Abstract
Objective:
Recent observational studies have reported that body fat distribution might be differentially associated with subclinical atherosclerosis. We previously reported that visceral fat area (VFA) ⩾80 cm2 is the optimal cutoff for identifying abdominal obesity in Chinese subjects. We examined whether VFA ⩾80 cm2 reflects the association between abdominal obesity and subclinical atherosclerosis, and if determination of the visceral fat quantity is useful for assessing subclinical atherosclerosis in asymptomatic individuals.
Methods and results:
Participants (N=1005, men 515, women 490, 34–66 years) free of cardiovascular disease underwent magnetic resonance imaging and carotid ultrasound assessment to quantify VFA and carotid intima–media thickness (C-IMT). Overweight/obese subjects (body mass index (BMI) ⩾25.0 kg m−2) had a higher C-IMT than lean subjects (BMI <25.0 kg m−2) (P<0.01). Subjects with VFA ⩾80 cm2 had significantly higher C-IMT than those without abdominal obesity regardless of BMI (P<0.01). By multivariate regression analysis adjusted for anthropometric measurements and cardiovascular risk factors, waist circumference but not BMI was independently correlated with C-IMT in men (P<0.001). Similar findings were observed with an accurate obesity indices adjusted model, which showed that VFA was an independent risk factor for increased C-IMT in men but not in women.
Conclusions:
VFA ⩾80 cm2 effectively identified carotid atherosclerosis for both lean and obese individuals in middle-aged Chinese men.
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Introduction
Obesity is a global epidemic and is strongly associated with metabolic disorders and cardiovascular disease (CVD).1 The relationship between obesity and CVD depends not only on the amount of total body fat but also on its distribution.2, 3, 4 In recent years, increasing evidence has shown that, compared with total body fat, visceral fat accumulation is more important for the development of insulin resistance, metabolic syndrome (Mets), type 2 diabetes and CVD.5, 6, 7, 8 Abdominal obesity is considered a fundamental pathology for Mets development, which is associated with increased risk of cardiovascular morbidity and mortality.9, 10
Most studies use waist circumference or waist-to-hip ratio to define abdominal obesity.2, 3, 4, 7, 8 However, measurement of these circumferences cannot distinguish between visceral and subcutaneous adipose tissue. The standard methods for quantifying visceral fat amount recommended by the International Diabetes Federation (IDF) are magnetic resonance imaging (MRI) and computed tomography.11 We previously reported that for a Chinese population, visceral fat area (VFA) ⩾80 cm2 is optimal for detecting two or more metabolic abnormalities. These include hyperglycemia, hypertension and dyslipidemia, using the IDF definition or the 2004 Chinese Diabetes Society definition.12 Whether VFA ⩾80 cm2 reflects an association between abdominal obesity and subclinical atherosclerosis is still unknown. Moreover, to our knowledge, no study has focused on the association between visceral fat amount and the extent of subclinical atherosclerosis in various body mass index (BMI) categories in a Chinese population.
Quantitative assessment of carotid intima–media thickness (C-IMT) is accepted as an indicator of preclinical atherosclerosis and may be used as a marker for cardiovascular mobidity and mortality.13, 14 Therefore, the aims of this study were to: (1) determine if visceral fat accumulation was a stronger risk factor of subclinical atherosclerosis than general obesity in a Chinese population; (2) evaluate whether VFA ⩾80 cm2 was the optimal value to reflect the association between abdominal obesity and subclinical atherosclerosis in both lean and overweight/obese subjects and (3) investigate if visceral fat quantity is useful for assessing subclinical atherosclerosis in asymptomatic individuals.
Subjects and methods
Subjects
A total of 1217 subjects, aged 30 to 70 years, were recruited from December 2009 to June 2010 in Baoshan community, Shanghai, China. The exclusion criteria were: (1) current treatment with systemic corticosteroids; (2) cirrhosis with ascites; (3) known hyperthyroidism or hypothyroidism; (4) presence of cancer; (5) severe disability and psychiatric disturbance; (6) pregnancy and (7) known history of CVD. The excluded were 182 with no MRI data, 3 with no carotid artery scans, 16 with incomplete anthropometric indices and 11 with incomplete lab data or C-reactive protein (CRP) ⩾10 mg l−1. We finally analyzed data from 1005 subjects (men 515, women 490) aged 34–66 years in this study.
All participants were invited to complete a questionnaire about present and past illness and medical therapy. The study was approved by the Ethics Committee of Shanghai Jiaotong University affiliated Sixth People's Hospital. Written informed consent was obtained from all the participants.
Clinical and laboratory assessments of risk factors
A physical examination, including measurement of height, weight, waist circumference (W) and blood pressure (BP), was performed for each participant. BMI was calculated as weight in kilograms divided by the square of height in meters. W was measured at the horizontal plane between the inferior costal margin and the iliac crest on mid-axillary line. Body fat percentage (%fat) was estimated by the TBF-410 Tanita Body Composition Analyzer (Tanita, Tokyo, Japan). BP was the average of three time measurements using a sphygmomanometer at an interval of 3 min.
After a 10-h overnight fast, blood samples were collected to measure plasma glucose level and lipid profile. Subjects without a validated history of diabetes underwent a 75-g oral glucose tolerance test. The 100-g carbohydrate (steamed bread meal) test was performed in diabetic patients.15 Fasting plasma glucose (FPG) and 2-h post-OGTT plasma glucose (2hPG) were assayed by the glucose oxidase method. Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were measured by enzymatic procedures using an autoanalyzer (Hitachi 7600-020, automatic analyzer, Tokyo, Japan). Glycated hemoglobin A1c (HbA1c) was determined by high-pressure liquid chromatography (Bio-Rad Inc., Hercules, CA, USA). The serum concentration of CRP was measured by particle-enhanced immunonephelometry using CardioPhase hs-CRP reagent (Siemens Healthcare Diagnostic Inc., Newark, NJ, USA). The detection limit of the assay was 0.175 mg l−1. The intra-assay coefficients of variation for hs-CRP levels were 2.3%, 4.6%, 2.6% and 2.1% at 0.69, 5.95, 9.23 and 179 mg l−1, respectively; inter-assay coefficients of variation were 2.3%, 4.0%, 1.3% and 1.1% at 0.69, 5.95, 9.23 and 179 mg l−1. Serum insulin concentration was measured by radioimmunoassay (Linco Research, St Charles, MO, USA). Insulin sensitivity was estimated by homeostasis model assessment-insulin resistance (HOMA-IR) based on fasting glucose and insulin measurements as follows: HOMA-IR=fasting serum insulin (mU l−1) × FPG (mmol l−1)/22.5.16 BMI ⩾25.0 kg m−2 was defined as overweight/obesity according to the World Health Organization criterion.15 The diagnostic definition for Mets followed the 2007 Joint Committee for Develo** Chinese Guidelines on prevention and treatment of dyslipidemia definition,26 we performed separate multiple stepwise regression analyses for men and women, adjusting for menopausal status in women. We found that obesity indices reflecting visceral rather than general obesity were associated with C-IMT, mainly in men. Although the correlation weakened after adjustment for other traditional cardiovascular risk factors and other obesity indices, W and VFA were still independent risk factors for increased C-IMT in men. These results might be explained by an association between adiposity and subclinical atherosclerosis mediated by CVD risk factors that are likely to be in a causal pathway from visceral fat accumulation to CVD.22, 27 As all the obesity measures of BMI, W, %fat, VFA and SFA were highly correlated with each other, the attenuation of associations by multivariate adjustment is understandable.28 Our findings are consistent with several studies that also reported a positive correlation of C-IMT to visceral fat accumulation.29, 30
Previous publications describe a possible role for visceral fat accumulation in atherosclerosis development. Ryuichi et al.31 found a graded and independent association between visceral obesity evaluated by B-mode ultrasonography and C-IMT in subjects aged ⩾50 years with a BMI ⩾23.0 kg m−2. Kim et al.,32 found that visceral fat amount was associated with carotid atherosclerosis in type 2 diabetic men with a normal W. However, we could not compare these findings directly with ours because of the indirect measurement of visceral fat and differences in study subjects. Our investigation suggested that subjects defined as not obese by BMI had increased C-IMT because some individuals were prone to visceral fat accumulation for a given BMI. Some people with higher BMI but a lower quantity of visceral fat might be categorized as high-risk obese subjects, even though they actually have a lower C-IMT and are at a low risk for metabolic complications.
Although a cause–effect relationship has not been established, possible mechanisms responsible for the relationship between visceral fat accumulation and subclinical atherosclerosis are as follows. Obesity is considered to be a chronic inflammation state, in which the excess accumulation of visceral adipose tissue has a central role.33 In this study, we also observed that CRP, a plasma marker of chronic low-grade inflammation, was significantly increased in subjects with abdominal obesity and correlated with C-IMT. However, this association was abolished in multivariable regression analysis after adjustment for parameters related to adiposity, insulin resistance, glucose and lipid metabolism. A possible explanation is that traditional cardiovascular risk factors display stronger pro-atherosclerotic effects than CRP. It is also possible that the relationship between CRP and atherosclerosis is mediated by abdominal obesity. In addition, visceral fat accumulation may be related to insulin resistance of the liver.34 East Asians are prone to have more visceral fat than people of European descent with the same BMI.35 Our results further demonstrate that the Chinese men show a greater propensity to develop CVD at a relatively low BMI.
The limitations of this study included the study population of primarily middle-aged Chinese, limiting the generalizability of our findings to other ethnic and age groups. The sample size of women, especially postmenopausal women, might not have been large enough for us to detect the contribution of visceral obesity to carotid atherosclerosis. Large population-based studies are required to confirm this association. Furthermore, the cross-sectional design precluded any inference of a casual relation between VFA, BMI and C-IMT. Future cardiovascular events and mortality should be recorded in well-controlled, prospective studies.
In conclusion, we investigated the association between VFA and C-IMT stratified by BMI. VFA positively correlated with C-IMT in a middle-aged Chinese population. VFA ⩾80 cm2 was effective for identifying carotid atherosclerosis for both lean and generally obese men.
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Acknowledgements
This work was funded by Chinese National 973 Project (2007CB914702), National Key Technology R&D Program of China (2009BAI80B01), the Shanghai United Develo** Technology Project of Municipal Hospitals (SHDC12010115), Major Program of Shanghai Municipality for Basic Research (08dj1400601) and Project of National Natural Science Foundation of China (81170788).
Author contributions
Y Bao and W Jia conceived and designed the study. X Ma, Y Wang, M Zhou, W Zong and Y Hao recruited the samples. X Ma, Y Wang and M Zhou did the statistical analyses. J Zhu and D Li performed the carotid artery ultrasound scans. Y **ao performed the MRI scans. X Ma and Y Wang wrote the first draft of the paper. X Ma, Y Wang, M Zhou, Y Bao and W Jia revised the paper and contributed to the discussion. M Zhou, L Zhang and W Zong provided the technical support. Y Wang and X Ma contributed equally to this work and are the guarantors.
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Wang, Y., Ma, X., Zhou, M. et al. Contribution of visceral fat accumulation to carotid intima–media thickness in a Chinese population. Int J Obes 36, 1203–1208 (2012). https://doi.org/10.1038/ijo.2011.222
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DOI: https://doi.org/10.1038/ijo.2011.222
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