A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in partial fulfilment of the requirements for the degree of Master of Sciences in Medicine (Emergency Medicine) Johannesburg, 2014 / Background: Patients with acute coronary syndrome (ACS) may present with a wide range of symptoms that may easily be misdiagnosed. Methods: This cross-sectional, hospital-based, descriptive, retrospective audit of medical records was based at the Ladysmith Provincial Hospital ED and consisted of the last 160 consecutive patients (from the date of initiation of data collection) with accessible medical records and with a final hospital discharge diagnosis of ACS. Results: The frequency of patients presenting with ACS was approximately 53 patients per annum. There was a male to female ratio of 1.3: 1. The mean age was 55.8 years (SD 12.8 years). The study population consisted of Asian (103/160, 64.4%), black (36/160, 22.5%) and white (21/160, 13.1%). The majority of the study patients were unemployed (98/160, 61.25%), urban resident (143/160, 89.4%), not alcohol users (137/160, 85.6%), and not smokers (88/160, 55.0%). Risk factors and comorbidity included previous acute coronary syndrome (44/160, 27.5%), family history (29/160, 18.1%), previous cardiovascular surgery (10/160, 6.25%), obesity (45/160, 28.1%), hypercholesterolemia (49/160, 30.6%), diabetes (42/160, 26.25%), hypertension (76/160, 47.5%), and renal failure (27/160, 16.9%). Approximately three quarters (119/160, 74.4%) of the study patients had typical chest pain, 16.3% (26/160) had atypical chest pain, and 9.4% (15/160) had no chest pain. The median length of hospital stay was 3 days and the in-hospital mortality was 8.1 % (13/160). Conclusion: The relatively high frequency of ACS reported in this study, when compared to other similar studies, is concerning. Also of concern in this study, is the alarming proportion of Asians that presented with ACS.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2009. / Härtill 4 uppsatser.

This qualitative descriptive study described the prodromal symptoms of older individuals, age 65 and above, experiencing acute coronary syndrome (ACS). Review of the literature establishes that older adults experiencing precursor symptoms of ACS are a high-risk group, one that experiences disparities in hospital emergency departments (EDs) and decreased ACS survival. Identification of early symptoms predictive of ACS may influence a patient's willingness to seek medical treatment and necessitate early, accurate diagnosis and treatment. The purpose of this study was to describe older individual's prodromal symptoms patterns and symptom experiences including perceptions, interpretations, and treatment seeking decisions. This study compared and contrasted symptom patterns of ACS among groups of older adult participants, age 65+ based upon age, gender, and other demographic characteristics (previous myocardial infarction, race, ethnicity, regular exercise, insurance, and comorbidity). Three specific aims were addressed in this study. Specific Aim 1 Explore the prodromal symptom patterns as perceived by the older individual encountering ACS. Specific Aim 2 Explore the older individual's interpretation of the prodromal symptom patterns encountering ACS. Specific Aim 3 Explore the treatment decision making processes used by older individuals when experiencing and interpreting prodromal symptom patterns in ACS. Participants included patients newly diagnosed with ACS and ≥ 65 years of age. For the qualitative description, participants (n=20) were recruited and a chart audit was conducted. Demographic information and data were obtained from the admitting ED history and physical, and discharge summary. Additionally, face-to-face semi-structured interviews were conducted with each participant. Content and matrix analyses were used to address the study aims. Research findings from this study elucidated early symptom indicators of myocardial ischemia/infarction (MI), which may be used for screening or developing ACS assessment guidelines specific to geriatric patients.

Introdução: As doenças cardiovasculares constituem a principal causa de morbimortalidade nacional e apresentam-se principalmente na forma de doença arterial coronariana, cujas principais manifestações se caracterizam pelas síndromes coronarianas agudas: angina instável e infarto agudo do miocárdio. Nesse sentido, realizou-se um estudo com o objetivo de caracterizar o perfil bio-psico-social dos pacientes após síndromes coronarianas agudas, identificando os fatores que possam interferir na adesão ao tratamento no que diz respeito ao não comparecimento às consultas, interrupção do tratamento e controle de pressão arterial, além de associar o perfil bio-psico-social dos pacientes com fatores relacionados à adesão. Casuística e Método: Estudo descritivo e exploratório, realizado em um hospital universitário da cidade de São Paulo, analisou 85 pacientes com diagnóstico de síndromes coronarianas agudas. Após receberem alta, os pacientes foram entrevistados em ambulatórios para obtenção de dados estruturais, socioeconômicos, hábitos de vida, conhecimento da doença e do tratamento. Com o intuito de avaliar o bem estar psicológico dos pacientes, o questionário de saúde geral de Goldberg foi aplicado. Os dados foram processados no sistema SPSS v.7.5. O nível de significância adotado foi 0,05. Resultados: Foram estudados 85 pacientes, 56% homens, 69% com companheiro, 59±9,6 anos, 85% pertencentes à etnia branca, 52% com ensino fundamental, 54% com renda entre 2 e 5 salários, 79% com antecedentes de hipertensão arterial, 62% com dislipidemia e 40% para infarto agudo do miocárdio. Cerca de 35% relataram o não comparecimento às consultas e a interrupção do tratamento. Em relação à atitude frente à necessidade de tomar medicamentos, 63% dos pacientes relatou esquecimento esporádico ou constante dos remédios. A análise de regressão logística indicou a associação independente para as seguintes variáveis (OD Odds ratio, IC intervalo de confiança a 95%): 1- não comparecimento às consultas, etnia branca (OR=0,27 IC 95% 0,08-0,86) e hábitos alimentares inadequados (OR=1,07 IC 1,00-1,45); 2- interrupção do tratamento associado com faltas às consultas (OR=6,09 IC 1,81-20,49), consumo de bebida alcoólica (OR=5,05 IC 1,61-15,76) e automedicação (OR=7,89 IC 2,39-26,05); 3- pressão arterial não controlada (=140/90 mmHg) com acompanhamento no ambulatório de coronária (OR=2,78, IC 1,01-7,65). A maior freqüência de alteração no quarto percentil nos domínios do questionário de saúde geral de Goldberg foram associados às seguintes variáveis: 1- estresse associado à automedicação (OR=6,09 IC 1,32-14,5) e HDLc =40mg/dL (OR=1,04 IC 1,00-1,08); 2- auto-eficácia com acompanhamento no ambulatório de coronária (OR=2,78 IC 1,19-12,23), automedicação (OR=4,62 IC 1,46-14,95) e HDLc =40mg/dL (OR=1,04 IC 1,19-12,23); 3- distúrbios do sono associados com referência de ansiedade (OR=5,61 IC 1,65-19,09), e colesterol total = 200 mg/Dl (OR=4,42 IC 1,36- 14,38); 4- distúrbios psicossomáticos associados ao sexo feminino (OR=6,57 IC 1,96-22,0) e relato de ansiedade (OR=4,06 IC 1,24-13,3); 5- severidade da ausência de saúde mental associado ao sexo feminino (OR=3,96 IC 1,26- 12,43) e automedicação (OR=3,39 IC 95% 1,07-10,70). Conclusão: Características estruturais e psicológicas, hábitos de vida inadequados e atitudes frente ao tratamento medicamentoso influenciaram aspectos da adesão ao tratamento, tais como o não comparecimento às consultas e a interrupção do tratamento. Em face dos dados obtidos, os profissionais de saúde devem implementar estratégias para atender os pacientes com síndrome coronariana aguda, visando à prevenção secundária. / Introduction: The cardiovascular diseases are the most important cause of mortality in the country and show mainly in the form of coronary arterial disease, which the main manifestations are characterized by the acute coronary syndrome: instable angina, acute attack of the myocardium. In this way, a study was made with the aim to characterized the bio-psychosocial profile of the patients after the acute coronary syndrome, recognizing the factors which could interfere in the adherence to the treatment about the non attendance to the appointments, interruption of the treatment and the control of the blood pressure, besides the association of the bio-psychosocial profile of the patients to the factors connected to the adherence. Method and Casuistic: A descriptive and exploring study, made in a University hospital in the city of São Paulo that analyzed 85 patients with the diagnostics of the acute coronary syndrome. After receiving the doctor’s avail to leave the hospital, the patients were interviewed in ambulatories in order to collect structure, socioeconomic, habits of life, knowledge of the disease and of the treatment data. The main purpose was to evaluate the psychological welfare state of the patients; the questionnaire of general health was used. The results were run in the system SPSS v. 7.5. and the significance level adopted was 0,05. Results: 85 patients were studied, 56% men, 69% ith companion, 59+-9,6 years old, 85% white, 52% finished the elementary school, 54% with the income of between 2 and 5 salaries, 79% with the precedents of high blood pressure, 62% with high blood cholesterol and 40% for the acute myocardium attack. About 35% of them spoke about the non attendance to the appointments and the interruption of the treatment. About the attitude towards the necessity to take medicines, 63% of the patients spoke about the constant or periodical carelessness of the medicines. The analysis of logistic regression indicated the independent association to the following varieties: (OD odds ratio, IC confidence break around 95%): 1 – non attendance to the appointments, white ethnic (OR = 0,27 IC 95% 0,08- 0,86) and bad eating habits (OR=1,07 IC 1,00-1,45); 2 – interruption of the treatment associated to the non attendance to the appointments (OR=6,09 IC 1,81-20,49), the alcoholic drinks consumption (OR=5,05 IC 1,61-15,76), and auto medication (OR=7,89 IC 2,39-26,05); 3 – high blood pressure out of control (=140/90 mmHg) with the accompaniment in the coronary ambulatory (OR=2,78, IC 1,01-7,65). The higher frequency of the alterations in the percentage board in the Goldberg’s general health questionnaire dominions was associated to the following variations: 1 – Stress associated to auto medication (OR=6,09 IC 1,32-14,5) and HDLc =40mg/dL (OR=1,04 IC 1,00-1,08); 2 – auto efficiency with accompaniment in the coronary ambulatory (OR=2,78 IC 1,19-12,23), auto medication (OR=4,62 IC 1,46-14,95) and HDLc =40mg/dL (OR=1,04 IC 1,19-12,23); 3 – Sleeping disturbance associated to anxiety reference (OR=5,61 IC 1,65- 19,09) and total cholesterol total = 200 mg/Dl (OR=4,42 IC 1,36-14,38); 4 – psychosomatic disturbances associated to the female genre (OR=6,57 IC 1,96-22,0) and the report of anxiety (OR=4,06 IC 1,24-13,3); 5 – health general rate of evaluation associated to the female genre (OR=3,96 IC 1,26-12,43) and auto medication (OR=4,06 IC 1,24-13,3); Conclusion: The structural and psychological characteristics, inadequate life habits and attitudes facing the medicine treatment influence the aspects of adherence to the treatment, such as the non attendance to the appointments and the interruption of the treatment. Facing all the searched data, the health professionals must implement strategies to support the patients with acute coronary syndrome, looking for the secondary prevention.

INTRODUÇÃO: A angiotomografia computadorizada com múltiplos detectores (ATCMD) apresenta alta acurácia para a detecção de estenose luminal significativa das artérias coronárias ( 50%) quando comparada à angiografia coronária invasiva (ACI). Recentemente, esse método vem sendo investigado na avaliação de pacientes com dor torácica aguda de baixo risco. No entanto, poucos estudos investigaram a capacidade da ATCMD na avaliação de pacientes com maior risco para síndrome coronária aguda (SCA). OBJETIVOS: Investigar a acurácia diagnóstica da ATCMD com 64 colunas de detectores para a detecção de estenose luminal coronária 50% definida pela ACI em indivíduos com suspeita de SCA sem supradesnível do segmento ST e comparar estes resultados com a acurácia encontrada em pacientes com suspeita de doença coronária crônica; avaliar a capacidade da ATCMD em predizer revascularização miocárdica nos 30 primeiros dias de seguimento. Adicionalmente objetivamos verificar a prevalência e a acurácia da presença de calcificação coronária para detecção de estenose luminal coronária significativa. MÉTODOS: Pacientes que participaram do estudo multicêntrico internacional CorE64 foram classificados nos grupos SCA e não-SCA de acordo com critérios clínicos, incluindo a presença de angina ao repouso, alterações isquêmicas ao ECG e elevação de marcadores de necrose miocárdica. Todos os pacientes foram submetidos à ATCMD e posteriormente à ACI e para a análise primária foram considerados apenas aqueles com escore de cálcio (EC) 600. RESULTADOS: Dos 291 pacientes incluídos, 80 (27%) foram classificados no grupo SCA. A prevalência de estenose coronária 50% foi de 68% neste grupo e de 52% no grupo não-SCA (p=0,015). A acurácia diagnóstica da ATCMD, em análise por paciente, para detecção de estenose coronária significativa demonstrada pela análise da área sob a Curva de Características Operacionais (AUC) foi de 0,95 (IC 95%: 0,90-0,99) e 0,92 (IC 95%: 0,89-0,96) nos grupos SCA e não-SCA, respectivamente (p=0,44). Nos 30 dias de seguimento, 98 pacientes foram submetidos à revascularização miocárdica (48 do grupo SCA e 50 do grupo não-SCA). A AUC da ATCMD e da ACI para predição de revascularização foi de 0,91 (95% IC: 0,83-0,99) e 0,89 (95% IC: 0,80-0,98), respectivamente, no grupo SCA (p=0,61) e 0,80 (95% IC: 0,74-0,86) e 0,79 (95% IC: 0,73-0,85) no grupo não-SCA, p=0,75. Comparando os dois grupos estudados, a ATCMD foi melhor preditora de revascularização no grupo SCA (p=0,035). No grupo SCA, 6 pacientes (7,5%) tinham EC zero e estenose coronária significativa, comparado a 8 indivíduos (3,8%) do grupo não-SCA (p=0,22). Considerando pacientes com EC baixo (0 a 9), 12 (15%) do grupo SCA e 11 (5,2%) do não- SCA apresentaram estenose coronária 50% (p=0,012). A acurácia do EC para detecção de estenose coronária significativa nos grupos SCA e não- SCA foi de 0,73 (IC 95%: 0,63-0,82) e 0,70 (IC 95%: 0,64-0,76), respectivamente (p=0,75), sendo que o valor preditivo negativo no grupo SCA foi estatisticamente menor que no grupo não-SCA [0,63 (IC95%: 0,39- 0,86) e 0,86 (IC 95%: 0,77-0,95), respectivamente, p=0,038]. CONCLUSÕES: A ATCMD apresentou alta acurácia diagnóstica para detecção de estenose coronária significativa nos grupos SCA e não-SCA, não havendo diferença significativa entre ambos. A ATCMD obteve acurácia semelhante à ACI na predição de revascularização, sendo maior no grupo SCA que no não-SCA. A acurácia do EC para a detecção de estenose coronária 50% foi moderada em ambos os grupos, sendo que um EC zero ou baixo não excluiu a ocorrência de estenose significativa, especialmente no grupo SCA / BACKGROUND: Multi-detector computed tomography angiography (MDCTA) has shown high accuracy to detect obstructive coronary luminal stenosis ( 50%) compared to invasive coronary angiography (ICA). Recently, this technology has been investigated in the evaluation of patients with low-risk acute chest pain. However, few studies investigated its diagnostic performance in higher-risk patients with suspected acute coronary syndrome (ACS). OBJECTIVES: To estimate the diagnostic accuracy of 64- row computed tomography angiography to detect significant coronary stenosis defined by ICA in a per-patient analysis and its ability to predict coronary revascularization in patients with suspected acute coronary syndrome and in those with chronic, stable coronary artery disease; to identify the prevalence and the diagnostic accuracy of coronary calcification to detect significant luminal stenosis in both groups. METHODS: Patients included in the international multicenter trial CorE64 were categorized as suspected ACS or non-ACS based on clinical data. A 64-row coronary MDCTA was performed before ICA and both exams were evaluated by blinded, independent core laboratories. RESULTS: From 291 patients with coronary calcium score (CCS) 600 included in the primary analysis, 80 were categorized as suspected ACS. The prevalence of obstructive coronary disease was 68% in suspected ACS and 52% in non-ACS group (p=0.015). Patient-based analysis showed an area under the receiver-operatingcharacteristic curve (AUC) for detecting coronary stenosis 50% of 0.95 (95% CI: 0.90-0.99) in ACS and 0.92 (95% CI: 0.89-0.96) in non-ACS group (p=0.44). After 30 days of follow-up, 98 patients were submitted to coronary revascularization (48 from the ACS and 50 from the non-ACS group). MDCTA was similar to ICA to predict coronary revascularization in both groups with AUC of 0.91 (95% CI: 0.83-0.99) for MDCTA versus 0.89 (95% CI: 0.80-0.98) for ICA in the ACS group (p=0.61) and 0.80 (95% CI: 0.74- 0.86) for MDCTA versus 0.79 (95% CI: 0.73-0.85) for ICA in non-ACS group (p=0.75). MDCTA was better to predict revascularization in ACS than in non- ACS group (p=0.035). In the suspected ACS group, 6 patients (7.5%) had no coronary calcification and coronary stenosis 50%, compared with 8 patients (3.8%) in the non-ACS group (p=0.22). Considering patients with zero or low (0 to 9) CCS, 12 (15%) in the ACS and 11 (5.2%) in the non-ACS group had significant coronary stenosis (p=0.012). The accuracy of CCS to detect obstructive coronary stenosis in the ACS and non-ACS groups were 0.73 (95% CI: 0.63-0.82) e 0.70 (95% CI: 0.64-0.76), p=0.75, and its negative predictive value in the suspected ACS group was lower than in non-ACS patients [0.63 (95% CI: 0.39-0.86) and 0.86 (95% CI: 0.77-0.95), respectively, p=0.038]. CONCLUSIONS: Coronary MDCTA diagnostic accuracy was high and comparable for both ACS and non-ACS patients. MDCTA predicted revascularization similarly to ICA and its prediction ability was significantly better in the ACS than in non-ACS group. The diagnostic accuracy of a positive CCS to detect luminal stenosis 50% was moderate in both groups and a zero or low CCS could not exclude reliably significant coronary stenosis, particularly in suspected ACS patients

The principal cause of non-ST-segment myocardial infarction (NSTEMI), a subclass of acute coronary syndrome (ACS), is thrombosis and the underlying cause is atherosclerosis. Percutaneous coronary intervention (PCI) is one of the treatments to attenuate the ischemic effects of severe coronary artery stenosis. However, restenosis following PCI (post-PCI) is a major problem for the long-term success of the procedure. Recently, the interaction of advanced glycation end products (AGE) with the receptor for advanced glycation end products (RAGE) has been implicated in the development of atherosclerosis in animal models. Interaction of AGE with RAGE results in activation of nuclear factor kappa-B (NF-êB), release of cytokines including tumor necrosis factor-alpha (TNF-á), the expression of adhesion molecules including soluble vascular adhesion molecule-1 (sVCAM-1) and induction of oxidative stress all of which have been implicated in the development of atherosclerosis. The soluble receptor for advanced glycation end products (sRAGE) acts as a decoy for RAGE ligands (AGEs) and this occurs by competing with RAGE. In animal models, balloon inflation and de-endothelialization of the carotid artery increase the concentration of AGE and RAGE in the arterial wall and induces neointimal hyperplasia and stenosis. Treatment with sRAGE in animal models reduces neointimal growth and decreases smooth muscle cell migration and proliferation and expression of extracellular matrix.<p> It is hypothesized that NSTEMI and post-PCI restenosis may be due to low levels of serum sRAGE resulting in increased AGE and RAGE interactions. Low levels of sRAGE would also increase the levels of serum TNF-á and sVCAM-1.<p> The objectives of this study were to determine whether: (1) the levels of serum sRAGE are lower and the levels of AGE, TNF-á and sVCAM-1 are higher in NSTEMI patients compared to control; (2) the levels of serum sRAGE are lower and the levels of AGE, TNF-á and sVCAM-1 are higher in NSTEMI patients with restenosis compared to those without restenosis; and (3) sRAGE or AGE/sRAGE ratio may serve as a biomarker/ predictor of NSTEMI and post-PCI restenosis.<p> The study objectives include 46 consecutive NSTEMI patients undergoing elective PCI and 28 healthy age-matched male controls. Pre-PCI and 6 month post-PCI angiography were performed in all NSTEMI patients. Blood samples were collected at designated intervals for the measurement of sRAGE, AGE, TNF-á, and sVCAM-1 using commercially available enzyme-linked immunosorbent assay (ELISA) kits.<p> The levels of serum sRAGE were lower and those of TNF-á, sVCAM-1, AGE and AGE/sRAGE were higher in NSTEMI patients compared to control subjects. (sRAGE, 884.55 ± 50 vs. 1287 ± 41.5 pg/mL{p<0.001}; TNF-á, 23.1 ± 2.3 vs. 10.3 ± 0.8 pg/mL {p<0.002}; sVCAM-1, 1059.62 ± 70.8 vs. 651 ± 35.5 ng/mL {p<0.0003}, AGE, 1192.50 ± 82.6 vs. 669.40 ± 47.9 ng/mL {p<0.001}; and AGE/sRAGE, 1.75 ± 0.17 vs. 0.52 ± 0.06 {p<0.001}).<p> The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the sRAGE biomarker test were 59%, 100%, 100%, 100% and 74% respectively, while those of the AGE/sRAGE test were 85%, 91%, 97%, 67% and 86%, respectively, in the diagnosis of patients with NSTEMI acute coronary syndrome. The pre-PCI levels of serum sRAGE in patients with restenosis were significantly lower (p<0.001) than in patients without restenosis (610.6 ± 24.1 vs. 1143.8 ± 52.5 pg/mL). The post-PCI levels of serum sRAGE were significantly lower (p<0.0001) in patients with restenosis compared to those without restenosis (477 ± 18.6 vs. 1106.7 ± 41.9 pg/mL). The pre-PCI levels of serum TNF-á and sVCAM-1 were significantly higher (p<0.001 and p<0.001) in patients with restenosis compared to those without restenosis (TNF-á, 37.9 ± 2.5 vs. 11.6 ± 0.41 pg/mL; sVCAM-1, 1381.8 ± 63.5 vs. 811.37 ± 26.5 ng/mL). The post PCI levels of serum TNF-á and sVCAM-1 were also significantly higher (p<0.0001 and p<0.0001) in patients with restenosis than in patients without restenosis (TNF-á, 48.4 ± 1.4 vs. 12.5 ± 0.44 pg/mL; sVCAM-1, 1381.8 ± 63.5 vs. 762.2 ± 26.4 ng/mL). The post-PCI levels sRAGE were lower while those of TNF-á and sVCAM-1 were higher compared to the pre-PCI levels in patients with restenosis. However, the pre- and post-PCI levels of serum sRAGE, TNF-á and sVCAM-1 were similar in patients without restenosis. The pre-PCI levels of serum AGE and AGE/sRAGE were significantly higher (p<0.001 and p<0.001) in patients with restenosis compared to those without restenosis (AGE, 1512.1 ± 84.53 vs. 891.7 ± 92.4 ng/mL; 2.39 ± 0.20 vs. 1.03 ± 0.17).<p> The sensitivity, specificity, PPV, NPV, and accuracy of the pre-PCI sRAGE tests were 73%, 100%, 100%, 80%, and 87%, respectively while those of the AGE/sRAGE tests were 81%, 94%, 93%, 84% and 88%, respectively in identifying patients with post-PCI restenosis.<p> In conclusion the results suggest that: (1) the levels of serum sRAGE are lower while those of TNF-á, sVCAM-1, AGE and AGE/sRAGE are higher in NSTEMI patients compared to control subjects; (2) serum levels of sRAGE are negatively correlated with the number of diseased vessels; (3) Both low sRAGE and high AGE/sRAGE may serve as a biomarker/predictor of NSTEMI, but AGE/sRAGE has a greater sensitivity compared to sRAGE; (4) the pre-PCI levels of serum sRAGE are lower while those of AGE/sRAGE are higher in patients with restenosis compared to those without restenosis; and (5) both low sRAGE and high AGE/sRAGE may serve as a predictor/ biomarker of post-PCI restenosis; however, AGE/sRAGE has a greater sensitivity than sRAGE.

The principal cause of non-ST-segment myocardial infarction (NSTEMI), a subclass of acute coronary syndrome (ACS), is thrombosis and the underlying cause is atherosclerosis. Percutaneous coronary intervention (PCI) is one of the treatments to attenuate the ischemic effects of severe coronary artery stenosis. However, restenosis following PCI (post-PCI) is a major problem for the long-term success of the procedure. Recently, the interaction of advanced glycation end products (AGE) with the receptor for advanced glycation end products (RAGE) has been implicated in the development of atherosclerosis in animal models. Interaction of AGE with RAGE results in activation of nuclear factor kappa-B (NF-êB), release of cytokines including tumor necrosis factor-alpha (TNF-á), the expression of adhesion molecules including soluble vascular adhesion molecule-1 (sVCAM-1) and induction of oxidative stress all of which have been implicated in the development of atherosclerosis. The soluble receptor for advanced glycation end products (sRAGE) acts as a decoy for RAGE ligands (AGEs) and this occurs by competing with RAGE. In animal models, balloon inflation and de-endothelialization of the carotid artery increase the concentration of AGE and RAGE in the arterial wall and induces neointimal hyperplasia and stenosis. Treatment with sRAGE in animal models reduces neointimal growth and decreases smooth muscle cell migration and proliferation and expression of extracellular matrix.<p> It is hypothesized that NSTEMI and post-PCI restenosis may be due to low levels of serum sRAGE resulting in increased AGE and RAGE interactions. Low levels of sRAGE would also increase the levels of serum TNF-á and sVCAM-1.<p> The objectives of this study were to determine whether: (1) the levels of serum sRAGE are lower and the levels of AGE, TNF-á and sVCAM-1 are higher in NSTEMI patients compared to control; (2) the levels of serum sRAGE are lower and the levels of AGE, TNF-á and sVCAM-1 are higher in NSTEMI patients with restenosis compared to those without restenosis; and (3) sRAGE or AGE/sRAGE ratio may serve as a biomarker/ predictor of NSTEMI and post-PCI restenosis.<p> The study objectives include 46 consecutive NSTEMI patients undergoing elective PCI and 28 healthy age-matched male controls. Pre-PCI and 6 month post-PCI angiography were performed in all NSTEMI patients. Blood samples were collected at designated intervals for the measurement of sRAGE, AGE, TNF-á, and sVCAM-1 using commercially available enzyme-linked immunosorbent assay (ELISA) kits.<p> The levels of serum sRAGE were lower and those of TNF-á, sVCAM-1, AGE and AGE/sRAGE were higher in NSTEMI patients compared to control subjects. (sRAGE, 884.55 ± 50 vs. 1287 ± 41.5 pg/mL{p<0.001}; TNF-á, 23.1 ± 2.3 vs. 10.3 ± 0.8 pg/mL {p<0.002}; sVCAM-1, 1059.62 ± 70.8 vs. 651 ± 35.5 ng/mL {p<0.0003}, AGE, 1192.50 ± 82.6 vs. 669.40 ± 47.9 ng/mL {p<0.001}; and AGE/sRAGE, 1.75 ± 0.17 vs. 0.52 ± 0.06 {p<0.001}).<p> The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the sRAGE biomarker test were 59%, 100%, 100%, 100% and 74% respectively, while those of the AGE/sRAGE test were 85%, 91%, 97%, 67% and 86%, respectively, in the diagnosis of patients with NSTEMI acute coronary syndrome. The pre-PCI levels of serum sRAGE in patients with restenosis were significantly lower (p<0.001) than in patients without restenosis (610.6 ± 24.1 vs. 1143.8 ± 52.5 pg/mL). The post-PCI levels of serum sRAGE were significantly lower (p<0.0001) in patients with restenosis compared to those without restenosis (477 ± 18.6 vs. 1106.7 ± 41.9 pg/mL). The pre-PCI levels of serum TNF-á and sVCAM-1 were significantly higher (p<0.001 and p<0.001) in patients with restenosis compared to those without restenosis (TNF-á, 37.9 ± 2.5 vs. 11.6 ± 0.41 pg/mL; sVCAM-1, 1381.8 ± 63.5 vs. 811.37 ± 26.5 ng/mL). The post PCI levels of serum TNF-á and sVCAM-1 were also significantly higher (p<0.0001 and p<0.0001) in patients with restenosis than in patients without restenosis (TNF-á, 48.4 ± 1.4 vs. 12.5 ± 0.44 pg/mL; sVCAM-1, 1381.8 ± 63.5 vs. 762.2 ± 26.4 ng/mL). The post-PCI levels sRAGE were lower while those of TNF-á and sVCAM-1 were higher compared to the pre-PCI levels in patients with restenosis. However, the pre- and post-PCI levels of serum sRAGE, TNF-á and sVCAM-1 were similar in patients without restenosis. The pre-PCI levels of serum AGE and AGE/sRAGE were significantly higher (p<0.001 and p<0.001) in patients with restenosis compared to those without restenosis (AGE, 1512.1 ± 84.53 vs. 891.7 ± 92.4 ng/mL; 2.39 ± 0.20 vs. 1.03 ± 0.17).<p> The sensitivity, specificity, PPV, NPV, and accuracy of the pre-PCI sRAGE tests were 73%, 100%, 100%, 80%, and 87%, respectively while those of the AGE/sRAGE tests were 81%, 94%, 93%, 84% and 88%, respectively in identifying patients with post-PCI restenosis.<p> In conclusion the results suggest that: (1) the levels of serum sRAGE are lower while those of TNF-á, sVCAM-1, AGE and AGE/sRAGE are higher in NSTEMI patients compared to control subjects; (2) serum levels of sRAGE are negatively correlated with the number of diseased vessels; (3) Both low sRAGE and high AGE/sRAGE may serve as a biomarker/predictor of NSTEMI, but AGE/sRAGE has a greater sensitivity compared to sRAGE; (4) the pre-PCI levels of serum sRAGE are lower while those of AGE/sRAGE are higher in patients with restenosis compared to those without restenosis; and (5) both low sRAGE and high AGE/sRAGE may serve as a predictor/ biomarker of post-PCI restenosis; however, AGE/sRAGE has a greater sensitivity than sRAGE.

名古屋大学博士学位論文 学位の種類:博士(医療技術学) (課程) 学位授与年月日:平成20年3月25日

名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成24年2月29日 石黒久昌氏の博士論文として提出された

Bakgrund: Efter akut kranskärlssjukdom är det viktigt att förändra sin livsstil då det har stor betydelse för framtidsutsikten för dessa patienter. Trots detta så förändrar inte alla patienter sina livsstilsvanor, eller klarar av att bibehålla de nyligen förändrade vanorna.   Syfte: Syftet var att studera vad som påverkar genomförandet av livsstilsförändringar hos personer i efterförloppet av akut kranskärlssjukdom.   Metod: Litteraturstudie med ett systematiskt tillvägagångssätt. Datainsamling genomfördes i databaserna CINAHL, PsycINFO, PubMed, Swemed+ och UniSearch. Efter datainsamling och kvalitetsgranskning inkluderades 15 artiklar varav nio kvalitativa artiklar och sex kvantitativa artiklar. För bearbetning av data utfördes en analys där fyra huvudkategorier identifierades.   Resultat: De fyra huvudkategorierna som identifierades var: Den enskilde individen, Kunskap, Inre faktorer och Yttre faktorer. Dessa områden kunde både främja och/eller hämma genomförandet av livsstilsförändring i efterförloppet av akut kranskärlssjukdom.    Konklusion: Sjuksköterskan bör vara medveten om den multifaktoriella process som livsstilsförändring innebär för patienten. Patientens behov kan tillgodoses genom tydlig information om sjukdomen men även andra aspekter såsom livsstilsförändring och hantering av förändring. Patienten behöver stöd från sjukvården, likasinnade och närstående för att kunna förändra sin livsstil.