(Hypertension. 2001;38:713.)
© 2001 American Heart Association, Inc.
Obesity- and Diabetes-Related Hypertension |
Ultrasonography for the Evaluation of Visceral Fat and Cardiovascular Risk
From the Divisions of Endocrinology (F.F.R.-F., A.N.F., M.T.Z.) and Nephrology (O.K., A.B.R.) and the Departments of Radiology (S.A.) and Preventive Medicine (S.R.G.F.), Federal University of São Paulo, São Paulo, Brazil.
Correspondence to Dr Fernando F Ribeiro Filho, Rua Machado Bittencourt, 300/112, São Paulo, SP Brazil 04044-000. E-mail fflexa{at}uol.com.br
Abstract
Abstract— —Visceral fat accumulation is associated with increased cardiovascular risk. Clinical evaluation of visceral fat is limited because of the lack of reliable and low-cost methods. To assess the correlation between ultrasonography and computed tomography (CT) for the evaluation of visceral fat, 101 obese women, age 50.5±7.7 years with a body mass index of 39.2±5.4 kg/m2, were submitted to ultrasonograph and CT scans. Visceral fat measured by ultrasonography, 1 cm above the umbilical knot, showed a high correlation with CT-determined visceral fat (r=0.67, P<0.0001). The ultrasonograph method showed good reproducibility with an intra-observer variation coefficient of <2%. Both ultrasonograph and CT visceral fat values were correlated with fasting insulin (r=0.29 and r=0.27, P<0.01) and plasma glucose 2 hours after oral glucose load (r=0.22 and r=0.34, P<0.05), indicating that ultrasonography is a useful method to evaluate cardiovascular risk. A significant correlation was also found between visceral fat by CT and serum sodium (r=0.18, P<0.05). A ultrasonograph-determined visceral-to-subcutaneous fat ratio of 2.50 was established as a cutoff value to define patients with abdominal visceral obesity. This value also identified patients with higher levels of plasma glucose, serum insulin and triglycerides and lower levels of HDL-cholesterol, which are metabolic abnormalities characteristic of the metabolic syndrome. Our data demonstrate that ultrasonography is a precise and reliable method for evaluation of visceral fat and identification of patients with adverse metabolic profile.
Key Words: obesity • ultrasonography • computed tomography • metabolism • cardiovascular diseases
Obesity has become a alarming public health problem because of its increasing prevalence and comorbidities—eg, diabetes, dyslipidemia, and hypertension—that elevate cardiovascular risk of affected people.1 Although pathophysiologic mechanisms linking obesity to those abnormalities were not completely clarified, it is well known that visceral fat accumulation and insulin resistance contribute to metabolic and hemodynamic changes found in obese people.2,3 Such a situation has been called the metabolic syndrome.4 Although some studies have focused on the role of visceral fat for the genesis of metabolic syndrome,5 others have aimed to find methods and their respective cutoff values able to identify obese people at high risk for cardiovascular disease.6,7 Computed tomography (CT) at abdominal level has provided the best estimation of visceral fat,8 and cutoff values have been proposed to predict morbidity.9 Considering the high ionizing radiation exposure, great expense, and low availability of CT, alternative noninvasive methods to quantify regional adiposity have been used in clinical and epidemiological studies. The use of waist circumference and/or waist-to-hip ratio (WHR), body composition by dual-energy x-ray absorptiometry, and more recently abdominal fat deposition by ultrasonography as predictors of cardiovascular risk have been investigated.10,11 Evidence in the literature has suggested that the visceral fat thickness measured by ultrasonography could be a reliable method to quantify visceral fat compared with that of CT.12,13 In addition, ultrasonography-determined visceral-to-subcutaneous fat ratios have also been shown to be highly correlated to CT measurements.14,15
Therefore, this study tested the correlation between CT and ultrasonograph measurements of abdominal adiposity and evaluated the use of the abdominal ultrasonography as an alternative method for identifying patients at high risk for cardiovascular disease.
Methods
Patients
Patients were recruited from the obesity outpatient clinic at the Federal University of São Paulo. Women, age 20 to 65 years, with a body mass index (BMI) 
30kg/m2 were screened for inclusion in the study.1 Exclusion criteria included self-reported diabetes mellitus, severe dyslipidemia (total cholesterol or triglycerides levels 7.8 mmol/L and 5.5 mmol/L, respectively), pregnancy, endocrinopathies (eg, Cushing syndrome and hypothyroidism), and weight loss >3 kg during the past 3 months. Patients with hypertension and mild-to-moderate disturbances of lipid profile were not excluded. The study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from all participants.
Anthropometric Data
In this cross-sectional study, all participants had their anthropometric data taken by the same investigator. BMI was calculated as weight divided by height squared. Waist circumference was measured at the midpoint between the lateral iliac crest and lowest rib; hip circumference, at the level of the trochanter major. Ambulatory blood pressure (BP) was recorded over a 24-hour period by automatic monitors (SpaceLabs 90202) that were set to record every 15 minutes during the day and every 30 minutes during the night. Time limits for day and night were set to coincide with the patient’s usual sleeping hours. A night BP fall was calculated by the percentage difference between day and night systolic BP.
Intra-abdominal fat area by CT scanning was obtained in a single tomographic slice, at the L4-L5 level, expressed in cm2. Using a 3.5-MHz probe located 1 cm from the umbilicus, 2 ultrasonographic measurements of intra-abdominal fat, defined as the distance between the internal face of reto-abdominal muscle and the anterior wall of the aorta, were taken.16 Intra-examination variation coefficient was 1.3%. Criteria used to define "visceral obesity" in CT scan was a visceral-to-subcutaneous fat ratio of 0.4, which has been used as an indicator of "central fat distribution."17 Cutoff points to define visceral obesity based on ultrasonograph parameters were not available in literature. In this study, the ultrasonograph values corresponding to the CT values of 110 cm2, obtained by the receiver operating characteristic (ROC) curve analysis, were used to characterize "visceral obesity" by ultrasonography.10
Patients underwent an oral glucose tolerance test with 75 g of glucose. Plasma glucose levels were determined in fasting condition and 30, 60, 90, and 120 minutes after glucose load; fasting insulin levels were also determined. Insulin resistance index was estimated by homeostasis model assessment18 and glucose area under the curve (AUC).
Plasma glucose was determined by the glucose-oxidase method. Cholesterol contents of lipoprotein fractions, serum triglycerides, uric acid, and apolipoprotein B were measured enzymatically. Insulin was measured by a commercial radioimmunoassay kit (Linco Research Inc).
Statistical Analysis
Statistical analysis was performed by using the SPSS software package (version 8.0). Student’s t test and 
2 were used to compare variables between groups. Correlations was tested by the Pearson coefficient; 
statistics were used to assess the concordance between diagnostic criteria for visceral obesity by ultrasonography and CT. Logarithmic transform of visceral fat by CT was used. Data were shown as SEM and SD. Level of significance was set at P<0.05.
Results
The 101 patients completed all the steps of the study. The mean age was 50.5±7.7 years, with a predominance of white (56%) and postmenopausal women (61%). The study sample showed a mean BMI of 39.2±5.4 kg/m2; 9.9% had glycemic values compatible with diabetes19 during the oral glucose tolerance test. Ultrasonograph estimations of intra-abdominal fat—distance (Figure 1) and visceral-to-subcutaneous fat ratio—were highly correlated with CT-determined visceral fat area (r=0.67 and r=0.46, respectively; P<0.01). The distance of 2.50 was chosen as the discriminator value (specificity of 75% and sensitivity of 55%) by the ROC curve to correspond to the CT-determined visceral-to-subcutaneous fat ratio of 0.4. Correlations of clinical and laboratory data with visceral fat estimation by both techniques are shown in Table 1. Cardiovascular risk factors implicated in the metabolic syndrome, such as plasma glucose, HDL cholesterol, triglycerides, insulin levels, apolipoprotein B, and uric acid were correlated with visceral fat. Similar coefficients were observed using either technique of visceral fat estimation. Also, a significant correlation was detected between serum sodium and CT-determined visceral fat (r=0.18, P<0.05). Prevalence of postmenopausal women was similar between visceral and nonvisceral patients defined by both techniques (data not shown).
|
|
Patients were stratified as visceral or nonvisceral obese, according to CT and ultrasonography(Table 2). The concordance between criteria of visceral obesity by ultrasonography and CT was 65%, with statistics of 0.30 (P<0.01). Patients with visceral obesity by CT and ultrasonography were older than those with nonvisceral obesity (48.1±8.2 versus 53.0±6.2 years and 49.2±8.4 versus 52.7±6.0 years, P<0.05, for CT and ultrasonography, respectively). Both techniques were concordant when identifying association of visceral fat deposition and deterioration of glucose and lipid metabolism. Prevalence rates of diabetes were higher in visceral obese people; insulin resistance index (HOMA) and glucose AUC were also higher in visceral obese people, independently of the estimation method (Figure 2). BP levels did not differ between groups with or without increased visceral fat by any criteria.
|
|
Discussion
Central obesity has been shown to be an important predictor for metabolic disturbances, including hyperinsulinemia, glucose intolerance, dyslipidemia, hypertension, and cardiovascular disease.2–5,20,21 Imaging methodologies have been used to assess body fat distribution, and CT is considered the one that best reflects visceral adiposity.8 Because of limitations for widespread use of CT, other methods were proposed, such as ultrasonography, which was shown to be accurate in directly measuring subcutaneous and intra-abdominal adipose tissue thickness.11 Our findings support the idea that ultrasonography could be alternatively used to estimate abdominal fat, because a strong correlation between CT and ultrasonography fat estimations was detected, as was reported previously.13 In addition, the reliability of ultrasonography estimations to predict cardiovascular disease is reinforced by its ability in identifying patients at high risk for metabolic abnormalities. Adverse metabolic profile was verified in people classified as visceral obese by any method. Anthropometric parameters continue to offer a fast, easy, and noninvasive method for assessing regional adiposity, particularly in epidemiological studies.6,7,22 However, their relatively low reproducibility may not be adequate for clinical purposes. In contrast, the ultrasonograph variation coefficient is low. In this study, the variation coefficient inter- and intra-observers were <2%, similar to those reported by others.11
In contrast to anthropometric and CT methods, cutoff values for ultrasonograph visceral fat measurements to define central obesity were not established yet. In this study, we determined such a value based on CT cutoff points of visceral fat area proposed in the literature by means of ROC curve. The nonvisceral/visceral ratio cutoff of 2.50 was shown to have high specificity but low sensitivity, particularly because our sample was consisted of obese people only.
The results obtained in this study are in agreement with others who suggested a key role for visceral fat in the genesis of insulin resistance syndrome.3,5,17,23,24 In fact, significant correlations of visceral adiposity with plasma glucose, insulin levels, and measurements of insulin sensitivity (HOMA and glucose AUC) were detected. Additionally, a worse glycemic profile among visceral obese people was observed compared with nonvisceral obese people diagnosed either by CT or ultrasonography methodology. The association of the main lipid abnormalities—low HDL cholesterol and hypertriglyceridemia—typical of the state of insulin resistance,3,4 corroborates to the proposition that ultrasonography is an accurate alternative method to estimate visceral fat. Besides higher triglycerides and lower HDL cholesterol, higher apolipoprotein B, reflecting the atherogenic small dense particles of cholesterol,25 was also observed among visceral obese group by ultrasonography, which reinforced its role in the identification of people at high risk for cardiovascular disease. Considering that exclusion criteria included diabetes and severe dyslipidemia, it is not surprising that the correlation between visceral fat and glucose and lipid assessments was rather weak.
Although some controversies may exist, epidemiological studies suggest that hyperuricemia is an independent cardiovascular risk factor.26 It has been shown to be part of the "expanded metabolic syndrome."27 In our study, visceral obese patients, identified by both CT and ultrasonograph measurements, showed higher uric acid levels, reflecting the higher degree of insulin resistance associated with visceral adiposity.
The association of visceral obesity with hypertension is well known.20,23,28 Several mechanisms, such as increased sodium reabsorption and sympathetic activity, have been proposed to explain BP elevation in obese patients.29,30 In our study, a positive correlation was found between measurements of visceral fat and systolic BP determined by ambulatory BP monitoring, although a significant difference in BP levels between visceral and nonvisceral obese patients could not be shown, possibly because both groups had patients under antihypertensive therapy. The weak but significant correlation between intra-abdominal fat and serum sodium might reflect the increased salt reabsorption associated with visceral obesity31 and insulin resistance.32
Higher heart rate among nonvisceral obese patients was not previously described. We speculate that such finding may be related to their higher leptin levels, because it is well known that leptin is mainly secreted by subcutaneous adipose tissue.33 In fact, recent evidence suggested that leptin may increase adrenergic tonus.34
In summary, our data indicate that ultrasonography is an accurate, noninvasive, reliable method for the assessment of visceral adiposity and identification of obese subjects with adverse cardiovascular profile. Further studies are needed to establish the usefulness of the ultrasonography visceral fat determination to predict cardiovascular morbidity and mortality.
Received March 28, 2001; first decision April 27, 2001; accepted May 16, 2001.
References
1. Obesity: Preventing and Managing the Global Epidemic. Geneva: World Health Organization; 1997.
2. Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Björntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13-year follow-up of participants in the study of men born in 1913. BMJ. . 1984; 288: 1401–1404.
3. DeFronzo RA, Ferraninni E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care. . 1991; 14: 173–194.[Abstract]
4. Reaven GM. Role of insulin resistance in human disease. Diabetes. . 1988; 37: 1595–1607.[Abstract]
5.
Björntorp P. Portal adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. . 1990; 10: 493–494.
6. Bray GA, Gray DS. Treatment of obesity: an overview. Diabetes Metab Ver. . 1988; 4: 653–679.
7.
Han TS, Van Leer EM, Seidell JC, Lean ME. Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample. BMJ. . 1995; 311: 1401–145.
8. Rössner S, Bo WJ, Hiltbrandt E, Hinson W, Karstaedt N, Santiago P, Sobol WT, Crouse JR. Adipose tissue determinations in cadavers: a comparison between cross-sectional planimetry and computed tomography. Int J Obes. . 1990; 14: 893–902.[Medline] [Order article via Infotrieve]
9. Williams MJ, Hunter GR, Kekes-Szabo T, Trueth MS, Snyder S, Berland L, Blaudeau T. Intra-abdominal adipose tissue cut-points related to elevated cardiovascular risk in women. Int J Obes Relat Metab Disord. . 1996; 20: 613–617.[Medline] [Order article via Infotrieve]
10. Seidell JC, Cigolini M, Charzewska J, Ellsinger BM, Deslypere JP, Cruz A. Fat distribuition in European men: a comparison of anthropometric measurements in relation to cardiovascular risk factors. Int J Obes Metab Disord. . 1992; 16: 17–22.[Medline] [Order article via Infotrieve]
11. Armellini F, Zamboni M, Rigo L, Todesco T, Bergamo-Andreis IA, Procacci C, Bosello O. The contribution of sonography to the measurement of intra-abdominal fat. J Clin Ultrasound. . 1990; 18: 563–567.[Medline] [Order article via Infotrieve]
12. Armellini F, Zamboni M, Robbi R, Todesco T, Rigo L, Bergamo-Andreis IA, Bosello O. Total and intra-abdominal fat measurements by ultrasound and computerized tomography. Int J Obes Relat Metab Disord. . 1993; 17: 209–214.[Medline] [Order article via Infotrieve]
13. Tornaghi G, Raiteri R, Pozzato C, Rispoili A, Bramani M, Cipolat M, Craveri A. Anthropometric or ultrasonic measurements in assessment of visceral fat?: a comparative study. Int J Obes Relat Metab Disord. . 1994; 18: 771–775.[Medline] [Order article via Infotrieve]
14. Suzuki R, Watanabe S, Hirai Y, Akiyama K, Nishide T, Matsushima Y, Murayama H, Ohshima H, Shinomiya M, Shirai K. Abdominal wall fat index, estimated by ultrasonography, for assessment of the ratio of visceral fat to subcutaneous fat in the abdomen. Am J Med. . 1993; 95: 309–314.[Medline] [Order article via Infotrieve]
15. Cucchi E, Piatti PM, Orena C, Pontiroli AE, Martino E, Paesano PL, Pozza G, Del Maschio A. Is echography na adequate method for assessing the thickness of intra-abdominal fat?: a comparison with computed tomography. Radiol Med. . 1997; 94: 329–334.
16. Armellini F, Zamboni M, Rigo L, Bergamo-Andreis IA, Robbi R, Marchi M, Bosello O. Sonography detection of small intra-abdominal fat variations. Int J Obesity. . 1991; 15: 847–852.[Medline] [Order article via Infotrieve]
17. Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in humam obesity. Metabolism. . 1987; 36: 54–57.[Medline] [Order article via Infotrieve]
18. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. . 1985; 28: 412–419.[Medline] [Order article via Infotrieve]
19. Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications: part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetic Med. . 1998; 15: 539–553.[Medline] [Order article via Infotrieve]
20.
Kaplan NM. The Deadly Quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med. . 1989; 149: 1514–1520.
21. Després JP, Nadeau A, Tremblay A, Ferland M, Lupien PJ. Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes. . 1989; 38: 304–309.[Abstract]
22. Pouliot MC, Despres JP, Lemieux S, Moorjani S, Bouchard C, Tremblay A, Nadeau A, Lupien PJ. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol. . 1994; 73: 460–468.[Medline] [Order article via Infotrieve]
23. Boyko EJ, Leonetti DL, Bergstrom RW, Newell-Morris L, Fujimoto WY. Visceral adiposity, fasting plasma insulin, and blood pressure in Japanese-Americans. Diabetes Care. . 1995; 18: 174–181.[Abstract]
24. Fujioka S, Matsuzawa Y, Tokunaga K, Kawamoto T, Kobatake T, Keno Y, Kotani K, Yoshida S, Tarui S. Improvement of glucose and lipid metabolism associated with selective reduction of intra-abdominal visceral fat in premenopausal women with visceral fat obesity. Int J Obes. . 1991; 15: 853–859.[Medline] [Order article via Infotrieve]
25. Lamarche B, Lemieux I, Després JP. The small, dense LDL phenotype and risk of coronary heart disease: epidemiology, pathophysiology and therapeutic aspects. Diabetes Metab. . 1999; 25: 199–211.[Medline] [Order article via Infotrieve]
26.
Fang J, Alderman MH. Serum uric acid and cardiovascular mortality: the NHANES I epidemiologic follow-up study, 1971–1992: National Health and Nutrition Examination Survey. JAMA. . 2000; 283: 2404–2410.
27. Reaven GM. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med. . 1993; 44: 121–131.[Medline] [Order article via Infotrieve]
28.
Kanai H, Matsuzawa Y, Kotani K, Keno Y, Kobatake T, Nagai Y, Fujioka S, Tokunaga K, Tarui S. Close correlation of intra-abdominal fat accumulation to hypertension in obese women. Hypertension. . 1990; 16: 484–490.
29. Landsberg L. Hyperinsulinemia: possible role in obesity-induced hypertension. Hypertension. . 1992; 19 (suppl I): I-61–I-66.
30. DeFronzo RA. Insulin and renal sodium handling: clinical implications. Int J Obesity. . 1981; 5 (suppl 1): 93–104.
31. Hall JE, Brands MW, Henegar JR, Shek EW. Abnormal kidney function as a cause and a consequence of obesity hypertension. Clin Exp Pharmacol Physiol. . 1998; 25: 58–64.[Medline] [Order article via Infotrieve]
32. Thomas GN, Tomlinson B, Chan JCN, Lee ZSK, Cockram CS, Critchley JAJH. An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome. Am J Hypertens. . 2000; 13: 745–752.[Medline] [Order article via Infotrieve]
33. Harmelen VV, Reynisdottir S, Eriksson P, Thörne A, Hoffstedt J, Lönnqvist F, Arner P. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. . 1998; 47: 913–917.[Abstract]
34. Haynes WG. Interaction between leptin and sympathetic nervous system in hypertension. Curr Hypertens Rep. . 2000; 2: 311–318.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  C. Denzer, D. Thiere, R. Muche, W. Koenig, H. Mayer, W. Kratzer, and M. Wabitsch Gender-Specific Prevalences of Fatty Liver in Obese Children and Adolescents: Roles of Body Fat Distribution, Sex Steroids, and Insulin Resistance J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3872 - 3881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Alevizaki, K. Saltiki, P. Voidonikola, E. Mantzou, C. Papamichael, and K. Stamatelopoulos Free thyroxine is an independent predictor of subcutaneous fat in euthyroid individuals Eur. J. Endocrinol., September 1, 2009; 161(3): 459 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Cascella, S. Palomba, I. De Sio, F. Manguso, F. Giallauria, B. De Simone, D. Tafuri, G. Lombardi, A. Colao, and F. Orio Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome Hum. Reprod., January 1, 2008; 23(1): 153 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Vlachos, A. Hatziioannou, A. Perelas, and D. N. Perrea Sonographic Assessment of Regional Adiposity Am. J. Roentgenol., December 1, 2007; 189(6): 1545 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-K. Kim, K.-Y. Hur, H.-J. Kim, W.-S. Shim, C.-W. Ahn, S.-W. Park, Y.-W. Cho, S.-K. Lim, H.-C. Lee, and B.-S. Cha The increase in abdominal subcutaneous fat depot is an independent factor to determine the glycemic control after rosiglitazone treatment Eur. J. Endocrinol., August 1, 2007; 157(2): 167 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Kim, H. J. Kim, K. Y. Hur, S. H. Choi, C. W. Ahn, S. K. Lim, K. R. Kim, H. C. Lee, K. B. Huh, and B. S. Cha Visceral fat thickness measured by ultrasonography can estimate not only visceral obesity but also risks of cardiovascular and metabolic diseases Am. J. Clinical Nutrition, April 1, 2004; 79(4): 593 - 599. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||