Relationship between C-reactive protein and the metabolic syndrome in overweight and obese patients
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《中华医药杂志》英文版 2006年第3期
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[Abstract]ObjectiveTo analyze the potential interrelationships between C-reactive protein(CRP) and the metabolic syndrome in the group of overweight and obese patients. MethodsCross-sectional study of the patients (N=182) who referred to the Dietetic Unit of the Belgrade Medical Faculty. A battery of risk factors and other variables were assessed which allowed classification of patients in obese (BMI≥30 )and non-obese (BMI<30) and those with [metabolic syndrom (Met Sy) present] and without the metabolic syndrome (Met Sy absent) on the basis of NCEP III criteria. ResultsThe prevalence of Met Sy was the highest in those with abdominal obesity (UPBO) with 46.9 % and the lowest in those with lower part body obesity (LPBO) with just two patients (3.6%) being diagnosed with metabolic syndrome. Significant differences in CRP levels emerged as a function of metabolic syndrome presence and type of body fat distribution. Metabolically unhealthy patients, those with Met Sy have statistically higher concentration of CRP (4.8±0.5 mg/L) compared to all others, Met Sy absent (2.9±0.3 mg/L), (P=0.0001). When distribution on the basis of CRP levels less than or greater than 3.0 mg/L, was assessed by Pearson Chi-Square across different categories, the highest prevalence of those with CRP>3mg/L was among patients with Met Sy, 62.3 % and the lowest among those with LPBO with 29.3 %. ConclusionsThe results obtained in this study show that abdominal obesity is the most prevalent component of the Met Sy which is on the other hand followed by increased levels of CRP. CRP levels should be detected in all obese patients, specially those with abdominal obesity to identify subjects at higher risk for atherosclerotic disease.
[Key words]C-reactive protein;metabolic sydrome;abdominal obesity
INTRODUCTION
Obesity is becoming common worldwide, both in developed and in developing countries averaging 12%~15% of total population. And even more, obesity can be seen as an underlying risk factor of atherosclerotic cardiovascular disease, as that is the foremost physical consequence of an excess of body fat[1].
It is also accompanied by several other risk factors such as hypertension, hyperglycaemia, and dyslipidemia, insulin resistance, better known as metabolic syndrome(Mes Sy). Recently the National Cholesterol Education Program Adult Treatment Panel Ⅲ(NCEP/ATP Ⅲ) report proposed a simple scheme for the routine diagnosis of metabolic syndrome including the presence of at least 3 of the following characteristics: abdominal obesity, elevated triglycerides, reduced levels of HDL cholesterol(HDL-C), high blood pressure, and high fasting glucose[2].
In 1997, it was first shown that by measuring C-reactive protein(CRP) in healthy individuals, physicians could predict the onset of future cardiovascular death independently of traditional cardiovascular risk factors[3]. It is a part of the concept according to which atherogenesis represents a state of chronic inflammation. Results obtained in last decade showed elevated levels of CRP in obesity particularly those with the metabolic syndrome, and Ridker has proposed CRP to be included in the definition of metabolic syndrome[4]. In 2003 the American Heart Association (AHA) and the US Centre for Disease Control and Prevention (CDC) issued joint clinical guidelines for the use of CRP[5], as a new option for risk detection.
Therefore this paper was aimed to evaluate the potential interrelationships between CRP and the metabolic syndrome in a group of patients with large range of body mass index(BMI), divided into non-obese and obese group.
METHODS
Patients
In first three months of 2004, 250 consecutive patients were referred to the outpatient Dietetic Unit for dietetic advice or nutritional medical therapy. Patients with eating disorders (anorexia nervosa and bulimia nervosa) and self-reported diabetes were excluded from the study. Thus, 182 patients were considered in the analyses. Of these, 151 were females [mean age (43.2 ± 1.0) years; mean BMI (33.3 ± 0.4) kg/m2], and 31 males [mean age (42.0 ± 2.2) years; mean BMI (33.1 ± 0.8) kg/m2]. According to WHO criteria, they were classified as non-obese (BMI<30 kg/m2), and obese (BMI≥30 kg/m2). According to NCEP/TP Ⅲ, patients were classified as having metabolic syndrome if they fulfilled 3 or more criteria: (1) triglycerides ≥1.7 mmol/L; (2) HDL-C < 1.0 mmol/L (men) and <1.3 mmol/L (women); (3) blood pressure ≥135/85 mm Hg; (4) obesity as defined by a waist circumference >102 cm (men) and >88 cm (women); and (5) abnormal glucose metabolism as defined by a fasting glucose ≥6.1 mmol/L. Seventy-one (39%) of all patients were diagnosed as having metabolic syndrome (10 from non-obese group，14.5%) and designated as Met Sy present, and all others were designated as Met Sy absent.
The study was reviewed and given ethical approval by the Ethics Committees at School of Medicine in Belgrade. All patients gave written, informed consent.
Anthropometric Parameters
Body weight was assessed by using a calibrated standard balance-beam, height was measured by a standard height bar, and BMI was calculated as weight (kg) divided by height (m2) and categorized according to WHO criteria[6].Waist circumference was measured at the midway between lower rib and crista illiaca, and according to WHO criteria[6],all patients were classified in upper part body obesity (UPBO) defined by a waist circumference >102 cm (men) and >88 cm (women), and lower part body obesity (LPBO). Body fat was calculated according to method proposed by Durnin and Womersley[7].
Cardiovascular Risk Factors
Blood pressure measurements were done by using appropriately sized cuffs and auscultatory method recommended by Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[8].
For estimation of metabolic parameters, blood glucose (FBG) and lipoproteins, blood samples were obtained after an overnight fast. Levels of FBG, total cholesterol (TC), serum triglycerides (TG), HDL-C and low-density lipoprotein cholesterol (LDL-C) were estimated using commercial kits (Abbot, IL,USA) on an automated analyzer (AEROSETTM, Abbot, IL, USA).
Levels of CRP were measured by using immunoturbidimetric fixed time test (Olympus Diagnostics, O`Callaghan’s Mills Co. Clare, Ireland). According to the manufacturers, the normal CRP concentration using this assay ranged from 0.00~5.00 mg/L, the lowest detectable limit being 0.00 mg/L.
Statistical Analysis
Data were analyzed by using SPSS package version 9. Significance level was set at P<0.05.
Analysis of variance were performed by employing multivariate MANOVA procedures for related areas of dependent variables. Pearson’s r was used for correlations and chi-square for the comparison of frequencies across categories. Finally, multiple regressions analysis were employed with CRP assigned as the dependent variable.
RESULTS
Demographic, clinical and biochemical characteristics of all subjects, by gender and the presence/absence of the Met Sy are showed in Table 1.
Table 1 Characteristics of the Study Population by Gender and Metabolic Syndrome Status(x±s)
Notice:ns means no significence
According to gender, there were no signifficant differences in age, BMI, arterial blood pressure, TC, LDL-C and in CRP levels. Men had higher waist circumference [(109.9±2.0) cm vs (98.5±1.0) cm，P<0.0001], triglycerides [(1.0±0.2) mmol/L vs (1.5±0.1) mmol/L，P=0.041], and fasting glucose [(5.8±0.6) mmol/L vs (5.1±0.1) mmol/L，P=0.038]. As expected, women had higher percent of body fat [(39.6±0.4)% vs (31.1±0.9)%,P<0.0001], and HDL-C [(1.3±0.0)mmol/L) vs (1.1±0.1) mmol/L,P<0.0001].
The analyses done according to the presence of Met Sy revealed the significant differences in all studied parameters, with the exception of %F (Table 1). Using the NCEP/ATP Ⅲ criteria the overall frequency of the Met Sy was 39.0% (Table 2), with no differences between men and women. When frequencies of the components of metabolic syndrome were tested, no difference was observed in any of them: abdominal obesity, high blood pressure, high fasting glucose, high triglycerides and low HDL-C, although men showed higher frequency in all of these. The distribution of number of Met Sy components was as follows: 15 (8.2%) with none, 37 (23%) with one component, 59 (32.4%) with two components, and 71 (39.0%) with three or more components.
Table 2 Frequencies of Metabolic Syndrome and its Components by Gendern(%)
As expected, CRP levels were significantly higher in those with Met Sy in all studied subjects (F=13.40，P<0.0001). There was increase in CRP levels from (3.1±0.8) mg/L in those without any component of Met Sy to (4.8±0.5) mg/L in those with three or more components. Also, CRP levels in women with Met Sy were significantly higher than in those without Met Sy (F=12.16，P=0.001). The same trend was recorded in BMI. The significant difference in BMI was found in female subjects (F=7.03，P=0.009) and in the group as a whole (F=8.93，P=0.003). The increase in BMI has been found in female subjects (Table 3).
Table 3 BMI and CRP Values by Gender and Metabolic Syndrome Components(x±s)
Notice:Compared with none and 1~2,△P<0.05;Compared with none,#P<0.05;Compared with 1~2 and>3,**P<0.05
CRP levels according to the presence or absence of each Met Sy component by gender are displayed in Table 4. Higher CRP levels were observed in those with abdominal obesity when compared to those without abdominal obesity (P=0.022). No significant difference in CRP levels were found according to the presence of other components. The linear regression model included CRP as dependent variable and gender, abdominal obesity, high blood pressure, high fasting glucose, high fasting triglycerides, low HDL-C, Met Sy, as predictors, has emerged as significant (F=3.21，P=0.003). The two variables that contributed significantly to the model were: Met Sy and abdominal obesity with 26% (Beta=0.26) and 18% (Beta=0.18).
Table 4 CRP Levels by Gender according to Each Metabolic Syndrome Component(x±s)
Notice:*gender
The highest CRP levels were observed in those Met Sy cases of abdominal obesity, specially in female [(5.2±0.6) mg/L vs (2.4±0.0) mg/L). Women with abdominal obesity were shown significantly higher CRP levels (F=9.99，P=0.002). Also, the same trend was observed in the women with Met Sy (F=12.16，P=0.001). Men didn’t show this difference, regardless of abdominal obesity and Met Sy (Table 5).
Table 5 CRP and BMI according to the Presence of Abdominal Obesity and Metabolic Syndrome in the Study Population(x±s)
Notice:Compared with Ao groups*P<0.05;Compared with no Met Sy groups△P<0.05
Using Pearson’s correlation several factors were examined to determine factors associated with CRP level. CRP correlated with BMI (r=0.18;P=0.013), waist circumference (r=0.18;P=0.017), and percent of body fat (r=0.18;P=0.013) in all study subjects. The same relationship was evident only in women (Table 6).
Table 6 Pearson Correlation Coefficients of C-Reactive Protein Levels with Selected Variables by Gender
The frequency of the high risk CRP group (CRP cut off 3mg/L) was the highest among overweight patients diagnosed with Met Sy (63.2%). Both abdominal obesity and BMI ≥30 kg/m2 were significant factors which caused high CRP level; 54.7% subjects with abdominal obesity and 53.5% subjects with BMI ≥30 kg/m2 had CRP higher than 3mg/L. Opposite to that, the frequency of high CRP values among overweight subjects with preferal type of body distribution (non-abdominal) was less than 30% (29.3%)(Figure 1).
Pearson Chi-Square (182,1) = 1.01; ns(BMI≥30 vs BMI<30)；Pearson Chi-Square (182,1) = 10.01; P=0.001(UPBO vs LPBO)；Pearson Chi-Square (182,1) = 6.39;P=0.011(Present vs. Absent)
Figure 1 Distribution(%)according to CRP categories [<3 mg/L or >3 mg/L] in observed subgroups
DISCUSSION
This study included 182 patients: 151 females, who were slightly older than 31 males, but these difference was not statistically significant. The results of this cross-sectional study have pointed out that the abdominal obesity is the most common component of the Met Sy. And above that, subjects with abdominal obesity and Met Sy have the highest CRP levels.
There are some studies suggesting that obesity may result in low grade inflamation, and indicating that CRP levels tend to be higher in women than in men, which may put women at higher risk[9]. In our study female had higher mean value than men [(3.67±3.50) mg/L vs (2.98±3.04) mg/L] but this difference was not significant. Altough there is small number of studies investigating the relationship between gender and CRP, some authors explained this difference by the fact that women have higher percent of body fat compared to men and larger subcutaneous fat depots, whereas men have larger intra-abdominal fat depots[10]. Second, some authors suggested that intra-abdominal or visceral fat depots have the strongest impact on inflamatory markers[11]. Third, sex hormones could influence levels of inflamatory markers in women. In the cross-sectional Kooperative study Gesund-heitsforschung in der region Augsburg-Cooperative Research in the region of Augsburg (KORA study) on 4 261 men and women between 25 and 74 years of age,have observed higher levels of CRP in women compared to men[9].
Abdominal obesity was the most important component of the Met Sy associated with increased CRP levels. In fact, abdominal obesity, expressed as waist circumference, was the single most important determinant of CRP levels.Elevated CRP in the presence of the Met Sy may reflect cytokine production by adipocytes[12], because IL-6 and CRP levels are closely related, particularly in obese subjects.Even though, Danesh et al[13] have shown strong relationship between abdominal obesity and Met Sy, they didn’t found relationsheep with other components of the Met Sy.
We found a higher value of CRP levels in subjects with increased abdominal obesity, blood pressure, fasting glucose and triglycerides, and low HDL-C. Our results are similar to other cross-sectional study[14]. In the study of 201 normal weight, overweight and obese subjects,Pannacciulli et al[15] shown an independent relationship of abdominal obesity with CRP. Also, we found that CRP levels were significantly higher in subjects with Met Sy, and that the number of metabolic features follow increasing CRP levels. Many studies shows that the components of the Met Sy and the Met Sy are associated with parameters of inflamation, such as CRP level[16].Festa et al[16] showed in the Insulin Resistance Atherosclerosis Study (IRAS) increasing CRP levels followed with number of metabolic disorders, which pointed a significant difference between all parameters except subjects with 3 and 4 features. Also, in a large population sample, which included 747 men and 956 women, Frhlich et al[17] reported that CRP values clearly increase with the number of manifestations of the Met Sy. CRP values were nearly twice as high in subjects with several components compared with those without it. Florez et al[18] have showen in their study of 190 subjects that the increase in CRP levels follow the numbers of metabolic syndrome components.
In the present study we observed that the nutritional state expressed as BMI increase with increasing components of Met Sy. Recent analyses from the NHANES Ⅲ database showed that when subjects (14 924) are stratified by BMI and waist , those with highest waist values were increasingly more likely to have components of Met Sy than those with lowest waist circumference[19].
Some studies evaluated the relationship between CRP, the Met Sy and the incidence of cardiovascular diseases (CVD) over an 8-year period of follow up[20]. In this study women with the Met Sy showed a 4- and 2.6-fold increase in the risk for CVD depending on whether CRP levels were over or under the cut-off 3 mg/L, when compared to those without Met Sy and lower CRP levels (<3 mg/L). The fact is that higher CRP levels were associated strongly with abdominal obesity in our study, but this is not enough for the prognosis for future cardiovascular events.
CONCLUSION
The results obtained in this study show that abdominal obesity is the most prevalent component of the Met Sy which is on the other hand followed by increased levels of CRP.
Obesity defined as BMI ≥30 kg/m2 is also significant factor which caused high CRP level. This suggests a potential role of obesity, especially abdominal obesity in the development on the inflamation associated with the metabolic syndrome initially and later cardiovascular and cerebrovascular events. CRP levels should be detected in all obese patients, specially those with abdominal obesity to identify subjects at higher risk for atherosclerotic diseases.
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3. Ridker PM, Cushman M, Stampfer MJ,et al.Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med,1997,336(14): 973-979.
4. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation,2003,107: 363-369.
5. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease. Application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation,2003,107(3): 499-511.
6. World Health Organization. Obesity:Preventing and Managing the Global Epidemic. Geneva:WHO, 1998.
7. Durnin JVGA, Womersley J. Body Fat assessed from Total Body Density and its Estimation from Skin fold Thickness; Measurements on 481 Men and Women Aged from 16 to 72 Years. Brit J Nutr,1974,32: 77- 97.
8. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension,2003,42: 1206-1252.
9. Thorand B, Baumert J, Dring A,et al. Sex differences in the relation of body composition to markers of inflammation. Atherosclerosis,2006,184: 216-224.
10. Thomas GN, Zhao HL, Ma YQ, et al. Relationship between obesity and cardiovascular risk factors in elderly Chinese subjects. Chinese Medical Journal,2002,115(6): 897-899.
11. Forouhi NG, Sattar N, Mckeigue PM. Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians. Int J Obes,2001,25: 1327-31.
12. Yudkin JS, Stehouwer CDA, Emeis JJ,et al.C-reactive protein in healthy subjects: associations with obesity, insulin resistance and endothelial dysfunction. A Potential Role for Cytokines Originating From Adipose Tissue. Arterioscler Thromb Vasc Biol,1999,19: 972-978.
13. Danesh J, Muir J, Wong Y-k, et al.Risk factors for coronary heart disease and acute-phase proteins: population based study. Eur Heart J,1999,20: 954-959.
14. Mendall MA, Patel P, Ballam L, et al.C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.BMJ，1996，312(7038): 1061-1065.
15. Pannacciulli N, Cantatore FP, Minenna A,et al. C-reactive protein is independently associated with total body fat, central fat, and insulin resistance in adult women. International Journal of Obesity，2001，25: 1416-1420.
16. Festa A, D’Agostino Jr, Howard G, et al. Chronic subclinical inflammation as part of the Insulin Resistance Syndrome. The Insulin Resistance Atheroslerosis Study (IRAS)，2000，102: 42-47.
17. Frhlich M, Imhof A, Berg G,et al. Association between C-reactive protein and Features of the Metabolic Syndrome. Diabetes Care，2000，23: 1835-1839.
18. Florez H, Florez-Castillo S, Mendez A,et al. C-reactive protein is elevated in obese patients with the metabolic syndrome. Diabetes Research and Clinical Practice，2006，71 :92-100.
19. Janssen I, Katzmarzyk PT , Ross R. Body mass index,waist circumference and health risk. Arch Intern,2002,162: 2074-2079.
20. Wu T, Dorn JP, Donahue RP,et al.Associations of serum C-reactive protein with fasting insulin, glucose and glycosylated hemoglobin. The Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol，2002，155(1): 65-71.
1 Institute of Hygiene and Medical Ecology, School of Medicine, University of Belgrade 11000, Serbia
2 Railway Health Care Institute “Beograd”, Belgrade, Serbia
Correspondence to Jagoda Jorga,Institute of Hygiene and Medical Ecology,School of Medicine, University of Belgrade,Pasterova 2,Belgrade 11000,Serbia
(Editor Emilia)(Jagoda B Jorga1, Ljiljana)
[Abstract]ObjectiveTo analyze the potential interrelationships between C-reactive protein(CRP) and the metabolic syndrome in the group of overweight and obese patients. MethodsCross-sectional study of the patients (N=182) who referred to the Dietetic Unit of the Belgrade Medical Faculty. A battery of risk factors and other variables were assessed which allowed classification of patients in obese (BMI≥30 )and non-obese (BMI<30) and those with [metabolic syndrom (Met Sy) present] and without the metabolic syndrome (Met Sy absent) on the basis of NCEP III criteria. ResultsThe prevalence of Met Sy was the highest in those with abdominal obesity (UPBO) with 46.9 % and the lowest in those with lower part body obesity (LPBO) with just two patients (3.6%) being diagnosed with metabolic syndrome. Significant differences in CRP levels emerged as a function of metabolic syndrome presence and type of body fat distribution. Metabolically unhealthy patients, those with Met Sy have statistically higher concentration of CRP (4.8±0.5 mg/L) compared to all others, Met Sy absent (2.9±0.3 mg/L), (P=0.0001). When distribution on the basis of CRP levels less than or greater than 3.0 mg/L, was assessed by Pearson Chi-Square across different categories, the highest prevalence of those with CRP>3mg/L was among patients with Met Sy, 62.3 % and the lowest among those with LPBO with 29.3 %. ConclusionsThe results obtained in this study show that abdominal obesity is the most prevalent component of the Met Sy which is on the other hand followed by increased levels of CRP. CRP levels should be detected in all obese patients, specially those with abdominal obesity to identify subjects at higher risk for atherosclerotic disease.
[Key words]C-reactive protein;metabolic sydrome;abdominal obesity
INTRODUCTION
Obesity is becoming common worldwide, both in developed and in developing countries averaging 12%~15% of total population. And even more, obesity can be seen as an underlying risk factor of atherosclerotic cardiovascular disease, as that is the foremost physical consequence of an excess of body fat[1].
It is also accompanied by several other risk factors such as hypertension, hyperglycaemia, and dyslipidemia, insulin resistance, better known as metabolic syndrome(Mes Sy). Recently the National Cholesterol Education Program Adult Treatment Panel Ⅲ(NCEP/ATP Ⅲ) report proposed a simple scheme for the routine diagnosis of metabolic syndrome including the presence of at least 3 of the following characteristics: abdominal obesity, elevated triglycerides, reduced levels of HDL cholesterol(HDL-C), high blood pressure, and high fasting glucose[2].
In 1997, it was first shown that by measuring C-reactive protein(CRP) in healthy individuals, physicians could predict the onset of future cardiovascular death independently of traditional cardiovascular risk factors[3]. It is a part of the concept according to which atherogenesis represents a state of chronic inflammation. Results obtained in last decade showed elevated levels of CRP in obesity particularly those with the metabolic syndrome, and Ridker has proposed CRP to be included in the definition of metabolic syndrome[4]. In 2003 the American Heart Association (AHA) and the US Centre for Disease Control and Prevention (CDC) issued joint clinical guidelines for the use of CRP[5], as a new option for risk detection.
Therefore this paper was aimed to evaluate the potential interrelationships between CRP and the metabolic syndrome in a group of patients with large range of body mass index(BMI), divided into non-obese and obese group.
METHODS
Patients
In first three months of 2004, 250 consecutive patients were referred to the outpatient Dietetic Unit for dietetic advice or nutritional medical therapy. Patients with eating disorders (anorexia nervosa and bulimia nervosa) and self-reported diabetes were excluded from the study. Thus, 182 patients were considered in the analyses. Of these, 151 were females [mean age (43.2 ± 1.0) years; mean BMI (33.3 ± 0.4) kg/m2], and 31 males [mean age (42.0 ± 2.2) years; mean BMI (33.1 ± 0.8) kg/m2]. According to WHO criteria, they were classified as non-obese (BMI<30 kg/m2), and obese (BMI≥30 kg/m2). According to NCEP/TP Ⅲ, patients were classified as having metabolic syndrome if they fulfilled 3 or more criteria: (1) triglycerides ≥1.7 mmol/L; (2) HDL-C < 1.0 mmol/L (men) and <1.3 mmol/L (women); (3) blood pressure ≥135/85 mm Hg; (4) obesity as defined by a waist circumference >102 cm (men) and >88 cm (women); and (5) abnormal glucose metabolism as defined by a fasting glucose ≥6.1 mmol/L. Seventy-one (39%) of all patients were diagnosed as having metabolic syndrome (10 from non-obese group，14.5%) and designated as Met Sy present, and all others were designated as Met Sy absent.
The study was reviewed and given ethical approval by the Ethics Committees at School of Medicine in Belgrade. All patients gave written, informed consent.
Anthropometric Parameters
Body weight was assessed by using a calibrated standard balance-beam, height was measured by a standard height bar, and BMI was calculated as weight (kg) divided by height (m2) and categorized according to WHO criteria[6].Waist circumference was measured at the midway between lower rib and crista illiaca, and according to WHO criteria[6],all patients were classified in upper part body obesity (UPBO) defined by a waist circumference >102 cm (men) and >88 cm (women), and lower part body obesity (LPBO). Body fat was calculated according to method proposed by Durnin and Womersley[7].
Cardiovascular Risk Factors
Blood pressure measurements were done by using appropriately sized cuffs and auscultatory method recommended by Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure[8].
For estimation of metabolic parameters, blood glucose (FBG) and lipoproteins, blood samples were obtained after an overnight fast. Levels of FBG, total cholesterol (TC), serum triglycerides (TG), HDL-C and low-density lipoprotein cholesterol (LDL-C) were estimated using commercial kits (Abbot, IL,USA) on an automated analyzer (AEROSETTM, Abbot, IL, USA).
Levels of CRP were measured by using immunoturbidimetric fixed time test (Olympus Diagnostics, O`Callaghan’s Mills Co. Clare, Ireland). According to the manufacturers, the normal CRP concentration using this assay ranged from 0.00~5.00 mg/L, the lowest detectable limit being 0.00 mg/L.
Statistical Analysis
Data were analyzed by using SPSS package version 9. Significance level was set at P<0.05.
Analysis of variance were performed by employing multivariate MANOVA procedures for related areas of dependent variables. Pearson’s r was used for correlations and chi-square for the comparison of frequencies across categories. Finally, multiple regressions analysis were employed with CRP assigned as the dependent variable.
RESULTS
Demographic, clinical and biochemical characteristics of all subjects, by gender and the presence/absence of the Met Sy are showed in Table 1.
Table 1 Characteristics of the Study Population by Gender and Metabolic Syndrome Status(x±s)
Notice:ns means no significence
According to gender, there were no signifficant differences in age, BMI, arterial blood pressure, TC, LDL-C and in CRP levels. Men had higher waist circumference [(109.9±2.0) cm vs (98.5±1.0) cm，P<0.0001], triglycerides [(1.0±0.2) mmol/L vs (1.5±0.1) mmol/L，P=0.041], and fasting glucose [(5.8±0.6) mmol/L vs (5.1±0.1) mmol/L，P=0.038]. As expected, women had higher percent of body fat [(39.6±0.4)% vs (31.1±0.9)%,P<0.0001], and HDL-C [(1.3±0.0)mmol/L) vs (1.1±0.1) mmol/L,P<0.0001].
The analyses done according to the presence of Met Sy revealed the significant differences in all studied parameters, with the exception of %F (Table 1). Using the NCEP/ATP Ⅲ criteria the overall frequency of the Met Sy was 39.0% (Table 2), with no differences between men and women. When frequencies of the components of metabolic syndrome were tested, no difference was observed in any of them: abdominal obesity, high blood pressure, high fasting glucose, high triglycerides and low HDL-C, although men showed higher frequency in all of these. The distribution of number of Met Sy components was as follows: 15 (8.2%) with none, 37 (23%) with one component, 59 (32.4%) with two components, and 71 (39.0%) with three or more components.
Table 2 Frequencies of Metabolic Syndrome and its Components by Gendern(%)
As expected, CRP levels were significantly higher in those with Met Sy in all studied subjects (F=13.40，P<0.0001). There was increase in CRP levels from (3.1±0.8) mg/L in those without any component of Met Sy to (4.8±0.5) mg/L in those with three or more components. Also, CRP levels in women with Met Sy were significantly higher than in those without Met Sy (F=12.16，P=0.001). The same trend was recorded in BMI. The significant difference in BMI was found in female subjects (F=7.03，P=0.009) and in the group as a whole (F=8.93，P=0.003). The increase in BMI has been found in female subjects (Table 3).
Table 3 BMI and CRP Values by Gender and Metabolic Syndrome Components(x±s)
Notice:Compared with none and 1~2,△P<0.05;Compared with none,#P<0.05;Compared with 1~2 and>3,**P<0.05
CRP levels according to the presence or absence of each Met Sy component by gender are displayed in Table 4. Higher CRP levels were observed in those with abdominal obesity when compared to those without abdominal obesity (P=0.022). No significant difference in CRP levels were found according to the presence of other components. The linear regression model included CRP as dependent variable and gender, abdominal obesity, high blood pressure, high fasting glucose, high fasting triglycerides, low HDL-C, Met Sy, as predictors, has emerged as significant (F=3.21，P=0.003). The two variables that contributed significantly to the model were: Met Sy and abdominal obesity with 26% (Beta=0.26) and 18% (Beta=0.18).
Table 4 CRP Levels by Gender according to Each Metabolic Syndrome Component(x±s)
Notice:*gender
The highest CRP levels were observed in those Met Sy cases of abdominal obesity, specially in female [(5.2±0.6) mg/L vs (2.4±0.0) mg/L). Women with abdominal obesity were shown significantly higher CRP levels (F=9.99，P=0.002). Also, the same trend was observed in the women with Met Sy (F=12.16，P=0.001). Men didn’t show this difference, regardless of abdominal obesity and Met Sy (Table 5).
Table 5 CRP and BMI according to the Presence of Abdominal Obesity and Metabolic Syndrome in the Study Population(x±s)
Notice:Compared with Ao groups*P<0.05;Compared with no Met Sy groups△P<0.05
Using Pearson’s correlation several factors were examined to determine factors associated with CRP level. CRP correlated with BMI (r=0.18;P=0.013), waist circumference (r=0.18;P=0.017), and percent of body fat (r=0.18;P=0.013) in all study subjects. The same relationship was evident only in women (Table 6).
Table 6 Pearson Correlation Coefficients of C-Reactive Protein Levels with Selected Variables by Gender
The frequency of the high risk CRP group (CRP cut off 3mg/L) was the highest among overweight patients diagnosed with Met Sy (63.2%). Both abdominal obesity and BMI ≥30 kg/m2 were significant factors which caused high CRP level; 54.7% subjects with abdominal obesity and 53.5% subjects with BMI ≥30 kg/m2 had CRP higher than 3mg/L. Opposite to that, the frequency of high CRP values among overweight subjects with preferal type of body distribution (non-abdominal) was less than 30% (29.3%)(Figure 1).
Pearson Chi-Square (182,1) = 1.01; ns(BMI≥30 vs BMI<30)；Pearson Chi-Square (182,1) = 10.01; P=0.001(UPBO vs LPBO)；Pearson Chi-Square (182,1) = 6.39;P=0.011(Present vs. Absent)
Figure 1 Distribution(%)according to CRP categories [<3 mg/L or >3 mg/L] in observed subgroups
DISCUSSION
This study included 182 patients: 151 females, who were slightly older than 31 males, but these difference was not statistically significant. The results of this cross-sectional study have pointed out that the abdominal obesity is the most common component of the Met Sy. And above that, subjects with abdominal obesity and Met Sy have the highest CRP levels.
There are some studies suggesting that obesity may result in low grade inflamation, and indicating that CRP levels tend to be higher in women than in men, which may put women at higher risk[9]. In our study female had higher mean value than men [(3.67±3.50) mg/L vs (2.98±3.04) mg/L] but this difference was not significant. Altough there is small number of studies investigating the relationship between gender and CRP, some authors explained this difference by the fact that women have higher percent of body fat compared to men and larger subcutaneous fat depots, whereas men have larger intra-abdominal fat depots[10]. Second, some authors suggested that intra-abdominal or visceral fat depots have the strongest impact on inflamatory markers[11]. Third, sex hormones could influence levels of inflamatory markers in women. In the cross-sectional Kooperative study Gesund-heitsforschung in der region Augsburg-Cooperative Research in the region of Augsburg (KORA study) on 4 261 men and women between 25 and 74 years of age,have observed higher levels of CRP in women compared to men[9].
Abdominal obesity was the most important component of the Met Sy associated with increased CRP levels. In fact, abdominal obesity, expressed as waist circumference, was the single most important determinant of CRP levels.Elevated CRP in the presence of the Met Sy may reflect cytokine production by adipocytes[12], because IL-6 and CRP levels are closely related, particularly in obese subjects.Even though, Danesh et al[13] have shown strong relationship between abdominal obesity and Met Sy, they didn’t found relationsheep with other components of the Met Sy.
We found a higher value of CRP levels in subjects with increased abdominal obesity, blood pressure, fasting glucose and triglycerides, and low HDL-C. Our results are similar to other cross-sectional study[14]. In the study of 201 normal weight, overweight and obese subjects,Pannacciulli et al[15] shown an independent relationship of abdominal obesity with CRP. Also, we found that CRP levels were significantly higher in subjects with Met Sy, and that the number of metabolic features follow increasing CRP levels. Many studies shows that the components of the Met Sy and the Met Sy are associated with parameters of inflamation, such as CRP level[16].Festa et al[16] showed in the Insulin Resistance Atherosclerosis Study (IRAS) increasing CRP levels followed with number of metabolic disorders, which pointed a significant difference between all parameters except subjects with 3 and 4 features. Also, in a large population sample, which included 747 men and 956 women, Frhlich et al[17] reported that CRP values clearly increase with the number of manifestations of the Met Sy. CRP values were nearly twice as high in subjects with several components compared with those without it. Florez et al[18] have showen in their study of 190 subjects that the increase in CRP levels follow the numbers of metabolic syndrome components.
In the present study we observed that the nutritional state expressed as BMI increase with increasing components of Met Sy. Recent analyses from the NHANES Ⅲ database showed that when subjects (14 924) are stratified by BMI and waist , those with highest waist values were increasingly more likely to have components of Met Sy than those with lowest waist circumference[19].
Some studies evaluated the relationship between CRP, the Met Sy and the incidence of cardiovascular diseases (CVD) over an 8-year period of follow up[20]. In this study women with the Met Sy showed a 4- and 2.6-fold increase in the risk for CVD depending on whether CRP levels were over or under the cut-off 3 mg/L, when compared to those without Met Sy and lower CRP levels (<3 mg/L). The fact is that higher CRP levels were associated strongly with abdominal obesity in our study, but this is not enough for the prognosis for future cardiovascular events.
CONCLUSION
The results obtained in this study show that abdominal obesity is the most prevalent component of the Met Sy which is on the other hand followed by increased levels of CRP.
Obesity defined as BMI ≥30 kg/m2 is also significant factor which caused high CRP level. This suggests a potential role of obesity, especially abdominal obesity in the development on the inflamation associated with the metabolic syndrome initially and later cardiovascular and cerebrovascular events. CRP levels should be detected in all obese patients, specially those with abdominal obesity to identify subjects at higher risk for atherosclerotic diseases.
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1 Institute of Hygiene and Medical Ecology, School of Medicine, University of Belgrade 11000, Serbia
2 Railway Health Care Institute “Beograd”, Belgrade, Serbia
Correspondence to Jagoda Jorga,Institute of Hygiene and Medical Ecology,School of Medicine, University of Belgrade,Pasterova 2,Belgrade 11000,Serbia
(Editor Emilia)(Jagoda B Jorga1, Ljiljana)