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Neutrophil-to-lymphocyte ratio and ambulatory blood pressure: Exploring the link between inflammation and hypertension
Relação neutrófilos/linfócitos e pressão arterial ambulatória. Explorando a relação entre inflamação e hipertensão
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CI: confidence interval; MR-proANP: mid-regional pro-atrial natriuretic peptide; NS: non-significant; NT-proBNP: N-terminal pro-brain natriuretic peptide; sST2: soluble ST2.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rui Plácido, Nuno Cortez-Dias, Susana Robalo Martins, Ana G. Almeida, Carina Calisto, Susana Gonçalves, Malha Sadoune, António Nunes Diogo, Alexandre Mebazaa, Fausto J. Pinto" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Rui" "apellidos" => "Plácido" ] 1 => array:2 [ "nombre" => "Nuno" "apellidos" => "Cortez-Dias" ] 2 => array:2 [ "nombre" => "Susana" "apellidos" => "Robalo Martins" ] 3 => array:2 [ "nombre" => "Ana G." 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"apellidos" => "Pinto" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S0870255116302153" "doi" => "10.1016/j.repc.2016.08.005" "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/S0870255116302153?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204916302665?idApp=UINPBA00004E" "url" => "/21742049/0000003600000002/v1_201702240018/S2174204916302665/v1_201702240018/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2174204917300272" "issn" => "21742049" "doi" => "10.1016/j.repce.2017.02.003" "estado" => "S300" "fechaPublicacion" => "2017-02-01" "aid" => "934" "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;36:97-105" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2781 "formatos" => array:3 [ "EPUB" => 146 "HTML" => 2231 "PDF" => 404 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "The relationship between 24-hour ambulatory blood pressure load and neutrophil-to-lymphocyte ratio" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "97" "paginaFinal" => "105" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "A relação entre a carga da pressão arterial em ambulatório durante 24 horas e a proporção neutrófilos/linfócitos" ] ] "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" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2676 "Ancho" => 3350 "Tamanyo" => 769304 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Pearson's correlation analysis demonstrating correlations between NLR and (A) 24-hour systolic BP; (B) 24-hour systolic BP load; (C) 24-hour diastolic BP; and (D) 24-hour diastolic BP load. BP: blood pressure; NLR: neutrophil-to-lymphocyte ratio.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Tolga Çimen, Hamza Sunman, Tolga Han Efe, Mehmet Erat, Haluk Furkan Şahan, Engin Algül, İlkin Guliyev, Ahmet Akyel, Mehmet Doğan, Sadık Açıkel, Ekrem Yeter" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Tolga" "apellidos" => "Çimen" ] 1 => array:2 [ "nombre" => "Hamza" "apellidos" => "Sunman" ] 2 => array:2 [ "nombre" => "Tolga Han" "apellidos" => "Efe" ] 3 => array:2 [ "nombre" => "Mehmet" "apellidos" => "Erat" ] 4 => array:2 [ "nombre" => "Haluk Furkan" "apellidos" => "Şahan" ] 5 => array:2 [ "nombre" => "Engin" "apellidos" => "Algül" ] 6 => array:2 [ "nombre" => "İlkin" "apellidos" => "Guliyev" ] 7 => array:2 [ "nombre" => "Ahmet" "apellidos" => "Akyel" ] 8 => array:2 [ "nombre" => "Mehmet" "apellidos" => "Doğan" ] 9 => array:2 [ "nombre" => "Sadık" "apellidos" => "Açıkel" ] 10 => array:2 [ "nombre" => "Ekrem" "apellidos" => "Yeter" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255116303869" "doi" => "10.1016/j.repc.2016.07.009" "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/S0870255116303869?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917300272?idApp=UINPBA00004E" "url" => "/21742049/0000003600000002/v1_201702240018/S2174204917300272/v1_201702240018/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Neutrophil-to-lymphocyte ratio and ambulatory blood pressure: Exploring the link between inflammation and hypertension" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "107" "paginaFinal" => "109" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Jorge Polónia" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Jorge" "apellidos" => "Polónia" "email" => array:1 [ 0 => "jjpolonia@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Medicina e Cintesis, Faculdade de Medicina da Universidade do Porto, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidade Hipertensão e Risco Cardiovascular do Hospital Pedro Hispano, Matosinhos, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Relação neutrófilos/linfócitos e pressão arterial ambulatória. Explorando a relação entre inflamação e hipertensão" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In the last decade a strong and definitive link has been established between inflammation and cardiovascular disease. Inflammation occurs in the vasculature as a response to several types of injury. Various risk factors, including hypertension, diabetes, and smoking, together with oxidized low-density lipoprotein cholesterol, trigger a chronic inflammatory reaction, the result of which is a vulnerable plaque, prone to rupture and thrombosis.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> Epidemiological and clinical studies have consistently shown links between markers of inflammation and risk of future cardiovascular events.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> Activation of macrophages, T lymphocytes, and smooth muscle cells leads to the release of additional mediators, including adhesion molecules, cytokines, chemokines, and growth factors, all of which play important roles in atherogenesis.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a> Inflammation plays a role in all stages of atherothrombosis, the underlying cause of approximately 80% of all sudden cardiac deaths.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The study by Çimen et al. published in this issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">4</span></a> examines the relationship between 24-hour ambulatory blood pressure (BP) and a systemic inflammation marker, the neutrophil-to-lymphocyte ratio (NLR). The authors claim to have shown for the first time that an increased NLR is independently associated with the severity of hypertension (HTN) in patients with untreated essential HTN. NLR is considered a marker of inflammatory status<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">5</span></a> and has been shown to predict risk of coronary disease,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> heart failure<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> and stroke,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> and has been associated with resistant hypertension.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> Since HTN is a significant risk factor in inflammatory conditions such as atherosclerosis<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">5</span></a> and inflammatory molecules such as C-reactive protein (CRP), vascular and intercellular adhesion molecules, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1 are increased in HTN,<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">10,11</span></a> the finding of a proportional increase of NLR with higher severity of HTN fits with the hypothesis of the inflammatory nature of hypertensive disease.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">12–14</span></a> Because inflammation may have a role in the pathogenesis and progression of hypertension,<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">10,11</span></a> the authors speculate that an increase in this inflammatory marker (which can be easily measured in clinical practice) may help to predict HTN severity and to guide therapy in hypertensive patients.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Other indices derived from blood count parameters have also been identified as inflammatory markers, including red cell distribution width (RDW), mean platelet volume (MPV) and platelet-to-lymphocyte ratio (PLR), and some have been associated with different degrees of hypertension severity.<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">15–17</span></a> Some authors have shown that patients with non-dipper hypertension have higher NLR and PLR than those with dipper hypertension, although only PLR (not NLR) was found to be an independent predictor of non-dipper status.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a> The most striking aspect of the present study is that HTN was defined on the basis of 24-hour ambulatory BP measurement, in contrast to other authors who used only the less accurate office BP and failed to find any difference in NLR between normotensives and hypertensives. In this study, log NLR values were found to be weakly but positively correlated with 24-hour systolic blood pressure (SBP), diastolic blood pressure (DBP), SBP load and DBP load, while in multivariate analysis, log NLR had an independent association with 24-hour BP and 24-hour BP load. However, one of the major limitations of this type of cross-sectional study lies in the general difficulty of proving causal relationships between variables merely because they appear to be associated in proportion. It is always possible that the relationship between these variables is not direct but rather an epiphenomenon. While not questioning the merit or the novelty of the present study, it would have been of considerable interest to determine whether other inflammatory markers which can be easily measured in clinical practice, such as CRP, RDW, MPV, PLR and leukocyte activation markers, were also seen to be associated with ambulatory HTN, which could thereby have confirmed the coherence, correspondence and validity of the observed data in this population. Also in this context it would have been useful to calculate a receiver operating characteristic curve of the diagnostic value of NLR for HTN.</p><p id="par0020" class="elsevierStylePara elsevierViewall">There is however another finding in this study that deserves some comment. In the interquartile analysis of the NLR distribution, the authors found a relationship between NLR, firstly predominantly with daytime and 24-hour BP values and daytime BP load but not with nighttime BP values, and secondly predominantly with DBP but much less with DBP. This is quite atypical. In several studies<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">19–24</span></a> nighttime SBP and SBP vs. DBP have been clearly shown to be the strongest independent predictors of cardiovascular events and prognosis among the different indices of BP measurement. We may ask why the relationships established in the present study with NLR were not mainly seen with the BP indices that are better determinants of cardiovascular risk (nighttime and systolic BP) but rather with daytime BP and with others with inferior reproducibility and lower predictive value (BP load and diastolic BP). One possible speculative explanation for this atypical finding may be the existence of a circadian rhythm of inflammatory immune responses, with day-to-day and day-to-night fluctuations in immune responses to stress. A number of studies have suggested that sleep disorders such as sleep loss, narcolepsy, and sleep apnea are associated with elevated inflammatory markers such as interleukin 6, tumor necrosis factor-alpha, CRP, and white blood cells.<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">25–27</span></a> For example it has been shown<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> that at the molecular level, >8% of the macrophage transcriptome oscillates in a circadian fashion, including many important regulators for pathogen recognition and cytokine secretion. In addition, time-of-day-dependent fluctuations in the number of neutrophils are not always in line with those of lymphocytes<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> and changes in NLR may be different during day and night. We do not know whether a different NLR measured in blood samples collected at night rather than in the morning could indicate a closer relationship between NLR and nighttime BP values.</p><p id="par0025" class="elsevierStylePara elsevierViewall">A systematic search for inflammatory markers that could enable early detection of the presence of hypertension and its complications in a simple routine blood count is a fascinating challenge. The study by Çimen et al. is within this context. However, further research is needed to precisely determine the scientific robustness of the diagnostic and prognostic value of the association between NLR and HTN at the various stages of the evolution of the disease.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0030" 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 "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inflammation as a cardiovascular risk factor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 4 | 11 |
| 2024 October | 50 | 30 | 80 |
| 2024 September | 39 | 20 | 59 |
| 2024 August | 48 | 24 | 72 |
| 2024 July | 36 | 24 | 60 |
| 2024 June | 35 | 20 | 55 |
| 2024 May | 33 | 19 | 52 |
| 2024 April | 37 | 30 | 67 |
| 2024 March | 28 | 28 | 56 |
| 2024 February | 33 | 29 | 62 |
| 2024 January | 23 | 27 | 50 |
| 2023 December | 22 | 19 | 41 |
| 2023 November | 29 | 28 | 57 |
| 2023 October | 14 | 15 | 29 |
| 2023 September | 21 | 20 | 41 |
| 2023 August | 21 | 21 | 42 |
| 2023 July | 22 | 15 | 37 |
| 2023 June | 19 | 14 | 33 |
| 2023 May | 35 | 25 | 60 |
| 2023 April | 17 | 1 | 18 |
| 2023 March | 35 | 36 | 71 |
| 2023 February | 30 | 14 | 44 |
| 2023 January | 19 | 20 | 39 |
| 2022 December | 41 | 31 | 72 |
| 2022 November | 35 | 18 | 53 |
| 2022 October | 28 | 15 | 43 |
| 2022 September | 22 | 33 | 55 |
| 2022 August | 25 | 21 | 46 |
| 2022 July | 30 | 31 | 61 |
| 2022 June | 27 | 14 | 41 |
| 2022 May | 20 | 26 | 46 |
| 2022 April | 22 | 27 | 49 |
| 2022 March | 21 | 25 | 46 |
| 2022 February | 23 | 22 | 45 |
| 2022 January | 32 | 25 | 57 |
| 2021 December | 14 | 26 | 40 |
| 2021 November | 32 | 34 | 66 |
| 2021 October | 53 | 38 | 91 |
| 2021 September | 19 | 25 | 44 |
| 2021 August | 21 | 29 | 50 |
| 2021 July | 19 | 21 | 40 |
| 2021 June | 21 | 10 | 31 |
| 2021 May | 28 | 40 | 68 |
| 2021 April | 30 | 40 | 70 |
| 2021 March | 64 | 20 | 84 |
| 2021 February | 56 | 18 | 74 |
| 2021 January | 34 | 17 | 51 |
| 2020 December | 36 | 6 | 42 |
| 2020 November | 36 | 21 | 57 |
| 2020 October | 27 | 25 | 52 |
| 2020 September | 42 | 15 | 57 |
| 2020 August | 14 | 7 | 21 |
| 2020 July | 32 | 7 | 39 |
| 2020 June | 34 | 3 | 37 |
| 2020 May | 28 | 9 | 37 |
| 2020 April | 39 | 12 | 51 |
| 2020 March | 24 | 8 | 32 |
| 2020 February | 31 | 15 | 46 |
| 2020 January | 29 | 5 | 34 |
| 2019 December | 14 | 1 | 15 |
| 2019 November | 30 | 11 | 41 |
| 2019 October | 41 | 3 | 44 |
| 2019 September | 14 | 6 | 20 |
| 2019 August | 25 | 8 | 33 |
| 2019 July | 33 | 11 | 44 |
| 2019 June | 18 | 6 | 24 |
| 2019 May | 31 | 11 | 42 |
| 2019 April | 17 | 19 | 36 |
| 2019 March | 82 | 11 | 93 |
| 2019 February | 32 | 12 | 44 |
| 2019 January | 25 | 4 | 29 |
| 2018 December | 55 | 10 | 65 |
| 2018 November | 88 | 10 | 98 |
| 2018 October | 168 | 16 | 184 |
| 2018 September | 32 | 9 | 41 |
| 2018 August | 21 | 5 | 26 |
| 2018 July | 13 | 2 | 15 |
| 2018 June | 35 | 6 | 41 |
| 2018 May | 42 | 20 | 62 |
| 2018 April | 66 | 2 | 68 |
| 2018 March | 51 | 7 | 58 |
| 2018 February | 57 | 4 | 61 |
| 2018 January | 50 | 7 | 57 |
| 2017 December | 56 | 8 | 64 |
| 2017 November | 52 | 9 | 61 |
| 2017 October | 24 | 11 | 35 |
| 2017 September | 23 | 12 | 35 |
| 2017 August | 24 | 11 | 35 |
| 2017 July | 14 | 6 | 20 |
| 2017 June | 33 | 7 | 40 |
| 2017 May | 41 | 9 | 50 |
| 2017 April | 17 | 21 | 38 |
| 2017 March | 58 | 26 | 84 |
| 2017 February | 8 | 5 | 13 |
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