Monitoring markers of oxidative stress in acute coronary syndrome

Doughty, Angela (2023) Monitoring markers of oxidative stress in acute coronary syndrome. PhD thesis, University of Worcester.

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Abstract

It is estimated that there are around 80,000 hospital admissions in the UK each year due to acute coronary syndrome (ACS). The term ACS refers to clinical presentation characterised by chest pain, which may be due to an acute myocardial infarction (AMI) or unstable angina. AMI (or heart attack) arises due to cardiovascular disease (CVD), in which the blood supply to the heart muscle is decreased leading to ischemia and ultimately myocardial death. Thus, diagnosing AMI in a timely manner is essential.
Currently, high-sensitive cardiac troponin (hs-cTn) is the gold standard biomarker for AMI diagnosis, since hs-cTn is released by myocardial cells immediately following an AMI. Whilst hs-cTn has high sensitivity and specificity for diagnosing AMI, there are limitations. For example, hs-cTn at diagnosis does not predict readmission. There are also challenges with diagnosing certain demographics i.e., young females. Moreover, hs-cTn levels at diagnosis have no prognostic value for patient readmissions following percutaneous coronary intervention (PCI). Given the negative impact associated with AMI readmissions, identifying novel biomarkers that can predictive is attractive.
Since AMI is caused by ischemia, oxidative stress in a prominent pathological feature. During acute and chronic oxidative stress, biomarkers reflecting this such as thioredoxin (TRX), thioredoxin reductase (TRXr), peroxiredoxin-2 (PRDX-2) and peroxiredoxin-4 (PRDX-4) may be elevated. Therefore, evaluating these in AMI patients at diagnosis and during recovery may allow predictions regarding prognosis e.g., readmission probability. Therefore, the aim of this study was to evaluate TRX, TRXr, PRDX-2 and PRDX-4 in AMI patients at diagnosis and follow-up.
A total of 145 participants were recruited into this study, which included 80 AMI patients along with 65 healthy donor controls. Blood plasma was subsequently analysed by ELISA for TRX, TRXr, PRDX-2 and PRDX-4. The data presented illustrate for the first time that, healthy volunteers had significantly lower plasma levels of PRDX-4, TRX and TRXr compared with the AMI cohort (p<0.05), with females being significantly lower overall (p<0.05). Receiver operator curve analysis revealed that all four biomarkers could correctly predict an AMI in 4/5 cases, as determined by the area under the curve >0.80 discriminative for AMI. Stratification of patients according to biomarker concentration and culprit lesion during PCI demonstrated that, plasma TRX >13.40 ng/ml at screening was associated with a higher readmission risk (p=0.009), whereas patients with plasma TRXr >2.00 ng/ml had significantly lower risk of readmission overall (p<0.05). For TRXr, this was particularly apparent for patients who received PCI to the left anterior descending artery (LAD). Finally, PRDX-2 >30.60 ng/ml at first follow-up (1-3 months) was associated with an increased risk of readmission (p=0.009) and was most apparent when culprit lesion was the LAD. This information may inform clinical outcome which in turn may highlight strategies to improve ACS readmission rates in England, e.g., recombinant PRDX-2 therapy for when culprit lesion during PCI is the LAD. Taken together, the findings of this study could significantly benefit the diagnosis and risk stratification of AMI, as well as inform clinical decisions.

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