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J Am Coll Cardiol, 2007; 49:1798-1805, doi:10.1016/j.jacc.2007.01.065
(Published online 13 April 2007). © 2007 by the American College of Cardiology Foundation |
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* Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China
Unilever Corporate Research, Colworth Park, Sharnbrook, Bedfordshire, United Kingdom.
Manuscript received September 25, 2006; revised manuscript received January 5, 2007, accepted January 15, 2007.
* Reprint requests and correspondence: Dr. Xu Lin, Institute for Nutritional Sciences, 294 Tai-Yuan Rd., Shanghai, 200031, China. (Email: xlin{at}sibs.ac.cn).
| Abstract |
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Background: Several studies have suggested that CRP is a risk factor of MetS. However, it remains unclear how CRP levels are distributed and whether they are associated with MetS in Chinese people.
Methods: We conducted a population-based cross-sectional survey in 2005 in Beijing and Shanghai, with a total of 1,458 men and 1,831 women age 50 to 70 years. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans.
Results: The median CRP level was 0.68 mg/l among the study population. The CRP levels were significantly higher among participants from Beijing or from urban areas than those in participants from Shanghai or from rural areas (p < 0.01). No gender difference in CRP levels was observed. The prevalence of MetS progressively increased with elevated CRP levels (p < 0.0001 for trend). In the highest quartile of CRP levels (>1.50 mg/l), the risk for MetS was substantially higher (odds ratio 5.97; 95% confidence interval 4.75 to 7.51) compared with that in the lowest quartile of CRP levels (
0.33 mg/l) after adjustment for age, gender, geographic location, lifestyle factors, educational attainment, and family history of chronic diseases. This association was observed in both obese and nonobese participants.
Conclusions: The overall plasma level of CRP is low but highly associated with the MetS among the middle-aged and elderly Chinese population. Prospective studies are needed to investigate the role of CRP in the development of MetS and related chronic diseases among Chinese people.
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Increasing evidence suggests that chronic low-grade inflammation may be part of the "common soil" involving the pathogenesis of MetS, type 2 diabetes, and cardiovascular disease (CVD) (3). C-reactive protein (CRP), an acute-phase reactant, is the most extensively studied biomarker of low-grade inflammation. Compelling evidence has shown that mildly increased CRP is a predictor for CVD (46), type 2 diabetes (7,8), and MetS (9,10) in healthy people. However, CRP levels vary among different populations (1114), and their relation with these diseases in non-Western populations remains unclear. In addition, CRP levels have also been reported to differ by gender (6,1416) and other factors such as obesity, smoking, alcohol consumption, and physical activity (17). Existing evidence also suggests that CRP might be more strongly correlated with MetS in women than in men (6,9,18,19). Nevertheless, most studies have been conducted in Western populations, and little is known about the CRP distribution and its relation with MetS among Chinese people. In this study, we aimed to investigate the distributions of CRP and its association with MetS in a representative middle-aged and elderly Chinese population.
| Methods |
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Data collection.
A home interview was conducted by trained physicians or public health workers from the local Centers for Disease Control and Prevention and community hospitals. Data of demographic variables, health status, health behavior, and physical activity (International Physical Activity Questionnaire, short last 7-day format) was collected using a standardized questionnaire. Smoking habit was defined as never, current (daily smoking, >6 months), and former (cessation of smoking, >6 months). Alcohol drinking was grouped into "yes" or "no." The physical activity level for each individual was classified as low, moderate, or high according to the questionnaire scoring protocol (20). Educational attainment of the participants was categorized into 3 groups according to the number of years of education (0 to 6, 7 to 9, and
10 years). Family history of chronic diseases was considered positive if the participants parents or siblings had a history of having 1 of the following diseases: coronary heart disease, stroke, type 2 diabetes, or hypertension.
All participants were invited to have a physical examination at the local health stations or the community clinics after the home interview. Participants were required to fast overnight. Anthropometric measurements were performed by trained medical professionals using a standardized protocol. Body weight and height were measured in light indoor clothing without shoes to the nearest 0.1 kg and 0.1 cm, respectively. Body mass index (BMI) was then calculated as weight (kg)/height (m)2. Participants were categorized as normal weight (<24.0 kg/m2), overweight (24.0 to 27.9 kg/m2), or obese (
28.0 kg/m2) (21). Waist circumference was obtained at the mid-point between the lowest rib and the iliac crest to the nearest 0.1 cm, after inhalation and exhalation. Blood pressure was measured by using an electronic blood pressure monitor (Omron HEM-705CP, OMRON Healthcare Inc., Vernon Hills, Illinois) on the right arm of the participant in a comfortable sitting position after at least 5-min rest. Participants were asked to avoid vigorous exercise, eating, drinking, smoking, or long exposure to cold or hot temperatures for 1 h before the measurement. Three measurements were taken, and the mean of the last 2 measurements was used for analysis.
Laboratory methods. Peripheral venous ethylenediaminetetraacetic acid blood samples were collected and centrifuged at 4°C, 3,000 rpm for 15 min. After being frozen, the samples were shipped in dry ice to the Institute for Nutritional Sciences and stored at 80°C until analysis. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and glucose were measured enzymatically on an automatic analyzer (Hitachi 7080, Japan) with reagents purchased from Wako Pure Chemical Industries (Osaka, Japan). Plasma CRP was measured by a particle-enhanced immunoturbidimetric assay (Ultrasensitive CRP kit, Orion Diagnostica, Espoo, Finland) using microparticles coated with anti-human CRP antibodies. The CRP calibrator was standardized against the International Federation of Clinical Chemistry reference material (certified reference material [CRM] 470). The lower detection limit of the assay was 0.25 mg/l. The intra-assay coefficients of variation of the CRP levels were 6.6%, 0.3%, and 0.8% at 0.62, 3.34, and 8.71 mg/l, respectively, while the inter-assay coefficients of variation were 11.9%, 2.1%, and 3.4% at 0.59, 5.53, and 9.12 mg/l, respectively.
Definition of MetS.
The MetS was defined based upon the updated NCEP-ATPIII for Asian Americans (22) as presenting 3 or more of the following components: 1) waist circumference
90 cm for men or
80 cm for women; 2) triglycerides
1.7 mmol/l; 3) HDL cholesterol <1.03 mmol/l for men or <1.30 mmol/l for women; 4) blood pressure
130/85 mm Hg or current use of anti-hypertensive medications; and 5) fasting glucose
5.6 mmol/l or previously diagnosed type 2 diabetes or on oral antidiabetic agents or insulin.
Statistical analyses. All undetectable CRP values (<0.25 mg/l) were replaced with 0.12 mg/l, and natural log transformations were performed to approximate normality. General linear model for continuous variables and Cochran-Mantel-Haenszel statistics for categorical variables were applied for the comparison between men and women after adjustment for region (Beijing/Shanghai) and residence (urban/rural). The median level of CRP was tested with Wilcoxon rank sum test when comparing between strata (men and women, Beijng and Shanghai, urban and rural). Spearman partial correlation coefficients of CRP, BMI, and elements of MetS were calculated after adjusting for age, gender, and residence. The Kruskal-Wallis test was used to evaluate the association of median CRP levels across numbers of MetS components. The prevalence of MetS was calculated after stratification by gender, region, and residence, respectively. Multivariate logistic regression models were used to estimate the odds ratios (ORs) for the components of MetS or MetS itself. Potential confounding variables associated with CRP and the MetS as suggested by previous publications were controlled in the regression models. The variables were age (continuous), smoking, alcohol drinking, physical activity, education, and family history of chronic diseases, along with gender, region, and residence. In addition, BMI was considered an intermediate factor in the regression model to be adjusted further. Analyses were also repeated in the subgroups of gender, region, and residence, respectively. To calculate the ORs for MetS according to the quartile of CRP levels and obesity status, considering the high correlation of BMI with waist circumference, we used a modified definition of MetS (composed as having 2 or more MetS components without central obesity). Data management and statistical analyses were performed with the SAS statistical package version 9.1 (SAS Institute, Cary, North Carolina). Statistical tests were 2-sided, and a p value <0.05 was considered statistically significant.
| Results |
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| Discussion |
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Previous studies have suggested that CRP levels may be lower in Chinese compared with Caucasian populations. Anand et al. (12) reported that Chinese living in Canada had the lowest CRP level (median 0.69 mg/l) whereas South Asian and native Canadians had higher levels compared with Caucasians (median 1.24 mg/l). Similar results were observed in the Study of Womens Health Across the Nation (13): CRP levels in Japanese (median 0.5 mg/l) and Chinese (median 0.7 mg/l) were lower while higher levels were observed in Hispanic and African-American compared with Caucasian women (median 1.4 mg/l). Interestingly, the CRP level in our study population was similar to the levels found in Chinese in these 2 studies (12,13). In contrast, Yen et al. (23) reported that the CRP level (median 1.5 mg/l) among healthy Chinese men in Taiwan was close to the level found in Western studies. However, 37% of the subjects had CRP levels below the lowest detectable limit (1.0 mg/l) in their study, and 2,046 of 8,374 were excluded for the CRP analysis. Shiesh et al. (24) found that the median CRP among healthy individuals age 45 to 81 years in Taiwan was 0.62 mg/l when using a much more sensitive assay, which was similar to the result in the present study. The reason why Chinese and most East Asians have significantly lower CRP levels than Western populations is unclear. Genetic diversity was reported to influence the baseline level of CRP (25). Relatively low BMI and environmental factors such as diet and lifestyle were also suggested to modulate the CRP concentration (17).
Although the present study further indicated a low overall CRP level in Chinese people, when region or residence was considered, Beijing and urban participants showed significantly higher CRP levels than their Shanghai and rural counterparts. One plausible explanation for increased CRP level may be the higher prevalence of obesity in Beijing and among urban residents (1). Previous studies have showed that higher BMI and waist circumference are related to elevated CRP levels (26). In fact, in this study, after adjusting for BMI, the differences in the CRP level between the regions attenuated remarkably, and the differences between the residences disappeared. However, the differences between the regions could not be fully explained by age, BMI, lifestyle factors, family history of chronic diseases, and MetS components (without central obesity). Other potential factors such as diet and anti-inflammatory drugs may also contribute to the differences in CRP levels (17). Consistent with the results from Chinese living in Canada (12) and Taiwan (24), no gender differences were observed for CRP levels in our study.
In line with the results in other population studies (6,9,18,19,2731), the CRP was highly associated with individual MetS features and MetS itself in our study population. A similar association was found between men and women in our study after controlling for most confounding factors (including BMI) although a slightly stronger association in women than in men was indicated in other populations even further adjusted for BMI (9,19). The discrepancy between our study and others may be due to the differences in age, BMI, and hormonal profiles (6,9,18,19). More studies are needed to explore whether gender-specific associations between CRP and MetS exist in Chinese people.
Consistent with the studies in other populations (9,10,19), BMI is a pivotal mediator for the association between CRP and the MetS in this Chinese population regardless of gender, region, and residence. However, even though BMI has a predominant influence on the CRP profile and the overall risk of MetS, data from the current study showed that the increased CRP levels per se were highly associated with the individual features of MetS and MetS itself.
Metabolic syndrome is a well-established risk factor for CVD (46). Though we did not investigate the relation between MetS and CVD, supporting evidence from a recent study showed a 1.7-fold increased risk of CVD among elderly Chinese people with MetS (32). Based on the high correlation observed in our study between CRP and MetS, it is reasonable to assume that an elevated CRP level might be associated with a higher risk of CVD in Chinese people. However, the CRP levels in our population were low, and approximately 50% of our participants with MetS had CRP levels below 1 mg/l (median for participants with MetS: 1.04 mg/l), which is considered "low risk" for subsequent CVD according to the criteria proposed by Centers for Disease Control and Prevention and the American Heart Association (33). The criteria were mainly generated from studies performed in Caucasian populations. Hence, prospective studies are warranted to investigate CRP, MetS, and other risk factors related to CVD to verify whether the suggested cutoff points are valid in the Chinese population.
To our knowledge, this is the first large-scale, population-based study to investigate CRP distribution and its relation with updated NCEP-ATPIII MetS among both genders in China. One of the advantages of this study was that participants had been recruited from the north (Beijing) and the south (Shanghai) and urban and rural areas, representing a relatively wide range of middle-aged and older Chinese people. In addition, most confounding factors for the risk of MetS in this study were carefully taken into consideration in the regression analyses. Furthermore, the field study was done within a relatively short period of time; thus the seasonal influence on the biomarkers and other lifestyle factors was minimized.
Admittedly, with the cross-sectional nature, it is not possible to establish a cause-effect relationship between CRP levels and MetS. In addition, a relatively large proportion (16.5%) of our study population had a CRP level below the detectable limit due to the overall low CRP level in the Chinese population. Nonetheless, the assay was standardized to the reference material 470, and the CRP levels in our study were consistent with those reported in the literature in which CRP kits were also standardized to CRM 470 (12,13,24). Finally, only 1 fasting blood sample was collected, and the magnitude of the intra-individual variation on the CRP concentration, lipids, and glucose could not be determined.
| Conclusions |
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| Acknowledgments |
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| Footnotes |
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| References |
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