The findings in this population-based study showed that Taiwanese individuals with elevated hs-CRP levels, predominantly within the reference range, had a significantly increased likelihood of having the metabolic syndrome in men and women, independent of their age, smoking, alcohol drinking and betel nut chewing (Table 2). However, associations were considerably stronger in women than in men. In addition, the results showed that hs-CRP was a significant risk factor of metabolic syndrome's components with a stronger association in women. We also found significant gender difference in the association of metabolic syndrome with hs-CRP after stratification according to the status of insulin resistance, obesity, microalbuminuria, cardiovascular risk, and arteriosclerosis (Table 3).
Despite evidence indicating that inflammation is related to metabolic syndrome [20, 39], data from epidemiologic studies are sparse. Yudkin et al. examined relationships between levels of hs-CRP and components of metabolic syndrome such as obesity, blood pressure, dyslipidemia and insulin resistance in a group of 107 healthy persons . However, their study focused on exploring the mechanisms underlying the relationship of inflammatory process and coronary heart disease and their finding require further testing in both epidemiological and clinical studies with larger sample size. In Laaksonen's study, they examined the association between CRP levels and the development of the metabolic syndrome and diabetes in 680 men with 11 years of follow-up . In Ridker work, although the relationship of hs-CRP with components of the metabolic syndrome was examined in a large-scale population , their study subjects restricted to healthy women, who participating in an ongoing trial of aspirin and vitamin E for primary prevention. Therefore both studies cannot examine the interaction of sex and CRP.
There were two studies examining the association between CRP and metabolic syndrome in Chinese [41, 42]. Both of these two studies measuring CRP, not hs-CRP, thus they could not detect CRP levels less than 0.25 mg/L. The median value of CRP in our study was more close to that reported by Chien's et al and much lower than that by Ye et al. Chien's study adopted both the updated WHO and NCEP-ATPIII definition of metabolic syndrome for Asian Americans and Ye's study adopted the NCEP-ATPIII definition while we adopted AHA/NHLBI one. Both of them identified significant association between CRP and metabolic syndrome and/or its components, but they did not examine whether there existed gender difference in this association.
There were limited studies examining whether there exists a sex difference in the association between a proinflammatory state and metabolic syndrome . Our observation that hs-CRP is more strongly associated with metabolic syndrome in women than in men is in line with results of Ahonen's study , which included subjects with elevated blood pressure. In addition, their results showed there was no gender difference in the level of hs-CRP in individuals without metabolic syndrome, but the level of hs-CRP was significantly lower in men with metabolic syndrome than in women with metabolic syndrome. In a study observing no gender difference in CRP level , an association between CRP and metabolic syndrome had been reported as a whole and gender difference in the association between CRP and metabolic syndrome had not been explored.
Hs-CRP was an easily measured inflammatory biomarker and has several direct effects at the level of the vessel wall . It has been shown hs-CRP has associations with endothelial dysfunction and insulin resistance syndrome . Our finding showed that sex difference in the association of metabolic syndrome with hs-CRP might suggest that hormone might play a role on the inflammatory mechanism. Whether sex hormone is responsible for the association of metabolic syndrome with hs-CRP needs to be explored.
Limitations of this study must be considered. The principal limitation relevant to the interpretation of our results is the use of cross-sectional data; thus, causal pathways underlying the observed relationships cannot be inferred. Second, these analyses were restricted to the first 1305 subjects entering the current study, thus potential selection bias might exist. To assess this possibility, we examined the demographic characteristics of the individuals with and without hs-CRP measurement by comparing age, sex, and administrative unit, and similar distributions were found. The non-differential distributions in age, sex, and administrative unit, indicate this kind of selection error might be random, thus, the results could be biased toward the null, a lesser threat to validity.
This finding would have implications for prevention. AHA/NHLBI metabolic syndrome definition, an update of the NCEP ATP III, has the primary purpose for diagnosing the persons with metabolic syndrome for lifestyle therapies to reduce long-term risk of developing cardiovascular disease and type 2 diabetes mellitus. This issue has become more important since recent reports have suggested prevention/delay of diabetes with lifestyle intervention [45, 46]. Thus, the stronger association between hs-CRP and metabolic syndrome by AHA/NHLBI definition in females indicates that lifestyle interventions should aim at female subpopulation with metabolic syndrome who will have a higher likelihood of development of diabetes and cardiovascular events.
In summary, the study demonstrates that elevated concentrations of hs-CRP showed a stronger association with metabolic syndrome in women than in men. This finding suggests that chronic inflammation may be of particular importance in the pathogenesis of metabolic syndrome in women. Our study finding has important implication on screening of metabolic syndrome.