Review article
Hypertension, coronary heart disease and stroke: Should the blood pressure J-curve be a concern?
Hipertensão arterial, doença coronária e acidente vascular cerebral. A curva em J deve preocupar-nos?
José Braz Nogueira
Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "139" "paginaFinal" => "144" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "José Braz Nogueira" "autores" => array:1 [ 0 => array:3 [ "nombre" => "José" "apellidos" => "Braz Nogueira" "email" => array:1 [ 0 => "jnogueira@fm.ul.pt" ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Hipertensão arterial, doença coronária e acidente vascular cerebral. A curva em J deve preocupar-nos?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Meta-analyses of epidemiological observational studies have demonstrated a linear relationship between systolic and diastolic blood pressure (BP) levels and risk of cerebrovascular and cardiovascular events for pressures as low as 115/70 mmHg upwards. The Prospective Studies Collaboration meta-analysis of 61 studies involving a million individuals without initial cardiovascular or cerebrovascular disease showed a doubling of mortality from stroke or myocardial infarction (MI) for every 20-mmHg increase in systolic BP or 10-mmHg increase in diastolic BP.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">However, in a 1979 paper published in the <span class="elsevierStyleItalic">Lancet</span>, Stewart<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> suggested that there was a paradoxical increase in the incidence of MI with lower diastolic BP levels. In 169 patients with severe hypertension, those with diastolic BP (defined as disappearance of Korotkoff sounds) less than 90 mmHg with antihypertensive medication were at greater risk of MI.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In 1987, Cruickshank et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> also detected a J-curve relationship between diastolic BP and mortality from MI but only in hypertensive patients with ischemic heart disease, a finding the authors attributed to the fact that coronary perfusion takes place during diastole. A subsequent meta-analysis by the same lead author of six studies involving over 14 000 hypertensive patients confirmed the J-curve relation, particularly between diastolic BP and ischemic heart disease, as well as in patients with a history of coronary heart disease (CHD).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The relationship between diastolic BP and coronary mortality was also seen in the Framingham study, but only in individuals with a history of MI<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>; there was no evidence of a J-curve for systolic BP. Similarly, a meta-analysis of 13 studies (48 000 hypertensives) by Farnett et al. demonstrated a J-curve relationship between diastolic BP and cardiovascular morbidity and mortality, more pronounced in the elderly and those with a history of ischemic heart disease.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Although some studies have found a similar relationship with stroke,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> most have not, and the PROGRESS trial showed that antihypertensive therapy actually reduced the risk of recurrent stroke with progressive lowering of BP.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Rashid et al. confirmed this finding in a subsequent review of randomized trials,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> while Turan et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> showed similar results in patients with ischemic stroke attributable to intracranial arterial stenosis, in whom the risk of stroke in the same territory was less in individuals with lower BP. A recent meta-analysis in nearly 74 000 diabetic patients showed a progressive reduction in stroke with reductions in BP, although the same was not seen for MI.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">However, Kannel et al.,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> using data from the Framingham study, reported that the increased risk of cardiovascular events with diastolic BP <80 mmHg was only found when systolic BP was higher than 140 or 160 mmHg. According to these authors, the J-curve is thus related to differential (pulse) pressure, which reflects increased arterial stiffness, already identified as an important cardiovascular risk factor. In support of this hypothesis, the SHEP trial and other studies in the elderly with isolated systolic hypertension have also shown the existence of a J-curve for diastolic BP <65/70 mmHg.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A meta-analysis of seven randomized clinical trials involving more than 40 000 hypertensive patients<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> showed that there is a J-curve (or U-curve) in both medicated and non-medicated hypertensives for both cardiovascular and non-cardiovascular mortality. This may be due to reverse causality, the paradoxical increase in events with lower BP levels being the consequence of poor health conditions – the result of cancer or other wasting disease, or heart failure with severely impaired systolic function.</p><p id="par0035" class="elsevierStylePara elsevierViewall">There are thus three possible explanations for the increase in cardiovascular events with lower BP (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>): reduced coronary perfusion with lower diastolic BP exceeding the lower limit of the autoregulation curve; increased pulse (differential) pressure due to low diastolic BP reflecting increased arterial stiffness; and reverse causality.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Whether or not the J-curve or U-curve actually exists, the important question is whether there are benefits in setting lower BP target levels, for example 130/80 rather than 140/90 mmHg. After the publication of the HOT<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and UKPDS<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> trials, the guidelines began to recommend target BP levels below 130/80 mmHg for high-risk hypertensives (those with diabetes, renal failure or cerebrovascular or cardiovascular disease). However, as pointed out in the reappraisal of European guidelines on hypertension management by the European Society of Hypertension and the European Society of Cardiology,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> these levels are rarely attained, and benefits are seen when BP falls below 140/90 mmHg, even if it does not reach 130/80 mmHg.</p><p id="par0045" class="elsevierStylePara elsevierViewall">A Cochrane review published in 2009,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> based on a meta-analysis of randomized clinical trials, also concluded that there was no justification for setting target BP levels below those usually recommended. However, the ADVANCE trial,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> in patients with type 2 diabetes (who have a similar risk to those with previous MI), showed a significant reduction in microvascular and macrovascular events when systolic BP of 135 mmHg was attained compared to 140 mmHg, mainly due to fewer renal events. In the ACCORD trial,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> a landmark study of 4733 patients with type 2 diabetes comparing the effects of intensive antihypertensive therapy to lower systolic BP below 120 mmHg with standard treatment (target of below 140 mmHg) in a mean follow-up of 4.7 years, the risk of fatal and non-fatal cardiovascular events did not differ significantly between the group with mean systolic BP of 119.3 mmHg and those with mean systolic BP of 133.5 mmHg except for stroke, which was significantly less common in the lower BP group.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In a meta-analysis of 13 randomized trials involving 37 736 diabetic or prediabetic patients<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> that compared microvascular and macrovascular events with more and less intensive antihypertensive therapy, systolic BP ≤135 mmHg was associated with a 10% reduction in overall mortality and a 17% reduction in stroke compared to ≤140 mmHg, although with 20% more serious adverse effects. However, there were no differences in other microvascular and macrovascular (cardiac, renal, and retinal) events. The authors also compared target BP of ≤130 mmHg and ≤135 mmHg and found no significant differences in microvascular and macrovascular events except for a larger reduction in stroke with lower BP, but with 40% more serious adverse effects.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Similarly, a subanalysis of the INVEST trial of 6400 diabetic hypertensives with CHD<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> showed that intensive therapy aiming at systolic BP <130 mmHg was not associated with a reduction in cardiovascular events compared to less intensive BP control (130–139 mmHg).</p><p id="par0060" class="elsevierStylePara elsevierViewall">In the HYVET study<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> in hypertensives 80 years of age or older, cardiovascular morbidity and mortality was reduced with antihypertensive therapy for BP levels below 150/80 mmHg, while the VALISH<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and JATOS<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> studies, also in elderly hypertensives, showed no reduction in cardiovascular morbidity and mortality with systolic BP of <140 mmHg compared to >140 mmHg.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In the last five or six years the question of the J-curve has again come to the fore, particularly after the INVEST, VALUE, ONTARGET, Syst-Eur and TNT trials demonstrated a paradoxical increase in cardiovascular events, especially MI, when systolic or diastolic BP was reduced below certain levels. All these trials involved hypertensives with high cardiovascular risk, particularly for CHD. In a secondary analysis of the INVEST trial<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> in 22 576 hypertensives with CHD, there was an increase in the primary outcome (all-cause mortality, non-fatal MI and non-fatal stroke) and in all-cause mortality and MI in patients in whom antihypertensive therapy had reduced diastolic BP to below 70–80 mmHg and systolic BP to below 120–130 mmHg (although the J-curve was considerably less pronounced than for diastolic BP), these effects being more marked in patients who had not undergone revascularization. The nadir of the J-curve for systolic BP rose to 140 mmHg in patients aged over 80 and to 70 mmHg for diastolic BP.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> In the VALUE trial<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> in hypertensive patients (46% with CHD), there was a higher incidence of stroke with systolic BP between 120 and 130 mmHg, while the Syst-Eur trial<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> showed increased risk for cardiovascular events with diastolic BP of less than 70 mmHg only for patients with CHD. Similarly, in a post-hoc analysis of the HOT trial, previously unpublished data revealed a J-curve relationship between diastolic BP and risk for MI, but only in patients with previous myocardial ischemia.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In the TNT trial,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> in 10 001 CHD patients treated aggressively to attain cholesterol and BP reduction, a higher cardiovascular event rate was seen in the group with the lowest BP values than in those with systolic BP 130–140 mmHg and diastolic BP 70–80 mmHg; there was much greater risk in those with BP levels of 110–120 and 60–70 mmHg. In the ON-TARGET study<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> (75% of patients with CHD), cardiovascular mortality and MI (but not stroke) increased for systolic BP values below 126–130 mmHg. In a subgroup analysis of this study in 9603 diabetic patients, increased cardiovascular mortality was seen with systolic BP <125 mmHg compared with <130 mmHg,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> while the VADT trial,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> in around 1800 diabetic hypertensives, found increased cardiovascular risk for diastolic BP <70 mmHg. In the subanalysis of the INVEST trial,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> tighter BP control (systolic BP <130 mmHg) in diabetic hypertensive patients with CHD was associated with higher overall mortality compared to 130–140 mmHg. However, this higher mortality was only seen with systolic BP ≤ 115 mmHg.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The PROVE-IT-TMI 22 trial<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> also demonstrated the existence of a J-curve relation with all-cause mortality and cardiovascular events and mortality following antihypertensive therapy after acute coronary syndromes, more evident with diastolic BP, and only in terms of BP levels during follow-up, not baseline levels. In this study the nadir of the systolic curve was between 130 and 140 mmHg and that of the diastolic curve was between 80 and 90 mmHg, although the curve was relatively flat between 110–130 mmHg and 70–90 mmHg.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The beginning of 2012 saw the publication of the SMART trial<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> of 5788 patients with manifest vascular disease (CHD, stroke, or peripheral arterial disease), in which Dorresteijn et al. reassessed the existence of the J-curve, relating baseline systolic, diastolic and differential pressures with the occurrence of vascular events and all-cause mortality. They showed that there was a J-curve with a nadir of 143/82 mmHg, and, assuming reverse causality was unlikely to be the cause (although impossible to exclude), claimed that BP above or below this level could be considered an independent risk factor for cardiovascular events.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The studies reviewed above thus show the existence of a J-curve relationship with cardiovascular events, especially CHD, particularly for diastolic BP but also for systolic BP (although the latter is usually less pronounced). Stroke is consistently the exception (except in the acute phase<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> or, according to a recent study, in the subacute phase of non-cardioembolic ischemic stroke<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>), which may be related to differences in coronary and cerebral autoregulation – with more effective autoregulation of cerebral blood flow preserving tissue perfusion when BP is sharply reduced, or with selectively compromised coronary autoregulation.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The controversy concerning the J-curve continues, and is at times lively, such as when Bryan Williams<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> suggests simply ignoring diastolic BP when systolic BP is elevated, since the latter mandates effective antihypertensive therapy to reduce stroke risk. By contrast, in a recent editorial,<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> NM Kaplan calls the J-curve “alive and threatening” and points out that the problem is the need to intensify antihypertensive therapy to control persistently high systolic BP, which can increase coronary risk through a parallel fall in diastolic BP, especially in the elderly with isolated systolic hypertension, who are more likely to have CHD.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The European Society of Hypertension document reappraising the 2007 hypertension guidelines states specifically that “on the basis of current data, it may be prudent to recommend lowering systolic/diastolic BP to values within the range 130–139/80–85 mmHg, and possibly close to lower values in this range, in all hypertensive patients.”<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Similarly, Chrysant,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> while pointing out that the J-curve is not a uniform phenomenon, highlights the fact that it is more likely to be found in elderly hypertensives at high risk due to concomitant CHD, diabetes or left ventricular hypertrophy, and recommends less aggressive BP control in such patients, avoiding levels below 130/80 mmHg. Flynn and Bakris<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> and Nilsson<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> set target BP levels in high-risk hypertensive patients with diabetes or chronic renal disease at less than 140/90 mmHg, stating that levels below 130/80 mmHg are only justified in cases of chronic proteinuric renal disease or when there is a high risk of stroke.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion, should the blood pressure J-curve be a concern? Although many questions on this subject remain unanswered and studies are scheduled to try to clarify the issue, we suggest a cautious, individualized approach to treatment, particularly in hypertensive patients with CHD or high risk for impaired coronary blood flow (such as the elderly and those with left ventricular hypertrophy). In these patients we advise against systolic BP levels below 120–125 mmHg and, particularly, diastolic BP below 70–75 mmHg.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "xres177671" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec166324" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres177670" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec166325" "titulo" => "Palavras-chave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Right to privacy and informed consent" ] ] ] 5 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-06-11" "fechaAceptado" => "2012-06-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec166324" "palabras" => array:4 [ 0 => "Hypertension" 1 => "J-curve" 2 => "Coronary heart disease" 3 => "Stroke" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec166325" "palabras" => array:4 [ 0 => "Hipertensão" 1 => "Curva J" 2 => "Doença coronária" 3 => "Acidente vascular cerebral" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The paradoxical increase in cardiovascular events in patients with treatment-induced low blood pressure (BP), particularly in hypertensives with pre-existing coronary artery disease, especially those with critically low diastolic BP, which conflicts with data from epidemiologic observational studies, is referred to as a J-curve. It was first described over 30 years ago and is still the subject of considerable controversy. Recent large clinical outcomes trials (INVEST, TNT, ONTARGET, PROVE IT-TIMI 22, SMART) and meta-analyses strongly support its existence for systolic and diastolic BP. The diastolic J-curve is commonly more pronounced. In contrast to cardiovascular complications related to coronary artery disease, no J-curve phenomenon was noted for stroke in most of these studies. This is explained by differences in cerebral and coronary autoregulation and because coronary perfusion occurs only during diastole. On the basis of this review, we suggest a cautious, individualized approach to treatment, particularly in hypertensive patients with coronary heart disease or high risk for impaired coronary blood flow. In these patients we advise against treatment that lowers systolic BP below 120–125 mmHg and, particularly, diastolic BP below 70–75 mmHg.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">O aumento paradoxal de eventos cardiovasculares quando a diminuição da pressão arterial ultrapassa determinados níveis críticos, em particular de pressão diastólica e em especial em hipertensos com doença coronária, contrariando os dados de estudos epidemiológicos observacionais, que é conhecido como curva em J e foi descrito há mais de 30 anos tendo suscitado muita controvérsia, foi novamente posto em evidência em vários estudos clínicos recentes (INVEST, TNT, ONTARGET, PROVE IT TIMI 22, SMART) e meta-análises. Na maioria destes estudos, a curva em J foi mais pronunciada para a pressão diastólica (pelo facto de a perfusão coronária se fazer durante a diástole) e não se evidenciou curva em J para acidente vascular cerebral, o que estará relacionado com diferenças nas curvas de autorregulação cerebral e coronária. Com base na análise de todos estes estudos, é nossa opinião que a atitude a tomar deverá ser prudente e individualizada, em especial em hipertensos com doença coronária comprovada ou risco acrescido para fluxo coronário comprometido (idosos, presença de hipertrofia ventricular esquerda), devendo evitar-se que se atinjam com a terapêutica anti-hipertensiva valores de pressão sistólica inferiores a 120-125 mmHg e, em particular, valores de pressão diastólica inferiores a 70-75 mmHg.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Nogueira JB. Hipertensão arterial, doença coronária e acidente vascular cerebral. A curva em J deve preocupar-nos? Rev Port Cardiol. 2013. <span class="elsevierStyleInterRef" href="doi:10.1016/j.repc.2012.06.008">http://dx.doi.org/10.1016/j.repc.2012.06.008</span>.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduction in coronary perfusion (which occurs in diastole) with critically low diastolic BP levels; \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased differential (pulse) pressure due to low diastolic BP, secondary to increased arterial stiffness; \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reverse causality. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab272104.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Pathophysiological mechanisms of the blood pressure J-curve.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:44 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Prospective Studies Collaboration" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2002" "volumen" => "360" "paginaInicial" => "1903" "paginaFinal" => "1913" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12493255" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relation of reduction in pressure to first myocardial infarction in patients receiving treatment for severe hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "I.M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 7 | 12 |
| 2024 October | 30 | 26 | 56 |
| 2024 September | 41 | 23 | 64 |
| 2024 August | 33 | 32 | 65 |
| 2024 July | 35 | 24 | 59 |
| 2024 June | 34 | 28 | 62 |
| 2024 May | 32 | 24 | 56 |
| 2024 April | 27 | 17 | 44 |
| 2024 March | 34 | 19 | 53 |
| 2024 February | 28 | 38 | 66 |
| 2024 January | 18 | 27 | 45 |
| 2023 December | 31 | 25 | 56 |
| 2023 November | 29 | 24 | 53 |
| 2023 October | 34 | 19 | 53 |
| 2023 September | 32 | 20 | 52 |
| 2023 August | 29 | 18 | 47 |
| 2023 July | 39 | 13 | 52 |
| 2023 June | 25 | 12 | 37 |
| 2023 May | 43 | 23 | 66 |
| 2023 April | 21 | 5 | 26 |
| 2023 March | 45 | 22 | 67 |
| 2023 February | 34 | 17 | 51 |
| 2023 January | 25 | 7 | 32 |
| 2022 December | 51 | 18 | 69 |
| 2022 November | 50 | 21 | 71 |
| 2022 October | 36 | 18 | 54 |
| 2022 September | 34 | 22 | 56 |
| 2022 August | 51 | 37 | 88 |
| 2022 July | 38 | 33 | 71 |
| 2022 June | 28 | 21 | 49 |
| 2022 May | 17 | 29 | 46 |
| 2022 April | 33 | 23 | 56 |
| 2022 March | 24 | 26 | 50 |
| 2022 February | 31 | 23 | 54 |
| 2022 January | 39 | 20 | 59 |
| 2021 December | 22 | 26 | 48 |
| 2021 November | 27 | 35 | 62 |
| 2021 October | 46 | 37 | 83 |
| 2021 September | 22 | 30 | 52 |
| 2021 August | 33 | 25 | 58 |
| 2021 July | 28 | 27 | 55 |
| 2021 June | 19 | 16 | 35 |
| 2021 May | 31 | 33 | 64 |
| 2021 April | 34 | 33 | 67 |
| 2021 March | 41 | 15 | 56 |
| 2021 February | 52 | 12 | 64 |
| 2021 January | 28 | 17 | 45 |
| 2020 December | 50 | 8 | 58 |
| 2020 November | 24 | 15 | 39 |
| 2020 October | 18 | 7 | 25 |
| 2020 September | 52 | 6 | 58 |
| 2020 August | 25 | 5 | 30 |
| 2020 July | 66 | 5 | 71 |
| 2020 June | 47 | 9 | 56 |
| 2020 May | 41 | 3 | 44 |
| 2020 April | 56 | 4 | 60 |
| 2020 March | 33 | 6 | 39 |
| 2020 February | 39 | 15 | 54 |
| 2020 January | 33 | 7 | 40 |
| 2019 December | 30 | 4 | 34 |
| 2019 November | 37 | 4 | 41 |
| 2019 October | 47 | 6 | 53 |
| 2019 September | 17 | 10 | 27 |
| 2019 August | 34 | 2 | 36 |
| 2019 July | 38 | 11 | 49 |
| 2019 June | 13 | 9 | 22 |
| 2019 May | 44 | 6 | 50 |
| 2019 April | 34 | 15 | 49 |
| 2019 March | 64 | 8 | 72 |
| 2019 February | 50 | 7 | 57 |
| 2019 January | 23 | 7 | 30 |
| 2018 December | 57 | 7 | 64 |
| 2018 November | 116 | 3 | 119 |
| 2018 October | 326 | 20 | 346 |
| 2018 September | 138 | 20 | 158 |
| 2018 August | 117 | 5 | 122 |
| 2018 July | 33 | 4 | 37 |
| 2018 June | 59 | 8 | 67 |
| 2018 May | 70 | 10 | 80 |
| 2018 April | 93 | 2 | 95 |
| 2018 March | 106 | 6 | 112 |
| 2018 February | 60 | 2 | 62 |
| 2018 January | 139 | 9 | 148 |
| 2017 December | 194 | 11 | 205 |
| 2017 November | 81 | 31 | 112 |
| 2017 October | 45 | 14 | 59 |
| 2017 September | 40 | 12 | 52 |
| 2017 August | 46 | 9 | 55 |
| 2017 July | 30 | 8 | 38 |
| 2017 June | 44 | 26 | 70 |
| 2017 May | 54 | 17 | 71 |
| 2017 April | 56 | 11 | 67 |
| 2017 March | 40 | 15 | 55 |
| 2017 February | 41 | 4 | 45 |
| 2017 January | 25 | 15 | 40 |
| 2016 December | 31 | 22 | 53 |
| 2016 November | 32 | 13 | 45 |
| 2016 October | 26 | 9 | 35 |
| 2016 September | 31 | 12 | 43 |
| 2016 August | 8 | 4 | 12 |
| 2016 July | 19 | 7 | 26 |
| 2016 June | 12 | 8 | 20 |
| 2016 May | 15 | 5 | 20 |
| 2016 April | 49 | 3 | 52 |
| 2016 March | 77 | 21 | 98 |
| 2016 February | 92 | 28 | 120 |
| 2016 January | 79 | 15 | 94 |
| 2015 December | 91 | 15 | 106 |
| 2015 November | 83 | 19 | 102 |
| 2015 October | 93 | 14 | 107 |
| 2015 September | 93 | 11 | 104 |
| 2015 August | 85 | 16 | 101 |
| 2015 July | 86 | 8 | 94 |
| 2015 June | 48 | 3 | 51 |
| 2015 May | 76 | 21 | 97 |
| 2015 April | 87 | 14 | 101 |
| 2015 March | 66 | 9 | 75 |
| 2015 February | 89 | 6 | 95 |
| 2015 January | 78 | 14 | 92 |
| 2014 December | 88 | 18 | 106 |
| 2014 November | 85 | 9 | 94 |
| 2014 October | 105 | 14 | 119 |
| 2014 September | 104 | 17 | 121 |
| 2014 August | 94 | 8 | 102 |
| 2014 July | 89 | 9 | 98 |
| 2014 June | 108 | 13 | 121 |
| 2014 May | 113 | 12 | 125 |
| 2014 April | 118 | 10 | 128 |
| 2014 March | 126 | 22 | 148 |
| 2014 February | 146 | 11 | 157 |
| 2014 January | 143 | 18 | 161 |
| 2013 December | 102 | 15 | 117 |
| 2013 November | 143 | 25 | 168 |
| 2013 October | 108 | 21 | 129 |
| 2013 September | 111 | 17 | 128 |
| 2013 August | 107 | 34 | 141 |
| 2013 July | 111 | 36 | 147 |
| 2013 June | 79 | 34 | 113 |
| 2013 May | 108 | 45 | 153 |
| 2013 April | 124 | 54 | 178 |
| 2013 March | 96 | 59 | 155 |
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