<p><strong>Background:</strong> Major adverse cardiac events, MACE – a composite endpoint of cardiac death and nonfatal myocardial infarction (MI) – are severe harmful outcomes that commonly arise after elective vascular surgeries. As current pre-operative risk prediction models are not as effective in predicting post-operative outcomes, this thesis will discuss the key results of an individual patient data meta-analysis that is based on data from six cohort studies of patients undergoing vascular surgery.</p> <p><strong>Objectives:</strong> The purpose of this thesis is to determine optimal thresholds of continuous covariates and create a prediction model for major adverse cardiac events (MACE), within 30 days after a vascular surgery. The goals include exploring the minimum p-value method to dichotomize cutpoints for continuous variables; employing logistic regression analysis to determine a prediction model for MACE; evaluating its validity against other samples; and assessing its sensitivity to clustering effects. The secondary objectives are to determine individual models for predicting all-cause mortality, cardiac death, and nonfatal MI within 30 days of a vascular surgery, using the final covariates assessed for MACE.<strong></strong></p> <p><strong>Methods: </strong>Both B-type naturietic peptide (BNP) and its N-terminal fragment (NTproBNP) are independently associated with cardiovascular complications after noncardiac surgeries, and particularly frequent after noncardiac vascular surgeries. In a previous study, these covariates were dichotomized using the receiver operating characteristic (ROC) curve approach and a simple logistic regression (SLR) model was created for MACE [1]. The first part of this thesis applies the minimum p-value method to determine a threshold for each natriuretic peptide (NP), BNP and NTproBNP. SLR is then used to model the prediction of MACE within 30 days after a patient’s vascular surgery. Comparisons were made with the ROC curve approach to determine the optimal thresholds and create a prediction model. The validity of this model was tested using bootstrap samples and its robustness was assessed using a mixed effects logistic regression (MELR) model and a generalized estimating equation (GEE). Finally, MELR was performed on each of the secondary outcomes.</p> <p><strong>Results:</strong>A variable, ROC_thrshld, was created to represent the cutpoints of Rodseth’s ROC curve approach, which identified 116pg/mL and 277.5pg/mL to be the optimal thresholds for BNP and NTproBNP, respectively [1]. The minimum p-value method dichotomized these NP thresholds as BNP: 115.57pg/mL (p</p> <p><strong>Discussion:</strong> One key limitation to this thesis is the small sample size received for NTproBNP. Also, determining only one cutpoint for each NP concentration may not be sufficient, since dichotomizing continuous factors can lead to loss of information along with other issues. Further research should be performed to explore other possible cutpoints along with performing reclassification to observe improvements in risk stratification. After validating our final model against other samples, we can conclude that MINP_thrshld, the type of surgery, and diabetes are significant covariates for the prediction of MACE. With the simplicity in only requiring a blood test to measure NP concentration levels and easily learning the status of the other two factors, minimal effort is needed in calculating the points and risk estimates for each patient. Further research should also be performed on the secondary outcomes to examine other factors that may be useful in prediction.</p> <p><strong>Conclusions: </strong>The minimum p-value method produced similar results to the ROC curve method in dichotomizing the NP concentration levels. The cutpoints for BNP and NTproBNP were 115.57pg/mL and 241.7 pg/mL, respectively. Further research needs to be performed to determine the optimality of the final prediction model of MACE, with covariates MINP_thrshld, type of surgery, and diabetes mellitus. <strong></strong></p> <p><strong><br /></strong></p> / Master of Science (MSc)

Os objetivos deste estudo foram: avaliar as freqüências de partos vaginais e cesáreas em mulheres portadoras de cardiopatias, bem como a distribuição dos partos nos diferentes subgrupos de doenças cardíacas: arritmias (A), cardiopatias congênitas (CC) e cardiopatias adquiridas (CA); analisar os fatores clínicos e obstétricos que estiveram relacionados à determinação da via de parto no grupo total de cardiopatas e também nos subgrupos, e avaliar a associação entre o tipo de parto e complicações clínicas e obstétricas. Foram analisados retrospectivamente os dados referentes a 571 gestações de 556 mulheres internadas para parto na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 2001 e 2005. A composição dos grupos foi: A - 57 casos (10%), CC - 163 casos (28,6%) e CA - 351 casos (61,4%). A taxas de cesárea foram 57,2% (total), 45,6% (A), 64,2% (CC) e 55,7% (CA). A indicação da cesárea foi obstétrica em 77% dos casos. Analisando os 425 casos sem cesáreas anteriores, as taxas de cesárea foram: 47,1% (total), 37,8% (A), 57,8% (CC) e 43,3% (CA). A probabilidade de parto cesáreo esteve relacionada à presença de cesárea anterior, idade gestacional no parto inferior a 37 semanas, presença de intercorrências obstétricas, diagnóstico de cardiopatia congênita, insuficiência cardíaca classe funcional (CF) III ou IV, e uso de medicamentos de ação cardiovascular. A paridade maior ou igual a um diminuiu a probabilidade de cesárea. A presença de cesárea anterior foi o principal fator relacionado à probabilidade de parto cesáreo nesta população. Nos subgrupos de cardiopatia (sem cesárea anterior) a probabilidade de cesárea esteve aumentada na presença dos seguintes fatores: A - uso de medicação cardiovascular; CC - CF III/IV e intercorrências obstétricas; CA -intercorrências obstétricas e idade gestacional no parto inferior a 37 semanas. A ocorrência de complicações obstétricas foi 6,8% (total), sendo maior em A (18,6%) e nos partos vaginais (10,7%); complicações clínicas maiores ocorreram em 2,5% dos casos e foram mais freqüentes nos casos de cesárea (3,8%). Conclusão: As taxas de cesárea observadas em gestante com cardiopatia foram elevadas (em especial nos casos de cardiopatia congênita) e correlacionadas à presença de cesárea anterior, insuficiência cardíaca CF III/IV, uso de medicamentos de ação cardiovascular, presença de intercorrências obstétricas e idade gestacional no parto inferior a 37 semanas. / This study reviewed the data of 571 pregnancies in 556 pregnant women with heart disease admitted for delivery in a tertiary university hospital between 2001 and 2005. The objectives were to assess the prevalence of cesarean sections and vaginal births among the whole group of cases and in three subgroups: patients with arrhythmias (A - 57 cases / 10%), congenital diseases (CD - 163 cases / 28,6%) and acquired diseases (AD - 351 cases / 61,4%), and to determine the clinical and obstetrical factors related to the mode of delivery in the whole population and in the subgroups, as well as the association between the mode of delivery and clinical and obstetrical complications. The frequencies of cesarean sections were: 57,2% (whole population), 45,6% (A), 64,2% (CD) and 55,7% (AD); the cesarean sections were performed due to obstetrical reasons in 77% of the cases. In the 425 cases with no previous cesarean sections, the frequencies of c-sections deliveries were 47,1% (whole group), 37,8% (A), 57,8% (CD) and 43,3% (AD). The factors related to a higher probability of cesarean section were: previous cesarean section, gestational age at delivery of less than 37 weeks, presence of obstetrical events, diagnosis of congenital heart disease, heart failure (NYHA functional class III/IV) and use of cardiovascular drugs. The parity above 1 was related to a lesser probability of csections, and previous cesarean was the main factor related to the risk of abdominal delivery. In the cases with no previous cesarean sections, according to the subgroups of heart disease, the probability of cesarean section was heightened in the presence of the following factors: group A: use of cardiovascular drugs, CD: functional class III/IV and obstetrical events and AD: obstetrical events and gestational age in delivery less than 37 weeks. The rate of obstetrical complications was 6,8%, most of them in group A and in vaginal birth. Major clinical complications occurred in 2,5% of the cases, and were more related to cesarean sections (3,8%). Conclusion: the rates of cesarean sections observed in pregnant women with heart disease were high (mainly in the CD group), and related to previous cesarean sections, heart failure, use of cardiovascular drugs, presence of obstetrical events and gestational age at delivery less than 37 weeks.

Os objetivos deste estudo foram: avaliar as freqüências de partos vaginais e cesáreas em mulheres portadoras de cardiopatias, bem como a distribuição dos partos nos diferentes subgrupos de doenças cardíacas: arritmias (A), cardiopatias congênitas (CC) e cardiopatias adquiridas (CA); analisar os fatores clínicos e obstétricos que estiveram relacionados à determinação da via de parto no grupo total de cardiopatas e também nos subgrupos, e avaliar a associação entre o tipo de parto e complicações clínicas e obstétricas. Foram analisados retrospectivamente os dados referentes a 571 gestações de 556 mulheres internadas para parto na Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 2001 e 2005. A composição dos grupos foi: A - 57 casos (10%), CC - 163 casos (28,6%) e CA - 351 casos (61,4%). A taxas de cesárea foram 57,2% (total), 45,6% (A), 64,2% (CC) e 55,7% (CA). A indicação da cesárea foi obstétrica em 77% dos casos. Analisando os 425 casos sem cesáreas anteriores, as taxas de cesárea foram: 47,1% (total), 37,8% (A), 57,8% (CC) e 43,3% (CA). A probabilidade de parto cesáreo esteve relacionada à presença de cesárea anterior, idade gestacional no parto inferior a 37 semanas, presença de intercorrências obstétricas, diagnóstico de cardiopatia congênita, insuficiência cardíaca classe funcional (CF) III ou IV, e uso de medicamentos de ação cardiovascular. A paridade maior ou igual a um diminuiu a probabilidade de cesárea. A presença de cesárea anterior foi o principal fator relacionado à probabilidade de parto cesáreo nesta população. Nos subgrupos de cardiopatia (sem cesárea anterior) a probabilidade de cesárea esteve aumentada na presença dos seguintes fatores: A - uso de medicação cardiovascular; CC - CF III/IV e intercorrências obstétricas; CA -intercorrências obstétricas e idade gestacional no parto inferior a 37 semanas. A ocorrência de complicações obstétricas foi 6,8% (total), sendo maior em A (18,6%) e nos partos vaginais (10,7%); complicações clínicas maiores ocorreram em 2,5% dos casos e foram mais freqüentes nos casos de cesárea (3,8%). Conclusão: As taxas de cesárea observadas em gestante com cardiopatia foram elevadas (em especial nos casos de cardiopatia congênita) e correlacionadas à presença de cesárea anterior, insuficiência cardíaca CF III/IV, uso de medicamentos de ação cardiovascular, presença de intercorrências obstétricas e idade gestacional no parto inferior a 37 semanas. / This study reviewed the data of 571 pregnancies in 556 pregnant women with heart disease admitted for delivery in a tertiary university hospital between 2001 and 2005. The objectives were to assess the prevalence of cesarean sections and vaginal births among the whole group of cases and in three subgroups: patients with arrhythmias (A - 57 cases / 10%), congenital diseases (CD - 163 cases / 28,6%) and acquired diseases (AD - 351 cases / 61,4%), and to determine the clinical and obstetrical factors related to the mode of delivery in the whole population and in the subgroups, as well as the association between the mode of delivery and clinical and obstetrical complications. The frequencies of cesarean sections were: 57,2% (whole population), 45,6% (A), 64,2% (CD) and 55,7% (AD); the cesarean sections were performed due to obstetrical reasons in 77% of the cases. In the 425 cases with no previous cesarean sections, the frequencies of c-sections deliveries were 47,1% (whole group), 37,8% (A), 57,8% (CD) and 43,3% (AD). The factors related to a higher probability of cesarean section were: previous cesarean section, gestational age at delivery of less than 37 weeks, presence of obstetrical events, diagnosis of congenital heart disease, heart failure (NYHA functional class III/IV) and use of cardiovascular drugs. The parity above 1 was related to a lesser probability of csections, and previous cesarean was the main factor related to the risk of abdominal delivery. In the cases with no previous cesarean sections, according to the subgroups of heart disease, the probability of cesarean section was heightened in the presence of the following factors: group A: use of cardiovascular drugs, CD: functional class III/IV and obstetrical events and AD: obstetrical events and gestational age in delivery less than 37 weeks. The rate of obstetrical complications was 6,8%, most of them in group A and in vaginal birth. Major clinical complications occurred in 2,5% of the cases, and were more related to cesarean sections (3,8%). Conclusion: the rates of cesarean sections observed in pregnant women with heart disease were high (mainly in the CD group), and related to previous cesarean sections, heart failure, use of cardiovascular drugs, presence of obstetrical events and gestational age at delivery less than 37 weeks.