Arterial stiffness and atrial fibrillation: A review

Arterial stiffness has been investigated as part of the physiopathology of arterial hypertension since the 1970s. Its role in increasing the “pulsatile load” imposed over the Left Ventricle (LV) has been intensely studied recently and has helped in understanding the mechanisms of Atrial Fibrillation (AF) in hypertensive patients. This paper aims to review the main evidence on this issue and establish possible mechanisms involved in the development of AF in patients with arterial stiffness. A PubMed search was performed, and selected articles were searched for references focusing on this topic. In the long term, lower blood pressure levels allow for arterial wall remodeling, leading to a lower stiffness index. To this day, however, there are no available treatments that directly promote the lowering of arterial wall stiffness. Most classes of anti-hypertensive drugs ‒ with stronger evidence for beta-blockers and diuretics ‒ could be effective in reducing arterial stiffness. There is strong evidence demonstrating an association between arterial stiffness and AF. New studies focusing on arterial stiffness and pre-fibrillatory stages would strengthen this causality relation.

Keywords:
Atrial fibrillation; Arterial stiffness; Atrial arrhythmia

Authorship

Joao Gabriel Batista Lage ^**Corresponding author. E-mail address: joao.lage@usp.br (J.G.B. Lage).

Instituto do Corçãao (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, BrazilUniversidade de São PauloBrazilSão Paulo, SP, BrazilInstituto do Corçãao (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil

http://orcid.org/0000-0003-0900-3681

Alexandre Lemos Bortolotto

http://orcid.org/0000-0002-3843-8046

Mauricio Ibrahim Scanavacca

http://orcid.org/0000-0001-7327-2275

Luiz Aparecido Bortolotto

http://orcid.org/0000-0002-4865-6442

Francisco Carlos da Costa Darrieux

http://orcid.org/0000-0001-5818-5958

*Corresponding author. E-mail address: joao.lage@usp.br (J.G.B. Lage).

Authors’ contributions

Lage JGB – Conceptualization, – Data curation, – Formal analysis, Resources AND Writing – review & editing. Bortolotto LA – Conceptualization, – Data curation. Bortolotto AL – Data curation, Writing review and editing. Scanavacca MI – Supervision, – Validation, – Visualization Darrieux FCC – Supervision, – Validation, – Visualization Anyway.

Declaration of Competing Interest

The authors declare no conflicts of interest.

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Figures | Tables

Figures (3)
Tables (2)

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Fig. 1
Adapted from Mendes-Pinto et al ^[19]19 Mendes-Pinto D, Rodrigues-Machado MDG. Applications of arterial stiffness markers in peripheral arterial disease. J Vasc Bras 2019;18:e20180093..

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Fig. 2
Adapted from Olsen et al ^[47]47 Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016;388(10060):2665–712..

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Fig. 3
Adapted from Gumprecht et al ^[51]51 Gumprecht J, Domek M, Lip GYH, Shantsila A. Invited review: hypertension and atrial fibrillation: epidemiology, pathophysiology, and implications for management. J Hum Hypertens 2019;33(12):824–36..

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Table 1
Methods to assess arterial stiffness.

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Table 2
Findings in previous observational studies.

Fig. 1 Adapted from Mendes-Pinto et al ^[19]19 Mendes-Pinto D, Rodrigues-Machado MDG. Applications of arterial stiffness markers in peripheral arterial disease. J Vasc Bras 2019;18:e20180093..

Fig. 2 Adapted from Olsen et al ^[47]47 Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016;388(10060):2665–712..

Fig. 3 Adapted from Gumprecht et al ^[51]51 Gumprecht J, Domek M, Lip GYH, Shantsila A. Invited review: hypertension and atrial fibrillation: epidemiology, pathophysiology, and implications for management. J Hum Hypertens 2019;33(12):824–36..

Table 1 Methods to assess arterial stiffness.

Carotid-Femoral Pulse Wave Velocity (cfPWV)	Gold-standard method.
Brachial-Ankle Pulse Wave Velocity (baPWV)	baPWV was calculated as: Distance (meters)/Δt (seconds).
Augmentation Index (AI)	Assessed by Applanation Tonometry. The augmentation pressure (AG) is the measure of contribution that the wave reflection makes to the systolic arterial pressure, and it is obtained by measuring the reflected wave coming from the peripheral to the central arteries.
Cardio-Ankle Vascular Index (CAVI)	CAVI is an index obtained by recording the distance from the level of the aortic valve (i.e., brachial level) to the measuring point (i.e., the ankle) and the time delay between the closing of the aortic valve to the detected change in arterial pressure wave at the set point. Information for CAVI computation, including PWV, systolic and diastolic blood pressure as well as arterial pulse waveforms, can then be acquired through the electrocardiogram, cardiac phonogram, and the pressure cuffs on the testing subject at the reference points.Thought to be or claimed to be blood pressure independent.
QKDh	The QKd interval is the time (measured in milliseconds) between the onset of depolarization on electro-cardiography (Q) and detection of the last Korotkoff sound (K) at the brachial artery during cuff deflation, corresponding to the diastolic blood pressure (d). This interval is inversely correlated with pulse wave velocity.
β Index	Stiffness Index Beta is derived from PWV, PP, SBP, DBP and viscosity and was calculated by an equation. Thought to be or claimed to be blood pressure independent
Ambulatory Arterial Stiffness Index (AASI)	The Ambulatory Arterial Stiffness Index (AASI) is an indirect arterial stiffness index, which can be simply calculated from 24-h Ambulatory Blood Pressure Monitoring (ABPM).

Table 2 Findings in previous observational studies.

Prospective	Roetker et al ^[42]42 Chirinos JA, Sardana M, Syed AA, Koppula MR, Varakantam S, Vasim I, et al. Aldosterone, inactive matrix gla-protein, and large artery stiffness in hypertension. J Am Soc Hypertens 2018;12(9):681–9.. Higher levels of systolic BP and PP, but not MAP or diastolic BP, were each individually associated with increased risk of AF after adjustment for all AF risk factors.
Retrospective	Chen et al.^[44]44 Hashmath Z, Lee J, Gaddam S, Ansari B, Oldland G, Javaid K, et al. Vitamin K status, warfarin use, and arterial stiffness in heart failure. Hypertension 2019;73(2):364–70. After full adjustment, the odds ratios of AF were significantly higher per quartile increase in CFPWV and β index.
Cross-Sectional	Cui et al ^[45]45 Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: A double-blind randomised clinical trial. Thromb Haemost 2015;113(5):1135–44.. The prevalence of atrial fibrillation and total arrhythmia were higher with larger AI (Augmentation Index) values.
Prospective	Cremer et al ^[46]46 Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev 2009;89(3):957–89.. Arterial stiffness (Assessed by QKDh) is a strong predictor of future atrial fibrillation in hypertensive patients, independently of age, 24-h pulse pressure and LAD.
Cross-Sectional	Lantelme et al ^[47]47 Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016;388(10060):2665–712.. PWV was associated with increased left atrium diameter and higher levels of NT-pro-BNP.
Prospective	Yoshida et al ^[48]48 Cruickshank JK, Silva MJ, Molaodi OR, Enayat ZE, Cassidy A, Karamanos A, et al. Ethnic differences in and childhood influences on early adult pulse wave velocity: the determinants of adolescent, now young adult, social wellbeing, and health longitudinal study. Hypertension 2016;–(6):1133–41.. Arterial stiffness was independently associated with LA phasic function, even in the absence of overt cardiovascular disease, which may explain the higher incidence of atrial fibrillation in individuals with increased arterial stiffness.
Cross-Sectional	Chung et al ^[68]68 Bekki M, Tahara N, Tahara A, Igata S, Honda A, Sugiyama Y, et al. Switching dipeptidyl peptidase-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 improve arterial stiffness evaluated by cardio-ankle vascular index in patients with type 2 diabetes: a pilot study. Curr Vasc Pharmacol 2019;17(4):411–20.. High arterial stiffness (assessed by CAVI) shows a significant association with AF in those with intermediate or high cardiovascular risk (Framingham) and can be used for further risk stratification of patients.

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Arterial stiffness and atrial fibrillation: A review

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[1] *Corresponding author. E-mail address: joao.lage@usp.br (J.G.B. Lage).