Abstract
Background: Obesity is associated with many risk factors, such as hyperlipidemia, hyperinsulinemia, hypertension and leads to early atherosclerosis. The aim of this study was to investigate the relation of the mean platelet volume (MPV) and the carotid intima media thickness (CIMT) on cardiac functions among obese children. Materials and Methods: Sixty obese children, with body mass index percentile were >95% and forty eight healthy controls were enrolled in the study. Triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), thyroid function tests, hemoglobin, white blood cell, MPV and insulin resistance were evaluated. CIMT was measured by using high-resolution ultrasound and echocardiography was performed to all individuals. Results: MPV and CIMT values were found significantly higher in obese children than controls. There was positive correlation between CIMT and age, body surface area (BSA), systolic and diastolic blood pressure, left ventricular meridional end-systolic wall stress (ESWSm), myocardial fiber stress (MFS), stroke volume (SV) and insulin and negative correlation with left ventricle end-systolic elastance by single beat technique (Ees(sb)) and arterial elastance (Ea). There was no correlation between LVM, cardiac risk profiles and CIMT. Multiple stepwise regression analyses revealed that ESWSm (β=0.337, P=0.049) was only independent factor on CIMT. MPV values showed negative correlation with ALT, AST, Free T4, thyroid stimulating hormone and positive correlation with age and BSA. Conclusion: Current study showed that obesity has an independent impact on CIMT and MPV values in children. Increased CIMT in obese children leads significant increase in ESWSm and decrease in Ea and Ees(sb).
Keywords: Cardiac functions, carotid intima-media thickness, children, mean platelet volume, obese
Introduction
Obesity is a chronic metabolic disorder related with cardiovascular disease and carries morbidity and mortality risk [1]. It is also suggested that the prevalence rate of atherosclerosis is high among individuals with non-alcoholic fatty liver disease (NAFLD) [2]. On the other hand atherosclerotic lesions in the aorta, coronary and the carotid arteries seem to be related with the risk factors, such as obesity, dyslipidemia, hypertension and diabetes mellitus (DM) [2]. Early childhood atherosclerosis may cause the coronary artery disease in adulthood [3]. The determination of the cardiovascular risk profile in children with obesity may make earlier diagnosis of the cardiovascular complications and thus preventive measures can be taken.
Platelet size is correlated with platelet activation and large platelets have more hemostatic activation [4]. So the mean platelet volume (MPV) may be used as a marker of platelet activation and may also be associated with atherosclerosis as a simple assessment tool [5]. Acute myocardial infarction, acute ischemic stroke, preeclampsia and renal artery stenosis leads to increase in MPV value. Also increased MPV value may indicate poor prognosis after myocardial infarction, restenosis after coronary angioplasty and during the period of preeclampsia [6]. Additionally measurement of carotid intima media thickness (CIMT) was used as a non-invasive predictive marker of atherosclerosis [7]. Subclinical carotid atherosclerosis is associated with impaired left ventricular (LV) functions and plays an important role in the development of heart failure [8].
The primary aim of the present study was to investigate the relation between MPV levels and CIMT measurements and LV meridional end-systolic wall stress (ESWSm), myocardial fiber stress (MFS), arterial elastance (Ea), LV elastance at end-systole derived by single-beat technique (Ees(sb)) and stroke volume (SV) as cardiac performances in obese children with NAFLD using conventional arterial ultrasound and echocardiography comparing with healthy controls. We also studied cardiovascular risk profiles in obese children related to the cardiac functions.
Materials and methods
After approval of the ethics committee and the signed informed consents of the patients’ parents or their legal guardians were obtained. The control group was selected randomly from outpatient population of the university hospital. Patients aged between 6-16 years, diagnosed as exogenous obesity and had NAFLD were included in the study. After measuring body weight and height, body mass index (BMI) of all children was calculated as, the individual’s body weight divided by the square of individual’s height. Obesity was defined as a BMI exceeding 95th percentile [9].
Exclusion criteria were to have DM, Cushing syndrome, growth hormone deficiency, hypertension, familial hypercholesterolemia, chronic liver disease and using of corticosteroids. All obese and healthy individuals were screened by the same experienced radiologist. The diagnosis of NAFLD was based on increased echogenicity determined by ultrasound compatible with fatty infiltration of the liver with or without elevated alanine aminotransferase (ALT) levels.
After 12-hours fasting, the blood samples were taken for glucose, insulin, triglyceride, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), ALT, AST, Free T3, Free T4, thyroid stimulant hormone (TSH), hemoglobin (Hb), white blood cell count (WBC), platelet count (PLT) and MPV calculation. Insulin resistance was calculated by a homeostasis model assessment-IR (HOMA-IR) index as described by Matthews et al. [10]. Body surface area (BSA) was calculated by Mosteller formula [11].
The carotid artery ultrasound performed by the same radiologist, according to the recommendations of the American Society of Echocardiography CIMT Task Force [12]. Echocardiographic assessments were performed by a single pediatric cardiologist. All calculations were done using the parameters derived from echocardiographic measurements. ESWSm was calculated by the method of Grossman [13] and MFS according to the formula recommended by Regen [14]. Ees(sb), Ea and SV were calculated as we described previously [15]. LVM was computed according to the Devereux Formula [16].
The statistical analyses were carried out by Statistical Package for Social Sciences 18 (SPSS). Variables were expressed as mean ± SD. Comparisons of variables were performed using unpaired Student t test. Bivariate associations of the variables were assessed using Pearson’s correlation coefficients. To find the parameters that explain the significance of the variance of the dependent variables, stepwise multivariate linear regression analysis was performed to correlated parameters with CIMT and P value <0.05 was considered as indication of statistical significance.
Results
BMI, BSA, systolic and diastolic BP, serum AST, total cholesterol, triglyceride, LDL, glucose, insulin, MPV, Platelet, FT3 levels were significantly higher and HDL levels lower in the NAFLD obese group compared with the controls. The control group showed lower HOMA-IR values than the obese group. The demographic characteristics and the clinical features of the patients and healthy controls are listed in Table 1.
Table 1.
Clinical features of healthy controls and obese children
| Variable | Obese children | Healthy controls | P value |
|---|---|---|---|
| 60 (M/F=27/33) | 48 (M/F=21/27) | ||
| Age (years) | 12.25 ± 3.14 | 10.8 ± 3.13 | 0.027* |
| Body mass index (kg/m2) | 27.6 ± 3.95 | 17.6 ± 3.48 | 0.000** |
| Body surface area (m2) | 1.66 ± 0.31 | 1.22 ± 0.31 | 0.000** |
| Systolic blood pressure (mmHg) | 114.5 ± 11.25 | 102 ± 15.72 | 0.000** |
| Diastolic blood pressure (mmHg) | 68.88 ± 7.85 | 63.77 ± 7.43 | 0.001** |
| Hemoglobin (gr/L) | 13 ± 0.81 | 13.34 ± 1.01 | 0.079 |
| White blood cell count (×103/mL) | 8.14 ± 2.01 | 7.64 ± 2.07 | 0.23 |
| Platelet (×103/mL) | 293.52 ± 54.34 | 247.91 ± 55.42 | 0.000** |
| Mean platelet volume (fL) | 7.44 ± 0.88 | 6.93 ± 0.87 | 0.003** |
| Glucose (mg/dL) | 89.19 ± 7.19 | 88.45 ± 9.13 | 0.65 |
| Alanine transaminase (IU/L) | 21.36 ± 5.73 | 22.19 ± 5.51 | 0.47 |
| Aspartate transaminase (IU/L) | 20.05 ± 9.78 | 14.53 ± 6.91 | 0.002** |
| Free T3 (pg/ml) | 3.74 ± 0.64 | 3.36 ± 0.49 | 0.002** |
| Free T4 (NG/DL) | 1.19 ± 0.14 | 1.17 ± 0.13 | 0.362 |
| Thyroid stimulating hormone (uIU/ml) | 3.63 ± 3.23 | 2.81 ± 2.99 | 0.191 |
| Triglyceride (mg/dL) | 119.39 ± 53 | 84.88 ± 32 | 0.000** |
| Total chollesterol (mg/dL) | 172.70 ± 38 | 152.49 ± 29 | 0.005** |
| High-density lipoprotein (mg/dL) | 42.78 ± 6.55 | 46.44 ± 10.56 | 0.039* |
| Low-density lipoprotein (mg/dL) | 103.82 ± 31.91 | 88.51 ± 24.58 | 0.008** |
| Insulin (uIU/mL) | 13.13 ± 7.93 | 7.40 ± 5.54 | 0.000** |
| HOMA-IR | 3.92 ± 1.85 | 1.45 ± 1.02 | 0.000** |
| Carotid intima-media thickness (mm) | 0.541 ± 0.021 | 0.352 ± 0.012 | 0.000** |
| Left ventricular mass (g) | 63.72 ± 16.80 | 56.49 ± 12.37 | 0.007** |
| Fiber stress (g/cm2) | 279.231 ± 65.41 | 228.298 ± 55.46 | 0.000** |
| End-systolic wall stress (g/cm2) | 213.26 ± 61.93 | 168.66 ± 52.52 | 0.000** |
| Arterial elastance (mmHg/ml) | 1.62 ± 0.42 | 1.97 ± 0.46 | 0.000** |
| Ventricular elastance (mmHg/ml) | 2.15 ± 0.78 | 2.79 ± 0.70 | 0.000** |
| Stroke volume (ml) | 70.56 ± 19.17 | 52.79 ± 14.60 | 0.000** |
Statistically significant (P<0.05).
Statistically significant (P<0.01).
HOMA-IR: homeostasis model assessment-IR.
The MPV was significantly higher in obese group (7.44-6.93 fl, P<0.01). And was positively correlated with age and BSA (r=0.263, P=0.034 and r=0.261, P=0.035, respectively) and negatively correlated with ALT, AST, FT4 and TSH (r=-0.310, P=0.015), (r=-0.315, P=0.014), (r=-0.264, P=0.033) and (r=-0.336, P=0.009) respectively. The multiple stepwise regression analysis revealed no correlation between MPV and these parameters.
In obese children ESWSm, MFS, SV values were significantly higher than healthy group (P=0.000) whereas Ea and Ees(sb) were lower in obese group (P=0.000). LVM was higher in obese group (P=0.007).
Also obese group with NAFLD exhibited significantly higher CIMT values than the control group. CIMT showed positive correlation with age, BSA, systolic BP, diastolic BP, ESWSm, MFS, SV, insulin and negative correlation with Ea and Ees(sb) (Table 2). There was no correlation between LVM, cardiac risk profiles and CIMT. Multivariate regression analyse was performed to correlated parameters with CIMT. CIMT was chosen as dependent variable, age, BSA, systolic BP, diastolic BP, ESWSm, MFS, SV, insulin, Ea and Ees(sb) were independent variables in the regression analysis. ESWSm (β=0.337, P=0.049) was found as an only independent factor on CIMT (Table 3).
Table 2.
Pearson’s correlations between carotid intima-media thickness and clinical laboratory and echocardiography parameters in obese children
| Variables | Carotid intima media thickness | Age | Body surface area |
|---|---|---|---|
| Age (year) | .407** | 1 | |
| Body surface area (m2) | .475** | .892** | 1 |
| Arterial elastance (mmHg/ml) | -.335** | -.440** | -.523** |
| Ventricular elastance (mmHg/ml) | -.371** | -.534** | -.562** |
| Sistolic BP (mmHg) | .345** | .389** | .487** |
| Diastolic BP (mmHg) | .288* | .423** | .401** |
| Stroke volume (ml) | .396** | .481** | .610** |
| End-systolic wall stress (g/cm2) | .419** | .278* | .413** |
| Fiber stress (g/cm2) | .433** | .300* | .466** |
| White blood cell count (×103/mL) | -.130 | -.132 | -.184 |
| Hemoglobin (gr/L) | -.142 | .081 | .102 |
| Platelet (×103/mL) | -.088 | -.264 | -.300 |
| Mean platelet volume (fL) | .178 | .304* | .265 |
| Triglyceride (mg/dL) | .060 | .076 | .121 |
| Total chollesterol (mg/dL) | -.121 | -.234 | -.362* |
| High-density lipoprotein (mg/dL) | -.136 | .044 | -0.029 |
| Low-density lipoprotein (mg/dL) | -.113 | -.242 | -.347* |
| Alanine transaminase (IU/L) | -.211 | -.481** | -.601** |
| Aspartate transaminase (IU/L) | .059 | -.084 | -.137 |
| Free T3 (pg/ml) | -.050 | -.396** | -.343* |
| Free T4 (NG/DL) | -.031 | -.007 | .029 |
| Thyroid stimulating hormone (uIU/ml) | -.066 | -.112 | -.234 |
| Glucose (mg/dL) | -.153 | .004 | -.145 |
| Insulin (uIU/mL) | .261* | .292* | .381** |
Correlation is significant at the .01 level (2-tailed).
Correlation is significant at the .05 level (2-tailed).
Table 3.
Analysis of the factors affecting CIMT by stepwise multiple linear regression
| Independent variables | Unstandardized Coefficients | Standardized Coefficients | t | Sig. | 95.0% Confidence Interval for B | ||
|---|---|---|---|---|---|---|---|
|
|
|
||||||
| B | Std. Error | Beta | Lower Bound | Upper Bound | |||
| (Constant) | .693 | .299 | 2.319 | .025 | .090 | 1.296 | |
| Age | .005 | .015 | .106 | .327 | .745 | -.025 | .034 |
| BSA | .017 | .158 | .039 | .106 | .916 | -.302 | .335 |
| Sist BP | .002 | .003 | .162 | .660 | .513 | -.004 | .009 |
| Diast BP | .001 | .003 | .072 | .390 | .699 | -.005 | .007 |
| ESWSm | .001 | .000 | .337 | 2.028 | .049* | .000 | .001 |
| MFS | .001 | .000 | .321 | 1.002 | .219 | .000 | .001 |
| SV | -.002 | .003 | -.284 | -.650 | .519 | -.008 | .004 |
| Ea | -.128 | .147 | -.400 | -.874 | .387 | -.424 | .168 |
| Ee(sb) | .007 | .043 | .040 | .162 | .872 | -.080 | .094 |
| Insulin | .004 | .003 | .215 | 1.374 | .177 | -.002 | .010 |
Dependent Variable: CIMT (carotid intima media thickness). R2: .342. Adjusted R2: .200.
Correlation is significant at the .05 level (2-tailed).
BSA: Body surface area, Sist BP: systolic blood pressure, Diast BP: Diastolic blood pressure, ESWSm: meridional end-systolic wall stress, MFS: Myocardial fiber stress, SV: stroke volume, Ea: arterial elastance, Ees(sb): left ventricle end-systolic elastance by single beat technique, CIMT: carotid intima media thickness.
Discussion
The present study revealed that the obese children with NAFLD had significantly higher MPV levels than healthy individuals. Coban et al. [17] showed that MPV levels of obese children were significantly higher than the controls and suggested that the higher MPV levels leads to increased risk of atherosclerosis. Arslan et al. [18] found a significant relationship between MPV and CIMT. We failed to demonstrate such relationship. Kilciler et al. [19] reported a positive relationship between MPV and carotid atherosclerosis in adult patients with NAFLD but not any difference between NAFLD and control group regarding MPV and CIMT.
MPV is a strong indicator of atherosclerosis. In present study we showed that the obese children with NAFLD demonstrate higher MPV values than control group. Ozhan et al. [20] suggested that MPV value may be accepted as a prognostic criterion in NAFLD patients indicating a possible enhancement of risk of developing cardiovascular disease. They showed that the MPV values were positively correlated with ALT and AST levels and negatively correlated with platelet and creatinine levels. We also demonstrated that the MPV levels show negative correlation with ALT, AST, FT4 and TSH and positive correlation with age and BSA.
NAFLD is the accumulation of excess fat in the liver without alcohol consumption and commonly coexists with the obesity. NAFLD is associated with increased risk of the atherosclerosis and the insulin resistance. Some studies showed that there was a positive relation between NAFLD and the atherosclerosis in the pediatric population. Schwimmer et al. [21] reported that the prevalence of atherosclerosis was increased among individuals with NAFLD. They also demonstrated that the obese children are at risk of developing atherosclerosis six times more than the children without fatty liver. Pacifico et al. [22] reported that the severity of NAFLD had been correlated with an increased degree of CIMT in obese children.
Ultrasonographic measurement of CIMT is a noninvasive, sensitive and reproducible technique to identify and quantify the degree of subclinical vascular disease and evaluate the risk factors for cardiovascular disease [23]. Nonsclerotic changes in arterial wall leads increase in CIMT. The association between increased CIMT and atherogenesis, hypercholesterolemia in obese children and young adults is well established [24]. In the present study we showed that there was no significant correlation between CIMT and hypercholesterolemia.
Our results agree with Iannuzzi et al. [25] who showed significantly increased CIMT in obesity. Previous studies showed that there was also a positive correlation between increased CIMT and triglyceride levels [26]. However there was no correlation between increased CIMT and triglyceride level in our study.
Sert et al. [27] showed that obese adolescents suffered from NAFLD and with increased CIMT had higher LVM. Although our study confirms that the LVM increases significantly among the obese children, there was no correlation between CIMT and LVM. This result raises the question of the effect of the duration of the obesity and the significant changes in CIMT and LVM. Also present study is evident that the obese children with NAFLD had increased CIMT and revealed positive correlation with age, BSA, Systolic BP, Diastolic BP, ESWSm, MFS, SV, insulin and negative correlation with Ea, Ees(sb) (Table 2). Multiple regression analysis model was performed in the NAFLD obese group and ESWSm was found as an independent factor on CIMT values (β=0.337, P=0.049) (Table 3).
In our series, systolic and diastolic blood pressures were found significantly higher in obese children compared with those of control group. Arterial wall alterations in obese children could be explained by the effects of hypertension. Remodeling of arterial wall in the presence of hypertension is controversy [28]. Systolic BP elevation is associated with deteriorated arterial compliance and leads to increase afterload of the heart. Elevated BP may coexist with increased CIMT and cardiac hypertrophy [29]. The present study revealed positive relation between CIMT and systolic BP (r=0.345, P=0.006). We suggest that the high systolic BP and increased CIMT may elevate the afterload and therefore causes increased ESWSm in obese children.
ESWSm has been used in the measurement of myocardial afterload, and as the counter force limiting left ventricular ejection [30]. Chamber geometry of cardiac structure has also an effect on both ventricular contractility and myocardial performance and identified by measurement of ESWSm and MFS. ESWSm seems to be related with chamber shape and mass/volume ratio and displays the forces opposing predominantly meridional and circumferential planes. ESWSm is an index of total forces per unit of myocardium. It may be helpful for estimation of true afterload. We observed high ESWSm and MFS values in obese individuals. These echocardiographic measurements provide important information about the myocardial mechanics.
MFS is known as an indicator for radial forces and when determining the myofiber afterload it is more decisive. It is shown that the wall stress is dependent on both chamber shape and mass/volume ratio; MFS is dependent on only the former, making it a more accurate index of afterload in the setting of ventricular hypertrophy or severe dilatation [31]. We showed that the MFS and ESWSm levels were significantly higher in obese children.
Ees(sb) is a major determinant of cardiac systolic function and ventricular-arterial interaction. Ea reflects afterload and sensitive to any kind of afterload changes such as BP. We demonstrated that Ea and Ees(sb) were lower and CIMT was negatively correlated with Ea and Ees(sb) in obese children. These findings are compatible with the risk of increased arterial and ventricular stiffness and decreased arterial elasticity in obese children. Previous studies showed that, risk factors such as high LDL-cholesterol, elevated BP and obesity have been associated with decreased arterial elasticity [32]. Koopman et al. [33] showed that CIMT and Ea/Eesb were higher in obese children than controls. They suggested that the changes in vascular parameters were correlated with the changes in longitudinal myocardial deformation parameters. We previously reported that the Ea and Ees(sb) show powerful negative correlation with BSA of normal children [15].
An excess of adipose tissue augments cardiac output (CO), SV and left ventricular filling pressure, expands intravascular volume, and lowers total peripheral resistance [34]. In current study SV was higher in obese subjects. Stelfox et al. [35] revealed that BMI was positively correlated with CO and SV and they suggested that each 1 kg/m2 increase in BMI was associated with 1.35 mL increase in SV.
Our results showed significant correlation between CIMT and ESWSm. In the literature, such a relationship in obese children is not previously detected so we think that this is the first report. We suggest that the echocardiographic assessment of ESWSm along with CIMT, Ea and Ees(sb) measurements may be accepted as an indicator of LV performance and/or dysfunction and vascular elasticity among obese children with NAFLD.
Conclusion
The current study demonstrates that the obesity had an impact on MPV, CIMT and increased ESWSm values and decreased arterial and ventricular elastance. In addition to these findings CIMT values were positively correlated with ESWSm which reflects afterload in obese children.
Disclosure of conflict of interest
None.
References
- 1.Poirier P, Eckel RH. Obesity and cardiovascular disease. Curr Atheroscler Rep. 2002;4:448–453. doi: 10.1007/s11883-002-0049-8. [DOI] [PubMed] [Google Scholar]
- 2.Berenson GS, Srinivasan SR, Bao W, Newman WP, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. N Engl J Med. 1998;338:1650–1656. doi: 10.1056/NEJM199806043382302. [DOI] [PubMed] [Google Scholar]
- 3.Li S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, Berenson GS. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study. JAMA. 2003;290:2271–2276. doi: 10.1001/jama.290.17.2271. [DOI] [PubMed] [Google Scholar]
- 4.Martin J, Trowbridge E, Salmon G, Plumb J. The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration. Thromb Res. 1983;32:443–460. doi: 10.1016/0049-3848(83)90255-4. [DOI] [PubMed] [Google Scholar]
- 5.Berger JS, Eraso LH, Xie D, Sha D, Mohler ER. Mean platelet volume and prevalence of peripheral artery disease, the National Health and Nutrition Examination Survey, 1999-2004. Atherosclerosis. 2010;213:586–591. doi: 10.1016/j.atherosclerosis.2010.09.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Bath P, Butterworth R. Platelet size: measurement, physiology and vascular disease. Blood Coagul Fibrinolysis. 1996;7:157–161. [PubMed] [Google Scholar]
- 7.Bonithon-Kopp C, Touboul PJ, Berr C, Leroux C, Mainard F, Courbon D, Ducimetière P. Relation of intima-media thickness to atherosclerotic plaques in carotid arteries The Vascular Aging (EVA) Study. Arterioscler Thromb Vasc Biol. 1996;16:310–316. doi: 10.1161/01.atv.16.2.310. [DOI] [PubMed] [Google Scholar]
- 8.Chahal NS, Lim TK, Jain P, Chambers JC, Kooner JS, Senior R. The distinct relationships of carotid plaque disease and carotid intimamedia thickness with left ventricular function. J Am Soc Echocardiogr. 2010;23:1303–1309. doi: 10.1016/j.echo.2010.08.021. [DOI] [PubMed] [Google Scholar]
- 9.Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11. 2002:1–190. [PubMed] [Google Scholar]
- 10.Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419. doi: 10.1007/BF00280883. [DOI] [PubMed] [Google Scholar]
- 11.Mosteller R. Simplified calculation of body-surface area. N Engl J Med. 1987;317:1098. doi: 10.1056/NEJM198710223171717. [DOI] [PubMed] [Google Scholar]
- 12.Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr. 2008;21:93–111. doi: 10.1016/j.echo.2007.11.011. [DOI] [PubMed] [Google Scholar]
- 13.Grossman W, Jones D, McLaurin L. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975;56:56. doi: 10.1172/JCI108079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Regen DM. Calculation of left ventricular wall stress. Circulat Res. 1990;67:245–252. doi: 10.1161/01.res.67.2.245. [DOI] [PubMed] [Google Scholar]
- 15.Khosroshahi H, Ozkan E, Kilic M. Arterial and left ventricular end-systolic elastance in normal children. Eur Rev Med Pharmacol Sci. 2014;18:3260–3266. [PubMed] [Google Scholar]
- 16.Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57:450–458. doi: 10.1016/0002-9149(86)90771-x. [DOI] [PubMed] [Google Scholar]
- 17.Coban E, Ozdogan M, Yazicioglu G, Akcit F. The mean platelet volume in patients with obesity. Int J Clin Pract. 2005;59:981–982. doi: 10.1111/j.1742-1241.2005.00500.x. [DOI] [PubMed] [Google Scholar]
- 18.Arslan N, Makay B, Hızlı Ş, Koçyiğit A, Demircioğlu F, Tuncel AS, Çakmakçı H. Assessment of atherosclerosis in obese adolescents: Positive correlation of mean platelet volume and carotid intima media thickness. J Paediatr Child Health. 2013;49:963–968. doi: 10.1111/jpc.12301. [DOI] [PubMed] [Google Scholar]
- 19.Kilciler G, Genc H, Tapan S, Ors F, Kara M, Karadurmus N, Ercin CN, Karslioglu Y, Kilic S, Bagci S. Mean platelet volume and its relationship with carotid atherosclerosis in subjects with non-alcoholic fatty liver disease. Ups J Med Sci. 2010;115:253–259. doi: 10.3109/03009734.2010.500062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Ozhan H, Aydin M, Yazici M, Yazgan O, Basar C, Gungor A, Onder E. Mean platelet volume in patients with non-alcoholic fatty liver disease. Platelets. 2010;21:29–32. doi: 10.3109/09537100903391023. [DOI] [PubMed] [Google Scholar]
- 21.Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, Lavine JE. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–649. doi: 10.1002/hep.20842. [DOI] [PubMed] [Google Scholar]
- 22.Pacifico L, Cantisani V, Ricci P, Osborn JF, Schiavo E, Anania C, Ferrara E, Dvisic G, Chiesa C. Nonalcoholic fatty liver disease and carotid atherosclerosis in children. Pediatr Res. 2008;63:423–427. doi: 10.1203/PDR.0b013e318165b8e7. [DOI] [PubMed] [Google Scholar]
- 23.Homma S, Hirose N, Ishida H, Ishii T, Araki G. Carotid plaque and intima-media thickness assessed by B-mode ultrasonography in subjects ranging from young adults to centenarians. Stroke. 2001;32:830–835. doi: 10.1161/01.str.32.4.830. [DOI] [PubMed] [Google Scholar]
- 24.Beauloye V, Zech F, Tran Thi Mong H, Clapuyt P, Maes M, Brichard SM. Determinants of early atherosclerosis in obese children and adolescents. J Clin Endocrinol Metab. 2007;92:3025–3032. doi: 10.1210/jc.2007-0619. [DOI] [PubMed] [Google Scholar]
- 25.Iannuzzi A, Licenziati MR, Acampora C, Salvatore V, Auriemma L, Romano ML, Panico S, Rubba P, Trevisan M. Increased carotid intima-media thickness and stiffness in obese children. Diabetes Care. 2004;27:2506–2508. doi: 10.2337/diacare.27.10.2506. [DOI] [PubMed] [Google Scholar]
- 26.Yilmazer MM, Tavli V, Carti ÖU, Mese T, Güven B, Aydın B, Devrim I, Tavlı T. Cardiovascular risk factors and noninvasive assessment of arterial structure and function in obese Turkish children. Eur J Pediatr. 2010;169:1241–1248. doi: 10.1007/s00431-010-1216-5. [DOI] [PubMed] [Google Scholar]
- 27.Sert A, Pirgon O, Aypar E, Yilmaz H, Odabas D. Relationship between left ventricular mass and carotid intima media thickness in obese adolescents with non-alcoholic fatty liver disease. J Pediatr Endocrinol Metab. 2012;25:927–934. doi: 10.1515/jpem-2012-0187. [DOI] [PubMed] [Google Scholar]
- 28.Aggoun Y, Farpour-Lambert NJ, Marchand LM, Golay E, Maggio AB, Beghetti M. Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure. Eur Heart J. 2008;29:792–9. doi: 10.1093/eurheartj/ehm633. [DOI] [PubMed] [Google Scholar]
- 29.Suurküla M, Agewall S, Fagerberg B, Wendelhag I, Widgren B, Wikstrand J. Ultrasound evaluation of atherosclerotic manifestations in the carotid artery in high-risk hypertensive patients. Risk Intervention Study (RIS) Group. Arterioscler Thromb. 1994;14:1297–1304. doi: 10.1161/01.atv.14.8.1297. [DOI] [PubMed] [Google Scholar]
- 30.Quinones MA, Gaasch WH, Cole JS, Alexander J. Echocardiographic determination of left ventricular stress-velocity relations. Circulation. 1975;51:689–700. doi: 10.1161/01.cir.51.4.689. [DOI] [PubMed] [Google Scholar]
- 31.de Simone G, Devereux RB, Roman MJ, Ganau A, Saba PS, Alderman MH, Laragh JH. Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension. J Am Coll Cardiol. 1994;23:1444–1451. doi: 10.1016/0735-1097(94)90390-5. [DOI] [PubMed] [Google Scholar]
- 32.Juonala M, Järvisalo MJ, Mäki-Torkko N, Kähönen M, Viikari JS, Raitakari OT. Risk Factors Identified in Childhood and Decreased Carotid Artery Elasticity in Adulthood The Cardiovascular Risk in Young Finns Study. Circulation. 2005;112:1486–1493. doi: 10.1161/CIRCULATIONAHA.104.502161. [DOI] [PubMed] [Google Scholar]
- 33.Koopman LP, McCrindle BW, Slorach C, Chahal N, Hui W, Sarkola T, Manlhiot C, Jaeggi ET, Bradley TJ, Mertens L. Interaction between myocardial and vascular changes in obese children: a pilot study. J Am Soc Echocardiogr. 2012;25:401–410. e401. doi: 10.1016/j.echo.2011.12.018. [DOI] [PubMed] [Google Scholar]
- 34.Messerli F. Cardiovascular effects of obesity and hypertension. Lancet. 1982;319:1165–1168. doi: 10.1016/s0140-6736(82)92234-6. [DOI] [PubMed] [Google Scholar]
- 35.Stelfox HT, Ahmed SB, Ribeiro RA, Gettings EM, Pomerantsev E, Schmidt U. Hemodynamic monitoring in obese patients: The impact of body mass index on cardiac output and stroke volume. Crit Care Med. 2006;34:1243–1246. doi: 10.1097/01.CCM.0000208358.27005.F4. [DOI] [PubMed] [Google Scholar]