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C-reactive Protein and Risk of Cardiovascular Disease

 

Jeppe Zacho

Summary

This PhD thesis is based on studies performed during my employment at the Department of ClinicalBiochemistry, Herlev Hospital, Copenhagen University Hospital. The results are presented in theform of a paper, and a response to “letters to the editor”, both of which have been published.1,2Today, ischemic cardiovascular disease is considered a chronic inflammatory disease.C-reactive protein (CRP) is an acute phase protein involved in the first line of defence againstinfectious agents, but it has also been recognized as being involved in the low grade inflammatorystate seen in ischemic cardiovascular disease. But like the old story about the chicken and the egg,there has been much discussion about whether the inflammatory process, and specifically elevatedCRP, is a marker or a causal factor in the development of ischemic cardiovascular disease.We set out to answer the question of causality for elevated CRP and risk of ischemiccardiovascular disease. First, we re-confirmed that CRP is robustly and independently associatedwith ischemic cardiovascular disease. Secondly, we showed that 4 CRP polymorphisms, and agenotype combination based upon the former, were associated with elevated plasma CRP levels.Thirdly and finally, we found that the CRP polymorphisms and the CRP genotype combinationswere not associated with increased risk of ischemic cardiovascular disease, indicating that CRP is amarker not a causal risk factor for ischemic cardiovascular disease.