In a prospective cohort study by Álvarez Zurro et al.1 the multivariate logistic regression analysis showed that increased preoperative and postoperative N terminal B-type natriuretic propeptide (NT-proBNP) levels were predictors of 30-day cardiovascular complications and all-cause mortality after noncardiac surgery in adults with cardiovascular risk factors. When the multivariable logistic regression analysis was used for controlling the potential effects of confounding variables on the measured outcomes in this study, however, we noted that only the revised cardiac risk index score was included in the models. In fact, the predictive value of the revised cardiac risk index for perioperative cardiovascular risk assessment has recently been questioned because of its suboptimal performance in patients undergoing noncardiac surgery with multiple risk factors.2 Moreover, addition of factors like age, general medical condition, more detailed classification of type of surgery and left bundle branch block, have been shown to improve predictive accuracy of the revised cardiac risk index for perioperative cardiovascular risk of noncardiac surgical patients.2–4 Thus, we believe that there are design limitations in the study by Álvarez Zurro et al.1 that make interpretation of their findings questionable.
First, illness severity, comorbidity and surgery burdens are mostly important determinants for postoperative short-term mortality of surgical patients. The study participants of this study were adults with cardiovascular risk factors undergoing elective noncardiac surgery and the mean age of the cohort was more than 70 years, but the authors did not provide the complete comparisons in the illness severity and comorbidity burden between patients with and without increased preoperative and postoperative NT-proBNP levels. Thus, it is unclear whether these patients were comparable with respect to the illness severity and comorbidity burden. Besides the six comorbidities included in the revised cardiac risk index, other preoperative characteristics of patients, such as anaemia and hypoalbuminemia, BMI more than 30, hepatic insufficiency and chronic obstructive pulmonary disease, have been shown to be important predictors of adverse cardiac events and death after noncardiac surgery.5,6 Actually, both the Deyo–Charlson index and the American Society of Anesthesiologists physical status classification have been recommended as reliable comorbidity burden instruments as they can assess the severity of disease with respect to surgical risk. Furthermore, the addition of functional capacity to the traditional American Society of Anesthesiologists physical status classification can improve its predictive value for short-term mortality and the occurrence of complications after noncardiac surgery.7 In addition, surgery burden of patients can also be assessed using the validated scoring systems, such as the Donati Surgical Risk Score, the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), the Estimation of Physiological Ability and Surgical Stress (E-PASS), the Surgical Risk Scale, and so forth.
Second, as a short-term outcome study, the important intraoperative and postoperative risk factors for short-term morbidity and mortality were not included in the multivariable models for adjusted odds ratios. In patients undergoing noncardiac surgery, intraoperative bleeding, hypotension, blood transfusion, use of a vasopressor, tachycardia and hypertension have been associated independently with postoperative myocardial injury and adverse cardiac outcomes.5 In comparison with current preoperative risk stratification indices, the inclusion of intraoperative elements has been shown to improve the ability to predict perioperative mortality and adverse cardiac events.8 Furthermore, the available literature provides compelling evidence that pulmonary complications are frequent after noncardiac surgery and are associated with increased postoperative short-term mortality.9 In addition, postoperative acute kidney injury, acute ischaemic stroke, delirium and deep vein thrombosis have been shown as significantly independent predictors of increased short-term mortality after noncardiac surgery.
In the study by Álvarez Zurro et al.1, the exclusion of the above mentioned perioperative factors in the multivariable logistic regression models may have confounded the associations of increased preoperative and postoperative NT-proBNP levels with short-term adverse cardiac outcomes after noncardiac surgery. Moreover, the multivariable logistic regression analysis is probably inadequate to differentiate whether increased preoperative or postoperative NT-proBNP level is a true determinant of postoperative outcomes or simply a synthetic manifestation of worse health status and heavier surgery burdens that can significantly increase postoperative short-term morbidity and mortality. Thus, we argue that the study by Álvarez Zurro et al.1 cannot prove whether statistical associations of high levels of preoperative and postoperative NT-proBNP levels with increased postoperative short-term adverse cardiac outcomes are causal relationships. To address these issues, researchers should perform large-scale, multicentre, randomised clinical trials in which the innumerable sources of bias that could contaminate the study end points are minimised.
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