| Background: The Centers for Disease Control and Prevention and American Heart Association (CDC/AHA) proposed that the C-reactive protein (CRP) levels were to be <1.0mg/L as low risk, 1.0 to 3.0 mg/L as intermediate risk and >3.0 mg/L as high risk for cardiovascular risk. However, the cutoffs have been derived almost exclusively from European or European American whites, and the applicability of these cutoffs to Chinese is unclear. Multi-ethnic studies have indicated that there were ethnic differences in prevalence and mortality of cardiovascular diseases, and the differences may be related to ethnic difference in CRP levels. However,present reports on the difference between whites and Asians are contrary, and some reports indicated that the CRP levels were higher in whites than in Asians, others reports indicated that the CRP levels were not different between whites and Asians or CRP higher in Asians than in whites.Measurement of CRP is advocated for cardiovascular risk assessment. However, before its use in cardiovascular risk assessment in clinic and screening peoples who are at high risk of cardiovascular diseases, it is important to investigate the distribution of CRP and its features and correlates in the general population. There were some studies on the distribution of CRP in Chinese, but the sample sizes were small or the subjects were lack of representation. So the data on the distribution of CRP are lack in a representative Chinese adult population, and more studies are needed to investigate the association between CRP and traditional risk factors of cardiovascular diseases.CDC/AHA proposed to investigate the distribution of CRP in different populations and explore cutoffs of CRP that were applicable to different population. However, there's no study on cutoffs of CRP which are to evaluate cardiovascular risk in general population of China or other East countries.Objectives: To review the evidence for ethnic differences of CRP between whites and Asians, and to explore whether CRP levels in Asians differ from those of whites and whether the present cutoffs used to evaluate cardiovascular risk are applicable in Chinese. Using epidemiological methods to investigate the baseline levels, distribution feathers of CRP and its association with traditional risk factors of cardiovascular diseases in Shanghai adults, and to explore the cutoff point that was appropriate for primary prevention of cardiovascular diseases in Chinese. Methods: Using Pubmed and Embase, we searched for literature on the CRP levels in whites and Asians published December 2008 or earlier, and a manual search was performed using reference lists of identified articles and all review articles. Quality assessing of the literature were done independently by two reviewer and the studies that met the criterion were included. A meta analysis was conducted to examine the difference of CRP levels between whites and Asians. At same time, a cross-sectional study was carried out in apparently healthy adults aged 18 to 80 years in Shanghai. A random, multi-stage and stratified sampling method was used to sample subjects. Questionnaires and laboratorial test were used to investigate the distribution and features of CRP and its association with traditional risk factors of cardiovascular diseases. The method of receiver operating characteristic (ROC) curve analysis was used to calculate the sensitivity, specificity and the distance in the ROC curve of the every appointed point of CRP to explore the best cutoff point of CRP to find three or more risk factors.Results: 9 studies were eligible for inclusion, and 4 of them reported the CRP levels in whites and East Asians, 4 of them in whites and South Asians and 1 of them in whites, East Asians and South Asians. The results of meta analysis indicate that there was no significant difference of CRP levels between whites and Asians with the weighted mean difference (WMD) 0.25 mg/L [95% confidence interval (CI):(-0.09, 0.59)], but there was obvious heterogeneity between individual studies (P<0.00001, I2=93.7%). Further subgroup analyses revealed that the WMD in the CRP levels between whites and East Asians was 0.84 mg/L [95% CI(0.76,0.91), P<0.00001] and between whites and South Asians the value was -0.29 mg/L [95% CI (-0.44, -0.13), P=0.0003]. There were no significant differences between individual studies in subgroup analyses.A total of 3153 people participated the investigation with a response rate of 87.58%, and 3133 people (1393 men and 1740 women) entered into the statistical analyses in the end. The median of CRP levels was 0.58 mg/L (0.64 mg/L in men and 0.53 mg/L in women). The CRP levels were significantly higher among participants in men or in urban areas than those in women or in rural areas, and they are increased with increasing age. More than 60% of participants have a CRP level less than 1.0 mg/L. CRP was not found to relate to smoking, drinking or physical activities in this study. Mean body mass index, waist circumference, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and fasting blood glucose (FBG) values were higher, whereas mean high-density lipoprotein cholesterol (HDL-C) values were lower with higer CRP in a linear fashion. Likewise, the prevalence of overweight, high TC, high LDL-C, high TC, high FBG and low HDL-C, as well as hypertension, were higher with higher CRP. After controlling all other factors, overweight, high LDL-C, high TG, hyperglycemia, hypertension and low HDL-C were associated with increased CRP. More than a half of participants with overweight, dyslipidemia (high LDL-C, low HDL-C or high TG), hyperglycemia and hypertension had CRP levels less than 1.0 mg/L. Even the increase of CRP in"normal"range, the prevalence of the risk factors increased with it. Traditional risk factors aggregation at individuals was widespread in the participants, and the line fashion between risk factors and CRP mainly caused by the prevalence of three or more risk factors. Both the point at which sensitivity equalled specificity and the shortest distance in the ROC curves for three or more of these risk factors suggested that a CRP cutoff of 0.7 mg/L was appropriate for prediction of cardiovascular risk for both men and women.Conclusions: Chinese have lower levels of CRP and the present CRP"reference intervals"are not applicable in Chinese. CRP is associated with many traditional risk factors of cardiovascular diseases and lower cutoff point is needed to evaluate cardiovascular risk in Chinese. We suggest that CRP of 0.7 mg/L was a better cutoff point to evaluate cardiovascular risk in Chinese.
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