Association of waist circumference with atherogenic cardiovascular risks in centrally obese Myanmar male subjects

Background and Aim: Central obesity is a major contributor to the development of cardiovascular (CV) risks. Several atherogenic indices had been derived from lipid profiles for predicting the risk of CV disease. The present study assessed atherogenic indices as CV risk in centrally obese men. Methods: A cross-sectional comparative study was undertaken in 34 apparently healthy centrally obese (waist circumference [WC] >90 cm) and 30 nonobese (WC < 90 cm) men aged between 18 and 35 years. The plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) were determined using spectrophotometry methods. The following atherogenic indices were calculated: TC/HDL-C, LDL-C/HDL-C, and atherogenic index of plasma (AIP). Insulin sensitivity was assessed by homeostasis model assessment method of insulin resistance (HOMA-IR). Results: Atherogenic indices and HOMA-IR values increased significantly in the centrally obese subjects than that of nonobese subjects. There was a significant positive correlation between WC and LDL-C/HDL-C ( r = 0.46, P < 0.01), TC/HDL-C ( r = 0.51, P < 0.01) and AIP ( r = 0.66, P < 0.001). Among them, AIP has the strongest and most significant correlation with WC. The risk of developing CV disease (AIP > 0.1) among centrally obese male subjects is 11.72 times (adjusted odds ratio = 11.72; 95% confidence interval = 1.84-72.81) greater than that of nonobese subjects. AIP can only express the association between (HOMA-IR > 2.52) and CV risk (AIP > 0.1) in central adiposity. Conclusion: AIP is a better indicator of CV risk than other previously used lipid parameters in centrally obese Myanmarese.

Association of waist circumference with atherogenic cardiovascular risks in centrally obese Myanmar male subjects INTRODUCTION Cardiovascular (CV) diseases are among the major leading causes of death worldwide. Dyslipidemia is recognized as prominent risk factor for the development of CV disease, [1] which may be primary or associated with hypertension, diabetes mellitus and obesity. Dyslipidemia considering the presence or absence of other important risk factors such as family history of early CHD, age, smoking, hypertension, diabetes mellitus, low physical activity, and obesity. LDL-C/HDL-C ratio is often calculated to estimate CV disease risk. Further, results of the prospective studies [7,8] have suggested high LDL-C/HDL-C ratio in combination with hypertriglyceridemia to be associated with high CV disease risk. This dyslipidemic state (lipid triad) has been described as atherogenic dyslipidemia. [9] On the other hand, it is reported that the LDL-C/HDL-C ratio may underestimate the magnitude of the dyslipidemic state in these patients since there is more cholesterol in the very low density lipoprotein fraction in individuals with elevated TG concentrations. Therefore, a risk assessment for CV disease is alternatively given by comparing the TC to HDL-C ratio (TC/HDL-C). [10] Atherogenic index of plasma (AIP) is based on the ratio of the values of TG to HDL-C levels, calculated according to the formula (AIP = Log [TG]/[HDL-C]) where both TG and HDL-C are measured in plasma and are expressed in molar concentration. TG and HDL-C reflect the balance between the atherogenic and protective lipoproteins. High serum TG level stimulates the activity of hepatic lipase, which results in the increase of HDL-C catabolism (degradation of HDL-C). Each degradation of 1 mg HDL-C will correlate with 2% increase in the risk CHD. [11,12] AIP value <0.1 in young children and increases up to 0.4 in men and subjects with other CV risk factors such as hypertension, diabetes and dyslipidemia. Indeed, it has been suggested that AIP values of <0.1 are associated with low risk, 0.1-0.24 with medium risk and above 0.24 with high CV risk. [13] Although several consensus documents have been reported, [3][4][5][6][7][8][9][10][11][12][13] there is no universal acceptance of how this information should be used and interpreted. Recently, Khazaál [14] studied 119 males with an established diagnosis of acute myocardial infarction and has concluded AIP as an index of highest sensitivity for predicting the acute coronary events. Although this AIP has been used to predict the risk of atherosclerosis in postmenopausal women, [15] type 1 and type 2 diabetes mellitus, beta-thalassemia, hypothyroidism [16] and chronic renal failure, [17] there is paucity of literature on its application to obese subjects especially in Myanmarse population. Therefore, the aim of this study was to assess atherogenic indices in centrally obese men compared with nonobese men. This study also determined the association between atherogenic indices and insulin resistance assessed by homeostasis model assessment of insulin resistance (HOMA-IR).

Subject selection
This was a cross-sectional study in which a total of 64 apparently healthy male medical students and teaching staff (between 18 and 35 years of age) from the University of Medicine 2, Yangon were recruited. History taking and clinical examination including anthropometric measurement was carried out. Healthy subjects without family history of diabetes mellitus, history of chronic smoking and alcohol drinking were included in the study. A written informed consent was obtained from all subjects individually. Anthropometric data such as height, weight, waist circumference (WC) and hip circumference were taken from all subjects. Those with WC <90 cm were selected for the control group and those with WC >90 cm were selected for centrally obese group.

Measurement of biochemical variables
Fasting blood sample (10 ml) was obtained from the antecubital vein and collected in two separate blood collecting tubes. 1 ml of blood was collected in tube containing 10 mg of sodium fluoride for determination of blood sugar and 9 ml of blood in another tube for serum separation. After the collection of blood sample, serum was promptly separated and stored at (−20°C) until the blood sample analysis. Fasting blood glucose was measured by glucose oxidase method (Glucose Liquicolor, Human, D-65205 Wiesbaden, Germany) and serum insulin level was measured by Insulin ELISA (DSL-10-1600, Diagnostic System Laboratories, Inc., Texas, USA) kit method. Insulin sensitivity was calculated by following formulas. [18] HOMA-IR = Insulin (µIU/mL) × glucose (mmol/L)/22.5 Reference interval of HOMA-IR has been established between 0.4 and 2.4, and HOMA-IR value > 2.5 is considered as insulin resistance. [19] TC and TG were assayed by enzymatic colorimetric test kits (Pars Azmoon Inc.,) and HDL-C was measured after precipitation of the apolipoprotein B-containing lipoproteins with phosphotungstic acid. LDL-C was calculated from serum TC, TG and HDL-C using the Friedewald formula. [20] The atherogenic indices were calculated as TC/HDL-C, LDL-C/HDL-C, and AIP. [11] Statistical analysis of data The data were expressed as mean ± standard deviation. The statistical analysis was performed with SPSS version 16 (SPSS Software Inc., Chicago, IL, USA). Comparison of the diabetes-related parameter, lipid parameter and atherogenic indices between nonobese and centrally obese groups was done by unpaired Student's t-test. Skewed data were computed by nonparametric tests, (Mann-Whittney Signed-Rank test). Correlation studies were done by Pearson's correlation. Chi-squared test was used to determine whether there is a significant association between the insulin resistance and CV risk. Differences were considered significant when P < 0.05. Table 1 shows the baseline characteristics of subjects participated in this study. Comparison of lipid parameter and atherogenic indices between centrally obese group and non obese group were shown in Table 2. Value of fasting blood glucose, fasting serum insulin and insulin resistance (HOMA-IR) were significantly higher in the centrally obese group compared to the non-obese group [ Table 2]. Table 3 depicts the correlation between WC, HOMA-IR, lipid profile and atherogenic indices. Figure 1 depicts the HOMA-IR score in low, medium and high risk of CV disease. There is a significant association (P < 0.001) between HOMA-IR (insulin sensitive < HOMA-IR 2.5, insulin resistance > HOMA-IR 2.5) and CV risk assessed by AIP (0-0.1 low risk, 0.1-0.24 medium risk and >0.24 high risk).

DISCUSSION
There is a growing body of evidence suggesting that abdominal adiposity rather than general adiposity is a more important risk factor for CV and metabolic disease. [11,21] The intra-abdominal visceral deposition of adipose tissue assessed by WC is a major contributor to the development of hypertension, elevated plasma insulin concentrations and insulin resistance, hyperglycemia and hyperlipidemia (metabolic syndrome). [22,23] According to the international obesity task force reference, overweight is defined as a body mass index (BMI) ≥23, and the recommended WC cutoffs are 90 cm for men and 80 cm for women among Asian populations [24] Therefore, in the present study, WC and BMI of the participants were assessed by Asian criteria.
In the present study, the centrally obese subjects have elevated TC, TG and LDL-C and low levels of HDL-C. The present findings were consistent with previous studies. [25,26] The atherogenic indices TC/HDL-C, LDL-C/HDL-C (P < 0.01) and AIP (P < 0.001) were found to be significantly increased in the centrally obese group.In addition, the present study also observed that WC was significantly and positively correlated with AIP (r = 0.66, P < 0.001), TC/HDL-C (r = 0.51, P < 0.01) and LDL-C/HDL-C (r = 0.46, P < 0.01). These findings contribute to the development of atherosclerosis, which are among the CV risks in centrally obese subjects. It was noted that CV risk, as assessed by atherogenic indices, increase significantly with a degree of the visceral fat deposition, which is expressed by WC. Among three atherogenic indices studied in the present study, it was found that AIP has the strongest and most significant relationship with WC. These findings also tend to strengthen the link between CV risk and visceral adiposity.
In the present study, it was found that 24 out of 64 subjects (37.5) were low risk, 9 out of 64 subjects (14%) were medium risk and 31 out of 64 subjects (48.5) were high-risk. The risk of developing CV disease in centrally obese male subjects is 11.72 times (age, smoking and physical activity adjusted odds ratio = 11.72; 95%     Several mechanisms whereby insulin resistance could cause an alteration in lipid metabolism have been described. Hyperinsulinemia is known to enhance hepatic fatty acid esterification, which forms TG, thus may directly contribute to the increased plasma TG. [27] Resistance to the action of insulin on lipoprotein lipase in peripheral tissues may also contribute to elevated TG. [28,29] Moreover, elevated serum TG level also stimulates the activity of hepatic lipase, which results in the increased rate of HDL-C degradation. [30] Accordingly, present study showed that HOMA-IR was significantly and positively correlated with AIP, but not with LDL-C/HDL-C and TC/HDL-C. In addition, it was also noted that high CV risk (AIP > 0.24) was significantly associated with insulin resistance (HOMA-IR > 2.5). Among three atherogenic indices studied in the present study, AIP can only express the linkage between CV risk and development of insulin resistance in centrally obese male subjects.

Limitations of the study
Since dyslipidemia in centrally obese male subjects in the present study are indicative of their susceptibility to atherosclerosis and other CV disorders, a follow-up of these subjects should have been done to find whether, they develop CV diseases in their later life. Future longitudinal studies should be carried out to detect the development of atherosclerosis and CV disease in dyslipidemic subjects.

CONCLUSION
Present study demonstrated decreased insulin sensitivity and dyslipidemia in centrally obese subjects compared to nonobese subjects. Atherogenic indices can significantly add value in assessing the CV risk in centrally obese men. Increasing AIP value was found to be associated with increasing HOMA-IR score in centrally obese subjects. It indicated that the degree of the visceral adiposity seems to worsen insulin resistance and enhance CV risk. The present result also suggests that AIP should be used as a standard risk assessment for CV disease.

ACKNOWLEDGMENTS
We are immensely grateful to all subjects who volunteered to participate in this study.