Atrial contractility and fibrotic biomarkers are associated with atrial fibrillation after elective coronary artery bypass grafting

Bening, C.; Mazalu, E.; Yaqub, Jonathan; Alhussini, K.; Glanowski, Michał; Kottmann, Tanja; Leyh, Rainer

doi:10.1016/j.jtcvs.2019.02.068

Cited by 22 publications

(27 citation statements)

References 47 publications

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“…The animal model showed that it could be used as a therapy target against fibrosis [ 20 ]. Since in AF patients, levels of TGF- β 1 and GDF-15 in serum and atrial tissue both elevate [ 15 – 17 , 21 , 22 ], and they are both members of the TGF- β family, we infer that GDF-15 also have an important role in atrial fibrosis. However, few studies had focused on how GDF-15 correlates with atrial structural remodeling and AF types in AF patients.…”

Section: Introductionmentioning

confidence: 99%

“…Research in the past showed that GDF-15 played an active role in left ventricular remodeling [ 14 ]. Moreover, GDF-15 in serum was higher in patients with atrial fibrillation [ 15 – 17 ], and it could be used as a prognostic indicator for bleeding and death [ 18 ]. It is recognized that human transforming growth factor β 1 (TGF- β 1 ), which is also a member of the TGF- β family, exhibited a profibrotic effect on cardiomyocytes and thus increased the chances to develop AF [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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The Predictive Value of Growth Differentiation Factor-15 in Recurrence of Atrial Fibrillation after Catheter Ablation

Ying

Liu

et al. 2020

Mediators of Inflammation

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The mechanisms underlying the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) are not well concerned. The study sought to explore the association between growth differentiation factor-15 (GDF-15) and the incidence of recurrent events among AF patients after the ablation procedure. We prospectively included 150 consecutive AF patients who underwent RFCA. Clinical information about the patients was collected. Blood samples on the second morning of hospital admission and three months after RFCA were collected, and enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of GDF-15. All participants were followed up at specific times (1st/3rd/6th/12th/18th/24th months) after RFCA to record recurrences events. During a median follow-up of 14.0 months, AF recurrence occurred in 37(24.7%) patients. Baseline serum GDF-15 level in the persistent AF group was significantly higher than the paroxysmal AF group [1140(854~1701)ng/L vs. 1062(651~1374)ng/L, P=0.039]. Baseline serum GDF-15 level in the recurrence group was significantly higher than the nonrecurrence group [1287(889~1768) ng/L vs. 1062(694~1373)ng/L, P=0.022]. Serum GDF-15 level at three months after RFCA was significantly lower than the baseline [870 (579~1270) ng/L vs. 1155 (735~1632)ng/L, P<0.001]. The baseline GDF-15 correlated significantly with LAP (r=0.296, P<0.001) and LAAV(r=−0.235, P=0.003). Kaplan-Meier analysis showed a significantly lower event-free survival time in the high baseline GDF-15 (≥1287.3 ng/L) group than the low baseline GDF-15 (<1287.3 ng/L) group (17.1 months vs. 20.4 months, Log Rank P=0.017). In the multivariate Cox regression, baseline GDF-15(HR 1.053, 95% CI 1.007-1.100, P=0.022) and LAD (HR 1.124, 95% CI 1.011-1.250, P=0.030) were independent predictors of AF recurrence after RFCA. Our study indicated increased preprocedural GDF-15 is associated with left atrial remodeling and acts as a predictor of AF recurrence after ablation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Predictive Value of Growth Differentiation Factor-15 in Recurrence of Atrial Fibrillation after Catheter Ablation

Ying

Liu

et al. 2020

Mediators of Inflammation

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“…Our result suggested that the circulating GDF-15 level was positive associated with the risk of AF. In community-based Individuals [ 30 ], postoperative patients [ 31 ] and hypertrophic cardiomyopathy (HCM) patients [ 32 ], those who had the higher GDF-15 levels were more vulnerable to AF than the lower. In addition, circulating GDF-15 level was reckoned independently associated with paroxysmal AF after multivariable analyses.…”

Section: Discussionmentioning

confidence: 99%

The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study

Wang

Yang

et al. 2020

BMC Cardiovasc Disord

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Background Growth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor β cytokine superfamily. Some evidence support that it’s involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it’s still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence. Methods Genetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses. Results Among 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. Conclusions The MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.

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“…Our result corresponds to a slice of previous randomized and observational studies. In community-based Individuals [25], postoperative patients [26] and hypertrophic cardiomyopathy (HCM) folks [27] who had a higher GDF-15 level were more vulnerable to AF than those remaining lower level. Rienstra, M., et al suggest that was associated with incident AF with the hazards ratios of 1.31 after adjusted for age and sex [25].…”

Section: Discussionmentioning

confidence: 99%

The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study

Wang

Yang

et al. 2020

Preprint

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Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Based on the instruments, GDF-15 level linked to the increasing risk of cardioembolic stroke (1.06, OR 1.09 per SD increase, 95% CI 1.01, 1.19) , atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06), coronary artery disease (OR 0.94 per SD increase, 95% CI 0.89, 0.99) and myocardial infarction (OR 0.94 per SD increase, 95% CI 0.90, 0.98). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our study. Conclusions: The result suggested that GDF-15 was causally associated with the risk of cardioembolic stroke,atrial fibrillation, coronary artery disease and myocardial infarction, providing us conceivable strategies to alleviate the burden of cardiovascular disease.

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Atrial contractility and fibrotic biomarkers are associated with atrial fibrillation after elective coronary artery bypass grafting

Cited by 22 publications

References 47 publications

The Predictive Value of Growth Differentiation Factor-15 in Recurrence of Atrial Fibrillation after Catheter Ablation

The Predictive Value of Growth Differentiation Factor-15 in Recurrence of Atrial Fibrillation after Catheter Ablation

The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study

The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study

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