Abstract
This study consisted of three sub-projects to investigate the association between C-reactive protein (CRP) levels, the metabolic syndrome (MetS) and cardiovascular risk in middle-aged and older Taiwanese adults. Three major aims were achieved using two types of study designs for the three studies. The nested case-control study evaluated whether CRP levels and MetS predicted stroke risk, in addition to the traditional cardiovascular disease risk factors. The other two parts of the study used a cross-sectional design to examine the association of CRP levels and MetS with carotid atherosclerosis by sex, and investigated the demographic and modifiable correlates for the CRP levels. Study subjects were participants in the 1994-1995 follow-up survey of the Chin-Shan Community Cardiovascular Cohort study. The cross-sectional study included 810 subjects who received measurements for CRP levels, MetS components, and ultrasound examinations for common carotid artery (CCA) intima-media thickness (IMT) and extra-cranial carotid artery plaques. However, for the study aimed to investigate CRP level correlates, participants with complete information on CRP were included regardless of the availability of ultrasound examination data (n=916). The individuals selected for the nested case-control study consisted of 65 first-ever strokes and 109 controls free of stroke during the 10-year follow-up period, from 1994 or 1995 until 2005. CRP levels in the plasma were determined using a high-sensitivity immunoturbidimetric assay. MetS was defined according to criteria from the U.S. National Cholesterol Education Program Adult Treatment PanelⅢ. Results of the cross-sectional study 1: Age, sex, marital status, body mass index, waist circumference, triglycerides, hypertension, diabetes and MetS were associated with CRP levels in univariate analyses. However, age, waist circumference and MetS were remained as the significant predictors of CRP levels in multiple linear regression analyses. Results of the cross-sectional study 2: Women had higher median CRP (1.3 vs. 1.1 mg/L) and higher MetS prevalence than men (58.8 vs. 34.2%). Thicker IMT was associated with MetS in women (adjusted odds ratio [OR] 2.07, 95 % confidence interval [CI] 1.04-4.11) but not in men. Compared to participants with CRP 3 mg/L had an elevated OR with the plaque presence (OR 1.99, 95 % CI 1.10-3.61) but not women. The odds ratio for the artery plague increased to 2.20 (p = 0.046) for individuals with MetS and CRP level > 3 mg/L, compared with men with CRP < 1 mg/L and no MetS. Results of the nested case-control study: The median CRP values in stroke cases and control subjects were 1.5 mg/L and 1.1 mg/L, respectively (p = 0.007). The logistic regression models showed that the multivariate-adjusted stroke OR was 2.55 (95% CI 1.05-6.23) for subjects at the top tertile CRP level compared with the bottom tertile levels in the controls. The risk was not attenuated after further adjustment for MetS or for hypertension. The risk for stroke associated with MetS was eliminated after including hypertension and diabetes in the model. The estimated risks were weaker, but the main results remained, when the Cox proportional hazard model was used for analyses. The area under receiver operating characteristic curves for traditional risk factors (0.68) was improved little by adding CRP or MetS (both 0.69) or the combination of these two variables (0.70). In conclusion, CRP is an independent risk factor associated with stroke. But, both CRP and MetS provide limited improvement for the stroke risk discrimination beyond the traditional risk factors. In the sub-clinical stage of the disease, CRP levels and MetS correlate with distinct phenotypes of carotid atherosclerosis among men and women. MetS is related to thicker IMT in women, while elevated CRP is associated with the presence of plaque in men. This association is enhanced by MetS. Finally, in addition to MetS, central obesity is strongly associated with CRP levels independent of BMI in this population.
Published Version
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