015, EUR HEART J, V36, P3392, DOI 10.1093/eurheartj/ehv587
  9. da Rosa DP, 2015, INFLAMM RES, V64, P21, DOI 10.1007/s00011-014-0778-5
  10. Dong JY, 2013, ATHEROSCLEROSIS, V229, P489, DOI 10.1016/j.atherosclerosis.2013.04.026
  11. Edfeldt K, 2002, CIRCULATION, V105, P1158, DOI 10.1161/circ.105.10.1158
  12. Edwards MH, 1997, CIRCULATION, V96, P4380
  13. Gerstein HC, 2002, DIABETES RES CLIN PR, V55, P209, DOI 10.1016/S0168-8227(01)00325-4
  14. Gilat H, 2014, MEDICINE, V93, DOI 10.1097/MD.0000000000000045
  15. Greyling A, 2016, ATHEROSCLEROSIS, V248, P196, DOI 10.1016/j.atherosclerosis.2016.03.011
  16. Hamburg NM, 2011, HYPERTENSION, V57, P390, DOI 10.1161/HYPERTENSIONAHA.110.160812
  17. Hayashi M, 2003, CHEST, V124, P936, DOI 10.1378/chest.124.3.936
  18. Hoffmann M, 2017, ARCH MED SCI, V13, P223, DOI 10.5114/aoms.2015.56490
  19. Hoyos CM, 2015, SLEEP MED REV, V20, P15, DOI 10.1016/j.smrv.2014.06.003
  20. Jacobsson LTH, 2005, J RHEUMATOL, V32, P1213
  21. Jang CH, 2006, RHEUMATOLOGY, V45, P703, DOI 10.1093/rheumatology/kei282
  22. Jung HJ, 2010, ARTHRITIS RHEUM-US, V62, P863, DOI 10.1002/art.27289
  23. Kerr G, 2014, ARTHRIT CARE RES, V66, P1619, DOI 10.1002/acr.22341
  24. Klein C, 2010, FREE RADICAL RES, V44, P907, DOI 10.3109/10715762.2010.489112
  25. Kuznik A, 2011, J IMMUNOL, V186, P4794, DOI 10.4049/jimmunol.1000702
  26. Lamberts M, 2014, J INTERN MED, V276, P659, DOI 10.1111/joim.12302
  27. Lesiak A, 2010, LUPUS, V19, P683, DOI 10.1177/0961203309356455
  28. Mansure AD, 2012, ARQ BRAS CARDIOL, V99, P755
  29. Martinez D, 2012, SLEEP BREATH, V16, P695, DOI 10.1007/s11325-011-0559-0
  30. Matsue Y, 2013, INT J CARDIOL, V168, P36, DOI 10.1016/j.ijcard.2012.09.021
  31. Matsuzawa Y, 2013, J AM HEART ASSOC, V2, DOI 10.1161/JAHA.113.000426
  32. Morris SJ, 2011, ARTHRIT CARE RES, V63, P530, DOI 10.1002/acr.20393
  33. Newby AC, 2015, MATRIX BIOL, V44-46, P157, DOI 10.1016/j.matbio.2015.01.015
  34. Park KH, 2015, J KOREAN MED SCI, V30, P1213, DOI 10.3346/jkms.2015.30.9.1213
  35. Peppard PE, 2000, NEW ENGL J MED, V342, P1378, DOI 10.1056/NEJM200005113421901
  36. PETRI M, 1994, AM J MED, V96, P254, DOI 10.1016/0002-9343(94)90151-1
  37. Petri M, 2011, CURR RHEUMATOL REP, V13, P77, DOI 10.1007/s11926-010-0141-y
  38. Quan SF, 2004, CIRCULATION, V109, P951, DOI 10.1161/01.CIR.0000118216.84358.22
  39. QUATRARO A, 1990, ANN INTERN MED, V112, P678, DOI 10.7326/0003-4819-112-9-678
  40. Rekedal LR, 2010, ARTHRITIS RHEUM-US, V62, P3569, DOI 10.1002/art.27703
  41. Rubinshtein R, 2010, EUR HEART J, V31, P1142, DOI 10.1093/eurheartj/ehq010
  42. Schnabel RB, 2011, CIRC-CARDIOVASC IMAG, V4, P371, DOI 10.1161/CIRCIMAGING.110.961557
  43. Senaratna CV, 2017, SLEEP MED REV, V34, P70, DOI 10.1016/j.smrv.2016.07.002
  44. Sharma TS, 2016, J AM HEART ASSOC, V5, DOI 10.1161/JAHA.115.002867
  45. Shukla AM, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0139226
  46. Solomon DH, 2011, JAMA-J AM MED ASSOC, V305, P2525, DOI 10.1001/jama.2011.878
  47. Somers VK, 2008, CIRCULATION, V118, P1080, DOI [10.1161/CIRCULATIONAHA.107.189420, 10.1161/CIRCULATIONAHA.107.189375]
  48. Tang C, 2012, INTERN MED J, V42, P968, DOI 10.1111/j.1445-5994.2012.02886.x
  49. Thijssen DHJ, 2011, AM J PHYSIOL-HEART C, V300, pH2, DOI 10.1152/ajpheart.00471.2010
  50. Tufik S, 2010, SLEEP MED, V11, P441, DOI 10.1016/j.sleep.2009.10.005
  51. Unnikrishnan D, 2015, REV ENDOCR METAB DIS, V16, P25, DOI 10.1007/s11154-014-9304-x
  52. WALLACE DJ, 1990, AM J MED, V89, P322, DOI 10.1016/0002-9343(90)90345-E
  53. Wang JY, 2015, J AM HEART ASSOC, V4, DOI 10.1161/JAHA.115.002454
  54. Wang X, 2013, INT J CARDIOL, V169, P207, DOI 10.1016/j.ijcard.2013.08.088
  55. Wasko MCM, 2007, JAMA-J AM MED ASSOC, V298, P187, DOI 10.1001/jama.298.2.187
  56. Wasko MCM, 2015, DIABETOLOGIA, V58, P2336, DOI 10.1007/s00125-015-3689-2
  57. Weber SM, 2000, J IMMUNOL, V165, P1534, DOI 10.4049/jimmunol.165.3.1534
  58. Xu Y, 2014, EUR HEART J-CARD IMG, V15, P736, DOI 10.1093/ehjci/jet256
  59. Yaggi HK, 2005, NEW ENGL J MED, V353, P2034, DOI 10.1056/NEJMoa043104

Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/65
Artigos e Materiais de Revistas Científicas - ODS/03