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A greater burden of atrial fibrillation is associated with worse endothelial dysfunction in hypertension


Atrial fibrillation (AF) and hypertension often co-exist and both are associated with endothelial dysfunction. We hypothesised that AF would further worsen endothelium-dependent flow-mediated dilatation (FMD) in hypertension patients compared to those without AF. In a cross-sectional comparison, we measured brachial artery diameter at rest and during reactive hyperaemia following 5 min of arterial occlusion in two patient groups: AF (and hypertension) (n = 61) and hypertension control groups (n = 33). The AF (and hypertension) subgroups: permanent AF (n = 30) and paroxysmal AF (n = 31) were also assessed. The permanent AF patients received heart rate and blood pressure (BP) control optimisation and were then followed up after eight weeks for repeat FMD testing. There was no significant difference in FMD between AF (and hypertension) group and hypertension control group (4.6%, 95% CI [2.6–5.9%] vs 2.6%, 95% CI [1.9–5.3%]; p = 0.25). There was a significant difference in FMD between permanent AF and paroxysmal AF groups (3.1%, 95% CI [2.3–4.8%] vs 5.9%, 95% CI [4.0–8.1%]; p = 0.02). Endothelium-dependent FMD response showed a non-significant improvement trend following eight weeks of heart rate and BP optimisation (3.1%, 95% CI [2.3–4.8%] (baseline) vs 5.2%, 95% CI [3.9–6.5%] (follow up), p = 0.09). Presence of AF generally does not incrementally worsen endothelial dysfunction in hypertension patients, although the duration and frequency of AF (paroxysmal AF to permanent AF) does lead to worsening endothelial function. Eight weeks of BP optimisation did not significantly improve endothelial dysfunction as measured by FMD.

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Fig. 1: Medication use by class of drugs.
Fig. 2: Complex interplay between hypertension.


  1. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998;82:2n–9n.

    Article  CAS  Google Scholar 

  2. Lau YF, Yiu KH, Siu CW, Tse HF. Hypertension and atrial fibrillation: epidemiology, pathophysiology and therapeutic implications. J Hum Hypertens. 2012;26:563–9.

    Article  CAS  Google Scholar 

  3. Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994;271:840–4.

    Article  CAS  Google Scholar 

  4. Nabauer M, Gerth A, Limbourg T, Schneider S, Oeff M, Kirchhof P, et al. The Registry of the German Competence NETwork on Atrial Fibrillation: patient characteristics and initial management. Europace. 2009;11:423–34.

    Article  Google Scholar 

  5. Dzeshka MS, Shantsila A, Shantsila E, Lip GYH. Atrial fibrillation and hypertension. Hypertension. 2017;70:854–61.

    Article  CAS  Google Scholar 

  6. Skalidis EI, Zacharis EA, Tsetis DK, Pagonidis K, Chlouverakis G, Yarmenitis S, et al. Endothelial cell function during atrial fibrillation and after restoration of sinus rhythm. Am J Cardiol. 2007;99:1258–62.

    Article  CAS  Google Scholar 

  7. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation. 1995;91:1314–9.

    Article  CAS  Google Scholar 

  8. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA. et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39:257–65.

    Article  Google Scholar 

  9. Iiyama K, Nagano M, Yo Y, Nagano N, Kamide K, Higaki J, et al. Impaired endothelial function with essential hypertension assessed by ultrasonography. Am Heart J. 1996;132:779–82.

    Article  CAS  Google Scholar 

  10. Simons LA, Sullivan D, Simons J, Celermajer DS. Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients with severe primary hypercholesterolaemia. Atherosclerosis. 1998;137:197–203.

    Article  CAS  Google Scholar 

  11. Lekakis J, Papamichael C, Anastasiou H, Alevizaki M, Desses N, Souvatzoglou A, et al. Endothelial dysfunction of conduit arteries in insulin-dependent diabetes mellitus without microalbuminuria. Cardiovasc Res. 1997;34:164–8.

    Article  CAS  Google Scholar 

  12. Thomas GN, Chook P, Yip TW, Kwong SK, Chan TY, Qiao M, et al. Smoking without exception adversely affects vascular structure and function in apparently healthy Chinese: implications in global atherosclerosis prevention. Int J Cardiol. 2008;128:172–7.

    Article  Google Scholar 

  13. Freestone B, Chong AY, Nuttall S, Lip GY. Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial fibrillation: relationship to plasma von Willebrand factor and soluble E-selectin levels. Thromb Res. 2008;122:85–90.

    Article  CAS  Google Scholar 

  14. Borschel CS, Rubsamen N, Ojeda FM, Wild PS, Hoffmann BA, Prochaska JH, et al. Noninvasive peripheral vascular function and atrial fibrillation in the general population. J Hypertens. 2019;37:928–34.

    Article  Google Scholar 

  15. Komatsu T, Kunugita F, Ozawa M, Satoh Y, Yoshizawa R, Owada S, et al. Relationship between impairment of the vascular endothelial function and the CHA2DS2-VASc score in patients with sinus rhythm and non-valvular atrial fibrillation. Intern Med. 2018;57:2131–9.

    Article  Google Scholar 

  16. Mazaris STD, Siasos G, Zisimos K, Oikonomou E, Kokkou E, Konsola T, et al. The role of endothelial function on paroxysmal and chronic atrial fibrillation. Circ J. 2014;130:A11548.

  17. Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, et al. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019;40:2534–47.

    Article  Google Scholar 

  18. Gemignani V, Bianchini E, Faita F, Giannarelli C, Plantinga Y, Ghiadoni L, et al. Ultrasound measurement of the brachial artery flow-mediated dilation without ECG gating. Ultrasound Med Biol. 2008;34:385–91.

    Article  Google Scholar 

  19. Junejo RT, May S, Alsalahi S, Alali M, Ogoh S, Fisher JP. Cerebrovascular carbon dioxide reactivity and flow-mediated dilation in young healthy South Asian and Caucasian European men. Am J Physiol-Heart Circulatory Physiol. 2020;318:H756–H763.

    Article  CAS  Google Scholar 

  20. Atkinson G, Batterham AM. Allometric scaling of diameter change in the original flow-mediated dilation protocol. Atherosclerosis. 2013;226:425–7.

    Article  CAS  Google Scholar 

  21. Felmeden DC, Spencer CGC, Chung NAY, Belgore FM, Blann AD, Beevers DG, et al. Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a Substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT]). Am J Cardiol. 2003;92:400–5.

    Article  Google Scholar 

  22. Kizhakekuttu TJ, Widlansky ME. Natural antioxidants and hypertension: promise and challenges. Cardiovasc Ther. 2010;28:e20–32.

    Article  CAS  Google Scholar 

  23. Schiffrin EL. The immune system: role in hypertension. Can J Cardiol. 2013;29:543–8.

    Article  Google Scholar 

  24. Guo Y, Lip GY, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012;60:2263–70.

    Article  CAS  Google Scholar 

  25. Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertens Rep. 2010;12:448–55.

    Article  Google Scholar 

  26. Harada M, Van Wagoner DR, Nattel S. Role of inflammation in atrial fibrillation pathophysiology and management. Circulation J: Off J Jpn Circulation Soc. 2015;79:495–502.

    Article  Google Scholar 

  27. Tousoulis D, Zisimos K, Antoniades C, Stefanadi E, Siasos G, Tsioufis C, et al. Oxidative stress and inflammatory process in patients with atrial fibrillation: the role of left atrium distension. Int J Cardiol. 2009;136:258–62.

    Article  Google Scholar 

  28. Guazzi M, Casali M, Berti F, Rossoni G, Colonna VD, Guazzi MD. Endothelium-mediated modulation of ergoreflex and improvement in exercise ventilation by acute sildenafil in heart failure patients. Clin Pharm Ther. 2008;83:336–41.

    Article  CAS  Google Scholar 

  29. Li Q, Youn J-Y, Cai H. Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension. J Hypertens. 2015;33:1128–36.

    Article  CAS  Google Scholar 

  30. Cai H, Li Z, Goette A, Mera F, Honeycutt C, Feterik K, et al. Downregulation of endocardial nitric oxide synthase expression and nitric oxide production in atrial fibrillation: potential mechanisms for atrial thrombosis and stroke. Circulation. 2002;106:2854–8.

    Article  CAS  Google Scholar 

  31. Fares F, Smith Y, Azzam N, Zafrir B, Lewis BS, Amir O. The 894G allele of the endothelial nitric oxide synthase 3 (eNOS) is associated with atrial fibrillation in chronic systolic heart failure. J Atr Fibrillation. 2012;5:757–757.

    PubMed  PubMed Central  Google Scholar 

  32. Siasos G, Mazaris S, Zisimos K, Oikonomou E, Kokkou E, Konsola T, et al. The impact of atrial fibrillation on endothelial dysfunction. J Am Coll Cardiol. 2015;65:A477.

    Article  Google Scholar 

  33. Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002;40:505–10.

    Article  Google Scholar 

  34. Ghiadoni L, Taddei S, Virdis A. Hypertension and endothelial dysfunction: therapeutic approach. Curr Vasc Pharmacol. 2012;10:42–60.

    Article  CAS  Google Scholar 

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The time and effort expended by all the participants is greatly appreciated.

Author contributions

GYHL has served as a consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife and Daiichi-Sankyo; and a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo. No personal fees received.

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Correspondence to Gregory Y. H. Lip.

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Khan, A.A., Junejo, R.T., Alsharari, R. et al. A greater burden of atrial fibrillation is associated with worse endothelial dysfunction in hypertension. J Hum Hypertens 35, 667–677 (2021).

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