Volume 16, Issue 7 p. 1693-1697
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Substantial Changes in Epicardial Fat Thickness After Weight Loss in Severely Obese Subjects

Gianluca Iacobellis

Corresponding Author

Gianluca Iacobellis

Department of Medicine, Cardiovascular Obesity Research and Management, McMaster University, Hamilton, Ontario, Canada

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Navneet Singh

Navneet Singh

Department of Medicine, Cardiovascular Obesity Research and Management, McMaster University, Hamilton, Ontario, Canada

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Sean Wharton

Sean Wharton

Department of Medicine, Cardiovascular Obesity Research and Management, McMaster University, Hamilton, Ontario, Canada

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Arya M. Sharma

Arya M. Sharma

Department of Medicine, Cardiovascular Obesity Research and Management, McMaster University, Hamilton, Ontario, Canada

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First published: 06 September 2012
Citations: 181

Abstract

We sought to evaluate the effect of weight loss on echocardiographic epicardial fat thickness, as index of visceral adiposity, and whether epicardial fat change after the weight loss can be proportionally different from overall body weight changes and related to cardiac parameters changes in severely obese subjects. This was an interventional study in 20 severely obese subjects (12 women, 8 men, BMI 45 ± 5 kg/m2, 35 ± 10 years) who underwent 6-month very low calorie diet weight loss program. Baseline and after 6-month weight loss anthropometrics, echocardiographic epicardial fat thickness, left ventricular mass (LVM), and diastolic function parameters were assessed. Subjects lost 20% of original body weight, BMI reduced by 19% of original BMI, waist circumference decreased by 23% of initial waist circumference. Epicardial fat thickness decreased from 12.3 ± 1.8 to 8.3 ± 1 mm P < 0.001 after the 6-month very low calorie diet, as −32% of baseline epicardial fat thickness. LVM and diastolic function changes were better correlated with epicardial fat changes. We showed that significant weight loss can be associated with significant reduction in the epicardial fat thickness, marker of visceral adiposity in severely obese subjects. Epicardial fat decrease, therefore visceral fat decrease, can be proportionally higher than overall adiposity decrease. Epicardial fat changes are significantly associated with obesity-related cardiac morphological and functional changes during weight loss. Measurement of echocardiographic epicardial fat thickness may provide an additional tool in understanding the metabolic risk associated with variation in fat distribution.

Introduction

Substantial and sustainable weight loss is the primary goal to reduce cardiometabolic risk in subjects with obesity and excess weight. Nevertheless, whether the fat loss during weight loss interventions is uniform across body fat compartments is still unclear. Whether the proportion changes in overall and visceral adiposity can be different is partially unanswered. Body of evidences shows that increased visceral adipose tissue may confer increased cardiometabolic risk (1,2). Easy and reliable markers of visceral adiposity may therefore provide a more complete understanding of metabolic risk associated with variation in fat distribution.

Recently, the scientific and clinical interest in epicardial adipose tissue is rapidly growing (3,4,5,6). We showed that echocardiographic assessment of epicardial adipose tissue can serve as a new index of cardiac and visceral adiposity. We also previously demonstrated that epicardial fat is clinically correlated with magnetic resonance imaging abdominal visceral adiposity (7), coronary artery disease (8,9), atherosclerosis (10,11), and major anthropometric and metabolic predictors of increased cardiometabolic risk (12,13,14). Emerging evidences suggest that epicardial fat may act as therapeutic target during therapeutic interventions modulating the adipose tissue (15). In fact, epicardial fat thickness decreases in severely obese patients who have substantial weight loss after bariatric surgery (16).

In this study, we sought to evaluate the effect of weight loss on echocardiographic epicardial fat thickness, as index of visceral adiposity, and whether epicardial fat change after the weight loss can be proportionally different from overall body weight changes and related to cardiac parameters changes in severely obese subjects.

Methods and Procedures

Study design

This was an interventional study in severely obese subjects (BMI >40 kg/m2) who underwent very low calorie diet weight loss program. The weight loss program included medical, behavior (e.g., lifestyle counseling), and nutrition intervention. The medical component monitored patient comorbidities and mandated calorie with specific monitoring of clinical and blood parameters. The very low calorie diet (900 kcal/day) intervention was composed of three phases (Phase 1—complete meal replacement, 12 weeks; Phase 2—transition period including healthy foods and partial meal replacement, 4–6 weeks; Phase 3—long-term maintenance). Baseline and after 6-month weight loss anthropometrics (body weight, BMI, waist circumference) were measured. Baseline and after 6-month weight loss echocardiographic measurements of epicardial fat thickness were performed in all study individuals. Baseline and after 6-month weight loss echocardiographic morphological, as well as left ventricular mass (LVM) and functional, such as diastolic function parameters were also calculated.

Subjects

All obese patients seeking treatment were consecutively recruited from the weight loss program at Hamilton General Hospital run by the Cardiovascular Obesity Research and Management Centre. Twenty consecutive white severely obese outpatients (BMI 45 ± 5 kg/m2, 12 women and 8 men, mean age of 35 ± 10 years) who were eligible for the 6-month weight loss program were enrolled in the study. Patients with coronary artery disease, cardiac, renal or hepatic failure, poorly controlled diabetes, hypertension, neoplastic diseases, and major psychiatric disorders were not included in this program. This study was conducted in accordance with the guidelines proposed in The Declaration of Helsinki and has been approved by ethical committee of McMaster University. All subjects gave informed consent before study began.

Methods

Each subject underwent transthoracic two-dimensional guided M-mode echocardiogram using commercially available equipment (Vivid 7, GE, Milwaukee, WI), and the images were digitized.

Standard parasternal and apical views were obtained in the left lateral decubitus position. Epicardial fat was identified as the echo-free space between the outer wall of the myocardium and the visceral layer of pericardium and its thickness was measured perpendicularly on the free wall of the right ventricle at end systole in three cardiac cycles. Because it is compressed during diastole, maximum epicardial fat thickness was measured in end systole. Epicardial fat was also identified as hyperechoic space, if in massive amount (>15 mm). Parasternal long- and short-axis views allow the most accurate measurement of epicardial adipose tissue on the right ventricle, with optimal cursor beam orientation in each view. Maximum epicardial fat thickness was measured at the point on the free wall of the right ventricle along the midline of the ultrasound beam, perpendicular to the aortic annulus, used as anatomical landmark for this view. For the midventricular parasternal short-axis assessment, maximum epicardial fat thickness was measured on the right ventricular free wall along the midline of the ultrasound beam, perpendicular to the interventricular septum at mid-chordal and tip of the papillary muscles level, as anatomic landmark. The average value of three cardiac cycles from each echocardiographic view was considered.

LVM was estimated using the anatomically validated formula of Devereux et al. (17). LVM was adjusted to height2.7, LVM/height2.7. Left ventricular diastolic function was evaluated using filling and relaxation Doppler echocardiographic parameters: early (E) and late (A) transmitral (E/A) ratio, isovolumic relaxation time, measured between the end of transaortic systolic flow (outflow) and the beginning of the E wave (inflow), respectively.

Anthropometrics

Weight and height were measured while the subjects were fasting and wearing only their undergarments. BMI was calculated as body weight divided by height squared. Minimum waist circumference (in centimeters; minimum circumference between the lower rib margin and the iliac crest, midwaist) was measured while the subjects were standing with their heels together.

Statistical analysis

Data in the text and table are expressed as mean ± s.d. The sample of 20 individuals provided us the statistical power of 80% (1α = 0.05) to detect differences in the epicardial fat thickness before and after the weight loss program. A t-test with 95% confidence interval (CI) was used to calculate differences between baseline and after 6-month weight loss epicardial fat thickness and anthropometric variables. Changes (Δ) in study parameters were calculated as difference between baseline and after 6-month weight loss. Relations between ΔBMI, Δwaist circumference, and Δepicardial fat and ΔLVM, ΔE/A after 6-month weight loss were calculated using simple linear regression analysis. Reliability of echocardiographic measurement of epicardial fat thickness was assessed by the intraclass correlation coefficient. Both pre- and postweight reduction echocardiographic measurement were performed by the first author (G.I.) and re-read by N.S., trained sonographer, who was blinded of both measurements. Inter- (G.I., N.S.) and intraobserver (G.I.) reproducibility was evaluated by the intraclass correlation coefficient in all subjects.

Results

All the 20 patients completed the study. No minor or major adverse events occurred during the duration of the weight loss program.

Anthropometric changes

Overall severely obese subjects had an expected weight loss after the 6-month very low calorie diet. Patients lost an average of 25 ± 10 kg after the 6-month very low calorie diet, as −20% of original body weight. Mean BMI reduced from 45 ± 5 kg/m2 to 38 ± 5 kg/m2 P < 0.001, as −19% of original BMI. Mean waist circumference decreased from 136 ± 15 to 108 ± 15 cm P < 0.001, as −23% of initial waist circumference. Percentage of body weight, BMI, and waist circumference changes did not significantly differ between men and women.

Echocardiographic changes

Epicardial fat thickness. Interobserver and intraobserver agreement on epicardial fat thickness measurement was excellent: intraclass correlation coefficient was 0.90 and 0.98, respectively, suggesting an excellent reproducibility of this measure.

Severely obese subjects had significantly higher epicardial fat thickness when compared to lean subjects (BMI 20–24.9 kg/m2), 11.7 ± 1.5 vs. 3.5 ± 1 in women and 13.1 ± 2 vs. 4 ± 1 in men, P < 0.01 for both). Epicardial fat thickness range in overall severely obese subjects who were enrolled in this study was 9.5–17 mm.

Epicardial fat thickness decreased from 12.3 ± 1.8 to 8.3 ± 1 mm P < 0.001 after the 6-month very low calorie diet, as −32% of baseline epicardial fat thickness (Figure 1). Percentage of epicardial fat reduction did not significantly differ between men and women.

Details are in the caption following the image

Changes in adiposity markers after weight loss. Overall severely obese subjects lost 20% of original body weight, BMI reduced by 19% of original BMI, waist circumference (waist) decreased by 23% of initial waist circumference. Epicardial fat thickness (Epi. fat) decreased by 32% of baseline epicardial fat thickness.

Table 1 shows epicardial fat thickness, weight, and BMI before and after weight loss and the delta (Δ) of epicardial fat thickness for each individual patient. This is to better appreciate the range of epicardial fat thickness, the magnitude of changes, and variation of results among patient, even in relation to the initial obesity degree.

Table 1. Changes in BMI, body weight, and epicardial fat thickness for each individual patient
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LVM and diastolic parameters. LVM, LVM/height2.7 significantly decreased after 6-month weight loss (P < 0.01), while E/A ratio and isovolumic relaxation time significantly increased after the weight loss (P < 0.01) (Table 2).

Table 2. Echocardiographic parameters before and after 6-month weight loss
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LVM change (ΔLVM) after 6-month weight loss was significantly correlated with epicardial fat changes (Δepicardial fat) (r = 0.60, P < 0.01), waist circumference changes (Δwaist), (r = 0.53, P < 0.01), and mildly with BMI changes (ΔBMI) (0.25, P < 0.05) (Figure 2).

Details are in the caption following the image

Relationship of Δ epicardial fat thickness, Δ waist circumference, ΔBMI with ΔLVM. Linear regression analysis: LVM change (ΔLVM) after 6-month weight loss was significantly correlated with (a) epicardial fat thickness changes (Δ epicardial fat thickness) (r = 0.60, P < 0.01), (b) waist circumference changes (Δ waist circumference), (r = 0.53, P < 0.01), and mildly with (c) BMI changes (ΔBMI) (0.25, P < 0.05).

E/A change (ΔE/A) after 6-month weight loss was significantly correlated with epicardial fat changes (Δepicardial fat) (r = 0.40, P < 0.01), waist circumference changes (Δwaist), (r = 0.38, P < 0.01), and not with BMI changes (ΔBMI) (0.22, P < 0.07).

Discussion

We believe that the major and novel findings of this study are: (i) weight loss during a short-term very low calorie diet program induces a significant reduction of epicardial fat thickness in severely obese subjects (ii) decrease of epicardial fat, index of visceral adiposity, is substantially higher than overall body weight loss, (iii) change in epicardial fat thickness is significantly higher than BMI and waist circumference changes during a short-term very low calorie diet program, (iv) weight loss-related improvement in both LVM and diastolic function is better correlated with epicardial fat reduction than with BMI and waist circumference changes.

Increased visceral adiposity is considered one of the key components of the metabolic syndrome. Visceral fat reduction is associated with a significant improvement of the cardiometabolic profile (18). However, it is presently unknown how much visceral adipose tissue loss is needed to induce favorable metabolic changes. In addition, how the overall and visceral fat loss can be proportionally different is also partially unclear. In the phase of rapid weight loss after laparoscopic bariatric surgery, a preferential mobilization of visceral abdominal fat, as compared with total and subcutaneous adiposity, was observed (19). However, this preferential visceral fat reduction seems to occur only in those patients presenting higher levels of visceral fat deposition at baseline and higher levels of weight loss (19).

In this study, we used the echocardiographic epicardial fat as marker of visceral adiposity, as previous studies from our group (7,12,14,20) and also from other authors (8,21) showed.

Our data are consistent with recent observation of Willens et al. of significant epicardial fat changes after laparoscopic bariatric surgery in severely obese subjects (16). However, we additionally observed a significant difference between the proportion of epicardial fat loss and overall body weight loss. In fact, our data clearly indicate that visceral fat loss, expressed by epicardial fat changes, may be higher than overall adiposity, as indicated by BMI changes.

Our study also suggests that changes in echocardiographic epicardial fat thickness can be used to estimate and monitor reduction in visceral adiposity easily during weight loss programs. We previously showed that echocardiographic epicardial fat reflects magnetic resonance imaging intra-abdominal visceral fat (7), and therefore echocardiographic assessment of epicardial visceral fat would certainly be less expensive than magnetic resonance imaging or computed tomography. Waist circumference is still the most practical and cheaper marker of visceral fat and cardiometabolic risk predictor. However, in this study, we observed a significant difference in the proportion of decrease between waist circumference and epicardial fat thickness. This could be explained by the poor sensitivity and specificity of waist circumference as a measure of visceral adiposity. Echocardiographic measurement of visceral adipose tissue provides a more sensitive and specific measure of true visceral fat content, avoiding the possible confounding effect of increased subcutaneous abdominal fat.

Finally, we know that severely obese subjects can present with high LVM and impaired diastole (22,23). In this study, we found that the weight loss significantly decreased LVM and improved diastolic function. Previous studies showed the effect of weight loss on cardiac performance (24,25); however, we showed for the first time that cardiac changes were better correlated with epicardial fat thickness changes than with BMI changes. This observation is consistent with the possible direct mechanical and functional effect of cardiac fat on heart morphology and function, as we showed previously (13,26,27). We believe that the closeness of the epicardial fat to the heart may make its echocardiographic measurement an additional tool in evaluating cardiac changes during weight loss.

In conclusion, we showed that significant weight loss can be associated with significant reduction in the epicardial fat thickness, marker of visceral adiposity, in severely obese subjects. Epicardial fat decrease, therefore visceral fat decrease, can be proportionally higher than overall adiposity decrease. Epicardial fat changes are significantly associated with obesity-related cardiac morphological and functional changes during weight loss. Measurement of echocardiographic epicardial fat thickness may provide an additional tool in understanding the metabolic risk associated with variation in fat distribution.

Albeit this study provides original and intriguing findings, it may have also some limitations. First, further studies in a larger population are necessary to confirm these data. Although the sample size is relatively small, but statistically significant to detect differences in the primary outcomes, we believe that these data are still of interest for their novelty and potential clinical and research application. Future studies will be necessary to confirm the effect of weight loss on epicardial fat even in obese population with lesser degree of obesity. Clearly, the role of epicardial fat as cardiometabolic risk marker might be stronger in association with other cardiovascular risk factors either singly or in combination. Metabolic parameters were not evaluated in this study that was focused to changes in some anthropometric and imaging markers of adiposity during weight loss. Echocardiography is not the optimal technique for quantification of epicardial fat. Echocardiographic epicardial fat thickness is a linear measurement and therefore may not reflect the total epicardial fat volume in which thickness varies at different locations around the myocardium. However, we believe that echocardiography is accurate, reliable, still easier, and more accessible than magnetic resonance imaging and computed tomography. In addition, we cannot exclude that the absence of physical activity during this weight loss program may explain, at least partially, the higher change in epicardial fat thickness than BMI and waist circumference changes. The well-known effect of exercise on lean and fat mass may induce better changes in anthropometric indices, as well as BMI and waist circumference. However, the relationship of physical activity with epicardial fat warrants future evaluations. Finally, follow-up echocardiograms after weight loss program interruption are currently undergoing in these obese subjects. Very preliminary results seem to indicate sustained epicardial fat thickness reduction.

Acknowledgment

G.I. holds a McMaster University Department of Medicine Internal Career Research Award.

    Disclosure

    The authors declared no conflict of interest.

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