|Year : 2017 | Volume
| Issue : 1 | Page : 12-17
Study of epicardial fat thickness as a marker of visceral adiposity in patients with hypothyroidism
Ritu Karoli, Nikhil Gupta, Jalees Fatima, Zeba Siddiqi
Department of Medicine, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
|Date of Web Publication||20-Feb-2017|
Department of Medicine, Era's Lucknow Medical College, Sarfarazganj, Hardoi Road, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Hypothyroidism has adverse effects on the cardiovascular system. Visceral adiposity, the fat deposited around the internal organs, is recognized as an important risk factor. Hence, the present study was undertaken to investigate the presence of visceral adiposity, epicardial fat thickness (EFT), and nonalcoholic fatty liver disease (NAFLD) in patients with hypothyroidism as compared to matched euthyroid controls. Materials and Methods: In a case–control hospital-based study, 100 patients of hypothyroidism and equal number of age-, gender-, and body mass index-matched euthyroid controls were enrolled. They were studied for EFT and the presence of NAFLD along with anthropometric and biochemical parameters. Results: Among the hypothyroid patients, 67% had serum thyroid-stimulating hormone (TSH) varying 4.5–10 mIU/L and 33% had serum TSH >10 mIU/L. Patients with hypothyroidism had higher waist circumference (92.4 ± 8.6 cm vs. 84 ± 6.2 cm, P = 0.002) and diastolic blood pressure (88 ± 4 mmHg vs. 72 ± 10 mmHg, P = 0.01) than controls. The hypothyroid patients had significantly higher levels of triglycerides, low-density lipoprotein cholesterol homeostasis model assessment of insulin resistance, and prevalence of metabolic syndrome (22% vs. 8%). Markers of visceral adiposity were significantly higher in hypothyroid patients, and EFT had positive correlation with serum TSH levels. Conclusion: We observed higher EFT in patients with hypothyroidism and a significant correlation between EFT and serum TSH levels. Whether increased epicardial thickness as a marker of visceral adiposity may be associated with the potential cardiovascular adverse effects of hypothyroidism warrants further research.
Keywords: Epicardial fat thickness, hypothyroidism, nonalcoholic fatty liver disease
|How to cite this article:|
Karoli R, Gupta N, Fatima J, Siddiqi Z. Study of epicardial fat thickness as a marker of visceral adiposity in patients with hypothyroidism. Thyroid Res Pract 2017;14:12-7
|How to cite this URL:|
Karoli R, Gupta N, Fatima J, Siddiqi Z. Study of epicardial fat thickness as a marker of visceral adiposity in patients with hypothyroidism. Thyroid Res Pract [serial online] 2017 [cited 2017 Jul 26];14:12-7. Available from: http://www.thetrp.net/text.asp?2017/14/1/12/200561
| Introduction|| |
Primary hypothyroidism is a common endocrine disease, and patients who present with weight gain are evaluated for thyroid dysfunction. In recent times with increased awareness of thyroid diseases among health-care professionals, the number of patients with thyroid dysfunction seems increasing. Unnikrishnan et al. reported prevalence rates of 3.5% and 8.02% for overt hypothyroidism and subclinical hypothyroidism, while Marwaha et al. reported 4.2% and 19.3%, respectively.
Adverse effects of overt hypothyroidism on cardiovascular health such as hypertension and lipoprotein abnormalities are well established., Emerging evidence suggests that not only overt but also subclinical hypothyroidism can have the same atherogenic potential.
The thyroid gland is significantly involved in energy homeostasis, lipid and carbohydrate metabolism, regulation of body weight, and adipogenesis. Hypothyroidism is associated with lowering of basal metabolic rate, disturbance of lipid metabolism, and increase in body mass and insulin resistance (IR). Whether it is also associated with increased visceral adiposity is not yet clear.
Visceral adiposity, the fat deposited around the internal organs, is recognized as an important risk factor for the development of IR, diabetes, dyslipidemia, and hypertension , and has been linked with all-cause mortality in elderly population.
Increased levels of abdominal visceral adipose tissue (VAT) are also associated with the metabolic syndrome (MS), Type 2 diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD); the common basic mechanism in all seems to be IR.
Transthoracic echocardiography has been validated as an easy and reliable method to quantify the presence of VAT by measuring epicardial fat thickness (EFT) also called as epicardial adipose tissue (EAT) thickness, which correlates very well with the presence of general VAT.,, The EAT thickness has been suggested as a new cardiometabolic risk indicator. It has been related to IR, hypertension, and dyslipidemia.
Hence, the present study was undertaken to investigate the correlation of EFT as a marker of visceral adiposity in patients with hypothyroidism.
| Materials and Methods|| |
This was a hospital-based case–control study carried out in the Department of Medicine, Era's Lucknow Medical College, Lucknow, between July 2014 and June 2015. The patients were enrolled from the medical outpatient department/endocrine clinic of medical college hospital. Inclusion criteria comprised patients (18–45 years) presenting with history and examination suggestive of hypothyroidism.
Thyroid function was assessed by measuring serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and total thyroxine (T4). A blood sample was drawn in the morning after 12 h of fasting. Serum samples were obtained from whole blood after clotting. Serum TSH, T4, FT4, and FT3 were analyzed using solid phase technique chemiluminescence immune assays (Roche Diagnostics, Mannheim, Germany). Reference values for thyroid function test were as follows: TSH (mIU/ml, reference range 0.5–4.5) and FT4 (ng/dl, reference range 0.8–2.3), T4 (µg/dl, reference range 5.5–12.8), and FT3 (3.7–8.6 pmol/L).
The diagnosis of hypothyroidism was based on serum TSH levels when found between 4.5 and 10 mIU/L with normal serum FT4 was defined as mild subclinical hypothyroidism and severe when TSH levels exceed 10 mIU/L in nonpregnant adults.
The study subjects were divided into two groups. Group 1 had patients with hypothyroidism. Group 2 consisted of age-, sex-, and body mass index (BMI)-matched euthyroid individual controls selected among hospital staff and attendants.
Exclusion criteria included patients with diabetes mellitus, smokers, alcohol users, those with pituitary-hypothalamic disorders, pregnant, critically ill, those taking levothyroxine, oral contraceptives, and statins within 3 months before enrollment, and patients with concomitant inflammatory disease, coronary artery disease, or cerebrovascular accidents. All study participants signed written informed consent form, and the study was approved by the Institutional Ethics Committee.
A general physical examination was performed including assessment of height in meters (without shoes), weight in kilogram, and waist circumference (minimum value between iliac crest and lateral costal margins) and hip circumference in centimeters. BMI was calculated as weight (kg)/height (m2) brachial artery in supine position after 10 min of rest using a pneumatic sphygmomanometer.
Biochemical evaluation in the form of fasting blood glucose, insulin and lipid profile, and renal and liver profile was done in all the study participants. IR was measured by homeostasis model assessment (HOMA-IR) method and was calculated by the formula: Fasting serum insulin (mU/ml) × fasting serum glucose (µmol/L)/22.5.
Measurement of EAT thickness - each subject underwent transthoracic two-dimensional guided M-mode echocardiography using commercially available equipment (General Electric Company, CT, USA). Standard parasternal and apical views were obtained in the left lateral decubitus position. Epicardial fat was identified as echocardiographic free space between the outer wall of the myocardium and the visceral layer of the pericardium. EFT was measured perpendicularly to the free wall of the right ventricle at end diastole in three cardiac cycles. The average value of three cardiac cycles from each echocardiographic view was considered.
In all study participants, conventional B-mode liver ultrasound was performed with a convex 3.5 MHz probe, by the same operator who was unaware of the aims of the study and blinded to laboratory values. Five-point ultrasonographic criteria for diagnosis of fatty liver disease recommended by Dasarty were used to diagnose NAFLD: (1) Increased hepatic brightness or hyperechogenicity, (2) posterior attenuation of the right lobe, (3) increased contrast between the right kidney and liver, (4) loss of visualization of right diaphragm, and (5) diminished visibility of the intrahepatic vessels.
MS was defined according to the International Diabetes Federation (IDF) criteria. MS by IDF may be defined as central obesity (defined as waist circumference ≥94 cm [male], ≥80 cm, or [female]) and any two of the following:
- Triglyceride (TG) >150 mg/dl (1.7 mmol/L)
- High-density lipoprotein cholesterol (HDL-C) <40 mg/dl (male), <50 mg/dl (female)
- Blood pressure ≥130/85 mmHg
- Fasting plasma glucose >100 mg/dl (5.6 mmol/L).
The statistical analysis was performed using the Statistical Package for the Social Sciences Version 20 (IBM Corporation, Armonk, NY, USA). Continuous variables were expressed as the mean ± standard deviation, and categorical variables were expressed as percentages. Comparisons between groups were performed with t-test and Chi-square test for continuous and categorical variables, respectively. The relationship between different variables and EFT was determined using logistic regression.
| Results|| |
Clinical and anthropometric variables of the study participants are shown in [Table 1]. Most of the subjects were females (73% and 72% in two groups). Among the hypothyroid patients, 67% had serum TSH between 4.5 and 10 mIU/L and 33% had serum TSH >10 mIU/L. There was no significant difference in age, gender, and BMI in two study groups. Patients with hypothyroidism had higher waist circumference (92.4 ± 8.6 cm vs. 84 ± 6.2 cm, P = 0.002), and diastolic blood pressure (88 ± 4 mmHg vs. 72 ± 10 mmHg, P = 0.01) than controls.
|Table 1: Clinical characteristics of patients with hypothyroidism and controls|
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[Table 2] shows laboratory parameters in the patients and controls. The hypothyroid patients had significantly higher levels of TGs and total and low-density lipoprotein (LDL) cholesterol and lower level of HDL-C. HOMA-IR was found to be significantly raised in patients with hypothyroidism.
|Table 2: Biochemical parameters of patients with hypothyroidism and controls|
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In hypothyroid group, higher prevalence of MS (22% vs. 8%) was observed. NAFLD was also significantly higher (34% vs. 10%) in these patients with thyroid dysfunction than controls.
EFT was significantly higher in hypothyroid patients than controls (5.6 ± 0.7 and 3.5 ± 0.6, P = 0.001). In univariate analysis [Table 3], EFT as dependent variable was associated with waist circumference, diastolic blood pressure, increased TGs, HOMA-IR, and NAFLD. EFT had positive correlation with TSH (r = 0.42, P = 0.002).
|Table 3: Univariate analysis between variables and epicardial fat thickness|
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Logistic regression analysis was performed including all the study participants of the two groups [Table 4]. Presence of hypothyroidism, MS, and NAFLD was found to be independent predictors of increased EFT.
| Discussion|| |
EAT is a visceral fat deposited in and around the heart. In the normal adult, it is concentrated in the atrioventricular and interventricular grooves and along the major branches of the coronary arteries, and, to a lesser extent, around the atria, over the free wall of the right ventricle and over the apex of the left ventricle.
EFT, the adipose tissue accumulated between the visceral pericardium and the myocardium measured by echocardiography strongly, reflects the intra-abdominal accumulation of visceral fat, and it is a marker of cardiometabolic risk. Increased EAT is positively associated with the risk of MS. We hypothesized that EFT might be increased in patients with hypothyroidism and could partially contribute to the detrimental effect of hypothyroidism in the development of cardiovascular disease. The present study was conducted to explore the association between EFT and hypothyroidism.
Our study included patients of hypothyroidism, who had higher waist circumference and diastolic blood pressure than age-, gender-, and BMI-matched controls. In hypothyroidism, weight gain occurs due to fluid retention. Nonetheless, mild thyroid dysfunction even within the normal range is likely to be relevant for obesity, and positive correlation between weight and TSH has been reported by various researchers.,
EAT has been shown to be implicated in the development of coronary artery disease. The EAT is in direct contact with the myocardium, and it is highly active metabolically. The epicardial adipocytes can secrete a large number of cytokines and vasoactive peptides, including free fatty acids, interleukin-6, tumor necrosis factor-alpha, angiotensin II, and plasminogen activator inhibitor. All of these molecules can increase cardiovascular risk.,
Assessment of EFT has not been extensively studied in patients with hypothyroidism. There are only few studies available which have conflicting results., Our study reveals a significant correlation between EFT and level of TSH similar to other reports.,
Moreover, higher TSH levels even in the normal range are associated with an increased mass of VAT, which is an independent risk factor for the development of coronary heart disease.
We observed higher prevalence of MS and NAFLD in our patients with hypothyroidism than controls. This association was observed in other studies as well., Eshraghian and Hamidian Jahromi, in a systematic review, concluded that thyroid dysfunctions are prevalent among patients with NAFLD, but further research was recommended to determine the relationship and the underlying mechanisms between hypothyroidism and NAFLD. A systemic review by Iwen et al. provided convincing evidence supporting the major impact of subclinical hypothyroidism on all components of MS.
Hypothyroidism might increase the propensity for visceral adiposity by several mechanisms. Hypothyroidism leads to IR in striated muscle and adipose tissue, which may be due at least in part to decreased translocation of GLUT4 to the cell membrane, impairing glucose transport. In addition, insulin clearance may be diminished in hypothyroidism coinciding with higher levels of counter-regulatory hormones, i.e., cortisol, glucagon, growth hormone, and adrenaline. In our study, patients with hypothyroidism had dyslipidemia in the form of significantly higher levels of TGs and total and LDL cholesterol and lower level of HDL-C. HOMA-IR was also observed to be significantly raised in patients with hypothyroidism. Disturbances in thyroid hormone concentrations may promote hyperlipidemia and visceral adiposity, thus contributing to NAFLD which was reported by several studies.,
There is increasing evidence favoring a close association of high EFT values and coronary atherosclerosis. Our study demonstrated increased EFT in patients with hypothyroidism compared with BMI-matched control subjects. Hence, this finding suggests that there is a relationship between hypothyroidism and visceral adiposity. Increased EFT might be a contributory factor in the development of cardiovascular disease in hypothyroid patients than controls. This may help explain the pathological mechanisms of thyroid dysfunctions related to coronary artery disease.
There are several limitations to our study. First, the number of patients is relatively small. Second, since our study being a cross-sectional one, we could not determine whether patients with increased EFT lead to an increased incidence of coronary artery disease or not. Further, our study design did not allow us to reveal the pathophysiological mechanisms responsible for increased EFT in hypothyroidism. The other important limitation of our study is the lack of data on the duration of thyroid dysfunction. We measured EFT by echocardiography while currently computed tomography and/or magnetic resonance imaging are the standard diagnostic methods for measuring EFT.
| Conclusion|| |
We observed higher EFT in patients with hypothyroidism and a significant correlation between EFT and TSH. Increased epicardial thickness as a marker of visceral adiposity may be associated with the potential cardiovascular adverse effects of hypothyroidism warrants further research.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]