Biomarkers of inflammation and oxidative stress indepently predict the progression of subclinical atherosclerosis

Objectives: Prediction of cardiovascular events by inflammation and oxidative stress biomarkers reflects their pivotal role in development of atherosclerosis. However, it is unclear whether such biomarkers are associated with an accelerated progression of subclinical atherosclerosis. Methods: 151 asymptomatic subjects with ≥3 RFs participating in the IMPROVE observational study were included (median age 63; 67 male). Carotid IMT was measured at baseline and after 30 months. At baseline biomarkers were measured in blood samples, including WBC and CRP, neopterin, soluble receptor for advanced glycation end products (AGEs), tissue inhibitor of metalloproteinase-1 (TIMP1) and metalloproteinase-9 (MMP9), and diene concentration and antibodies against oxidized LDL (oxLDL), and autofluorescence, noninvasively measured in skin (SAF) as a marker for tissue accumulation of AGEs. Results: At baseline most conventional RFs correlated significantly with CIMT. Of the biomarkers, only SAF correlated with CIMT (r=0.24, p=0.001). At follow-up, a small increase was observed in the CIMT (0.020 (0.086) mm, p=0.006). In contrast to RFs, the biomarkers, including CRP (r=0.22, p=0.007), oxLDL (r=0.21, p=0.012), TIMP1 (r=0.29, p=0.001), and WBC (r=0.23, p=0.004) correlated with CIMT progression. After stepwise, multiple regression, TIMP1 (beta=0.28, p=0.001) and oxLDL (beta=0.25, p=0.003) remained independently associated with CIMT. Conclusions: In asymptomatic subjects at high cardiovascular risk, conventional RF and SAF reflected the initial atherosclerosis profile, but several biomarkers independently predicted the 30 month progression of CIMT. These observational data strengthen the hypothesis that inflammation and oxidative stress promote the progression of subclinical atherosclerosis and thus are of clinical relevance in detecting high risk subjects.