Siew Wai, Fong
(2015)
Plaque instability biomarkers: a comparison between acute coronary syndrome and chronic stable angina patients.
Masters thesis, Universiti Sains Malaysia.
Abstract
Biomarkers play a pivotal role in the diagnosis and management of patients with
acute coronary syndrome (ACS). Some biomarkers, such as C-reactive protein (CRP),
soluble CD40 ligand (sCD40L), placental growth factor (PlGF) and myeloperoxidase
(MPO) have been reported to be involved in plaque destabilization. The levels of
these biomarkers were studied in ACS and chronic stable angina (CSA) patients aged
≤ 45 years and aged > 45 years. The relationship between these biomarkers in the
coronary circulation and peripheral circulation was also investigated. This study was
the first attempt to investigate the expression of peroxisome proliferator-activated
receptors (PPARs) in ACS. A total of 79 patients (ACS: n = 39, CSA: n = 40) was
recruited. The blood was sampled from the occluded coronary artery (coronary
circulation) and also from the median cubital vein antecubital fossa (peripheral
circulation). The serum protein levels of CRP, sCD40L and PlGF and plasma levels
of MPO were measured using ELISA. The intracellular levels of PPARs were semiquantified
using Western blot. The mRNA levels of the biomarkers were measured
by real-time PCR. All ACS patients that underwent six months clinical follow-up was assessed for major adverse cardiac events (MACE) after the acute event. The
peripheral levels of CRP, MPO, sCD40L and PlGF were significantly increased in
ACS compared to CSA patients. Furthermore, the peripheral concentrations of these
biomarkers were significantly correlated with the concentrations found in the
coronary circulation. The patients aged below 45 years and above 45 years shared
similar profiles of biomarkers. The expression of PPAR-γ was significantly increased
in the ACS patients and correlated with both sCD40L and MPO. Serum CRP
demonstrated the highest area under the curve value of 0.79 (p < 0.001) in
discriminating ACS, followed by PlGF, MPO and sCD40L. In addition, the
biomarkers also showed their promising prognostic abilities in predicting 30-day and
six-month MACE in ACS patients. In conclusion, this study provided additional
information on the proteins and gene expression profiles of plaque instability
markers in both CSA and ACS patients. The biomarkers contribute to the formation
of unstable plaque by triggering vascular inflammation, firous cap thinning and
formation of large lipid core in coronary plaque. Their accuracies in discriminating
ACS and predicting MACE also showed promising results.
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