Midtveisevaluering - Øistein R. Mjelva

Abstract:

Atherosclerosis and the development of atheromatous plaques involve a vascular inflammatory response initiated by the accumulation of cholesterol and lipoproteins in the wall of the arteries. Rupture of these plaques activates the coagulation system. This development is mainly a subclinical process, in which the magnitude of the disease is not always reflected by the degree of symptoms and traditional clinical findings. We have therefore focused on four markers of vascular inflammation (the long Pentraxin 3 (PTX3), calprotectin, pregnancy associated plasma protein-a (PAPP-A) and neopterin) together with two markers of coagulation (D-dimer and fibrin monomer), and hypothesize that the selected biomarkers will reflect the atherothrombogenic burden and future risk.

In the first phase of the PhD-project, we have assessed the prognostic importance of troponin-T (TnT), high-sensitive C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) in patients admitted with chest pain and borderline values of TnT in a combined cohort from the RACS (Risk in the Acute Coronary Syndrome) and the ARRA-RACS study (ARgentinean Risk Assessment Registry in ACS). Here, borderline TnT values (> 0.01 and ≤0.1 ng/mL) as well as hsCRP did not render prognostic information, whereas BNP was found to be a strong prognostic indicator of 2-year total and cardiac mortality. We then looked at PTX3, D-Dimer, PAPP-A and calprotectin in the RACS cohort, assessing their prognostic utility and comparing them to traditional CV risk factors and established biomarkers of prognosis including TnT, BNP and hsCRP. Neither PAPP-A nor calprotectin were found to be independent predictors of long-term prognosis (7 years follow-up data), but both PTX3 and D-dimer were independent predictors of total mortality during this follow-up period, adding prognostic information to both the traditional CV risk factors and the established biomarkers (TnT, BNP and hsCRP).

In the next phase of the PhD-project, we plan to assess the relation between levels of the systemic biomarkers of interest and the degree of coronary thromboatheromatosis among patients who underwent coronary angiography in the RACS study. In addition, we will assess the prognostic utility of fibrinogen and neopterin and possible effect modification of these, in patients with stable coronary artery disease (combined cohort of the WENBIT trial  and the BECAC cohort ((Bergen Coronary Angiography Cohort)).