Elevated Homocysteine Levels Associated with Atrial Fibrillation and Recurrent Atrial Fibrillation

Rong, Hao; Huang, Lei; Jin, Nake; Hong, Jun Yeong; Hu, Jianan; Wang, Shanshan; Xie, Ying; Pu, Jun

doi:10.1536/ihj.20-099

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…Previous epidemiological studies have shown that elevated plasma Hcy levels are popular in the general population and are associated with increased risk of hypertension, cardiovascular disease, and stroke. 35,36) FA supplementation improves arterial endothelial function in adults with relative Hhcy, with potentially beneficial effects on the atherosclerotic process. 37) Enalapril maleate and FA tablets reduced Hcy levels in hypertensive rats with Hhcy and alleviated endoplasmic reticulum stress and vascular remodeling.…”

Section: Discussionmentioning

confidence: 99%

Low Dose of Folic Acid Can Ameliorate Hyperhomocysteinemia-Induced Cardiac Fibrosis and Diastolic Dysfunction in Spontaneously Hypertensive Rats

et al. 2021

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To evaluate whether lowering plasma homocysteine (Hcy) levels at different doses of folic acid (FA) could reduce cardiac fibrosis and diastolic dysfunction in spontaneously hypertensive rats (SHRs) with hyperhomocysteinemia (Hhcy) and investigate the possible mechanism of action.We randomly divided 32 male SHRs into control, Hhcy, Hhcy + low-dose FA (LFA), and Hhcy + highdose FA (HFA) groups. Echocardiography and Masson staining of cardiac tissue were used to assess diastolic function and cardiac fibrosis. Blood pressure (BP) and Hcy levels were measured during the experiment. We also measured the indicators of oxidative stress (OS) and examined the expression of nuclear factor erythroid 2related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes and proteins using real-time polymerase chain reaction (PCR), immunohistochemistry, and western blotting to explore the possible mechanism of action.FA treatment reversed SHR cardiomyocyte interstitial and perivascular collagen deposition and diastolic dysfunction exacerbated by Hhcy. These effects were associated with promoting the translocation of Nrf2 from the cytoplasm to the nucleus, activating HO-1 expression and inhibiting OS. However, HFA did not show any additional benefit from LFA in reducing cardiac injury.Even at a low dose, FA can ameliorate Hhcy-induced cardiac fibrosis and diastolic dysfunction in SHRs by activating Nrf2/HO-1 pathway and inhibiting OS, independent of BP, providing evidence for the efficacy of LFA in the treatment of hypertension associated with Hhcy.

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Section: Discussionmentioning

confidence: 99%

Low Dose of Folic Acid Can Ameliorate Hyperhomocysteinemia-Induced Cardiac Fibrosis and Diastolic Dysfunction in Spontaneously Hypertensive Rats

et al. 2021

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“…As mentioned earlier, tHcy causes structural deformation of the heart, which increases blood stasis and leads to the development of thrombi. 14 , 15 , 17 tHcy can also activate the prothrombotic tendency of blood, which promotes the development of an intracardiac thrombus. 7 , 17 , 24 This generated thrombus can result in additional embolic events, leading to unfavorable outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…However, an elevated tHcy level also seems to be involved in the structural or electrophysiological remodeling of the heart. 14 , 15 , 16 , 17 It is associated with left atrial enlargement, myocyte size increase, cardiac fibrosis, and remodeling of the sodium/potassium ion channel, leading to the development of a cardiac environment prone to atrial fibrillation (AF). 14 , 15 , 16 , 17 Given this theoretical background, the tHcy level seems to be able to have a significant effect on the occurrence of ischemic stroke in patients with AF.…”

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confidence: 99%

“… 14 , 15 , 16 , 17 It is associated with left atrial enlargement, myocyte size increase, cardiac fibrosis, and remodeling of the sodium/potassium ion channel, leading to the development of a cardiac environment prone to atrial fibrillation (AF). 14 , 15 , 16 , 17 Given this theoretical background, the tHcy level seems to be able to have a significant effect on the occurrence of ischemic stroke in patients with AF. 16 , 18 However, there is a lack of research on the effect of tHcy on the prognosis of patients who have ischemic stroke and AF at the same time (collectively termed AF‐related stroke ).…”

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confidence: 99%

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Plasma Total Homocysteine Level Is Related to Unfavorable Outcomes in Ischemic Stroke With Atrial Fibrillation

Nam

Kim

et al. 2022

JAHA

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Background Unlike patients with stroke caused by other mechanisms, the effect of elevated plasma total homocysteine (tHcy) on the prognosis of patients with both ischemic stroke and atrial fibrillation (AF) is unknown. This study aimed to evaluate the association between tHcy level and the functional outcome of patients with AF‐related stroke. Methods and Results We included consecutive patients with AF‐related stroke between 2013 and 2015 from the registry of a real‐world prospective cohort from 11 large centers in South Korea. A 3‐month modified Rankin Scale score ≥3 was considered an unfavorable outcome. Since tHcy is strongly affected by renal function, we performed a subgroup analysis according to the presence of renal dysfunction. A total of 910 patients with AF‐related stroke were evaluated (mean age, 73 years; male sex, 56.0%). The mean tHcy level was 11.98±8.81 μmol/L. In multivariable analysis, the tHcy level (adjusted odds ratio, 1.04; 95% CI, 1.01–1.07, per 1 μmol/L) remained significantly associated with unfavorable outcomes. In the subgroup analysis based on renal function, tHcy values above the cutoff point (≥14.60 μmol/L) showed a close association with the unfavorable outcome only in the normal renal function group (adjusted odds ratio, 3.10; 95% CI, 1.60–6.01). In patients with renal dysfunction, tHcy was not significantly associated with the prognosis of AF‐related stroke. Conclusions A higher plasma tHcy level was associated with unfavorable outcomes in patients with AF‐related stroke. This positive association may vary according to renal function but needs to be verified in further studies.

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“…Apart from the well-known risk factors triggered by IR, hyperhomocysteinemia is also present in PCOS due to the dysregulation of enzymes participating in homocysteine metabolism [i.e., Methyltetrahydrofolate Reductase (MTHFR) and hepatic Cystathione β-Synthase (CBS)] [ 36 ]. Hyperhomocysteinemia induces increased inflammatory cytokine expression/activity, the injury of endothelial cells and proliferation of muscle cells, and has also been linked with increased risk for AF development and major adverse cardiovascular events [ 37 ]. Furthermore, a reasonable question arises: whether these comorbidities—known for their arrhythmogenic effects [ 38 ]—trigger AF, and PCOS is just a confounder and not the cause of the arrhythmia.…”

Section: Discussionmentioning

confidence: 99%

Polycystic Ovary Syndrome Triggers Atrial Conduction Disorders: A Systematic Review and Meta-Analysis

Moysidis

Papazoglou

Tsagkaris

et al. 2022

EJIHPE

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Background: Polycystic ovary syndrome (PCOS) is closely related to various adverse cardiovascular manifestations and increased cardiovascular risk. However, atrial fibrillation (AF) development and atrial conduction abnormalities have not been thoroughly studied in patients with PCOS. Methods: This meta-analysis (CRD42021261375) was conducted in accordance with the PRISMA guidelines. Our aim was to investigate associations between PCOS and disorders in atrial conduction parameters linked with an increased risk for AF occurrence. Results: Five cohort studies with aggregate data on 406 adult women (229 with PCOS and 177 age-matched without PCOS) were included in this analysis. Our results showed a significantly increased mean difference in P-wave maximum duration (+7.63 ± 7.07 msec; p < 0.01) and P-wave dispersion (+11.42 ± 5.22 msec; p = 0.03) of patients with PCOS compared to healthy women. The mean difference in P-wave minimum duration (−2.22 ± 2.68 msec; p = 0.11) did not reach the statistical threshold between the compared groups. Echocardiographic measurements of atrial electromechanical delay (AED) also indicated a statistically significant mean difference in favour of the PCOS group in all assessed parameters, except for atrial electromechanical coupling (PA) in the tricuspid annulus. Particularly, PCOS was associated with increased lateral PA, septal PA, inter- and intra-AED durations (mean difference: +17.31 ± 9.02 msec; p < 0.01, +11.63 ± 7.42 msec; p < 0.01, +15.31 ± 9.18 msec; p < 0.01, +9.31 ± 6.85 msec; p < 0.01, respectively). Conclusions: PCOS is strongly associated with alterations in several electrocardiographic and echocardiographic parameters indicating abnormal atrial conduction. Therefore, PCOS could be considered as a causal or triggering factor of AF. Larger studies are needed to confirm these results and investigate direct associations between PCOS and AF.

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Elevated Homocysteine Levels Associated with Atrial Fibrillation and Recurrent Atrial Fibrillation

Cited by 12 publications

References 23 publications

Low Dose of Folic Acid Can Ameliorate Hyperhomocysteinemia-Induced Cardiac Fibrosis and Diastolic Dysfunction in Spontaneously Hypertensive Rats

Low Dose of Folic Acid Can Ameliorate Hyperhomocysteinemia-Induced Cardiac Fibrosis and Diastolic Dysfunction in Spontaneously Hypertensive Rats

Plasma Total Homocysteine Level Is Related to Unfavorable Outcomes in Ischemic Stroke With Atrial Fibrillation

Polycystic Ovary Syndrome Triggers Atrial Conduction Disorders: A Systematic Review and Meta-Analysis

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