The Correlation Clinical Study of Renin Angiotensin System Inhibitors and Outcomes in Patients Undergoing Cardiac Surgery
|Keywords||cardiac surgery prognosis renin-angiotensin system inhibitors acutekidney injury|
BackgroundWith China’s rapid economic development, the aging of society and modernizing lifestyles, coronary heart disease gradually increased, but also degenerative valvular disease gradually increased. Cardiac surgery is still the primary means of treatment of complex coronary artery disease and severe valvular disease.While in the past few decades, the field of cardiac surgery has made great progress, but cardiac surgery-related complications and mortality remains relatively high. According to the Society of Thoracic Surgeons (STS)2009year Report:valve replacement plus coronary artery bypass surgery mortality rate was6.8%, overall incidence of complications was30.1%, of which, stroke was2.9%, kidney failure9.1%, reoperation11.9%, prolonged ventilator21.2%and sternal infection0.7%.To reduce mortality and other related complications and improve the prognosis of patients, a personalized treatment plan for cardiac surgery were developed, such as off-pump coronary artery bypass surgery, minimally invasive surgery, robotic surgery and different myocardial protection strategies. However, there were still lacking clinically effective prevention to protect the heart, the brain and the kidney. Therefore, it is imperative for anesthesiologist to explore better strategies to reduce mortality and major organ complications in patients undergoing cardiac surgeryRenin-angiotensin system (RAS) plays an important role in the pathological mechanisms of atherosclerosis, hypertension, left ventricular hypertrophy, myocardial infarction(MI) and congestive heart failure (CHF). RAS inhibitors, including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin Ⅱ receptor blocker (ARB) have been shown to be effective in the treatment of hypertension and reducing cardiovascular morbidity and mortality. They were often used to treat high blood pressure, coronary heart disease, and diabetic nephropathy. It was reported that long-term use of RAS inhibitors can provide end-organ protection and reduction of cardiovascular and renal events in patients. However, preoperative RAS inhibitors on prognosis of cardiac surgery remained uncertain, and the conclusions of the existing literature were still conflicting. The purpose of this study was to evaluate preoperative RAS inhibitors on the prognosis of cardiac surgery.MethodsThis study is a clinical research. The study population was patients undergoing cardiac surgery at a U.S. University Medical Center from January2001to December2011. All patients treated with ACEi/ARBs constituted the RAS inhibitor group. They were compared with the remaining patients who had not received ongoing RAS inhibitor therapy (non-RAS inhibitor group) preoperatively.Data were abstracted from a single institution’s Society of Thoracic Surgeons (STS) database and hospital medical records including demographics, preoperative risk factors, preoperative medications, intraoperative data, postoperative cardiocerebral events, renal function and operative mortality. Independent investigators prospectively collected the data on each patient during the course of hospitalization.Acute kidney injury (AKI) was defined using Acute Kidney Injury Network (AKIN) classification using creatinine criteria. Stage1, increase of serum creatinine by≥0.3mg/dl or increase to≥150-200%from baseline (postoperative creatinine level divided by last creatinine level); stage2, increase of serum creatinine to>200%-300%from baseline; and stage3, increase of serum creatinine to greater than300%from baseline or serum creatinine level≥4mg/dl or treatment with new renal replacement therapy.Statistical analysis Categorical variables were expressed as a percentage, continuous variables were expressed as mean±standard deviation, and the chi-square test were used for categorical variables; the t-test were used for continuous variables using. Propensity score was used to mitigate selection bias. Logistic regression models were developed for analysing risk factors and protective factors of the outcomes of cardiac surgery. Kaplan-Meier methods were used to calculate survival rate, and log-rank test were used for comparing them. Cox proportional hazards regression model was developed to analyse risk factors and protective factors for survival time. Statistical analysis was performed with SAS version9.3(Cary, NC).Results1Baseline characteristicRAS inhibitor group were more associated with diabetes, heart disease, hypertension, hyperlipidemia, cerebrovascular disease (CVD), chronic lung disease, myocardial infarction, low cardiac output, the use of intraaortic balloon counterppulsation (IABP) history, preoperative lipid-lowering drugs, aspirin and nitrates treatment(P<0.05). In age, gender, body mass index (BMI), smoking, peripheral vascular disease (PVD), preoperative serum creatinine, renal failure (RF), chronic heart failure (CHF), preoperative P-blockers, the two groups have no significant difference (P>0.05). There were more Caucasians in the non-RAS inhibitor group (P=0.006).2Intraoperative characteristicThere was no significant difference in cardiopulmonary bypass time and aortic clamping time between two groups.3postoperative outcome (prognosis)3.1Operative mortalityOver all, the operative mortality was3.7%(87/2,322). This study showed that the operative mortality was2.99%(37/1,239) for patients who received pre-op RAS inhibitors and4.62%(50/1,083) for patients who did not take pre-op RAS inhibitors (P=0.039, odds ratio (OR):0.636,95%confidence interval (CI):0.42-0.981)3.2Acute kidney injury (AKI)The incidence of acute kidney injury was27.2%in the RAS inhibitor group and it was34.0%in the non-RAS inhibitor group. RAS inhibitor can significantly reduce the incidence of the acute kidney injury (P=0.0007), and OR (odds ratio) is0.726,95%CI (confidence interval)0.60-0.87. There was a significant difference between the two groups in AKI Stage1patients (23.1%vs.28.2%,p=0.007). Although the results were in favor of RAS inhibitor group, there were no statistical significances between the two groups in AKI Stage II and III.3.3SepticemiaThe incidence of sepsis was significantly different between two groups. RAS inhibitors can reduce the incidence of sepsis (1.9%vs3.5%,95%CI:0.324-0.912, P=0.019). 3.4Other OutcomesCardiac arrest (1.7%vsl.8%, P=0.966), permanent stroke (1.1%vs1.6%, P=0.268) and deep sternum infection (1.0%vs1.2%, P=0.589), the incidence of them in RAS inhibitor group were lower than them in non-inhibitor group, but there were no significant difference between two groups. There were no significant differences in the incidence of perioperative myocardial infarction, heart block, transient stroke, ICU time, postoperative ventilator time, readmission equal and/or less than30days between two groups.4Logistic regression modelsWe created three logistic regression models for operative mortality, acute kidney injury and sepsis as the dependent variable, respectively. Selection of independent variables was based on the literature, clinical rationality and variables in database. These variables include RAS inhibitors, age, gender, race, body mass index (BMI), diabetes, hypertension, hypercholesterolemia, renal failure, smoking, chronic lung disease, cerebrovascular disease, peripheral vascular disease, myocardial infarction, congestive heart failure, ejection fraction (EF), aortic balloon counterpulsation (IABP), CPB time and aortic clamping time.The discriminatory ability of the multivariate logistic model was acceptable for operative mortality (C statistic:0.819), AKI (C statistic:0.651), and septicemia (C statistic:0.827). The model was well calibrated among deciles of observed and expected risks for operative mortality (Hosmer-Lemeshow P=0.1026), AKI (Hosmer-Lemeshow P=0.4461), and septicemia (Hosmer-Lemeshow P=0.2409).4.1Operative mortalityRAS inhibitor therapy is the independent protective factor (OR:0.539,95%CI:0.384-0.758, P=0.0004). While the aged, female, non-white race, renal failure, low ejection fraction, chronic lung disease, IABP and CPB time were independent risk factors.4.2Acute kidney injury (AKI)For AKI, the preoperative RAS inhibitor therapy is an independent protective factor (OR:0.764,95%CI:0.67-0.873, P<0.0001). The aged, diabetes, hypertension, chronic lung disease, heart valve surgery and emergency surgery are risk factors for AKI.4.3SepticemiaRAS inhibitor therapy is an independent protective factor for septicemia (OR:0.515,95%CI:0.348-0.761, P=0.0009). Female, non-white race, renal failure, myocardial infarction, CPB time, emergency surgery and heart valve surgery are risk factors.5One-year mortality and survival analysis5.1One-year mortality after surgeryOne-year mortality was4.12%in the RAS inhibitors group versus7.39%in the non-RAS inhibitors group(OR,0.538;95%CI,0.377-0.868; P=0.003)5.2Analysis of survival after surgeryKaplan-Meier method were used to calculate survival rates. Survival rate in RAS inhibitor group was significantly higher than the non-RAS inhibitor group (corrected by propensity score,95.6%vs92.1%, P=0.004).5.3. Cox proportional hazards regression modelSurvival time as the dependent variable, RAS inhibitors and other preoperative and intraoperative risk factors as covariates, we establish Cox proportional hazards regression model. RAS inhibitors are protective factors that can help to prolong the survival time, but age, renal failure, low EF and cardiopulmonary bypass time are risk factors.ConclusionOur study show that preoperative RAS inhibitors can significantly reduce AKI, sepsis and operative mortality in patients undergoing cardiac surgery and was more likely to have better one-year survival.