Blockade of the renin–angiotensin system in atrial fibrillation

Kuzniatsova, Nadzeya; Shantsila, Eduard; Lip, Gregory Y. H.

doi:10.1038/nrcardio.2010.103

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…However, caution is necessary for such interpretation, as the modest degree of direct effect of AF on brain volume phenotypes, not mediated by ischemic stroke, could have been unrevealed because of the potential false-negative bias in two-sample MR [16], particularly considering the low conditioned F statistics of AF phenotype when adjusted for the genetic effects towards ischemic stroke trait. As AF is linked to diverse biological consequences, including subclinical brain hemodynamic compromises or neurohormonal responses [8,48,49], a future study is still necessary to investigate whether ischemic stroke-independent effects of AF on brain volume or cognitive function are present.…”

Section: Discussionmentioning

confidence: 99%

Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

Park

Lee

Kim

et al. 2021

BMC Med

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Background Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis. Methods The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance–weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR. Results A higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta −0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E−12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta −0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome. Conclusions This study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

Park

Lee

Kim

et al. 2021

BMC Med

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“…The copyright holder for this this version posted December 19, 2020. ; https://doi.org/10.1101/2020.12.17.20248314 doi: medRxiv preprint activation of the renin-angiotensin-aldosterone system, 26,27 which mechanistically causes cerebral vasoconstriction. 28 Brain volume loss in AF patients showed greater accentuation in those with persistent AF than in those with paroxysmal AF, suggesting that the cumulative burden of AF might influence decreased brain volume.…”

Section: Discussionmentioning

confidence: 99%

“…8 Moreover, AF causes atrial dysfunction with impaired ventricular filling, consequently adversely affecting cardiac output. 25 AF is also closely associated with adverse neurohormonal responses, including activation of the renin-angiotensin-aldosterone system, 26,27 which mechanistically causes cerebral vasoconstriction. 28 Brain volume loss in AF patients showed greater accentuation in those with persistent AF than in those with paroxysmal AF, suggesting that the cumulative burden of AF might influence decreased brain volume.…”

Section: Discussionmentioning

confidence: 99%

Causal effect of atrial fibrillation on brain white or grey matter volume: A Mendelian randomization study

Park

Lee

Kim³

et al. 2020

Preprint

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BackgroundAtrial fibrillation (AF) and brain volume loss are prevalent in older individuals. Further study investigating the causal effect of AF on brain volume is warranted.MethodsThis study was a Mendelian randomization (MR) analysis. The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis and included 537,409 individuals of European ancestry. The outcome summary statistics for quantile-normalized white or grey matter volume measured by magnetic resonance imaging were provided by the previous GWAS of 8426 white British UK Biobank participants. The main MR method was the inverse variance weighted method, supported by sensitivity MR analysis including MR-Egger regression and the weighted median method. The causal estimates from AF to white or grey matter volume were further adjusted for effects of any stroke or ischemic stroke by multivariable MR analysis.ResultsA higher genetic predisposition for AF (one standard deviation increase) was significantly associated with lower white matter volume [beta −0.128 (−0.208, −0.048)] but not grey matter volume [beta −0.041 (−0.101, 0.018)], supported by all utilized sensitivity MR analyses. The multivariable MR analysis indicated that AF is causally linked to lower white matter volume independent of the stroke effect.ConclusionsAF is a causative factor for white matter volume loss. The effect of AF on grey matter volume was inapparent in this study. A future trial is necessary to confirm whether appropriate AF management can be helpful in preventing cerebral white matter volume loss or related brain disorders in AF patients.

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“…In patients with left ventricular hypertrophy, as is commonly seen in HCM, decreased left ventricular volume forces blood to back up into the left atrium, enlarging it. This activates stretch receptors in the left atrium which prompt the production of angiotensin II and an increase in the number of angiotensin receptors, leading to cardiomyocyte hypertrophy and increased fibrosis [12]. In addition, a mutation in a gene encoding for angiotensin-converting enzyme (ACE) is a significant predictor of AF in HCM patients, further indicating that the RAS plays a role in its development [9].…”

Section: Research Protocol Open Accessmentioning

confidence: 99%

“…While ARBs are used as an alternative for individuals with ACE inhibitor intolerance, both are understood to be equally effective in reducing outcomes such as cardiovascular death, stroke, and new-onset heart failure in patients as there is no sufficient evidence to suggest otherwise [13]. Various studies have shown that ACE inhibitors and ARBs can significantly reduce the incidence of AF, particularly recurring AF, both on their own and in conjunction with antiarrhythmics [9,12,[14][15][16][17]. These studies have also shown that they are most useful in vulnerable populations, such as those with hypertension or left ventricular hypertrophy, and while it is not recommended to use ACE inhibitors and ARBs solely to prevent AF in the general population, it may be considered in vulnerable populations.…”

Section: Research Protocol Open Accessmentioning

confidence: 99%

Preventing Atrial Fibrillation in Hypertrophic Cardiomyopathy using Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs)

Kathirgamanathan,

Nair

2024

URNCST Journal

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Hypertrophic cardiomyopathy (HCM), a genetic cardiovascular disease, is the leading cause of cardiac death in young people, often due to atrial fibrillation (AF). AF is generally treated using antiarrhythmics and anticoagulants, which have adverse side effects after long-term use, and are therefore unsuitable for young HCM patients. AF is characterized by a rapid and irregular atrial heartbeat, marked by a short action potential duration and atrial effective refractory period in atrial cardiomyocytes. Prior studies have indicated that the renin-angiotensin system is involved in lowering both, so it has been hypothesized that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which inhibit the renin-angiotensin system, could prevent AF. Therefore, in this study, we propose a research protocol to examine the viability of ACE inhibitors and ARBs as prophylactic measures against the development of AF in HCM patients. To test this, we suggest extracting atrial cardiomyocytes from HCM patients by performing enzyme dissociation on myocardial tissue. The isolated cardiomyocytes will then be treated in vitro with an ACE inhibitor, an ARB, a combination of both, or a control saline solution, and the patch-clamp technique will be used to determine the frequency and duration of their action potentials. We expect action potential duration and atrial effective refractory period to be longer in treated cells, while neither medication will provide a greater advantage, and, as prior research suggests, the combination will not yield significant benefits. The study will continue by testing the effects of ACE inhibitors and ARBs on the function of atrial myocardial organoids created from differentiated stem cells with an HCM mutation. The results of this study could present a new preventative measure against AF for HCM patients which would be safe for long-term use.

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Blockade of the renin–angiotensin system in atrial fibrillation

Cited by 8 publications

References 10 publications

Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

Causal effect of atrial fibrillation on brain white or grey matter volume: A Mendelian randomization study

Preventing Atrial Fibrillation in Hypertrophic Cardiomyopathy using Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs)

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