Coronary Artery Bypass Grafting (CABG) is an effective and invasive cardiac surgery to salvage blocked coronary artery. Cardiopulmonary bypass (CPB) is usually applied to support circulation during temporary cardiac arrest. Studies have demonstrated that cardiac injury, inflammation, and oxidative stress could be induced during CABG with CPB. We conducted two studies to investigate the release of cardiac biochemical markers and inflammatory response as well as to compare the effect of different coating biomaterial of CPB on the induction of inflammation and oxidative stress during CPB. We investigated the release patterns and the serum levels of cardiac markers as well as inflammatory markers in patients undergoing elective CABG at different time points after initiation of CPB. In this study, we demonstrated that cardiac markers such as creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) and inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were highly elevated after CPB. Moreover, we confirmed that cTnI is still a better biochemical marker for cardiac injury than others following CABG with CPB. Other nonspecific but highly sensitive markers such as lactate dehydrogenase (LDH), lactate, TNF-alpha, IL-6, and hsCRP could be potential surrogate markers for evaluation of cardiac injury following CPB. Based on these findings, we conducted a further investigation to demonstrate our hypothesis that different biocompatible materials used in CPB may affect the inflammation and oxidative stress differently. Biocompatible materials are thinly coated on CPB tubes to provide similar environment like endothelial cells during cardiac surgery. There are several biocompatible materials available in the market. Each of them has unique characteristics. Inflammatory response is one of the bodys fundamental defense mechanisms against foreign invaders. However, inappropriate or excessive response can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. CPB-induced inflammatory response can be one of the factors, which can affect surgical outcomes. Depending on the presence of different biocompatible materials in CPB circuits, the degree of immunoreactions can be varied. In this study, we analyzed hsCRP, an acute phase protein, and tau protein, a marker of neurocognitive deficiency. Furthermore we analyzed inflammatory cytokines including TNF-alpha, IL-6, IL-10, and interferon-gamma (IFN-gamma) to evaluate the levels of inflammation. Serum levels of oxidized nitric oxide as a marker of oxidative stress were also assessed. We demonstrated that different biocompatible material has different impacts on inflammation and oxidative stress. In the aspect of anti-inflammation, heparin-coated biocompatible material is better than others whereas surface-modifying additives biocompatible material is worse than others. Overall, different coating biomaterial of CPB results in various inflammatory response. In terms of oxidative stress, we did not observe significant difference between different biomaterial-coated CPB.

Coronary Artery Bypass Grafting (CABG) is an effective and invasive cardiac surgery to salvage blocked coronary artery. Cardiopulmonary bypass (CPB) is usually applied to support circulation during temporary cardiac arrest. Studies have demonstrated that cardiac injury, inflammation, and oxidative stress could be induced during CABG with CPB. We conducted two studies to investigate the release of cardiac biochemical markers and inflammatory response as well as to compare the effect of different coating biomaterial of CPB on the induction of inflammation and oxidative stress during CPB. We investigated the release patterns and the serum levels of cardiac markers as well as inflammatory markers in patients undergoing elective CABG at different time points after initiation of CPB. In this study, we demonstrated that cardiac markers such as creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) and inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were highly elevated after CPB. Moreover, we confirmed that cTnI is still a better biochemical marker for cardiac injury than others following CABG with CPB. Other nonspecific but highly sensitive markers such as lactate dehydrogenase (LDH), lactate, TNF-alpha, IL-6, and hsCRP could be potential surrogate markers for evaluation of cardiac injury following CPB. Based on these findings, we conducted a further investigation to demonstrate our hypothesis that different biocompatible materials used in CPB may affect the inflammation and oxidative stress differently. Biocompatible materials are thinly coated on CPB tubes to provide similar environment like endothelial cells during cardiac surgery. There are several biocompatible materials available in the market. Each of them has unique characteristics. Inflammatory response is one of the bodys fundamental defense mechanisms against foreign invaders. However, inappropriate or excessive response can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. CPB-induced inflammatory response can be one of the factors, which can affect surgical outcomes. Depending on the presence of different biocompatible materials in CPB circuits, the degree of immunoreactions can be varied. In this study, we analyzed hsCRP, an acute phase protein, and tau protein, a marker of neurocognitive deficiency. Furthermore we analyzed inflammatory cytokines including TNF-alpha, IL-6, IL-10, and interferon-gamma (IFN-gamma) to evaluate the levels of inflammation. Serum levels of oxidized nitric oxide as a marker of oxidative stress were also assessed. We demonstrated that different biocompatible material has different impacts on inflammation and oxidative stress. In the aspect of anti-inflammation, heparin-coated biocompatible material is better than others whereas surface-modifying additives biocompatible material is worse than others. Overall, different coating biomaterial of CPB results in various inflammatory response. In terms of oxidative stress, we did not observe significant difference between different biomaterial-coated CPB.

In the present study clinical performance of new highly cardiospecific biochemical markers of myocardial injury was investigated and these markers were compared with conventional enzymes. The multimarker risk assessment score index, including biochemical markers of myocardial injury, inflammation and haemostasis, was developed for the prognosis of patients after ACS. The prognostic value of BNP concentration changes in predicting LV remodeling and dysfunction after MI was evaluated along with other biochemical markers of myocardial injury.

(1) Background: Highly sensitive cardiac troponin T (hs-cTnT) plays an essential role in the diagnosis of myocardial injury. The upper reference limit of the respective assay is generally applied, irrespective of age, renal function, or sex. We aimed to identify age-adjusted and sex-adjusted upper reference limits in relation to renal function in a large population-based cohort without cardiac diseases. (2) Methods: We included 5428 subjects of the population-based LIFE-Adult cohort, free of diagnosed cardiac diseases. Sex-adjusted and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained. (3) Results: The hs-cTnT values were higher in men of all age groups. In both sexes, an increasing age positively correlated with higher hs-cTnT values. Hs-cTnT weakly correlated with serum creatinine. The three-dimensional analysis of age, creatinine, and hs-cTnT showed no relevant additional effect of creatinine on hs-cTnT. In men aged above 60 and women above 70, the calculated 99th percentiles clearly exceeded the commonly applied thresholds. (4) Conclusion: Age and sex have a major impact on the serum concentration of hs-cTnT, while renal function does not. We propose to consider age-adjusted and sex-adjusted reference values.

Thesis (MCur)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Background: Coronary artery disease is a form of cardiovascular disease (CVD) which manifests itself in three ways: angina pectoris, acute coronary syndrome and cardiac death. Thirty-three people die daily of a myocardial infarction (cardiac death) and 7.5 million deaths annually are caused by CVD (51% from strokes and 45% from coronary artery disease) worldwide. Globally, the CVD death rate is a mere 4% compared to South Africa which has a 42% death rate. It is predicted that by the year 2030 there will be 25 million deaths annually from CVD, mainly in the form of strokes and heart disease. The WHO compared the death rates of high-income countries to those of low- and middle-income countries, like South Africa, and the results show that CVD deaths are declining in high-income countries but rapidly increasing in low- and middle-income countries. Although there are several risk prediction tools in use worldwide, to predict ischemic risk, South Africa does not use any of these tools. Current practice in South Africa to diagnose acute coronary syndrome is the use of a physical examination, ECG changes and positive serum cardiac maker levels. Internationally the same practice is used to diagnose acute coronary syndrome but risk assessment tools are used additionally to this practise because of limitations of the ECG and serum cardiac markers when it comes to NSTE-ACS. Objective: The aim of this study was to systematically appraise evidence on the accuracy of acute coronary syndrome risk prediction tools in adults. Methods: An extensive literature search of studies published in English was undertaken. Electronic databases searched were Cochrane Library, MEDLINE, Embase and CINAHL. Other sources were also searched, and cross-sectional studies, cohort studies and randomised controlled trials were reviewed. All articles were screened for methodological quality by two reviewers independently with the QUADAS-2 tool which is a standardised instrument. Data was extracted using an adapted Cochrane data extraction tool. Data was entered in Review Manager 5.2 software for analysis. Sensitivity and specificity was calculated for each risk score and an SROC curve was created. This curve was used to evaluate and compare the prediction accuracy of each test. Results: A total of five studies met the inclusion criteria of this review. Two HEART studies and three GRACE studies were included. In all, 9 092 patients participated in the selected studies. Estimates of sensitivity for the HEART risks score (two studies, 3268 participants) were 0,51 (95% CI 0,46 to 0,56) and 0,68 (95% CI 0,60 to 0,75); specificity for the HEART risks score was 0,90 (95% CI 0,88 to 0,91) and 0,92 (95% CI 0,90 to 0,94). Estimates of sensitivity for the GRACE risk score (three studies, 5824 participants) were 0,03 (95% CI0,01 to 0,05); 0,20 (95% CI 0,14 to 0,29) and 0,79 (95% CI 0,58 to 0,93). The specificity was 1,00 (95% CI 0,99 to 1,00); 0,97 (95% CI 0,95 to 0,98) and 0,78 (95% CI 0,73 to 0,82). On the SROC curve analysis, there was a trend for the GRACE risk score to perform better than the HEART risk score in predicting acute coronary syndrome in adults. Conclusion: Both risk scores showed that they had value in accurately predicting the presence of acute coronary syndrome in adults. The GRACE showed a positive trend towards better prediction ability than the HEART risk score. / AFRIKAANSE OPSOMMING: Agtergrond: Koronêre bloedvatsiekte is ‘n vorm van kardiovaskulêre siekte. Koronêre hartsiekte manifesteer in drie maniere: angina pectoris, akute koronêre sindroom en hartdood. Drie-en-dertig mense sterf daagliks aan ‘n miokardiale infarksie (hartdood). Daar is 7,5 miljoen sterftes jaarliks as gevolg van kardiovaskulêre siektes (51% deur beroertes en 45% as gevolg van koronêre hartsiektes) wêreldwyd. Globaal is die sterfte syfer as gevolg van koronêre vaskulêre siekte net 4% in vergelyking met Suid Afrika, wat ‘n 42% sterfte syfer het. Dit word voorspel dat teen die jaar 2030 daar 25 miljoen sterfgevalle jaarliks sal wees, meestal toegeskryf aan kardiovaskulêre siektes. Die hoof oorsaak van sterfgevalle sal toegeskryf word aan beroertes en hart siektes. Die WHO het die sterf gevalle van hoeinkoms lande vergelyk met die van lae- en middel-inkoms lande, soos Suid Afrika, en die resultate het bewys dat sterf gevalle as gevolg van kardiovaskulêre siekte is besig om te daal in hoe-inkoms lande maar dit is besig om skerp te styg in lae- en middel-inkoms lande. Daar is verskeie risiko-voorspelling instrumente wat wêreldwyd gebruik word om isgemiese risiko te voorspel, maar Suid Afrika gebruik geen van die risiko-voorspelling instrumente nie. Huidiglik word akute koronêre sindroom gediagnoseer met die gebruik van n fisiese ondersoek, EKG verandering en positiewe serum kardiale merkers. Internationaal word die selfde gebruik maar risiko-voorspelling instrumente word aditioneel by gebruik omdat daar limitasies is met EKG en serum kardiale merkers as dit by NSTE-ACS kom. Doelwit: Die doel van hierdie sisematiese literatuuroorsig was om stelselmatig die bewyse te evalueer oor die akkuraatheid van akute koronêre sindroom risiko-voorspelling instrumente vir volwassenes. Metodes: 'n Uitgebreide literatuursoektog van studies wat in Engels gepubliseer is was onderneem. Cochrane biblioteek, MEDLINE, Embase en CINAHL databases was deursoek. Ander bronne is ook deursoek. Die tiepe studies ingesluit was deurnsee-studies, kohortstudies en verewekansigde gekontroleerde studies. Alle artikels is onafhanklik vir die metodologiese kwaliteit gekeur deur twee beoordeelaars met die gebruik van die QUADAS-2 instrument, ‘n gestandaardiseerde instrument. ‘n Aangepaste Cochrane data instrument is gebruik om data te onttrek. Data is opgeneem in Review Manager 5.2 sagteware vir ontleding. Sensitiwiteit en spesifisiteit is bereken vir elke risiko instrument en ‘n SROC kurwe is geskep. Die SROC kurwe is gebruik om die akkuraatheid van voorspelling van elke instrument te evalueer en te toets. Resultate: Twee HEART studies en drie GRACE studies is ingesluit. In total was daar 9 092 patiente wat deelgeneeem het in die gekose studies. Skattings van sensitiwiteit vir die HEART risiko instrument (twee studies, 3268 deelnemers) was 0,51 (95% CI 0,47 to 0,56) en 0,68 (95% CI 0,60 to 0,75) spesifisiteit vir die HEART risiko instrument was 0,89 (95% CI 0,88 to 0,91) en 0,92 (95% CI 0,90 to 0,94). Skattings van sensitiwiteit vir die GRACE risiko instrument (drie studies, 5824 deelnemers) was 0,28 (95% CI 0,13 to 0,53); 0,20 (95% CI 0,14 to 0,29) en 0,79 (95% CI 0,58 to 0,93). Die spesifisiteit vir die GRACE risiko instrument was 0,97 (95% CI 0,95 to 0,99); 0,97 (95% CI 0,95 to 0,98) en 0,78 (95% CI 0,73 to 0,82). Met die SROC kurwe ontleding was daar ‘n tendens vir die GRACE risiko instrument om beter te vaar as die HEART risiko instrument in die voorspelling van akute koronêre sindroom in volwassenes. Gevolgtrekking: Altwee risiko instrumente toon aan dat albei instrumente van waarde is. Albei het die vermoë om die teenwoordigheid van akute koronêre sindroom in volwassenes te voorspel. Die GRACE toon ‘n positiewe tendens teenoor beter voorspelling vermoë as die HEART risiko instrument.