Epicardial adipose tissue volume and cardiovascular disease in hemodialysis patients

doi:10.1016/j.atherosclerosis.2012.10.061

Atherosclerosis

Volume 226, Issue 1, January 2013, Pages 129-133

https://doi.org/10.1016/j.atherosclerosis.2012.10.061 Get rights and content

Abstract

Objective

Epicardial adipose tissue (EAT) is proposed as a cardiovascular risk marker in non-uremic subjects. However, little is known about its role in patients with higher cardiovascular risk profile such as chronic kidney disease. The aim of this study was to investigate the relationship between EAT and several cardiovascular surrogate markers (coronary artery calcification (CAC), arterial stiffness and atherosclerosis) in patients on maintenance hemodialysis.

Methods

A total of 191 prevalent hemodialysis patients were enrolled in this cross-sectional study. EAT and CAC scores (CACs) were determined by multi-slice computerized tomography, arterial stiffness by carotid-femoral pulse wave velocity (PWV), and carotid artery intima-media thickness (CA-IMT) by B-mode doppler ultrasonography.

Results

Mean age was 59 ± 13 years and time on hemodialysis 75 ± 44 months. Twenty percent of the patients had diabetes. Mean EAT volume was 62.6 ± 26.8 cm³/m². Mean CA-IMT and PWV values increased across the EAT tertiles. EAT was correlated with age, female gender, body mass index, albumin and lipid parameters. Additionally, CA-IMT and PWV values were positively correlated with EAT. EAT volume was significantly higher in patients with CACs >10 compared to the patients with CACs ≤10. Despite the univariate associations between EAT and cardiovascular surrogate markers, only age, body mass index and total cholesterol levels were associated with EAT in adjusted models.

Conclusions

In prevalent hemodialysis patients, EAT is correlated with atherosclerosis, arterial stiffness and the presence of CAC. However, this correlation is not independent of other risk factors.

Highlights

► Epicardial adipose tissue is correlated with cardiovascular surrogate markers. ► However, this correlation is not independent of other risk factors. ► It may be both the cause and single surrogate marker “on its own” for CVD disorders.

Introduction

Epicardial adipose tissue (EAT) is the visceral adipose tissue surrounding the heart, especially the subepicardial coronary vessels. It has the same origin as abdominal visceral fat, which has been strongly associated with coronary artery disease (CAD). Although, little is known about its physiologic and metabolic roles, EAT has been implicated as a cardiovascular risk factor in non-uremic patients [1]. Recently, it has been shown that EAT can produce and secrete several proatherosclerotic and proinflammatory hormones and cytokines such as TNF-α, IL-6, and adipocytokines that might underlie its association with the presence of CAD [2], [3], [4], [5]. Furthermore, this association has been shown to be independent of body mass index and diabetic status [6]. Although EAT volume was significantly associated with atherosclerosis and coronary artery calcification (CAC) in patients without chronic kidney disease in several studies [7], [8], [9], [10], [11], some studies could not confirm the relation between EAT and CAD [12]. In a recently published meta-analysis, both EAT thickness and volume was associated with CAD, but not specifically with CAC [13].

In patients with chronic renal disease, inflammatory burden is much more pronounced than the general population suggesting that EAT may end up with more deleterious outcomes. Thus, in a recent study, Turkmen et al. [14] reported higher EAT in dialysis patients compared to healthy controls and a significant association of EAT with malnutrition-inflammation-atherosclerosis-calcifi-cation syndrome (MIAC). However, the association between EAT and cardiovascular disease still remains unclear in dialysis patients who have higher cardiovascular risk profile compared to the general population.

The aim of this study was to investigate the relationships between EAT determined by multi-slice tomography and carotid artery intima-media thickness (CA-IMT), arterial stiffness and coronary artery calcification in hemodialysis (HD) patients.

Section snippets

Patients

Study group consisted of a subgroup of patients participated in a clinical trial, EGE Study (Clinicaltrials ID NCT00295191). EGE Study was a randomized controlled trial to explore the effects of membrane flux and dialyzate purity on cardiovascular outcomes. Main inclusion criteria were aged 18–80 years and undergoing thrice weekly HD; main exclusion criterion was life expectancy less than a year. Multi-slice computerized tomography, pulse wave analysis and carotid artery ultrasonography were

Results

The clinical characteristics and laboratory data of the whole study population are summarized in Table 1. Briefly, mean age was 59 ± 13 years and time on HD 75 ± 44 months. Twenty percent of the patients had a history of diabetes and 19% history of CVD. Prevalence of the patients with a body mass index above 25 and 30 kg/m² were 33% and 10%, respectively.

Mean EAT volume was 62.6 ± 26.8 cm³/m² (107.2 ± 47.4 cm³). Distribution of EAT of the study population is presented in Fig. 1. Severe CAC

Discussion

This is the first study investigating the relationship between EAT volume, hypothesized as a cardiovascular risk factor, and several cardiovascular surrogate markers in patients on maintenance HD. Our results show that EAT volume is correlated with carotid artery atherosclerosis and arterial stiffness. While the correlation between CACs and EAT volume is borderline, patients with higher EAT were more likely to develop CAC. However, the associations of EAT with atherosclerosis, arterial

Conflict of interest

EO is a member of scientific board of Fresenius Medical Care, Turkey. The other authors declare no conflict of interest.

Acknowledgments

We thank all staff of the participating hemodialysis centers and patients for their help and support.

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Cited by (28)

Epicardial fat tissue, coronary arterial calcification and mortality in patients with advanced chronic kidney disease and hemodialysis
2021, Nefrologia
Citation Excerpt :
The quantification of EAT is not standardized, the studies are heterogeneous in terms of radiological technique and the location of the fat, and there is no consensus on the reference ranges.13,18 In patients with advanced CKD or undergoing renal replacement therapy, the volume of EAT has been linked to coronary artery calcification (CaC), atherosclerosis, inflammation and malnutrition.12,19–22 However, there are few data on their predictive ability of CV events and mortality in these patients.23
Epicardial and mediastinal adipose tissue (EAT, MAT) are linked to metabolic syndrome and coronary artery disease. Patients with chronic kidney disease (CKD) have thicker EAT. We assessed if EAT and MAT could be associated with increased mortality and cardiovascular events in patients with advanced CKD and haemodialysis therapy.
A post-hoc study was performed. We analyzed a prospective series of 104 cases. EAT thickness was quantified by a multislice synchronized computed tomography (MSCT).
The follow-up period was 112.68 (109.94–115.42) months. The optimal cut-off point of EAT for prediction of total mortality was 11.45 mm (92.86% and 43.75%). EAT thickness was associated with serum albumin levels, serum triglyceride levels, phosphorus and calcium phosphate product. The EAT was greater in haemodialysis patients compared to those with advanced CKD (P < .001). Patients with diabetes mellitus had greater EAT and MAT thickness (P = .018). At the end of follow up, the survival average time of patients with EAT thickness <11.45 mm was 97.48 months vs. 76.65 months for thickness > 11.45 mm (P = .007).
A higher EAT and MAT thickness was associated with increased mortality. Furthermore, EAT was associated with lower free survival time to fatal and non-fatal cardiovascular events. The measurement of EAT and MAT by MSCT could be a prognostic tool to predict cardiovascular events and mortality risk in advanced CKD patients.
El tejido graso epicardico (EAT) y mediastínico (MAT) se relaciona con el síndrome metabólico y la enfermedad arterial coronaria. Los pacientes con enfermedad renal crónica (ERC) tienen mayor volumen de EAT. El objetivo de nuestro estudio fue determinar si estos depósitos adiposos podrían estar relacionados con un aumento de mortalidad y eventos cardiovasculares en pacientes con ERC avanzada y en hemodiálisis.
Se realizó un análisis post hoc de una serie prospectiva, de 104 casos, con una tomografía computarizada sincronizada multicorte (MSCT) que permitiera cuantificar el grosor EAT.
El periodo de seguimiento fue de 112,68 (109,94-115,42) meses. El punto de corte de EAT con mayor sensibilidad y especificidad para predecir mortalidad total fue 11,45 mm (el 92,86 y el 43,75%, respectivamente). Las variables que se correlacionaron con el EAT fueron la albúmina, el nivel sérico de triglicéridos, de fósforo y el producto fosfo-cálcico. El EAT fue mayor en pacientes en hemodiálisis respecto aquellos con ERC avanzada (p < 0,001). Los pacientes con diabetes mellitus tenían mayor grosor de EAT y MAT (p = 0,018). La supervivencia media de los pacientes con EAT < 11,45 mm fue de 97,48 meses vs. 76,65 meses para un grosor > 11,45 mm (p = 0,007).
Un mayor grosor de EAT y MAT se relacionó con un incremento de mortalidad total. Además, el EAT se asoció con una menor supervivencia libre de eventos cardiovasculares fatales y no fatales. La cuantificación de EAT y MAT mediante MSCT podría tener valor pronóstico para pacientes con ERC avanzada y hemodiálisis.
Increased serum renalase in peritoneal dialysis patients: Is it related to cardiovascular disease risk?
2017, Nefrologia
Citation Excerpt :
Recently, epicardial adipose tissue (EAT), the visceral adipose tissue surrounding the heart and subepicardial coronary vessels, has been found to correlate with several cardiac comorbidities, including coronary artery disease and left ventricular dysfunction in patients undergoing peritoneal dialysis (PD) or hemodialysis.4–6 The relation between EAT and CVD is not fully understood but has been attributed to the several proatherosclerotic and proinflammatory hormones and cytokines such as TNF-a, IL-6, and adipocytokines, which are secreted from EAT and influence cardiac function.5,7 Renalase, a recently discovered enzyme with monoamine oxidase activity, is implicated in degradation of catecholamines.
Renalase, with possible monoamine oxidase activity, is implicated in degradation of catecholamines; which suggests novel mechanisms of cardiovascular complications in patients with chronic kidney diseases. Epicardial adipose tissue (EAT) has been found to correlate with cardiovascular diseases (CVD) in dialysis patients. The present study aimed to evaluate the association of serum renalase levels with EAT thickness and other CVD risk factors in peritoneal dialysis (PD) patients.
The study included 40 PD patients and 40 healthy controls. All subjects underwent blood pressure and anthropometric measurements. Serum renalase was assessed by using a commercially available assay. Transthoracic echocardiography was used to measure EAT thickness and left ventricular mass index (LVMI) in all subjects.
The median serum renalase level was significantly higher in the PD patients than in the control group [176.5 (100–278.3) vs 122 (53.3–170.0) ng/ml] (p = 0.001). Renalase was positively correlated with C-reactive protein (r = 0.705, p < 0.001) and negatively correlated with RRF (r = −0.511, p = 0.021). No correlation was observed between renalase and EAT thickness or LVMI. There was a strong correlation between EAT thickness and LVMI in both the PD patients and the controls (r = 0.848, p < 0.001 and r = 0.640, p < 0.001 respectively).
This study indicates that renalase is associated with CRP and residual renal function but not with EAT thickness as CVD risk factors in PD patients.
La renalasa, posiblemente con actividad monoaminooxidasa, está implicada en la degradación de catecolaminas, lo que indica nuevos mecanismos de complicaciones cardiovasculares en pacientes con enfermedades renales crónicas. Se ha encontrado que el tejido adiposo epicárdico (TAE) se correlaciona con las enfermedades cardiovasculares (ECV) en pacientes de diálisis. El presente estudio tuvo como objetivo evaluar la asociación de los niveles de renalasa sérica con el espesor del EAT y otros factores de riesgo de ECV en pacientes de diálisis peritoneal (DP).
El estudio incluyó a 40 pacientes de DP y a 40 controles sanos. Se tomaron la presión arterial y las medidas antropométricas de todos los individuos. Se evaluó la renalasa sérica mediante un ensayo disponible comercialmente. Se utilizó la ecocardiografía transtorácica para medir el espesor del TAE y el índice de masa ventricular izquierda (IMVI) en todos los individuos.
La mediana del nivel de renalasa sérica fue significativamente mayor en los pacientes de DP que en el grupo control (176,5 [100-278,3] frente a 122 [5,3-170,0] ng/ml) (p = 0,001). La renalasa se correlacionó positivamente con la proteína C reactiva (r = 0,705; p < 0,001) y negativamente con la FRR (r = -0,511, p = 0,021). No se observó correlación entre la renalasa y el espesor del TAE ni el IMVI. Hubo una fuerte correlación entre el espesor del TAE y el IMVI tanto en los pacientes de DP como en los controles (r = 0,848; p < 0,001 y r = 0,640; p < 0,001, respectivamente).
Este estudio indica que la renalasa está asociada con la proteína C reactiva y la función renal residual, pero no con el espesor del TAE, como factores de riesgo de ECV en pacientes de DP.
Correlation between epicardial adipose tissue and severity of coronary artery stenosis evaluated by 64-MDCT
2016, Clinical Imaging
Citation Excerpt :
Echocardiography is another commonly used modality in evaluating epicardial fat [16]. Earlier studies have showed a close association between echocardiographic EAT thickness and EAT volume obtained by magnetic resonance imaging [17]. Despite of its easy operation and low cost, echocardiography could not provide accurate measurement of EAT volume.
The purpose was to investigate the correlation between epicardial adipose tissue (EAT) thickness, EAT volume, and severity of coronary artery stenosis.
We retrospectively enrolled 188 patients that underwent coronary computed tomography (CT) angiography for clinically suspected coronary artery disease using 64-MDCT. Images were reconstructed using a retrospective electrocardiogram-gated algorithm with 0.625-mm-thick sections. EAT thickness and volume were calculated.
The coronary CT angiography showed 106 patients who had coronary artery pathology (178 lesions), 21 patients with moderate stenosis (27 lesions), 12 patients with severe stenosis (18 lesions), and 6 patients with complete occlusion (8 lesions). EAT thickness, EAT volume, and Gensini score were statistically different among groups (F_T = 32.306, F_V = 27.743, F = 110.483, P = .000). Pearson correlation analysis showed that Gensini score had significantly positive correlation with EAT thickness and volume, respectively.
EAT thickness and volume demonstrated a positive correlation with severity of coronary artery stenosis.
Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis
2014, Atherosclerosis
Citation Excerpt :
Ding et al. also reported that pericardial adipose tissue is a predictor of incident cardiovascular events in the Framingham Heart Study [21]. In patients receiving hemodialysis, a population at extremely elevated cardiovascular risk and high incidence of arterial calcifications [60], EAT was shown to be associated with coronary artery calcium [61], and be an independent predictor of mortality [62]. The association of EAT with coronary atherosclerosis and cardiometabolic risk has been observed in other populations at high cardiovascular risk such as HIV infected patients receiving anti-retroviral therapy (ART) [63], and patients with rheumatologic disorders [64,65].
The current epidemic of obesity with the associated increasing incidence of insulin resistance, diabetes mellitus and atherosclerosis affecting a large proportion of the North American and Western populations, has generated a strong interest in the potential role of visceral adipose tissue in the development of atherosclerosis and its complications. The intra-abdominal and epicardial space are two compartments that contain visceral adipose tissue with a similar embryological origin. These visceral fats are highly inflamed in obese patients, patients with the metabolic syndrome and in those with established coronary artery disease; additionally they are capable of secreting large quantities of pro-inflammatory cytokines and free fatty acids. There is accumulating evidence to support a direct involvement of these regional adipose tissue deposits in the development of atherosclerosis and its complicating events, as will be reviewed in this article.
Epicardial fat tissue thickness is correlated with diminished levels of co-enzyme Q10, a major antioxidant molecule among hemodialysis patients
2014, Clinical Biochemistry
Citation Excerpt :
In another study by Turan et al. EFT volume was correlated with carotid intima thickness and pulse wave velocity which are markers of atherosclerosis and ED [15]. In our recently published study, we demonstrated that EFT thickness was inversely correlated with CFR among HD patients [17].
Accelerated atherosclerosis is the major cause of mortality in patients on chronic maintenance hemodialysis (HD). Epicardial fat tissue (EFT) is a new risk factor in cardiovascular disease (CVD). The aim of this study was to evaluate the relation between plasma coenzyme Q10 levels (Co-Q10) which is a potent physiologic antioxidant and EFT thickness in HD patients.
Seventy one chronic HD patients and 65 age and sex matched healthy individuals were included in the study. Plasma Co-Q10 levels were performed by high-performance liquid chromatography (HPLC) measurements. EFT was measured by transthoracic echocardiograpy (TTE) performed with a VIVID 7 instrument.
Plasma Co-Q10 levels (1.36 ± 0.43 vs 2.53 ± 0.55, p < 0.001) were significantly lower in HD patients compared to controls. EFT was significantly increased in HD patients compared to healthy controls (6.53 ± 1.01 vs. 5.79 ± 1.06 mm respectively, p < 0.001). Correlation analysis showed that plasma Co-Q10 levels were inversely correlated with EFT (r = − 0.263, p < 0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. According to linear regression analysis, age, BMI, total cholesterol and Co-Q10 levels were found to be independent predictors of EFT (adjusted r² = 0.38, p < 0.001).
This study demonstrated that EFT thickness was significantly higher among HD patients compared to healthy controls. In addition; this study was the first to demonstrate an inverse correlation between EFT thickness and Co-Q10 levels in this patient population.
Gender-related differences in chronic kidney disease-associated vascular calcification risk and potential risk mediators: A scoping review
2021, Healthcare (Switzerland)

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Epicardial adipose tissue volume and cardiovascular disease in hemodialysis patients

Abstract

Objective

Methods

Results

Conclusions

Highlights

Introduction

Section snippets

Patients

Results

Discussion

Conflict of interest

Acknowledgments

Am Heart J

Atherosclerosis

Atherosclerosis

Atherosclerosis

J Am Coll Cardiol

Am J Kidney Dis

Visceral fat is an independent predictor of all-cause mortality in men

Obesity (Silver Spring)

Adiposity and cardiovascular disorders: disturbance of the regulatory system consisting of humoral and neuronal signals

Circ Res

Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease

Cardiovasc Diabetol

Adipose tissue: from lipid storage compartment to endocrine organ

Diabetes

Human epicardial adipose tissue is a source of inflammatory mediators

Circulation