Introdução. A elevação dos marcadores inflamatórios e de necrose miocárdica, após intervenção coronária percutânea, pode interferir nos resultados clínicos. No entanto, pouco se conhece sobre a terapia com estatinas pré-procedimento na redução destes marcadores em pacientes estáveis de baixo risco. Objetivo. Avaliar se o uso de estatina, antes do implante eletivo de stent coronário (ISC), reduz os níveis plasmáticos de marcadores inflamatórios e de necrose miocárdica, em pacientes com doença arterial coronária (DAC), estáveis e de baixo risco. Métodos. Neste estudo observacional prospectivo, 100 pacientes (n=50 em uso de estatina vs n=50 sem uso de estatina) com DAC estável foram submetidos à implante eletivo de stent coronário. Marcadores inflamatórios (proteína C reativa [PCR], interleucina[IL] -6, fator de necrose tumoral- e matrix metaloproteinase-9) e marcadores de necrose miocárdica (troponina I e CK-MB ) foram dosados antes e 24 horas após o implante eletivo de stent coronário. Resultados. Todos os pacientes apresentaram um aumento significativo de PCR e IL-6, após ISC. No entanto, esse aumento foi anulado em pacientes que faziam uso de estatina antes de ISC em relação àqueles que não tomavam estatina: 75% vs 150% (p <0,001) e 192% vs 300% (p <0,01) respectivamente. Os outros marcadores pró-inflamatórios foram semelhantes para os dois grupos de pacientes. Troponina I e CK-MB não se alterou, após ISC, independentemente, da terapia com estatina anterior ou não. Conclusão. O pré-tratamento com estatina reduz a magnitude da inflamação após ISC, demonstrada por aumentos significativamente menores de PCR e IL-6, em pacientes com DAC, estável e de baixo risco. Lesão miocárdica periprocedimento foi irrelevante e não foi afetada pela terapia com estatina pré-procedimento nesta população / Background. The elevation of markers of inflammatory and myocardial necrosis after percutaneous coronary intervention may interfere on clinical outcome. However, little is known concerning preprocedural statin therapy on the reduction of these markers in stable patients at low-risk. Objective. To evaluate if statin therapy prior to elective coronary stent implantation (CSI) reduces the plasma levels of markers inflammatory and myocardial necrosis in patients with low-risk stable coronary artery disease (CAD). Methods. In this prospective, observational study, 100 patients (n=50 on statin therapy vs n=50 not on statin) with stable CAD underwent elective CSI. Inflammatory (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor-a and matrix metalloproteinase-9) and myocardial necrosis markers (troponin I and CK-MB) were determined before and 24 hours after CSI. Results. All patients presented a significant increase of CRP and IL-6 after CSI. However, this increase was blunted in patients on statin therapy prior to CSI than those without statin therapy: 75% vs 150% (p<0.001), and 192% vs 300% (p<0.01), respectively for PCR and IL-6. The other pro-inflammatory markers were not affected in both sets of patients. Troponin I and CK-MB did not change after CSI regardless of previous statin therapy or not. Conclusions. Previous treatment with statins reduces the magnitude of procedural inflammation, denoted by markedly lower increases of CRP and IL-6 levels, in elective CSI on stable CAD patients. Periprocedural myocardial injury was not significant in this population

Despite increasingly sophisticated perioperative management, cardiovascular complications continue to be major challenges for the clinician. As a growing number of elderly patients with known coronary artery disease (CAD) or with risk factors for CAD are undergoing non-cardiac surgery, cardiovascular complications will remain a significant clinical problem in the future. The overall objective of this thesis was to study the incidence of myocardial damage and perioperative adverse cardiac events, to determine predictors of poor outcome and to assess the effect of a medical intervention in patients at risk undergoing non-cardiac surgery. The studies in this thesis were conducted on a total of 952 patients undergoing non-cardiac surgery. Studies I and IV were multicenter studies; whereas the patients included in studies II and III underwent non-cardiac surgery at Linkoping University Hospital, Sweden. The correlation between postoperative myocardial damage and short- and long-term outcome were studied in 546 patients, aged 70 years or older undergoing non-cardiac surgery of at least 30 minutes duration. This study showed a close correlation between postoperative myocardial damage and poor short- as well as long-term outcome. Elevated Troponin T was a strong independent predictor of mortality within one year of surgery. In 186 patients with ASA physical status classification III or IV undergoing non-elective surgery, the incidence of myocardial damage was 33%. In this study preoperative myocardial damage was an independent predictor of major adverse cardiac events in the postoperative period. In 69 patients with ASA physical status classification III &amp; IV undergoing acute hip surgery, we found a close correlation between elevated NT-proBNP value prior to surgery and cardiac complications in the postoperative period. To study the effect of acetylsalicylic acid on postoperative myocardial damage and cardiovascular events, 220 patients at risk were randomized to receive 75 mg of acetylsalicylic acid or placebo 7 days prior to surgery until the third postoperative day. This study showed that treatment with acetylsalicylic acid resulted in an 8% (95% CI 1-15%) absolute risk reduction of having a postoperative major adverse cardiac event. No statistically significant differences of bleeding complications were seen between the groups. In conclusion, this thesis contributes to the understanding of the clinical relevance of elevated cardiac markers (with or without clinical or ECG signs of myocardial damage) in patients undergoing elective or emergency surgery. Moreover, we have identified predictors of poor outcome in the perioperative period that could be used as tools for identifying patients at risk. Finally, we have shown that continuing acetylsalicylic acid in the perioperative period reduced the risk of major adverse cardiac events within 30 days of surgery.

Introdução. A elevação dos marcadores inflamatórios e de necrose miocárdica, após intervenção coronária percutânea, pode interferir nos resultados clínicos. No entanto, pouco se conhece sobre a terapia com estatinas pré-procedimento na redução destes marcadores em pacientes estáveis de baixo risco. Objetivo. Avaliar se o uso de estatina, antes do implante eletivo de stent coronário (ISC), reduz os níveis plasmáticos de marcadores inflamatórios e de necrose miocárdica, em pacientes com doença arterial coronária (DAC), estáveis e de baixo risco. Métodos. Neste estudo observacional prospectivo, 100 pacientes (n=50 em uso de estatina vs n=50 sem uso de estatina) com DAC estável foram submetidos à implante eletivo de stent coronário. Marcadores inflamatórios (proteína C reativa [PCR], interleucina[IL] -6, fator de necrose tumoral- e matrix metaloproteinase-9) e marcadores de necrose miocárdica (troponina I e CK-MB ) foram dosados antes e 24 horas após o implante eletivo de stent coronário. Resultados. Todos os pacientes apresentaram um aumento significativo de PCR e IL-6, após ISC. No entanto, esse aumento foi anulado em pacientes que faziam uso de estatina antes de ISC em relação àqueles que não tomavam estatina: 75% vs 150% (p <0,001) e 192% vs 300% (p <0,01) respectivamente. Os outros marcadores pró-inflamatórios foram semelhantes para os dois grupos de pacientes. Troponina I e CK-MB não se alterou, após ISC, independentemente, da terapia com estatina anterior ou não. Conclusão. O pré-tratamento com estatina reduz a magnitude da inflamação após ISC, demonstrada por aumentos significativamente menores de PCR e IL-6, em pacientes com DAC, estável e de baixo risco. Lesão miocárdica periprocedimento foi irrelevante e não foi afetada pela terapia com estatina pré-procedimento nesta população / Background. The elevation of markers of inflammatory and myocardial necrosis after percutaneous coronary intervention may interfere on clinical outcome. However, little is known concerning preprocedural statin therapy on the reduction of these markers in stable patients at low-risk. Objective. To evaluate if statin therapy prior to elective coronary stent implantation (CSI) reduces the plasma levels of markers inflammatory and myocardial necrosis in patients with low-risk stable coronary artery disease (CAD). Methods. In this prospective, observational study, 100 patients (n=50 on statin therapy vs n=50 not on statin) with stable CAD underwent elective CSI. Inflammatory (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor-a and matrix metalloproteinase-9) and myocardial necrosis markers (troponin I and CK-MB) were determined before and 24 hours after CSI. Results. All patients presented a significant increase of CRP and IL-6 after CSI. However, this increase was blunted in patients on statin therapy prior to CSI than those without statin therapy: 75% vs 150% (p<0.001), and 192% vs 300% (p<0.01), respectively for PCR and IL-6. The other pro-inflammatory markers were not affected in both sets of patients. Troponin I and CK-MB did not change after CSI regardless of previous statin therapy or not. Conclusions. Previous treatment with statins reduces the magnitude of procedural inflammation, denoted by markedly lower increases of CRP and IL-6 levels, in elective CSI on stable CAD patients. Periprocedural myocardial injury was not significant in this population

Background: Once aortic stenosis (AS) is severe, patients develop symptoms at different stages. Indeed, symptom status may correlate poorly with the grade of valve narrowing. Multiple pathophysiological mechanisms, other than valvular load, may explain the link between AS and symptom severity. We aimed to describe the relationship between the severity of symptoms and the characteristics of a cohort of patients with severe AS already referred for aortic valve replacement (AVR). Methods: We analyzed 118 consecutive patients (70 ± 9 years, 55% men) with severe AS referred for AVR. We identified 84 patients with New York Heart Association (NYHA) I–II, and 34 with NYHA III–IV symptoms. Clinical and echocardiographic parameters were compared between these two groups. Left ventricular ejection fraction (LVEF), global longitudinal peak systolic strain (GLPS), NT-pro-B-type natriuretic peptide (BNP), and high-sensitive troponin T (hs-TNT) were determined at the time of admission. Results: AS severity was similar between groups. Compared with the NYHA I–II group, patients in NYHA III–IV group were older and more likely to have comorbidities, worse intracardiac hemodynamics and more LV damage. Variables independently associated with NYHA III–IV symptomatology were the absence of sinus rhythm, higher E/e0 ratio, and increased hs-TNT. GLPS showed a good correlation not only with hs-TNT as a marker of myocardial damage, but also with markers of increased afterload imposed on LV, being not directly related with advanced symptoms. Conclusions: Advanced symptoms in patients with severe AS referred for AVR are associated with worse intracardiac hemodynamics, absence of sinus rhythm, and more myocardial damage. It supports the concept of transition from adaptive LV remodeling to myocyte death as an important determinant of symptoms of heart failure. :Einführung................................................................................................3 Publikationsmanuskript...........................................................................12 Zusammenfassung..................................................................................19 Literaturverzeichnis..................................................................................24 Erklärung über die eigenständige Abfassung der Arbeit.........................28 Darstellung des eigenen Beitrags............................................................29 Curriculum vitae.......................................................................................30 Danksagung.............................................................................................36