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Lipid profile and some cardiac functions in children with obesity
Egyptian Paediatric Association Gazette (2013) 60, 15–22
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FULL LENGTH ARTICLE
Lipid profile and some cardiac functions in children with obesity Amr M. Zoair a, Khaled T. Muhammad Mahmoud M. Motawea a a b
a,*
, Desoky E. Abu-Ammo b,
Department of Pediatrics, Tanta University, Egypt Department of Clinical Pathology, Tanta University, Egypt
Received 15 March 2012; accepted 27 June 2012 Available online 4 June 2013
KEYWORDS Obesity; Lipid profile; Echocardiography; Children
Abstract Background: Risk factors of childhood obesity include; energy intake, positive family history and lifestyle. Obesity is associated with numerous co-morbidities such as cardiovascular diseases and type 2 diabetes. Objective: To study serum lipid profile and evaluate the left ventricular systolic and global functions in obese children, and define the preclinical effects of obesity, per se, on myocardial function and cardiovascular system. Patients and methods: This is a 9-Month prospective controlled study, done in Pediatrics Department Tanta University Hospital. 30 patients were included (24 males, six females); aged 6–15 years with BMI > age and sex specific cut off points. Exclusion criteria included organic causes of obesity, hormonal medications, corticosteroids, hypertension and diabetes mellitus. Twenty healthy children age and sex matched were set as the control group. Studied children were subjected to: anthropometric measurements: weight, height and BMI. Echocardiographic evaluation: LVEF,
Abbreviations: BMI, body mass index; CVD, cardiovascular diseases; ET, ejection time; IVCT, isovolumetric contraction; IVRT, relaxation time; LDL, low density lipoprotein cholesterol; LMPI, left ventricular myocardial performance index; LV, left ventricular; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; LVFS, left ventricular fractional shortening; LVH, left ventricular hypertrophy; LVM, left ventricular mass; LVMI, left ventricular mass index; TCh, total cholesterol; TG, triglycerides * Corresponding author. E-mail address: [email protected] (K.T. Muhammad). Peer review under responsibility of The Egyptian Paediatric Association.
Production and hosting by Elsevier 1110-6638 ª 2013 Production and hosting by Elsevier B.V. on behalf of The Egyptian Paediatric Association. http://dx.doi.org/10.1016/j.epag.2013.04.005
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A.M. Zoair et al. LVFS, LVEDD, predicted LVEDD, % LVEDD, LVM, LVMI and LMPI. Lipid profile assessment: included serum TCh, LDL, TCh/HDL ratio and TG. Results: There was highly significant increase in body weight, serum TCh, LVEDD, LVM and LVMI; significant increase in BMI, LDL, HDL, serum TG, TCh/HDL-cholesterol ratio, % LVEDD, predicted LVEDD and LMPI of obese as compared to controls. There was no significant difference between the two studied groups as regards height, LVEF and LVFS. There was significant decrease in HDL in obese patients as compared to the control group. Conclusions: Complete evaluation of cardiac function in obese children should include echocardiography along with LMPI (useful marker for early detection of LV global dysfunction), in combination with measurement of lipid profile. ª 2013 Production and hosting by Elsevier B.V. on behalf of The Egyptian Paediatric Association.
1. Introduction Individuals whose body mass index (BMI) exceeds the agegender-specific 95th percentile are obese, while those whose BMI is between 85th and 95th percentiles are overweight and are at an increased risk for obesity and related co-morbidities.1 Worldwide, over 22 million children under the age of five are severely overweight, as are 155 million children of school age. This implies that one in 10 children worldwide is overweight.2 In Egypt, childhood obesity has been on the rise over the past 10 years. The national study on obesity revealed that, among teenagers obesity ranged at around 10% among girls and 7% among boys. In children, aged 6–11, obesity among girls was 6.5% and 4.5% among boys. From age 2–6, obesity reached 3% among girls and 1.7% among boys.3 The potential risk factors include; frequency of obesity among the family, eating habits, energy intake and the family’s lifestyle.4 The prevalence of overweight and obesity has significantly increased in the pediatric population, warning against a world epidemic. This is alarming because metabolic changes and the consequences of obesity, formerly observed only in the adults, are now observed in younger individuals.5 It is important to distinguish between simple obesity and the rarer situation of secondary obesity owing to genetic disorders, endocrine diseases, central nervous system lesions, or iatrogenic causes. Detailed medical history, physical examination, and laboratory tests are helpful.6 Health consequences fall into two broad categories: those attributable to the effects of increased fat mass (such as osteoarthritis, obstructive sleep apnea, social stigmatization), and those due to the increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease).7 Increases in body fat alter the body’s response to insulin, potentially leading to insulin resistance. Increased fat also creates a pro-inflammatory state8 and a prothrombotic state.9 Obesity is associated with numerous co-morbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, dyslipidemias, certain cancers, osteoarthritis, proteinuria, sleep apnea; sleep disordered breathing, depression and anxiety. Furthermore, childhood obesity is associated with endothelial dysfunction and is an independent predictor of coronary artery disease and premature death in adults.10 Obese adolescents exhibit changes in the left ventricular (LV) mass related to increase in cardiac workload.11 Even with normal ventricular mass, overweight children exhibit subtle
changes in LV systolic and diastolic function that may have implications for their future cardiovascular health.12 The aim of this study was to evaluate the left ventricular systolic and global functions in children with obesity, to study serum lipid profile in obese children, and to define the preclinical effects of obesity, per se, on myocardial function and cardiovascular system. 2. Patients and methods 2.1. Patients Thirty obese children of both sexes were enrolled in this study aged 6–15 years, (24 males and six females). They were chosen after anthropometric assessment as their BMI > age and sex specific cut off points13 from those attending the outpatient clinic or pediatric endocrinology and metabolism******. This study was done in Clinic of Tanta University hospital, in the period from January 2010 to September 2010. Any Obese child who had any known organic cause of obesity, received any hormonal medication or corticosteroids, had hypertension, diabetes mellitus, endocrine disorder, hereditary or genetic syndrome associated with obesity such as Prader– Willi syndrome, obstructive sleep apnea or any chronic disease was excluded due to the influence of possible co-morbidities of obesity. Twenty healthy children matched for age and sex, chosen from schools were set as a control group. Studied cases and their parents were instructed about the study and informed consent was obtained. 2.2. Methods All studied children were subjected to the following: (I) History taking including: Time of beginning of increased body weight, associated increased appetite, types of foods, daily activities, past history of any medical problems or any drugs taken, any similar condition in the family, any cardiovascular problems in the patient or family members, any chest complaint like tachypnea or dyspnea, if the child feels drowsiness, hypoactivity or sleepiness. (II) Clinical examination including: Anthropometric measurements
Lipid profile and some cardiac functions in children with obesity (a) Body weight: with the patient bare-feet, and jackets and pullovers taken off. Using spring scale, placed on a hard, leveled uncarpeted floor. Weight was measured to the nearest half kilogram, expressed as % of ideal body weight for age (50th percentile weight for age). (b) Body height: measured standing bare-feet, head was looking directly forward and the patient stretching his/her fullest height. Using a standard tape fixed vertically on the wall, the patients were instructed to adhere tightly to the wall at the shoulders, buttocks, back of knees and heel. Height was measured in centimeters to the nearest half centimeter. It was calculated as percent from the ideal height (50th percentile height for age). (c) Body mass index (BMI): {weight in kilograms divided by square of the height in meters; kg/m2} is compared with age and reference standards.14 Obese children had BMI P95th percentile. (III) Investigations: (A) Echocardiographic evaluation: using a Vivid 7 ultrasound machine (GE Medical System, Horten, Norway with a 3.5-MHz multifrequency transducer). Echocardiographic (ECHO) examination of Obese and controls included the following parameters: (a) LV systolic function15: (1) Left ventricular ejection fraction (LVEF %). Where LVEF (%) = {[left ventricular end diastolic dimension (LVEDD)3 left ventricular end systolic dimension (LVESD)3]/ 3 (LVEDD) } · 100. (2) Left ventricular fractional shortening (LVFS %). Where LVFS (%) = {[LVEDD LVESD]/LVEDD} · 100. [LVEDD in (mm) and LVESD in (mm)]. (b) LV dimensions: (using M-mode echocardiography). (3) LVEDD.15 (4) The predicted LVEDD: was calculated using the Henry equation16: 2
Predicted LVEDD ¼ ½45:3 body surface area ðm Þ ½0:03 age ðyearsÞ 7:2 where: body surface area (m2) = (weight · 4) ± 7 weight + 90 (5) % LVEDD: the ratio of left ventricular end-diastolic dimension to predicted LVEDD expressed in percentage (% LVEDD) was calculated using the following formula17:
17 LVMI ¼ LVM=height ðmÞ2:7 It was used to evaluate left ventricular hypertrophy (LVH) adjusted to body size.18(c) LV global function assessment: by Doppler-derived Left ventricular Myocardial Performance Index (LMPI)19: Mitral inflow and left ventricular outflow velocity–time intervals were used to measure Doppler time intervals: isovolumetric contraction (IVCT), relaxation time (IVRT) and ejection time (ET). The interval ‘‘a’’ from the cessation to the onset of mitral inflow was equal to the sum of IVCT, ET, and IVRT (a = IVCT + ET + IVRT). Left ventricular ET ‘‘b’’ was the duration of left ventricular velocity profile. Thus, the sum of IVCT and IVRT was obtained by subtracting ‘‘b’’ from ‘‘a’’. The MPI was calculated as: (a b)/b [MPI = (a b)/b]. The normal range for LMPI in children (3–18 years) is 0.33 ± 0.05. (B) Lipid profile assessment: 5 ml morning blood samples (without anticoagulant) were collected from all children after a minimum of 12-h fasting, and with the routine procedure (determination of total cholesterol (TCh), high-density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), and TG was performed by colorimetric enzyme method on a RA-50 Chemistry Analyser spectrophotometer (Bayer), using LABTEST reagents), and using an automated instrument, these investigations for lipid profile assessment were done20: (1) (2) (3) (4) (5) (6)
Serum TCh HDL-cholesterol. LDL-cholesterol from the equation: LDL = TCh (HDL + TG/5)20 TCh/HDL-cholesterol ratio. Serum TG.
3. Results Table 1 shows that there was no significant difference between control (9.60 ± 2.56) and obese (10.56 ± 2.82) groups regarding age (years), (p > 0.05). Also, there was no significant difference between control (14 males and six females) and obese (24 males and six females) groups regarding sex (p > 0.05).
Table 1
Demographic data of the studied groups.
% LVEDD ¼ ½ðMeasured LVEDDÞ=ðPredicted LVEDDÞ 100
(6) Left ventricular mass (LVM): was calculated using the following formula17: LVM ðgÞ ¼ 0:8 ½1:04ðLVEDD IVSD LVPWDÞ3 LVEDD3 0:6 where, IVSD is inter-ventricular septum dimension (cm) and LVPWD is left ventricular posterior wall dimension (cm). (7) Left ventricular mass index (LVMI): was calculated using the following formula:
Age (years) Range Mean ±SD t test p value Sex Male N (%) Female N (%) Chi-square
Control (n = 20)
Obese (n = 30)
6–13 9.60 2.56 1.225 0.325
6–15 10.56 2.82
14 (70%) 6 (30%) v2 = 0.625 p = 0.428
24 (80%) 6 (20%)
18
A.M. Zoair et al.
Table 2 groups.
Anthropometric measurements of the two studied Control
Obese
Regarding weight (kg) Range Mean ±SD t test p value
20–48 39.92 11.26 3.703 0.001*
32–98 59.48 21.69
Regarding height (cm) Range Mean ±SD t test p value
116–166 139.40 16.10 0.438 0.752
96–159 139.63 17.43
Regarding BMI (kg/m2) Range Mean ±SD t test p value
14.7–22.8 20.15 2.32 16.523 0.009*
28.7–39.8 33.02 3.03
*
= significant.
3.1. Anthropometric measurements Table 2 shows that the control had mean weight of 39.92 ± 11.26 kg while obese had 59.48 ± 21.69 kg. There was highly significant increase of body weight of obese as compared to control (p 6 0.001). Also, it shows that the control had a mean height of 139.40 ± 16.10 and obese children had 139.63 ± 17.43 cm. there was no significant difference between the two studied groups as regards height (p > 0.05). In addition, the control had mean BMI of 20.15 ± 2.32 and obese 33.02 ± 3.03 kg/m2. There was significant increase of BMI in obese as compared to the control group (p < 0.05). 3.2. Lipid profile Table 3 shows that the control had mean TCh level of 146.10 ± 16.14 and obese 197.80 ± 24.63 mg/dl. There was highly significant increase of serum TCh in obese children as compared to the control group (p 6 0.001). Also, it shows that the control had mean LDL-cholesterol level of 76.88 ± 11.36 and obese 110.82 ± 59.33 mg/dl. There was significant increase in LDL-cholesterol levels in obese children as compared to the control group (p < 0.05). In addition, the control had a mean HDL-cholesterol level of 59.63 ± 13.36 and obese 56.14 ± 14.25mg/dl. There was significant decrease in HDL-cholesterol levels in obese children as compared to control group (p < 0.05). Moreover, the controls had mean TG level of 101.10 ± 12.30 and obese 136.56 ± 47.12 mg/dl. There was significant increase of serum TG in obese children as compared to the control group (p < 0.05). Table 3 also shows that controls had mean cholesterol/ HDL ratio of 2.648 ± 0.543 and obese 4.586 ± 2.95. There was a significant increase of TCh/HDL-cholesterol ratio in obese children as compared to the control group (p < 0.05).
Table 3
Lipid profile of the two studied groups. Control
Obese
Control
Obese
Regarding TCh (mg/dl) Range Mean ±SD t test p value
120–175 146.10 16.14 10.325 0.001*
107–395 197.80 24.63
Regarding LDL (mg/dl) Range Mean ±SD t test p value
66–86.4 76.88 11.36 4.325 0.009*
45–297.4 110.82 59.33
Regarding HDL (mg/dl) Range Mean ±SD t test p value
48–75 59.63 13.36 2.996 0.044*
21–128 56.14 14.25
Regarding TG (mg/dl) Range Mean ±SD t test p value
80–120 101.10 12.30 3.539 0.003*
36–200 136.56 47.12
Regarding TCh/HDL ratio Range 1.7–3.3 Mean 2.648 ±SD 0.543 t test 2.412 p value 0.035* *
1.6–9.6 4.586 2.95
= significant.
Table 4 groups.
Echocardiographic evaluation of the two studied Control
Obese
Regarding LVEF (%) Range Mean ±SD t test p value
57.5–75.47 67.82 5.31 1.325 0.091
54.5–85.3 71.29 7.27
Regarding LVFS (%) Range Mean ±SD t test p value
30.3–43.7 37.53 5.33 1.536 0.079
30–47.4 40.91 6.30
Regarding LVEDD (%) Range Mean ±SD t test p value
43.5–94.9 77.73 14.15 3.528 0.004*
63–111.9 90.79 11.77
*
= significant.
Lipid profile and some cardiac functions in children with obesity 3.3. Echocardiographic evaluation Table 4 shows that the controls had mean LVEF of 67.82 ± 5.31 and obese 71.29 ± 7.27%. There was no significant difference between the two studied groups as regards ejection fraction (p > 0.05).
Table 5 groups.
Echocardiographic evaluation of the two studied
Regarding LVEDD (cm) Range Mean ±SD t test p value
Control
Obese
1.8–4.1 3.30 0.647 4.817 0.001*
3.1–4.9 4.11 0.535
Regarding predicted LVEDD (cm) Range 3.48–4.7 Mean 4.25 ±SD 0.48 t test 2.431 p value 0.019* *
3.4–4.9 4.53 0.33
= significant.
Table 6 groups.
Echocardiographic evaluation of the two studied Control
Obese
Control
Obese
Regarding LVM (g) Range Mean ±SD t test p value
36.05–76.4 47.04 16.23 6.938 0.001*
66.6–217 108.71 39.52
Regarding LVMI (g) Range Mean ±SD t test p value
12.06–40.7 20.33 8.86 5.325 0.001*
29.9–90.2 46.42 19.23
*
= significant.
Table 7 Comparison between the two studied groups regarding LMPI. LMPI
Control
Obese
Range Mean ±SD t test p value
0.28–0.38 0.330 0.051 4.632 0.009*
0.40–2.1 0.681 0.571
*
= significant.
19 Also, it shows that the controls had mean LVFS of 37.53 ± 5.33 and obese 40.91 ± 6.30%. There was no significant difference between the two studied groups as regards fractional shortening (p > 0.05). Additionally, it shows that the controls had mean % LVEDD of 77.73 ± 14.15 and obese 90.79 ± 11.77%. There was significant increase of the % LVEDD in obese children as compared to control group (p < 0.05). Table 5 shows that the controls had mean LVEDD of 3.30 ± 0.647 and obese 4.11 ± 0.535 cm. There was highly significant increase of the LVEDD in obese children as compared to the control group (p 6 0.001). Likewise, it shows that the controls had mean predicted LVEDD of 4.25 ± 0.48 and obese 4.53 ± 0.33 cm. there was significant increase of the predicted LVEDD in obese children as compared to the control group (p < 0.05). Table 6 shows that the controls had mean LVM of 47.04 ± 16.23 and obese 108.71 ± 39.52 g. There was highly significant increase of the LVM in obese as compared to the control group (p 6 0.001). Also, the controls had mean LVMI of 20.33 ± 8.86 and obese 46.42 ± 19.23. There was highly significant increase of the LVMI in obese as compared to the control group (p 6 0.001) Table 7 shows that the controls had mean LMPI of 0.330 ± 0.051 and obese 0.681 ± 0.571. There was significant increase of the LMPI in obese children as compared to the control group (p < 0.05). 4. Discussion The extent of the epidemic of childhood obesity is increasing so that children are suffering chronic complications that were once only seen in adults.21 The World Health Organization describes the ‘‘escalating global epidemic’’ of obesity as ‘‘one of today’s most blatantly visible – yet most neglected – public health problems’’.22 Our study was done on two groups of comparable age and sex; obese children and control group of non-obese children. As regards age, the study revealed no significant difference between the two groups. A critical period for the development of adult obesity is adolescence. Obesity that develops in or persists into adolescence is not only the most difficult to treat, but is also associated with the greatest risk of serious complications.23 Our study revealed that there was no significant difference between gender and obesity. There are contradictory results about this item; Pyke,24 found no significant difference between boys’ and girls’ obesity. However, LaFrance et al.25 stated that boys’ obesity was higher than girls’ obesity. But Raja’a and Bin-Mohanna,26 reported that prevalence of overweight and obesity was higher among females. These differences may be due to the difference in localities, sample size, cultural and/or socioeconomic causes. The present study shows that the BMI was significantly higher in obese children as compared to non-obese children. The use of WHO standards for BMI-for-age in 2006 provides only a crude measure of body fatness, since it does not distinguish between weight associated with muscle and weight associated with fat.27 Regarding lipid profile, this study demonstrated that HDL was significantly lower in obese as compared to non-obese chil-
20 dren. However, LDL, serum TG, serum TCh and TCh/HDL ratio were significantly higher in obese children as compared to control. This was in accordance with Freedman et al.28 and Reinhr et al.29 who found that overweight is strongly related to concentrations of HDL-cholesterol and TG and weakly related to concentrations of LDL-cholesterol; while Kim et al.30 found that all types of lipids were significantly associated with overweight and obesity. Also, Chinali et al.11 stated that obese adolescents had significantly higher total TG and lower highdensity lipoprotein. Moreover, Lima et al.31 stated that Total and LDL-cholesterol levels were higher in obese than normal weight children. But HDL-cholesterol showed borderline values. Horri and Vakil i32 stated that serum TG and cholesterol levels were significantly higher in obese children and adolescents. Also, there is significant positive correlation between BMI percentiles and serum TG, total and LDL-cholesterol. In addition, HDL-cholesterol was significantly lower in the obese children than control. Obesity predisposes to hypertension because of concomitant metabolic and hemodynamic abnormalities leading to inadequate lowering of systemic resistance and, therefore, to more severe cardiovascular burden.33 Many of cardiovascular complications related to obesity may begin in childhood and adolescence. Furthermore, it has been shown that obesity is associated with the development of early myocardial and coronary artery changes in children.17 When complications of obesity are already established, as coronary artery disease, positive correlations are observed between markers of lipid peroxidation, total cholesterol and TG and negative ones are noted with high-density lipoproteins (HDL).34 As regards echocardiographic evaluation, there was no significant difference between the two studied groups as regards the LVEF (%) and the LVFS (%). Hence all children had normal LV systolic function. These results were in agreement with those of Mehta et al.,12 Di Salvo et al.35 and Khositseth et al.17 On the other hand, Chinali et al.11 found a significantly lower ejection fraction in obese adolescents as compared to non-obese group. Moreover, Alpert36 found that obese subjects demonstrated evidence of diminished myocardial function, which was directly related to the severity and duration of their adiposity. The hearts of these subjects were characterized by reduced LVEF; which were often independent of effects of hypertension or coexistent coronary artery disease. Gutin et al.37 reported that among children aged 7– 13 years, percent body fat correlated negatively with lower mid-wall ventricular shortening fraction. Mensah et al.38 found a significant negative association between LVSF and central adiposity in a group of 15-year old subjects. The explanation for these differences in depression of myocardial function is related to both severity and duration of excess adiposity, myocardial fatigue due to chronic volume overwork, and metabolic derangements associated with obesity such as insulin resistance which modify myocardial substrate utilization, increase in myocardial fatty acid oxidation and oxygen consumption and leading to myocardial dysfunction.39,40 As regards the LV dimensions in our study, there was significant increase in the LVEDD, predicted LVEDD and % LVEDD in obese than controls, indicating left ventricular
A.M. Zoair et al. enlargement. Positive cross-sectional associations between body fat content and cardiac chamber dimensions have been evident among cohorts of obese subjects41 as well as in studies in the general pediatric population.11,37,38,42,43 Chinali et al.11 reported that cardiac enlargement in obesity is caused by response to a chronically increased hemodynamic load. Moreover, Rowland40 found a correlation between body mass index and left ventricular end diastolic dimension in a group of early adolescent females. An obese child is characterized by an expanded circulatory system reflecting somatic growth, increased plasma volume, hypertrophy of myocardial fibers, and cardiac chamber enlargement.40 LV-mass has been established as an independent risk factor for cardiovascular morbidity and mortality.44,45 Since LVmass is affected by body size, a variety of factors have been proposed for indexing LV-mass.44 In our study, the standard echocardiographic evaluation of obese, non-hypertensive children showed significant increase in the left ventricular mass (LVM) and left ventricular mass index (LVMI) as compared to the control group, which indicated left ventricular hypertrophy (LVH). These results were in agreement with those of Chinali et al.11 Khositseth et al.17 and Di Salvo et al.35 Attention has been focused on the role of the anabolic effects of hyperinsulinemia on myocardial hypertrophy, a reflection of the insulin resistance commonly observed in obese individuals.45–48 The American Heart Association (AHA) has stressed the importance of obesity as a modifiable, independent risk factor for coronary artery disease, ventricular dysfunction, congestive heart failure, and cardiac arrhythmias.49 Similarly, adolescent obesity is strongly related to adult obesity and may progress to type 2 diabetes and/or hypertension.50 Adult obesity has been shown to be associated with increased left ventricular mass (LVM) and both systolic and diastolic dysfunction,36 all are important predictors of adverse cardiovascular outcome and identification of a pre-clinical cardiovascular disease.51 Chinali et al.11 stated that even in adolescents, the severity of obesity parallels early cardiac changes, including high prevalence of LVH and increased hemodynamic load. Moreover, Friberg et al.52 reported that the increased LVM occurs to sustain the increased cardiac workload. At higher stages of obesity, increase in LVM is not depending only on hemodynamic load but also on non-hemodynamic factors; neuro-hormonal effects of clustered metabolic factors influencing LV growth,11 high blood pressure and dietary sodium intake.53 However, LV dilatation and hypertrophy are independent of the level of blood pressure.54 The LMPI indicates both systolic and diastolic myocardial functions. LMPI significantly increased in obese as compared to the control group. This was in agreement with Khositseth et al.17 who reported that despite normal LV dimensions and systolic function in obese children of their study, the abnormal LMPI may be one of the sensitive indicators for the early detection of LV global dysfunction in those children. So, LMPI may be an indicator for early recognition of the cardiac related complications of obesity in children. This simple reproducible index may be useful to identify the high-risk patients requiring an aggressive weight-control/reduction program.17
Lipid profile and some cardiac functions in children with obesity 5. Conclusions Complete evaluation of cardiac function in obese children should include echocardiography along with LMPI (as a useful marker for early detection of LV global dysfunction), in combination with measurement of lipid profile. Also it helps to identify the high-risk obese children requiring weight-control/ reduction programs to encourage healthy life styles and reduce morbidity and mortality. It is recommended in the future studies, to clarify the effects of obesity on cardiac function and lipid profile, even in infants and young children.
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21 19. Eto G, Ishii M, Tie C, et al. Assessment of global left ventricular function in normal children and in children with dilated cardiomyopathy. J Am Soc Echocardiogr 1999;12:1058–64. 20. Rifai N, Warnick G. Measurement of lipids, lipoproteins, and apolipoproteins. In: Burtis CA, Ashwood ER, Bruns DE, editors. Tietz textbook of clinical chemistry and molecular diagnosis. 4th ed. St. Louis, Missouri: Elsevier Saunders; 2006. p. 938–52. 21. Le Stunff C, Fallin D, Schork N, et al. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity. Nat Genet 2000;26:444–6. 22. World Health Organization. Nutrition. Controlling the global obesity epidemic. Available at: www.who.int/nut/obs.htm (accessed Nov 2004). 23. Dietz W. Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics 1998;101:S518–25. 24. Pyke J. Australian Health and Fitness Survey 1985. Adelaide, SA: Australian Council for Health, Physical Education and Recreation Inc; 1987. 25. LaFrance S, Nolan M, Page J. et al. New hampshire childhood obesity report, foundation for healthy community; 2005. 26. Raja’a Y, Bin Mohanna M. Overweight and obesity among school children in Sana’a City, Yemen. Ann Nutr Metab 2005;49:342–5. 27. WHO Child Growth Standards. Length/height-for-age, weightfor-age, weight-for-length, weight-for-height, and body mass index-for-age. Methods and development. World Health Organization, Geneva 2006. 28. Freedman D, Dietz W, Srinivasan S, et al. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa heart study. Pediatrics 1999;103:1175–82. 29. Reinhr T, Andler W, Denzer C. Cardiovascular risk factors in overweight German children and adolescents: relation to gender, age and degree of overweight. Nutr Metab Cardiovasc Dis 2005;15: 181–7. 30. Kim H, Park J, Kim H, et al. Obesity and cardiovascular risk factors in Korean children and adolescents aged 10–18 years. Am J Epidemiol 2006;164:787–93. 31. Lima S, Arrais R, Almeida M, et al. Plasma lipid profile and lipid peroxidation in overweight or obese children and adolescents. J Pediatr 2004;80(1):23–8. 32. Horri M, Vakili R. Evaluation of cardiovascular and lipid profile abnormalities in obese children and adolescents. IJMS 2006;31(2):87–90. 33. Palmieri V, de Simone G, Arnett D, et al. Relation of various degrees of body mass index in patients with systemic hypertension to left ventricular mass, cardiac output, and peripheral resistance (the hypertension genetic epidemiology network study). Am J Cardiol 2001;88:1163–8. 34. Mahapatra S, Pahiary K, Mishra T, et al. Study on body mass index, lipid profile and lipid peroxidation status in coronary artery disease. J Indian Med Assoc 1998;96:39–41. 35. Di Salvo G, Pacileo G, Giudice E. Abnormal myocardial deformation properties in obese, non-hypertensive children: an ambulatory blood pressure monitoring, standard echocardiographic, and strain rate imaging study. Eur Heart J 2006;27:2689–95. 36. Alpert M, Lambert C, Terry B, et al. Influence of left ventricular mass on left ventricular diastolic filling in normotensive morbid obesity. Am Heart J 1995;130:1068–73. 37. Gutin B, Treiber F, Owens S, et al. Relations of body composition to left ventricular geometry and function in children. J Pediatr 1998;132:1023–7. 38. Mensah G, Treiber F, Kapuku G. Patterns of body fat deposition in youth and their relation to left ventricular markers of adverse cardiovascular prognosis. Am J Cardiol 1999;84:583–8. 39. Peterson L, Herrero P, Schechtman K. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 2004;109:2191–6. 40. Rowland T. Effect of obesity on cardiac function in children and adolescents. J Sports Sci Med 2007;6:319–26.
22 41. Humphries M, Gutin B, Barbeau P, et al. Relations of adiposity and effects of trainingon the left ventricle in obese youths. Med Sci Sports Exerc 2002;34:1428–35. 42. Kono Y, Yoshinaga M, Oku S, et al. Effect of obesity on echocardiographic parametersin children. Int J Cardiol 1994;46: 7–13. 43. Papavassiliou D, Treiber F, Strong W, et al. Anthropometric, demographic, and cardiovascularpredictors of left ventricular mass in young children. Am J Cardiol 1996;78:232–326. 44. Gutgesell H, Paquet M, Duff D, et al. Evaluation of left ventricular size and function by echocardiography. Results in normal children. Circulation 1977;56:457–62. 45. Gidding S, Nehgme R, Heise C. Severe obesity associated with cardiovascular deconditioning, high prevalence of cardiovascular risk factors, diabetes mellitus/hyperinsulinemia, and respiratory compromise. J Pediatr 2004;144:766–9. 46. Giordano U, Ciampalini P, Turchetta A. Cardiovascular hemodynamics: relationships with insulin resistance in obese children. Pediatr Cardiol 2003;24:548–52. 47. Sasson Z, Rasooly Y, Bhesania T, et al. Insulin resistance is an important determinant of left ventricular mass in the obese. Circulation 1993;88:1431–6.
A.M. Zoair et al. 48. Wong C, O’Moore-Sullivan T, Leano R, et al. Alterations of left ventricular myocardial characteristics associated with obesity. Circulation 2004;110:3081–7. 49. Klein S, Burke L, Bray G, et al. Clinical implications of obesity with specific focus on cardiovascular disease. Circulation 2004;110: 2952–67. 50. Guo S, Huang C, Maynard L, et al. Body mass index during childhood, adolescence, and young adulthood in relation to adult overweight and adiposity: the Pels longitudinal study. Int J Obes Relat Metab Disord 2000;24:1628–35. 51. Devereux R, Alderman M. Role of preclinical cardiovascular disease in the evolution from risk factor exposure to development of morbid events. Circulation 1993;88:1444–55. 52. Friberg P, Allansdotter-Johnsson A, Ambring A, et al. Increased left ventricular mass in obese adolescents. Eur Heart J 2004;25: 987–92. 53. Daniels S, Meyer R, Loggie J. Determinants of cardiac involvement in children and adolescents with essential hypertension. Circulation 1990;82:1243–8. 54. Messerli F, Sundgaard-Riise K, Reisin E, et al. Dimorphic cardiac adaptation to obesity and arterial hypertension. Ann Intern Med 1983;99:757–61.
Contents lists available at SciVerse ScienceDirect
Egyptian Paediatric Association Gazette journal homepage: http://ees.elsevier.com/epag
FULL LENGTH ARTICLE
Lipid profile and some cardiac functions in children with obesity Amr M. Zoair a, Khaled T. Muhammad Mahmoud M. Motawea a a b
a,*
, Desoky E. Abu-Ammo b,
Department of Pediatrics, Tanta University, Egypt Department of Clinical Pathology, Tanta University, Egypt
Received 15 March 2012; accepted 27 June 2012 Available online 4 June 2013
KEYWORDS Obesity; Lipid profile; Echocardiography; Children
Abstract Background: Risk factors of childhood obesity include; energy intake, positive family history and lifestyle. Obesity is associated with numerous co-morbidities such as cardiovascular diseases and type 2 diabetes. Objective: To study serum lipid profile and evaluate the left ventricular systolic and global functions in obese children, and define the preclinical effects of obesity, per se, on myocardial function and cardiovascular system. Patients and methods: This is a 9-Month prospective controlled study, done in Pediatrics Department Tanta University Hospital. 30 patients were included (24 males, six females); aged 6–15 years with BMI > age and sex specific cut off points. Exclusion criteria included organic causes of obesity, hormonal medications, corticosteroids, hypertension and diabetes mellitus. Twenty healthy children age and sex matched were set as the control group. Studied children were subjected to: anthropometric measurements: weight, height and BMI. Echocardiographic evaluation: LVEF,
Abbreviations: BMI, body mass index; CVD, cardiovascular diseases; ET, ejection time; IVCT, isovolumetric contraction; IVRT, relaxation time; LDL, low density lipoprotein cholesterol; LMPI, left ventricular myocardial performance index; LV, left ventricular; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; LVFS, left ventricular fractional shortening; LVH, left ventricular hypertrophy; LVM, left ventricular mass; LVMI, left ventricular mass index; TCh, total cholesterol; TG, triglycerides * Corresponding author. E-mail address: [email protected] (K.T. Muhammad). Peer review under responsibility of The Egyptian Paediatric Association.
Production and hosting by Elsevier 1110-6638 ª 2013 Production and hosting by Elsevier B.V. on behalf of The Egyptian Paediatric Association. http://dx.doi.org/10.1016/j.epag.2013.04.005
16
A.M. Zoair et al. LVFS, LVEDD, predicted LVEDD, % LVEDD, LVM, LVMI and LMPI. Lipid profile assessment: included serum TCh, LDL, TCh/HDL ratio and TG. Results: There was highly significant increase in body weight, serum TCh, LVEDD, LVM and LVMI; significant increase in BMI, LDL, HDL, serum TG, TCh/HDL-cholesterol ratio, % LVEDD, predicted LVEDD and LMPI of obese as compared to controls. There was no significant difference between the two studied groups as regards height, LVEF and LVFS. There was significant decrease in HDL in obese patients as compared to the control group. Conclusions: Complete evaluation of cardiac function in obese children should include echocardiography along with LMPI (useful marker for early detection of LV global dysfunction), in combination with measurement of lipid profile. ª 2013 Production and hosting by Elsevier B.V. on behalf of The Egyptian Paediatric Association.
1. Introduction Individuals whose body mass index (BMI) exceeds the agegender-specific 95th percentile are obese, while those whose BMI is between 85th and 95th percentiles are overweight and are at an increased risk for obesity and related co-morbidities.1 Worldwide, over 22 million children under the age of five are severely overweight, as are 155 million children of school age. This implies that one in 10 children worldwide is overweight.2 In Egypt, childhood obesity has been on the rise over the past 10 years. The national study on obesity revealed that, among teenagers obesity ranged at around 10% among girls and 7% among boys. In children, aged 6–11, obesity among girls was 6.5% and 4.5% among boys. From age 2–6, obesity reached 3% among girls and 1.7% among boys.3 The potential risk factors include; frequency of obesity among the family, eating habits, energy intake and the family’s lifestyle.4 The prevalence of overweight and obesity has significantly increased in the pediatric population, warning against a world epidemic. This is alarming because metabolic changes and the consequences of obesity, formerly observed only in the adults, are now observed in younger individuals.5 It is important to distinguish between simple obesity and the rarer situation of secondary obesity owing to genetic disorders, endocrine diseases, central nervous system lesions, or iatrogenic causes. Detailed medical history, physical examination, and laboratory tests are helpful.6 Health consequences fall into two broad categories: those attributable to the effects of increased fat mass (such as osteoarthritis, obstructive sleep apnea, social stigmatization), and those due to the increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease).7 Increases in body fat alter the body’s response to insulin, potentially leading to insulin resistance. Increased fat also creates a pro-inflammatory state8 and a prothrombotic state.9 Obesity is associated with numerous co-morbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, dyslipidemias, certain cancers, osteoarthritis, proteinuria, sleep apnea; sleep disordered breathing, depression and anxiety. Furthermore, childhood obesity is associated with endothelial dysfunction and is an independent predictor of coronary artery disease and premature death in adults.10 Obese adolescents exhibit changes in the left ventricular (LV) mass related to increase in cardiac workload.11 Even with normal ventricular mass, overweight children exhibit subtle
changes in LV systolic and diastolic function that may have implications for their future cardiovascular health.12 The aim of this study was to evaluate the left ventricular systolic and global functions in children with obesity, to study serum lipid profile in obese children, and to define the preclinical effects of obesity, per se, on myocardial function and cardiovascular system. 2. Patients and methods 2.1. Patients Thirty obese children of both sexes were enrolled in this study aged 6–15 years, (24 males and six females). They were chosen after anthropometric assessment as their BMI > age and sex specific cut off points13 from those attending the outpatient clinic or pediatric endocrinology and metabolism******. This study was done in Clinic of Tanta University hospital, in the period from January 2010 to September 2010. Any Obese child who had any known organic cause of obesity, received any hormonal medication or corticosteroids, had hypertension, diabetes mellitus, endocrine disorder, hereditary or genetic syndrome associated with obesity such as Prader– Willi syndrome, obstructive sleep apnea or any chronic disease was excluded due to the influence of possible co-morbidities of obesity. Twenty healthy children matched for age and sex, chosen from schools were set as a control group. Studied cases and their parents were instructed about the study and informed consent was obtained. 2.2. Methods All studied children were subjected to the following: (I) History taking including: Time of beginning of increased body weight, associated increased appetite, types of foods, daily activities, past history of any medical problems or any drugs taken, any similar condition in the family, any cardiovascular problems in the patient or family members, any chest complaint like tachypnea or dyspnea, if the child feels drowsiness, hypoactivity or sleepiness. (II) Clinical examination including: Anthropometric measurements
Lipid profile and some cardiac functions in children with obesity (a) Body weight: with the patient bare-feet, and jackets and pullovers taken off. Using spring scale, placed on a hard, leveled uncarpeted floor. Weight was measured to the nearest half kilogram, expressed as % of ideal body weight for age (50th percentile weight for age). (b) Body height: measured standing bare-feet, head was looking directly forward and the patient stretching his/her fullest height. Using a standard tape fixed vertically on the wall, the patients were instructed to adhere tightly to the wall at the shoulders, buttocks, back of knees and heel. Height was measured in centimeters to the nearest half centimeter. It was calculated as percent from the ideal height (50th percentile height for age). (c) Body mass index (BMI): {weight in kilograms divided by square of the height in meters; kg/m2} is compared with age and reference standards.14 Obese children had BMI P95th percentile. (III) Investigations: (A) Echocardiographic evaluation: using a Vivid 7 ultrasound machine (GE Medical System, Horten, Norway with a 3.5-MHz multifrequency transducer). Echocardiographic (ECHO) examination of Obese and controls included the following parameters: (a) LV systolic function15: (1) Left ventricular ejection fraction (LVEF %). Where LVEF (%) = {[left ventricular end diastolic dimension (LVEDD)3 left ventricular end systolic dimension (LVESD)3]/ 3 (LVEDD) } · 100. (2) Left ventricular fractional shortening (LVFS %). Where LVFS (%) = {[LVEDD LVESD]/LVEDD} · 100. [LVEDD in (mm) and LVESD in (mm)]. (b) LV dimensions: (using M-mode echocardiography). (3) LVEDD.15 (4) The predicted LVEDD: was calculated using the Henry equation16: 2
Predicted LVEDD ¼ ½45:3 body surface area ðm Þ ½0:03 age ðyearsÞ 7:2 where: body surface area (m2) = (weight · 4) ± 7 weight + 90 (5) % LVEDD: the ratio of left ventricular end-diastolic dimension to predicted LVEDD expressed in percentage (% LVEDD) was calculated using the following formula17:
17 LVMI ¼ LVM=height ðmÞ2:7 It was used to evaluate left ventricular hypertrophy (LVH) adjusted to body size.18(c) LV global function assessment: by Doppler-derived Left ventricular Myocardial Performance Index (LMPI)19: Mitral inflow and left ventricular outflow velocity–time intervals were used to measure Doppler time intervals: isovolumetric contraction (IVCT), relaxation time (IVRT) and ejection time (ET). The interval ‘‘a’’ from the cessation to the onset of mitral inflow was equal to the sum of IVCT, ET, and IVRT (a = IVCT + ET + IVRT). Left ventricular ET ‘‘b’’ was the duration of left ventricular velocity profile. Thus, the sum of IVCT and IVRT was obtained by subtracting ‘‘b’’ from ‘‘a’’. The MPI was calculated as: (a b)/b [MPI = (a b)/b]. The normal range for LMPI in children (3–18 years) is 0.33 ± 0.05. (B) Lipid profile assessment: 5 ml morning blood samples (without anticoagulant) were collected from all children after a minimum of 12-h fasting, and with the routine procedure (determination of total cholesterol (TCh), high-density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), and TG was performed by colorimetric enzyme method on a RA-50 Chemistry Analyser spectrophotometer (Bayer), using LABTEST reagents), and using an automated instrument, these investigations for lipid profile assessment were done20: (1) (2) (3) (4) (5) (6)
Serum TCh HDL-cholesterol. LDL-cholesterol from the equation: LDL = TCh (HDL + TG/5)20 TCh/HDL-cholesterol ratio. Serum TG.
3. Results Table 1 shows that there was no significant difference between control (9.60 ± 2.56) and obese (10.56 ± 2.82) groups regarding age (years), (p > 0.05). Also, there was no significant difference between control (14 males and six females) and obese (24 males and six females) groups regarding sex (p > 0.05).
Table 1
Demographic data of the studied groups.
% LVEDD ¼ ½ðMeasured LVEDDÞ=ðPredicted LVEDDÞ 100
(6) Left ventricular mass (LVM): was calculated using the following formula17: LVM ðgÞ ¼ 0:8 ½1:04ðLVEDD IVSD LVPWDÞ3 LVEDD3 0:6 where, IVSD is inter-ventricular septum dimension (cm) and LVPWD is left ventricular posterior wall dimension (cm). (7) Left ventricular mass index (LVMI): was calculated using the following formula:
Age (years) Range Mean ±SD t test p value Sex Male N (%) Female N (%) Chi-square
Control (n = 20)
Obese (n = 30)
6–13 9.60 2.56 1.225 0.325
6–15 10.56 2.82
14 (70%) 6 (30%) v2 = 0.625 p = 0.428
24 (80%) 6 (20%)
18
A.M. Zoair et al.
Table 2 groups.
Anthropometric measurements of the two studied Control
Obese
Regarding weight (kg) Range Mean ±SD t test p value
20–48 39.92 11.26 3.703 0.001*
32–98 59.48 21.69
Regarding height (cm) Range Mean ±SD t test p value
116–166 139.40 16.10 0.438 0.752
96–159 139.63 17.43
Regarding BMI (kg/m2) Range Mean ±SD t test p value
14.7–22.8 20.15 2.32 16.523 0.009*
28.7–39.8 33.02 3.03
*
= significant.
3.1. Anthropometric measurements Table 2 shows that the control had mean weight of 39.92 ± 11.26 kg while obese had 59.48 ± 21.69 kg. There was highly significant increase of body weight of obese as compared to control (p 6 0.001). Also, it shows that the control had a mean height of 139.40 ± 16.10 and obese children had 139.63 ± 17.43 cm. there was no significant difference between the two studied groups as regards height (p > 0.05). In addition, the control had mean BMI of 20.15 ± 2.32 and obese 33.02 ± 3.03 kg/m2. There was significant increase of BMI in obese as compared to the control group (p < 0.05). 3.2. Lipid profile Table 3 shows that the control had mean TCh level of 146.10 ± 16.14 and obese 197.80 ± 24.63 mg/dl. There was highly significant increase of serum TCh in obese children as compared to the control group (p 6 0.001). Also, it shows that the control had mean LDL-cholesterol level of 76.88 ± 11.36 and obese 110.82 ± 59.33 mg/dl. There was significant increase in LDL-cholesterol levels in obese children as compared to the control group (p < 0.05). In addition, the control had a mean HDL-cholesterol level of 59.63 ± 13.36 and obese 56.14 ± 14.25mg/dl. There was significant decrease in HDL-cholesterol levels in obese children as compared to control group (p < 0.05). Moreover, the controls had mean TG level of 101.10 ± 12.30 and obese 136.56 ± 47.12 mg/dl. There was significant increase of serum TG in obese children as compared to the control group (p < 0.05). Table 3 also shows that controls had mean cholesterol/ HDL ratio of 2.648 ± 0.543 and obese 4.586 ± 2.95. There was a significant increase of TCh/HDL-cholesterol ratio in obese children as compared to the control group (p < 0.05).
Table 3
Lipid profile of the two studied groups. Control
Obese
Control
Obese
Regarding TCh (mg/dl) Range Mean ±SD t test p value
120–175 146.10 16.14 10.325 0.001*
107–395 197.80 24.63
Regarding LDL (mg/dl) Range Mean ±SD t test p value
66–86.4 76.88 11.36 4.325 0.009*
45–297.4 110.82 59.33
Regarding HDL (mg/dl) Range Mean ±SD t test p value
48–75 59.63 13.36 2.996 0.044*
21–128 56.14 14.25
Regarding TG (mg/dl) Range Mean ±SD t test p value
80–120 101.10 12.30 3.539 0.003*
36–200 136.56 47.12
Regarding TCh/HDL ratio Range 1.7–3.3 Mean 2.648 ±SD 0.543 t test 2.412 p value 0.035* *
1.6–9.6 4.586 2.95
= significant.
Table 4 groups.
Echocardiographic evaluation of the two studied Control
Obese
Regarding LVEF (%) Range Mean ±SD t test p value
57.5–75.47 67.82 5.31 1.325 0.091
54.5–85.3 71.29 7.27
Regarding LVFS (%) Range Mean ±SD t test p value
30.3–43.7 37.53 5.33 1.536 0.079
30–47.4 40.91 6.30
Regarding LVEDD (%) Range Mean ±SD t test p value
43.5–94.9 77.73 14.15 3.528 0.004*
63–111.9 90.79 11.77
*
= significant.
Lipid profile and some cardiac functions in children with obesity 3.3. Echocardiographic evaluation Table 4 shows that the controls had mean LVEF of 67.82 ± 5.31 and obese 71.29 ± 7.27%. There was no significant difference between the two studied groups as regards ejection fraction (p > 0.05).
Table 5 groups.
Echocardiographic evaluation of the two studied
Regarding LVEDD (cm) Range Mean ±SD t test p value
Control
Obese
1.8–4.1 3.30 0.647 4.817 0.001*
3.1–4.9 4.11 0.535
Regarding predicted LVEDD (cm) Range 3.48–4.7 Mean 4.25 ±SD 0.48 t test 2.431 p value 0.019* *
3.4–4.9 4.53 0.33
= significant.
Table 6 groups.
Echocardiographic evaluation of the two studied Control
Obese
Control
Obese
Regarding LVM (g) Range Mean ±SD t test p value
36.05–76.4 47.04 16.23 6.938 0.001*
66.6–217 108.71 39.52
Regarding LVMI (g) Range Mean ±SD t test p value
12.06–40.7 20.33 8.86 5.325 0.001*
29.9–90.2 46.42 19.23
*
= significant.
Table 7 Comparison between the two studied groups regarding LMPI. LMPI
Control
Obese
Range Mean ±SD t test p value
0.28–0.38 0.330 0.051 4.632 0.009*
0.40–2.1 0.681 0.571
*
= significant.
19 Also, it shows that the controls had mean LVFS of 37.53 ± 5.33 and obese 40.91 ± 6.30%. There was no significant difference between the two studied groups as regards fractional shortening (p > 0.05). Additionally, it shows that the controls had mean % LVEDD of 77.73 ± 14.15 and obese 90.79 ± 11.77%. There was significant increase of the % LVEDD in obese children as compared to control group (p < 0.05). Table 5 shows that the controls had mean LVEDD of 3.30 ± 0.647 and obese 4.11 ± 0.535 cm. There was highly significant increase of the LVEDD in obese children as compared to the control group (p 6 0.001). Likewise, it shows that the controls had mean predicted LVEDD of 4.25 ± 0.48 and obese 4.53 ± 0.33 cm. there was significant increase of the predicted LVEDD in obese children as compared to the control group (p < 0.05). Table 6 shows that the controls had mean LVM of 47.04 ± 16.23 and obese 108.71 ± 39.52 g. There was highly significant increase of the LVM in obese as compared to the control group (p 6 0.001). Also, the controls had mean LVMI of 20.33 ± 8.86 and obese 46.42 ± 19.23. There was highly significant increase of the LVMI in obese as compared to the control group (p 6 0.001) Table 7 shows that the controls had mean LMPI of 0.330 ± 0.051 and obese 0.681 ± 0.571. There was significant increase of the LMPI in obese children as compared to the control group (p < 0.05). 4. Discussion The extent of the epidemic of childhood obesity is increasing so that children are suffering chronic complications that were once only seen in adults.21 The World Health Organization describes the ‘‘escalating global epidemic’’ of obesity as ‘‘one of today’s most blatantly visible – yet most neglected – public health problems’’.22 Our study was done on two groups of comparable age and sex; obese children and control group of non-obese children. As regards age, the study revealed no significant difference between the two groups. A critical period for the development of adult obesity is adolescence. Obesity that develops in or persists into adolescence is not only the most difficult to treat, but is also associated with the greatest risk of serious complications.23 Our study revealed that there was no significant difference between gender and obesity. There are contradictory results about this item; Pyke,24 found no significant difference between boys’ and girls’ obesity. However, LaFrance et al.25 stated that boys’ obesity was higher than girls’ obesity. But Raja’a and Bin-Mohanna,26 reported that prevalence of overweight and obesity was higher among females. These differences may be due to the difference in localities, sample size, cultural and/or socioeconomic causes. The present study shows that the BMI was significantly higher in obese children as compared to non-obese children. The use of WHO standards for BMI-for-age in 2006 provides only a crude measure of body fatness, since it does not distinguish between weight associated with muscle and weight associated with fat.27 Regarding lipid profile, this study demonstrated that HDL was significantly lower in obese as compared to non-obese chil-
20 dren. However, LDL, serum TG, serum TCh and TCh/HDL ratio were significantly higher in obese children as compared to control. This was in accordance with Freedman et al.28 and Reinhr et al.29 who found that overweight is strongly related to concentrations of HDL-cholesterol and TG and weakly related to concentrations of LDL-cholesterol; while Kim et al.30 found that all types of lipids were significantly associated with overweight and obesity. Also, Chinali et al.11 stated that obese adolescents had significantly higher total TG and lower highdensity lipoprotein. Moreover, Lima et al.31 stated that Total and LDL-cholesterol levels were higher in obese than normal weight children. But HDL-cholesterol showed borderline values. Horri and Vakil i32 stated that serum TG and cholesterol levels were significantly higher in obese children and adolescents. Also, there is significant positive correlation between BMI percentiles and serum TG, total and LDL-cholesterol. In addition, HDL-cholesterol was significantly lower in the obese children than control. Obesity predisposes to hypertension because of concomitant metabolic and hemodynamic abnormalities leading to inadequate lowering of systemic resistance and, therefore, to more severe cardiovascular burden.33 Many of cardiovascular complications related to obesity may begin in childhood and adolescence. Furthermore, it has been shown that obesity is associated with the development of early myocardial and coronary artery changes in children.17 When complications of obesity are already established, as coronary artery disease, positive correlations are observed between markers of lipid peroxidation, total cholesterol and TG and negative ones are noted with high-density lipoproteins (HDL).34 As regards echocardiographic evaluation, there was no significant difference between the two studied groups as regards the LVEF (%) and the LVFS (%). Hence all children had normal LV systolic function. These results were in agreement with those of Mehta et al.,12 Di Salvo et al.35 and Khositseth et al.17 On the other hand, Chinali et al.11 found a significantly lower ejection fraction in obese adolescents as compared to non-obese group. Moreover, Alpert36 found that obese subjects demonstrated evidence of diminished myocardial function, which was directly related to the severity and duration of their adiposity. The hearts of these subjects were characterized by reduced LVEF; which were often independent of effects of hypertension or coexistent coronary artery disease. Gutin et al.37 reported that among children aged 7– 13 years, percent body fat correlated negatively with lower mid-wall ventricular shortening fraction. Mensah et al.38 found a significant negative association between LVSF and central adiposity in a group of 15-year old subjects. The explanation for these differences in depression of myocardial function is related to both severity and duration of excess adiposity, myocardial fatigue due to chronic volume overwork, and metabolic derangements associated with obesity such as insulin resistance which modify myocardial substrate utilization, increase in myocardial fatty acid oxidation and oxygen consumption and leading to myocardial dysfunction.39,40 As regards the LV dimensions in our study, there was significant increase in the LVEDD, predicted LVEDD and % LVEDD in obese than controls, indicating left ventricular
A.M. Zoair et al. enlargement. Positive cross-sectional associations between body fat content and cardiac chamber dimensions have been evident among cohorts of obese subjects41 as well as in studies in the general pediatric population.11,37,38,42,43 Chinali et al.11 reported that cardiac enlargement in obesity is caused by response to a chronically increased hemodynamic load. Moreover, Rowland40 found a correlation between body mass index and left ventricular end diastolic dimension in a group of early adolescent females. An obese child is characterized by an expanded circulatory system reflecting somatic growth, increased plasma volume, hypertrophy of myocardial fibers, and cardiac chamber enlargement.40 LV-mass has been established as an independent risk factor for cardiovascular morbidity and mortality.44,45 Since LVmass is affected by body size, a variety of factors have been proposed for indexing LV-mass.44 In our study, the standard echocardiographic evaluation of obese, non-hypertensive children showed significant increase in the left ventricular mass (LVM) and left ventricular mass index (LVMI) as compared to the control group, which indicated left ventricular hypertrophy (LVH). These results were in agreement with those of Chinali et al.11 Khositseth et al.17 and Di Salvo et al.35 Attention has been focused on the role of the anabolic effects of hyperinsulinemia on myocardial hypertrophy, a reflection of the insulin resistance commonly observed in obese individuals.45–48 The American Heart Association (AHA) has stressed the importance of obesity as a modifiable, independent risk factor for coronary artery disease, ventricular dysfunction, congestive heart failure, and cardiac arrhythmias.49 Similarly, adolescent obesity is strongly related to adult obesity and may progress to type 2 diabetes and/or hypertension.50 Adult obesity has been shown to be associated with increased left ventricular mass (LVM) and both systolic and diastolic dysfunction,36 all are important predictors of adverse cardiovascular outcome and identification of a pre-clinical cardiovascular disease.51 Chinali et al.11 stated that even in adolescents, the severity of obesity parallels early cardiac changes, including high prevalence of LVH and increased hemodynamic load. Moreover, Friberg et al.52 reported that the increased LVM occurs to sustain the increased cardiac workload. At higher stages of obesity, increase in LVM is not depending only on hemodynamic load but also on non-hemodynamic factors; neuro-hormonal effects of clustered metabolic factors influencing LV growth,11 high blood pressure and dietary sodium intake.53 However, LV dilatation and hypertrophy are independent of the level of blood pressure.54 The LMPI indicates both systolic and diastolic myocardial functions. LMPI significantly increased in obese as compared to the control group. This was in agreement with Khositseth et al.17 who reported that despite normal LV dimensions and systolic function in obese children of their study, the abnormal LMPI may be one of the sensitive indicators for the early detection of LV global dysfunction in those children. So, LMPI may be an indicator for early recognition of the cardiac related complications of obesity in children. This simple reproducible index may be useful to identify the high-risk patients requiring an aggressive weight-control/reduction program.17
Lipid profile and some cardiac functions in children with obesity 5. Conclusions Complete evaluation of cardiac function in obese children should include echocardiography along with LMPI (as a useful marker for early detection of LV global dysfunction), in combination with measurement of lipid profile. Also it helps to identify the high-risk obese children requiring weight-control/ reduction programs to encourage healthy life styles and reduce morbidity and mortality. It is recommended in the future studies, to clarify the effects of obesity on cardiac function and lipid profile, even in infants and young children.
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