was read the article
array:26 [ "pii" => "S2174204917301265" "issn" => "21742049" "doi" => "10.1016/j.repce.2017.04.007" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "991" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2017" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2017;36:353-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2114 "formatos" => array:3 [ "EPUB" => 164 "HTML" => 1599 "PDF" => 351 ] ] "Traduccion" => array:1 [ "pt" => array:20 [ "pii" => "S0870255117302627" "issn" => "08702551" "doi" => "10.1016/j.repc.2017.03.004" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "991" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2017;36:353-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2640 "formatos" => array:3 [ "EPUB" => 205 "HTML" => 1976 "PDF" => 459 ] ] "pt" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Comentário editorial</span>" "titulo" => "Ameaças à validade interna em estudos de desnervação simpática renal" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "353" "paginaFinal" => "355" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Threats to internal validity in renal sympathetic denervation trials" ] ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eduardo Infante de Oliveira" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Infante de Oliveira" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204917301265" "doi" => "10.1016/j.repce.2017.04.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917301265?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117302627?idApp=UINPBA00004E" "url" => "/08702551/0000003600000005/v2_201705270134/S0870255117302627/v2_201705270134/pt/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2174204917301241" "issn" => "21742049" "doi" => "10.1016/j.repce.2016.09.013" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "951" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2017;36:357-64" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3472 "formatos" => array:3 [ "EPUB" => 216 "HTML" => 2603 "PDF" => 653 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Study of conicity index, body mass index and waist circumference as predictors of coronary artery disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "357" "paginaFinal" => "364" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Estudo do índice de conicidade, índice de massa corporal e circunferência abdominal como preditores de doença arterial coronariana" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1810 "Ancho" => 1536 "Tamanyo" => 119846 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Areas under the receiver operating characteristic curve for waist circumference, conicity index and coronary artery disease.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Paula Caitano Fontela, Eliane Roseli Winkelmann, Paulo Ricardo Nazario Viecili" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Paula" "apellidos" => "Caitano Fontela" ] 1 => array:2 [ "nombre" => "Eliane Roseli" "apellidos" => "Winkelmann" ] 2 => array:2 [ "nombre" => "Paulo Ricardo" "apellidos" => "Nazario Viecili" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S0870255117300185" "doi" => "10.1016/j.repc.2016.09.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117300185?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917301241?idApp=UINPBA00004E" "url" => "/21742049/0000003600000005/v1_201706110143/S2174204917301241/v1_201706110143/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2174204917301344" "issn" => "21742049" "doi" => "10.1016/j.repce.2016.09.014" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "990" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2017;36:343-51" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1719 "formatos" => array:3 [ "EPUB" => 200 "HTML" => 1181 "PDF" => 338 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Changes in albumin-to-creatinine ratio at 12-month follow-up in patients undergoing renal denervation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "343" "paginaFinal" => "351" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Rácio albumina-creatinina aos 12 meses de seguimento após desnervação renal" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1555 "Ancho" => 2333 "Tamanyo" => 91158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio and estimated glomerular filtration rate at 12 months after renal denervation. There was a significant reduction in the median values of ACR and the percentage of patients with ACR >30 mg/g, without significant changes in eGFR. ACR: albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Henrique Sousa, Patrícia Branco, Manuel de Sousa Almeida, Pedro de Araújo Gonçalves, Augusta Gaspar, Hélder Dores, João Mesquita, Maria João Andrade, Nuno Neuparth, Ana Aleixo, Miguel Mendes, José Diogo Barata" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Henrique" "apellidos" => "Sousa" ] 1 => array:2 [ "nombre" => "Patrícia" "apellidos" => "Branco" ] 2 => array:2 [ "nombre" => "Manuel" "apellidos" => "de Sousa Almeida" ] 3 => array:2 [ "nombre" => "Pedro" "apellidos" => "de Araújo Gonçalves" ] 4 => array:2 [ "nombre" => "Augusta" "apellidos" => "Gaspar" ] 5 => array:2 [ "nombre" => "Hélder" "apellidos" => "Dores" ] 6 => array:2 [ "nombre" => "João" "apellidos" => "Mesquita" ] 7 => array:2 [ "nombre" => "Maria João" "apellidos" => "Andrade" ] 8 => array:2 [ "nombre" => "Nuno" "apellidos" => "Neuparth" ] 9 => array:2 [ "nombre" => "Ana" "apellidos" => "Aleixo" ] 10 => array:2 [ "nombre" => "Miguel" "apellidos" => "Mendes" ] 11 => array:2 [ "nombre" => "José Diogo" "apellidos" => "Barata" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255117302615" "doi" => "10.1016/j.repc.2016.09.019" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117302615?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917301344?idApp=UINPBA00004E" "url" => "/21742049/0000003600000005/v1_201706110143/S2174204917301344/v1_201706110143/en/main.assets" ] "asociados" => array:1 [ 0 => array:20 [ "pii" => "S2174204917301344" "issn" => "21742049" "doi" => "10.1016/j.repce.2016.09.014" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "990" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2017;36:343-51" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1719 "formatos" => array:3 [ "EPUB" => 200 "HTML" => 1181 "PDF" => 338 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Changes in albumin-to-creatinine ratio at 12-month follow-up in patients undergoing renal denervation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "343" "paginaFinal" => "351" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Rácio albumina-creatinina aos 12 meses de seguimento após desnervação renal" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1555 "Ancho" => 2333 "Tamanyo" => 91158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio and estimated glomerular filtration rate at 12 months after renal denervation. There was a significant reduction in the median values of ACR and the percentage of patients with ACR >30 mg/g, without significant changes in eGFR. ACR: albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Henrique Sousa, Patrícia Branco, Manuel de Sousa Almeida, Pedro de Araújo Gonçalves, Augusta Gaspar, Hélder Dores, João Mesquita, Maria João Andrade, Nuno Neuparth, Ana Aleixo, Miguel Mendes, José Diogo Barata" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Henrique" "apellidos" => "Sousa" ] 1 => array:2 [ "nombre" => "Patrícia" "apellidos" => "Branco" ] 2 => array:2 [ "nombre" => "Manuel" "apellidos" => "de Sousa Almeida" ] 3 => array:2 [ "nombre" => "Pedro" "apellidos" => "de Araújo Gonçalves" ] 4 => array:2 [ "nombre" => "Augusta" "apellidos" => "Gaspar" ] 5 => array:2 [ "nombre" => "Hélder" "apellidos" => "Dores" ] 6 => array:2 [ "nombre" => "João" "apellidos" => "Mesquita" ] 7 => array:2 [ "nombre" => "Maria João" "apellidos" => "Andrade" ] 8 => array:2 [ "nombre" => "Nuno" "apellidos" => "Neuparth" ] 9 => array:2 [ "nombre" => "Ana" "apellidos" => "Aleixo" ] 10 => array:2 [ "nombre" => "Miguel" "apellidos" => "Mendes" ] 11 => array:2 [ "nombre" => "José Diogo" "apellidos" => "Barata" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255117302615" "doi" => "10.1016/j.repc.2016.09.019" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117302615?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917301344?idApp=UINPBA00004E" "url" => "/21742049/0000003600000005/v1_201706110143/S2174204917301344/v1_201706110143/en/main.assets" ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Threats to internal validity in renal sympathetic denervation trials" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "353" "paginaFinal" => "355" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Eduardo Infante de Oliveira" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Eduardo" "apellidos" => "Infante de Oliveira" "email" => array:1 [ 0 => "e.infante.de.oliveira@gmail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Serviço de Cardiologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Centro Académico Médico de Lisboa, Lisboa, Portugal" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Ameaças à validade interna em estudos de desnervação simpática renal" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The development of catheter-based renal sympathetic denervation aroused great hopes for the treatment of hypertension, the principal modifiable cardiovascular risk factor. Initial trials reported reductions of around 30 mmHg in systolic blood pressure in patients with resistant hypertension.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2</span></a> The therapeutic effect appeared to be so strong and obvious that the technique was soon widely adopted in many countries. More than 50 denervation systems were developed<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> and national and international registries confirmed significant falls in blood pressure. However, surprisingly, SYMPLICITY HTN-3, the largest randomized trial on renal denervation and the first to be blinded and placebo-controlled, showed no significant effect.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> A lively debate ensued. Theories concerning ethnicity, techniques and concomitant drug therapy were put forward, but there was little discussion of the central question of the design of previous studies and of threats to their validity.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The article by Sousa et al. in the current issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> presents results from a registry of 31 patients with resistant systemic hypertension who underwent catheter-based renal denervation. Patient selection was based on criteria in accordance with the most important clinical trials on this intervention.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1,2,4</span></a> One-year data focused on patients’ hemodynamic response and renal function parameters. The authors report significant decreases in office and 24-hour ambulatory blood pressure measurements. What is striking about this study is the significant reduction in the urine albumin-to-creatinine ratio – from 25.6 mg/g (interquartile range [IQR] 8.7-382.8 mg/g) to 15.9 mg/g (IQR 4.4-55.0 mg/g), p=0.009 – in the subgroup with significant decreases in blood pressure (responders).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> This finding is particularly interesting because at first sight it appears to be an indication of the effectiveness of the treatment, establishing a causal chain between denervation, falls in blood pressure, and improvement or reversal of target organ damage. In the current climate of skepticism concerning the therapeutic effectiveness of denervation, this result could be seen as a positive sign, suggesting that denervation may have benefits beyond reducing blood pressure. Albuminuria is an independent marker of renal and cardiovascular risk, and is an objective, investigator-independent parameter that is uninfluenced by the placebo effect. This finding is not unprecedented, as there are other reports in the literature of reduced albuminuria following renal denervation.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> The effect appears to be dependent on reducing blood pressure, since in a series of 54 patients in whom blood pressure decreased only slightly following denervation, no significant decrease in albuminuria was seen.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> A similar result was seen in the subgroup on non-responders in the article under discussion.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However, it is important to point out the main limitation of the study's patient registry. Of the 65 patients enrolled between July 2011 and April 2015,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> only 31 completed the assessment process, even though all patients had had more than 12 months of follow-up by the time the article was submitted. The authors do not specify why over half the patients did not complete the follow-up protocol. This may affect the interpretation of the results. The 31 patients who completed the protocol may have been better at complying with the follow-up schedule and with the drug regimen, in which case the falls in blood pressure and in albuminuria may have occurred independently of the denervation procedure. If this group were particularly motivated to modify their lifestyles and adhere to therapy, and also had access to additional consultations at the hypertension clinic, this by itself could explain the results. In other words, the authors describe a benefit that, due to the characteristics of the study population and the nature of the follow-up, is not necessarily only to be interpreted as a biological response to renal denervation. There is thus an important threat to the study's internal validity, one described in the literature as differential mortality or experimental mortality<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> (‘mortality’ in this sense meaning loss of subjects during the study, not necessarily by literal death). Subjects who remain may be more motivated and thus more likely to comply with study requirements.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Other threats to internal validity are commonly found in almost all clinical studies on renal denervation.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> The effect of renal denervation on resistant hypertension is an interesting case study on experimental design and threats to internal validity.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> Most studies are open and do not include a control group. Patient selection is mainly based on blood pressure above a certain limit. Given the natural variability of blood pressure, this method will tend to select individuals who at that point presented a higher value than their long-term average, and naturally, over the course of the trial their observed levels will move closer to the long-term average for each individual – the effect known as regression to the mean,<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11,12</span></a> by which individuals selected on the basis of extreme characteristics will tend to regress to their long-term average irrespective of treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Over the course of the trial, another threat to internal validity may appear, arising from the method of measuring blood pressure. After the patient starts an antihypertensive treatment, the physician will tend in practice to interpret measurements that do not indicate a fall in blood pressure as incorrect and will usually repeat the measurement, ignoring the initial reading.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> Lower readings are interpreted as correct and higher readings as due to the white coat effect or simple measurement error, particularly when the therapy is believed to be effective. If in a registry or open trial not all measurements have to be recorded, this may result in underestimation of blood pressure after beginning of therapy. This effect has been termed asymmetrical data handling<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> and is an important threat to the internal validity of trials on hypertension. It can be overcome by implementing rigorous recording protocols, the use of digital blood pressure monitors that record all measurements taken, and/or ambulatory blood pressure monitoring.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Another important threat is when there is an actual fall in blood pressure that is not caused by a biological effect of the treatment under study, but is in fact due to confounding factors. This may result from a strong conviction of the benefit of the therapy, i.e. the placebo effect,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> or the psychological effect of increased motivation, good adherence to medical therapy and adoption of a healthier lifestyle following inclusion in an innovative treatment program that brings access to more consultations and improved surveillance. The mere awareness of being observed improves performance (the Hawthorne effect).<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In a recent meta-analysis, Howard et al.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> elegantly quantified these three threats to internal validity in studies of renal denervation: regression to the mean, asymmetrical data handling, and confounding effects. The effect of regression to the mean was not significant, but this is the only one of the three types of bias that can be overcome by the inclusion of a randomized control group in an open trial. The other two resulted in a combined mean underestimation of blood pressure of around 19 mmHg, and could only have been avoided by blinding and by sham procedures in the control group.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> The authors give the example of a greater fall in blood pressure as measured in the office than in ambulatory monitoring, only in open trials. The same effect has been found in open trials of antihypertensive drugs,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> but was not seen in blinded trials, including those which demonstrated a beneficial effect of the drug under study.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, registries and open clinical trials, even when rigorous and correctly performed, are unable to overcome the most important threats to the internal validity of studies testing new treatments for hypertension. Improvement in markers of target organ damage in patients with blood pressure reductions only increases the likelihood that this reduction is real rather than resulting from regression to the mean or asymmetrical data handling. However, even then, it does not guarantee that a biological effect of the new treatment is responsible, since the observed changes could be due to confounding effects.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 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: Infante de Oliveira E. Ameaças à validade interna em estudos de desnervação simpática renal. Rev Port Cardiol. 2017;36:353–355.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Krum" 1 => "M. Schlaich" 2 => "R. Whitbourn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60566-3" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2009" "volumen" => "373" "paginaInicial" => "1275" "paginaFinal" => "1281" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19332353" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.D. Esler" 1 => "H. Krum" 2 => "P.A. Sobotka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)62039-9" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "376" "paginaInicial" => "1903" "paginaFinal" => "1909" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21093036" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Endovascular treatment of resistant and uncontrolled hypertension: therapies on the horizon" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.C. Bunte" 1 => "E. Infante De Oliveira" 2 => "M.H. Shishehbor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcin.2012.09.005" "Revista" => array:6 [ "tituloSerie" => "JACC Cardiovasc Interv" "fecha" => "2013" "volumen" => "6" "paginaInicial" => "1" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23266234" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A controlled trial of renal denervation for resistant hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D.L. Bhatt" 1 => "D.E. Kandzari" 2 => "W.W. O’Neill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1402670" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "volumen" => "370" "paginaInicial" => "1393" "paginaFinal" => "1401" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24678939" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes in albumin-to-creatinine ratio at 12-month follow-up in patients undergoing renal denervation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Sousa" 1 => "P. Branco" 2 => "M. de Sousa Almeida" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.repc.2016.09.019" "Revista" => array:6 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2017" "volumen" => "36" "paginaInicial" => "343" "paginaFinal" => "351" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28456548" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improvement of albuminuria after renal denervation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Ott" 1 => "F. Mahfoud" 2 => "A. Schmid" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2014.03.017" "Revista" => array:6 [ "tituloSerie" => "Int J Cardiol" "fecha" => "2014" "volumen" => "173" "paginaInicial" => "311" "paginaFinal" => "315" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24681017" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of renal denervation on end organ damage in hypertensive patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "W.L. Verloop" 1 => "E.E. Vink" 2 => "W. Spiering" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/2047487314556003" "Revista" => array:6 [ "tituloSerie" => "Eur J Prev Cardiol" "fecha" => "2015" "volumen" => "22" "paginaInicial" => "558" "paginaFinal" => "567" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25326543" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of renal sympathetic denervation on left ventricular structure and function at 1-year follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. de Sousa Almeida" 1 => "P. de Araújo Gonçalves" 2 => "P. Branco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0149855" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2016" "volumen" => "11" "paginaInicial" => "e0149855" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26934735" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of experimental mortality on the internal and external validity of the randomized comparative experiment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.G. Jurs" 1 => "G.V. Glass" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "J Exp Educ" "fecha" => "1971" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Overcoming the three biases obscuring the science of renal denervation in humans: big-day bias, check-once-more bias and I-will-take-it-now bias" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.P. Howard" 1 => "D.P. Francis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.tcm.2014.10.011" "Revista" => array:6 [ "tituloSerie" => "Trends Cardiovasc Med" "fecha" => "2015" "volumen" => "25" "paginaInicial" => "116" "paginaFinal" => "118" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25467244" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regression to the mean: what it is and how to deal with it" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.G. Barnett" 1 => "J.C. van der Pols" 2 => "A.J. Dobson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ije/dyh299" "Revista" => array:6 [ "tituloSerie" => "Int J Epidemiol" "fecha" => "2004" "volumen" => "34" "paginaInicial" => "215" "paginaFinal" => "220" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15333621" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quantifying the 3 biases that lead to unintentional overestimation of the blood pressure-lowering effect of renal denervation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.P. Howard" 1 => "M.J. Shun-Shin" 2 => "A. Hartley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/CIRCOUTCOMES.115.002533" "Revista" => array:6 [ "tituloSerie" => "Circ Cardiovasc Qual Outcomes" "fecha" => "2016" "volumen" => "9" "paginaInicial" => "14" "paginaFinal" => "22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26758193" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surgery as placebo: a quantitative study of bias. 1961" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.K. Beecher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/AIA.0b013e318142cb79" "Revista" => array:6 [ "tituloSerie" => "Int Anesthesiol Clin" "fecha" => "2007" "volumen" => "45" "paginaInicial" => "35" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18049267" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What happened at Hawthorne? New evidence suggests the Hawthorne effect resulted from operant reinforcement contingencies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H. Parsons" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.183.4128.922" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "1974" "volumen" => "183" "paginaInicial" => "922" "paginaFinal" => "932" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17756742" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Size of blood pressure reduction from renal denervation: insights from meta-analysis of antihypertensive drug trials of 4,121 patients with focus on trial design: the CONVERGE report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.P. Howard" 1 => "A.N. Nowbar" 2 => "D.P. Francis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/heartjnl-2013-304238" "Revista" => array:6 [ "tituloSerie" => "Heart" "fecha" => "2013" "volumen" => "99" "paginaInicial" => "1579" "paginaFinal" => "1587" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24038167" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21742049/0000003600000005/v1_201706110143/S2174204917301265/v1_201706110143/en/main.assets" "Apartado" => array:4 [ "identificador" => "9917" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21742049/0000003600000005/v1_201706110143/S2174204917301265/v1_201706110143/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917301265?idApp=UINPBA00004E" ]
Year/Month | Html | Total | |
---|---|---|---|
2024 November | 7 | 5 | 12 |
2024 October | 28 | 29 | 57 |
2024 September | 41 | 28 | 69 |
2024 August | 36 | 24 | 60 |
2024 July | 32 | 25 | 57 |
2024 June | 28 | 18 | 46 |
2024 May | 33 | 20 | 53 |
2024 April | 27 | 21 | 48 |
2024 March | 22 | 23 | 45 |
2024 February | 26 | 31 | 57 |
2024 January | 21 | 34 | 55 |
2023 December | 20 | 24 | 44 |
2023 November | 23 | 22 | 45 |
2023 October | 19 | 13 | 32 |
2023 September | 20 | 19 | 39 |
2023 August | 20 | 12 | 32 |
2023 July | 18 | 17 | 35 |
2023 June | 29 | 12 | 41 |
2023 May | 29 | 20 | 49 |
2023 April | 29 | 10 | 39 |
2023 March | 34 | 20 | 54 |
2023 February | 31 | 13 | 44 |
2023 January | 16 | 11 | 27 |
2022 December | 33 | 26 | 59 |
2022 November | 31 | 22 | 53 |
2022 October | 27 | 20 | 47 |
2022 September | 18 | 23 | 41 |
2022 August | 16 | 19 | 35 |
2022 July | 27 | 22 | 49 |
2022 June | 16 | 25 | 41 |
2022 May | 20 | 31 | 51 |
2022 April | 26 | 28 | 54 |
2022 March | 26 | 39 | 65 |
2022 February | 31 | 35 | 66 |
2022 January | 19 | 19 | 38 |
2021 December | 27 | 26 | 53 |
2021 November | 35 | 33 | 68 |
2021 October | 43 | 39 | 82 |
2021 September | 27 | 25 | 52 |
2021 August | 28 | 32 | 60 |
2021 July | 16 | 16 | 32 |
2021 June | 27 | 19 | 46 |
2021 May | 20 | 38 | 58 |
2021 April | 35 | 49 | 84 |
2021 March | 69 | 14 | 83 |
2021 February | 60 | 16 | 76 |
2021 January | 42 | 10 | 52 |
2020 December | 36 | 11 | 47 |
2020 November | 42 | 7 | 49 |
2020 October | 15 | 11 | 26 |
2020 September | 54 | 11 | 65 |
2020 August | 29 | 12 | 41 |
2020 July | 44 | 4 | 48 |
2020 June | 36 | 13 | 49 |
2020 May | 45 | 4 | 49 |
2020 April | 28 | 11 | 39 |
2020 March | 42 | 18 | 60 |
2020 February | 40 | 18 | 58 |
2020 January | 18 | 5 | 23 |
2019 December | 29 | 5 | 34 |
2019 November | 30 | 8 | 38 |
2019 October | 39 | 6 | 45 |
2019 September | 21 | 7 | 28 |
2019 August | 24 | 7 | 31 |
2019 July | 32 | 9 | 41 |
2019 June | 27 | 8 | 35 |
2019 May | 28 | 7 | 35 |
2019 April | 23 | 13 | 36 |
2019 March | 13 | 17 | 30 |
2019 February | 30 | 6 | 36 |
2019 January | 25 | 6 | 31 |
2018 December | 37 | 9 | 46 |
2018 November | 86 | 11 | 97 |
2018 October | 143 | 10 | 153 |
2018 September | 62 | 11 | 73 |
2018 August | 35 | 9 | 44 |
2018 July | 14 | 6 | 20 |
2018 June | 41 | 7 | 48 |
2018 May | 46 | 7 | 53 |
2018 April | 69 | 8 | 77 |
2018 March | 79 | 2 | 81 |
2018 February | 61 | 2 | 63 |
2018 January | 83 | 6 | 89 |
2017 December | 119 | 13 | 132 |
2017 November | 69 | 8 | 77 |
2017 October | 25 | 17 | 42 |
2017 September | 48 | 22 | 70 |
2017 August | 53 | 28 | 81 |
2017 July | 47 | 17 | 64 |
2017 June | 89 | 34 | 123 |
2017 May | 21 | 6 | 27 |