Editorial article
Search for biomarkers to identify surgical patients at high cardiovascular and perioperative mortality risk
Búsqueda de biomarcadores para la identificación de pacientes quirúrgicos de alto riesgo cardiovascular y mortalidad perioperatoria elevada
Servicio de Anestesia y Reanimación, Hospital Universitario de la Princesa, Madrid, Spain
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Rodríguez-Villar, J.L. Rodríguez-García, J. Arévalo-Serrano, M. Sánchez-Casado, H. Fletcher" "autores" => array:5 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Rodríguez-Villar" ] 1 => array:2 [ "nombre" => "J.L." "apellidos" => "Rodríguez-García" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Arévalo-Serrano" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Sánchez-Casado" ] 4 => array:2 [ "nombre" => "H." "apellidos" => "Fletcher" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0034935617301044" "doi" => "10.1016/j.redar.2017.03.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935617301044?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192917301622?idApp=UINPBA00004N" "url" => "/23411929/0000006400000010/v1_201711240853/S2341192917301622/v1_201711240853/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "Search for biomarkers to identify surgical patients at high cardiovascular and perioperative mortality risk" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "547" "paginaFinal" => "549" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Planas, F. Ramasco" "autores" => array:2 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Planas" "email" => array:1 [ 0 => "antonioplanas@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "F." "apellidos" => "Ramasco" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Anestesia y Reanimación, Hospital Universitario de la Princesa, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Búsqueda de biomarcadores para la identificación de pacientes quirúrgicos de alto riesgo cardiovascular y mortalidad perioperatoria elevada" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Since the second half of the 20th century, surgery has taken centre stage in public health. What was once an exceptional event to treat wounds, amputate limbs, etc., is now the first-choice treatment in many oncological and cardiovascular diseases, or to improve the quality of life of patients with chronic diseases such as osteoarthritis. Since the mid 1950s, the number of surgical interventions worldwide has increased exponentially, and current estimates suggest that over 300 million patients undergo surgery each year, which is equivalent to 1 surgical intervention for every 25 inhabitants/year. The rate of surgical interventions in developed countries is even higher, affecting 1 in 10 inhabitants per year.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> In Spain, nearly five million surgical procedures are performed per year, of which approximately one third require hospitalisation for at least 24<span class="elsevierStyleHsp" style=""></span>h.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The real mortality rate associated with surgery is not known. While there are solid data showing the mortality rate of diseases such as myocardial infarction, cerebrovascular accident or pneumonia, perioperative mortality is not a primary diagnosis and its incidence has not been accurately estimated. The European Surgical Outcomes Study (EuSOS)<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> conducted in 2011 using data from about 50,000 adult patients undergoing non-cardiac surgery who required hospitalisation for at least 24<span class="elsevierStyleHsp" style=""></span>h, reported a crude mortality rate of 4% in the first 60 postoperative days. Even accepting lower mortality rates of 1%–2% and serious cardiovascular complication rates of 4%–8%, the high number of surgical interventions means that thousands of people are annually at risk of perioperative morbidity and mortality. Although surgery has great potential to cure and help patients, the enormous volume of surgical interventions also leads to a large number of perioperative deaths – a health problem that will only increase in the near future. Population ageing will drive up the number of surgical interventions performed on patients with more comorbidities, and this in turn will have an enormous impact on clinical outcomes.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The causes of perioperative mortality are not entirely clear, either, but data suggest that in about half of all cases it is due to cardiovascular complications. Although the number of deaths from cardiovascular causes is decreasing in the general population, the prevalence of cardiovascular risk factors and heart failure has increased, and cardiovascular diseases are now the most prevalent comorbidities in surgical patients. Surgery aggravates these conditions because it triggers a stress response initiated by tissue damage and mediated by neuroendocrine and neurovegetative factors, which increase myocardial oxygen consumption, fluid retention and risk of thrombosis. Other perioperative factors, such as hypothermia, haemorrhage, hypoxaemia or arterial hypotension ultimately contribute to perioperative ischaemia and myocardial dysfunction. Thus, perioperative cardiovascular complications will appear in patients with known or silent coronary disease or myocardial dysfunction undergoing surgical procedures associated with stress.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Because of this, early (preoperative) identification of patients at greater risk of morbidity and mortality is crucial in order to fully inform both them and their family members, and to allow the different medical teams to work together and form a realistic opinion of the surgical treatment and use certain evidence-based strategies that will reduce the rate of complications and interoperative mortality.</p><p id="par0025" class="elsevierStylePara elsevierViewall">High-risk patients are usually identified by means of cardiovascular risk indexes, with the Revised Cardiac Risk Index (Lee Index) being the most widely used and recommended by clinical guidelines for perioperative risk assessment.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> This Index assesses 5 risk factors in patients scheduled for high-risk surgery:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0030" class="elsevierStylePara elsevierViewall">History of ischaemic heart disease;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0035" class="elsevierStylePara elsevierViewall">History of congestive heart failure;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0040" class="elsevierStylePara elsevierViewall">History of cerebrovascular disease;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0045" class="elsevierStylePara elsevierViewall">Pre-operative treatment with insulin;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0050" class="elsevierStylePara elsevierViewall">Pre-operative creatinine >2<span class="elsevierStyleHsp" style=""></span>mg/d/176.8<span class="elsevierStyleHsp" style=""></span>μmol/L.</p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">The presence of 3 or more of these factors predicts, with certain limitations, a >10% rate of serious in-hospital cardiovascular complications, including cardiac death, compared with 0.5%–3.5% when no factor is present.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Biomarkers</span><p id="par0060" class="elsevierStylePara elsevierViewall">The term “biomarker” is used to define a “characteristic” or physiological, biochemical or morphological alteration that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Literally hundreds of new biomarkers are identified annually, and their use is revolutionising medical practice. Among them, N-terminal pro b-type natriuretic peptide (NT-proBNP) belongs to a family of polypeptide hormones involved in cardiovascular homeostasis and remodelling, mainly synthesised in ventricular cardiomyocytes in response to an increase in myocardial wall stress, inflammation or ischaemia. The physiological effects of this hormone are increased natriuresis and decreased peripheral vascular resistance. The determination of plasma levels of NT-proBNP has been used as a prognostic indicator in non-surgical patients with cardiac diseases, since plasma levels of this peptide are directly related to the severity of myocardial damage.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> The preoperative detection of NT-proBNP plasma levels has also proven useful for the prediction of perioperative morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In a recent study in 304 patients conducted in Spain, we determined the preoperative incidence of elevated serum levels of NT-proBNP in adult patients scheduled for major non-cardiac surgery who presented some of the 5 cardiovascular risk factors, and its association with 30-day mortality.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> Overall mortality in the first 30 postoperative days was 4.28% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>13). Of the 304 patients studied, 52% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>157) presented normal preoperative NT-proBNP levels; 30-day mortality in this group was 0.6% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1). Moderately high preoperative NT-proBNP levels were detected in 26% patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>79); 30-day mortality in this group was 3.8% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3). Finally, the remaining 22% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>68) presented pathological preoperative NT-proBNP levels; 30-day mortality in this group was 13.2% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9).</p><p id="par0070" class="elsevierStylePara elsevierViewall">In our opinion, the most important finding of our study was that about 50% of patients scheduled for non-cardiac surgery whose clinical history included some cardiac risk factors showed high preoperative levels of NT-proBNP. This multiplied the risk of 30-day mortality by a factor of up to 29.14. It is also important to note the negative predictive value of NTpro-BNP levels, in other words, the association between normal preoperative biomarker values and a favourable postoperative prognosis.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Given the prognostic significance of these findings, the Guidelines on non-cardiac surgery: cardiovascular assessment and management published in 2014 by the European Society of Cardiology and the European Society of Anaesthesiology,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> recommend considering preoperative NT-proBNP levels in preoperative risk stratification in patients scheduled for major non-cardiac surgery presenting at least 1 Lee index risk factor, in the case of vascular surgery, or 2 factors in the case of major non-vascular surgery (Class IIb; Level B).</p><p id="par0080" class="elsevierStylePara elsevierViewall">More recently, the Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment in non-cardiac surgery, published in 2017, recommend that NT-proBNP levels be measured before elective non-cardiac surgery in all patients aged ≥65 years, or between 45-65 years with “significant” cardiovascular disease, or with a Cardiac Risk Index score ≥1 (strong recommendation, moderate evidence).<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> These guidelines consider economic cost to be a determining factor in the decision to only measure biomarkers in patients with an estimated >5% risk of mortality or non-fatal postoperative myocardial infarction. Data from the VISION study (<span class="elsevierStyleItalic">V</span>ascular Events <span class="elsevierStyleItalic">i</span>n Noncardiac <span class="elsevierStyleItalic">S</span>urgery Pat<span class="elsevierStyleItalic">i</span>ents C<span class="elsevierStyleItalic">o</span>hort Evaluatio<span class="elsevierStyleItalic">n</span>)<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a> show that patients aged ≥65 years, or between 45 and 65 years with “significant” cardiovascular disease, present a >5% risk vs. a ≤2% risk in patients without these characteristics.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Preoperative determination of NT-proBNP in at-risk patients is a quick, objective, measurable and reliable preoperative risk stratification tool. Effective risk assessment is a major factor in programming shared care strategies involving Cardiology, Surgery, Intensive Care, Internal Medicine, Rehabilitation, Nursing and other hospital departments in accordance with evidence-based perioperative care protocols. This is the essence of the multidisciplinary teamwork and shared decision-making that forms the basis of Perioperative Medicine. Further studies are needed to corroborate the association between biomarkers and prognosis, new biomarkers need to be identified and pre-, intra- and postoperative protocols that can improve the outcomes need to be drawn up. These are the main challenges facing us in the future.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Biomarkers" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Planas A, Ramasco F. Búsqueda de biomarcadores para la identificación de pacientes quirúrgicos de alto riesgo cardiovascular y mortalidad perioperatoria elevada. Rev Esp Anestesiol Reanim. 2017;64:547–549.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0065" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An estimation of the global volume of surgery: a modelling strategy based on available data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.G. Weiser" 1 => "S.E. Regenbogen" 2 => "K.D. Thompson" 3 => "A.B. Haynes" 4 => "S.R. Lipsitz" 5 => "W.B. 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