Interactive role of dyslipidemia, oxidative stress and inflammation in atherosclerosis and other diseases: genetic and biochemical markers

Genetic and acquired risk factors linked to dyslipidemia, oxidative stress and inflammation will be studied in patients with cardiovascular, cerebrovascular, renal and pulmonary diseases. Risk factors will be investigated at three levels: (1) genetic polymorphisms (cholesterol ester transfer protein, paraoxonases), (2) gene expression (superoxide dismutases and other genes involved in oxidative and inflammatory pathways) and (3) concentrations of inflammatory, oxidative stress, hemostatic and lipid parameters, including small, dense LDL and HDL particles. Analytical methods for qualitative and quantitative investigations of the risk factors will be optimized and validated. Sources of intra-individual and inter-individual variations will be studied in healthy and diseased subjects. Complex interrelationships between numerous risk factors and their associations with the diseases will be investigated by factor analysis in order to identify a smaller set of independent clusters and their role in risk prediction. The risk factors will be evaluated as markers of the occurrence, severity and prognosis of the disease and their clinical usefulness will be compared by ROC-curve analysis. Cost-effectiveness of the additional diagnostic or prognostic information obtained by laboratory analysis of each marker will be assessed. This will be the basis for designing rational diagnostic strategies to identify individuals at higher risk and ultimately improve prevention and treatment.