Review article
Is regression of atherosclerotic plaque possible?
¿Es posible la regresión de la placa aterosclerótica?
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(A) Chemical structures and transformations of the organosulphurs present in garlic (<span class="elsevierStyleItalic">Allium sativum</span> L). Biosynthesis of alkenyl-cysteine-sulphoxide compounds (including alliin), from sulphate absorbed by the roots. Alliinase-mediated alliin lysis and allicin production. Decomposition of allicin through cooking. (B) In <span class="elsevierStyleItalic">Brassica</span>, isothiocyanates formed as a result of myrosinase-mediated hydrolysis of glucosinolates The figure shows the main isothiocyanates that are formed in broccoli (<span class="elsevierStyleItalic">Brassica oleracea italica</span> L): sulforaphane, indol-3-carbinol, and allyl-isothiocyanate.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alejandra B. Camargo, Walter Manucha" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Alejandra B." 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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "46" "paginaFinal" => "50" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "José A. Páramo, Fernando Civeira" "autores" => array:2 [ 0 => array:4 [ "nombre" => "José A." "apellidos" => "Páramo" "email" => array:1 [ 0 => "japaramo@unav.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Fernando" "apellidos" => "Civeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Hematología, Laboratorio de Aterotrombosis, Clínica Universidad de Navarra, Pamplona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Servicio de Medicina Interna, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Es posible la regresión de la placa aterosclerótica?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The pathogenesis of acute cardiovascular syndromes is related to the breakage or erosion of a vulnerable atherosclerotic plaque.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Stabilising that plaque, by reducing the lipid core and/or increasing the fibrous cap, would be one of the potentially beneficial mechanisms observed with anti-atherosclerosis agents.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a> The concept of stabilising atheroma plaque was developed to explain the beneficial effect of lipid-lowering treatment with no appreciable changes in the size and morphology of the atherosclerotic lesion using angiography (“angiographic paradox”).</p><p id="par0010" class="elsevierStylePara elsevierViewall">At present, the development of new non-invasive imaging techniques (intravascular ultrasonography [IVUS]<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>virtual histology, optical coherence tomography [OCT], magnetic resonance imaging, positron emission tomography [PET], etc.) enable atheroma plaques in the vascular tree to be identified early, as well as their volume, size, and composition. Therefore it is possible to characterise the most vulnerable plaques and, as a result, those most susceptible to breaking and thrombosis.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">3</span></a> Stabilising vulnerable plaques, by reducing the lipid core and/or increasing the fibrous cap, would be one of the potentially important clinical benefits observed with some anti-atherosclerotic agents, primarily statins.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Identifying high risk/vulnerable plaques</span><p id="par0015" class="elsevierStylePara elsevierViewall">Plaque composition, more than the degree of stenosis, is the critical determining factor for the risk of breaking and subsequent thrombogenicity. Specifically, the necrotic core, fibrous cap, and inflammation are the main factors playing a role in plaque vulnerability. Of these, a thin fibrous cap (<54<span class="elsevierStyleHsp" style=""></span>μm), abundant necrotic core, and the degree of inflammatory infiltrate are considered to be the best discriminating factors of vulnerability.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> Advances in understanding the cellular and molecular bases of plaque progression have enabled the physiopathological role of inflammation in vulnerable plaques to be established.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a> At present, it is known that inflammatory mediators associated with leucocyte activation promote progression; a clear example is interleukin 6 (IL-6), a cytokine associated with increased production of C-Reactive Protein, which is an established marker of cardiovascular risk.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Better understanding the physiopathology of atherosclerosis and the development of new imaging techniques has enabled high-risk plaques to be better characterised.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Coronary angiography has traditionally been the imaging test that best determines the degree of stenosis and it continues to be the technique used to guide revascularisation procedures, both surgical and intravascular catheterisation. Angiography provides information about the number and size of vascular stenoses; however, a low correlation has been observed between angiographic findings and risk factor modification, and moreover, it does not tell us anything about the plaque's composition.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Intravascular ultrasonography (IVUS) plus virtual histology enable atheroma plaques in the vascular tree to be identified, and can quantify the size, volume, composition, and distribution of the plaque. Similarly, IVUS can detect lesions in vessels without stenosis in the angiographic test and precisely identify areas with positive and negative remodelling, as well as the atherosclerotic “burden”.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Optical coherence tomography (OCT) enables several variables related to plaque morphology and composition to be detected, as well as the presence of calcium deposits, which are correlated with the extent of the atherosclerosis, although there is some controversy regarding the correlation between calcification and vulnerability.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Magnetic resonance imaging possesses advantages over other imaging techniques, by not requiring the use of intravascular ionic contrasts. It also enables images to be obtained on several planes and provides information about vascular tissue composition. Recent research has demonstrated that it is possible to obtain images of not only the vascular lumen, but also the composition of the artery wall.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Carotid ultrasonography detects the presence of focal atherosclerotic plaques and quantifies the carotid intima-media thickness (IMT). This is a non-invasive procedure that is standardised and has been validated in several studies. IMT, preferably measured in the common carotid artery, has been correlated with cardio- and cerebrovascular risk in different risk groups.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Measuring plaque response to systemic therapy</span><p id="par0050" class="elsevierStylePara elsevierViewall">Statins have changed the natural history of atherosclerotic disease in general and coronary and cerebrovascular syndromes in particular, as demonstrated by the reduction in cardiovascular morbimortality in primary and secondary prevention studies.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">12,13</span></a> What seems clear is that an “aggressive” lipid-lowering strategy to maintain LDLc levels <70<span class="elsevierStyleHsp" style=""></span>mg/dL is the one that achieves the best results (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Nevertheless, it has been postulated that statins act independently of the reduction in cholesterol (pleiotropic effects),<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">14,15</span></a> without these potential effects having demonstrated any significant clinical repercussions.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Several clinical studies have found a clear correlation between reducing cholesterol and clinical benefit in several patient categories, from those with established heart disease to asymptomatic subjects with cardiovascular risk and subjects with carotid artery disease, which cannot be explained in quantitative terms (plaque anatomy), but only qualitative terms (plaque biology).<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">16–23</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">A prospective study incorporating IVUS and OCT has demonstrated a significant decrease in plaque volume and an increase in the fibrous cap in the group treated with 4<span class="elsevierStyleHsp" style=""></span>mg of pitavastatin versus the control group.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> The YELLOW study compared IVUS and infrared spectroscopy in 87 patients undergoing coronary intervention who were randomised to rosuvastatin (40<span class="elsevierStyleHsp" style=""></span>mg/day) or standard therapy. After 7 weeks of treatment, it was observed that the high statin doses were associated with a significant reduction in the necrotic core and decreased atheroma plaque progression.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> Subanalysis of the <span class="elsevierStyleItalic">Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin</span> Versus <span class="elsevierStyleItalic">Atorvastatin</span> (SATURN) evaluated the effect of aggressive lipid-lowering therapy on the plaque characteristics identified via virtual histology in 1039 patients. Rosuvastatin 40<span class="elsevierStyleHsp" style=""></span>mg was compared against atorvastatin 80<span class="elsevierStyleHsp" style=""></span>mg over a 24-month period in patients with stable atherosclerotic disease. Although no changes in the percentage of the plaque occupied by fibrotic tissue were observed, an increase in the percent of intraplaque calcium was reported.<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">20,21</span></a> In subjects receiving an intracoronary stent due to myocardial infarction in the IBIS-4 study, a high-dose statin regimen (rosuvastatin 20–40<span class="elsevierStyleHsp" style=""></span>mg/day) was associated with a considerable reduction in the lesion volume measured with virtual histology.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a> In the STABLE study, a double-blind, randomised study in patients with an indication for angiography or percutaneous intervention, one year of treatment with rosuvastatin 40<span class="elsevierStyleHsp" style=""></span>mg (and also 10<span class="elsevierStyleHsp" style=""></span>mg) significantly reduced the percent of necrotic core (from 21.3% to 18%), increased fibrofatty tissue volume (from 11.7% to 14.8%), and decreased the plaque volume percent (from 51.4% to 50.4%)<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Lastly, a recent meta-analysis of prospective studies investigating the effect of statins on plaque volume and composition using IVUS and virtual histology (9 studies with 16 treatment arms with statins and 830 patients) concluded that the treatment induced favourable changes in the plaque, especially in the elastic membrane and fibrous tissue, with no significant effect on the lesion volume or necrotic core content.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">There is also evidence that intensive treatment with statins can have beneficial effects on plaque morphology in the carotid artery, which can be detected using ultrasound, magnetic resonance imaging, or PET. Different studies have also demonstrated that statins reduce carotid IMT progression and have a favourable impact in symptomatic patients undergoing carotid endarterectomy, although what the best technique is for quantifying changes in the atherosclerotic plaque has not been established. Magnetic resonance angiography and PET can provide additional information on the degree of plaque inflammation and identify the most vulnerable.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">25,26</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Mechanisms by which statins may stabilise atheroma plaques</span><p id="par0070" class="elsevierStylePara elsevierViewall">Some of the results cannot be attributed exclusively to a reduction in LDLc, but rather to pleiotropic effects related to higher fibrous tissue content, as well as decreased thrombogenicity and inflammation in the plaque.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a> In this sense, in the IBIS-4 study, necrotic core stabilisation in myocardial infarction patients who received high statin doses was limited to those who achieved a greater reduction in CRP levels during treatment.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">A new frontier: PCSK9 inhibition</span><p id="par0075" class="elsevierStylePara elsevierViewall">Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition represents one of the major advances that have occurred in the last two years with a spectacular reduction in LDL-c.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a> An interesting fact is that in addition to decreasing LDL-c, PCSK9 is expressed in human atherosclerotic plaques,<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> likely playing a role in the vascular inflammation process and apoptosis. Moreover, the ATHEROREMO-IVUS study demonstrated that serum levels of PCSK9 were correlated with necrotic core volume as measured by IVUS and virtual histology.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">31</span></a> On-going studies with PCSK9 inhibitors (GLAGOV) will enable the scale of the LDL-c reduction and the other actions of these drugs on the composition and behaviour of high-risk plaques to be established.<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">32,33</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="par0080" class="elsevierStylePara elsevierViewall">Research in recent years has enabled the molecular and cellular mechanisms underlying the biology of atheroma plaques to be established. The development of new vascular imaging techniques has contributed to this. Statins have changed the natural history of atherosclerosis, since there is clinical evidence that an “aggressive” lipid-lowering treatment can promote stabilisation and even regression of the atherosclerotic plaque, which is an important milestone in cardiovascular medicine. The atheroma plaque regression process includes favourable changes in the plaque's morphology and composition, more than its size or the degree of stenosis. On-going studies will enable the plaque response to systemic therapy to be more precisely defined.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Ethical responsibilities</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Protection of people and animals</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were conducted on human beings or animals for this research.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Confidentiality of data</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work site regarding the publication of patient data.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Right to privacy and informed consent</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that no patient data is contained in this paper.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres801249" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec799603" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres801248" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec799602" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Identifying high risk/vulnerable plaques" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Measuring plaque response to systemic therapy" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Mechanisms by which statins may stabilise atheroma plaques" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "A new frontier: PCSK9 inhibition" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusion" ] 10 => array:3 [ "identificador" => "sec0035" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-04-20" "fechaAceptado" => "2016-05-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec799603" "palabras" => array:4 [ 0 => "Atherosclerosis" 1 => "Plaque stabilisation" 2 => "Non-invasive assessment of atherosclerosis" 3 => "Lipid-lowering therapy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec799602" "palabras" => array:4 [ 0 => "Aterosclerosis" 1 => "Estabilización de la placa" 2 => "Técnicas no invasivas de imagen vascular" 3 => "Hipolipemiantes" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilisation via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilisation was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion (‘angiographic paradox’). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An ‘aggressive’ lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilising effects.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La patogenia de los síndromes coronarios agudos está relacionada con la rotura o erosión de una placa aterosclerótica vulnerable. La estabilización de dicha placa, por reducción del núcleo lipídico y/o aumento de la capa fibrosa, sería uno de los mecanismos potencialmente beneficiosos observados con agentes antiateroscleróticos. El concepto de estabilización de la placa de ateroma se desarrolló para explicar el efecto beneficioso del tratamiento hipolipemiante, sin cambios apreciables en el tamaño y la morfología de la lesión aterosclerótica («paradoja angiográfica»). En la actualidad, el desarrollo de nuevas técnicas de imagen no invasivas (ultrasonido vascular e histología virtual, resonancia magnética, tomografía de coherencia óptica, etc.) permite determinar el volumen, el tamaño y la composición de la placa, con lo que es posible caracterizar las placas más vulnerables y, por consiguiente, más susceptibles de rotura. Una estrategia hipolipemiante «agresiva» puede estabilizar e incluso reducir de forma significativa la carga aterosclerótica y la incidencia de episodios vasculares, al menos en parte, a través de un efecto estabilizador de la placa.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Páramo JA, Civeira F. ¿Es posible la regresión de la placa aterosclerótica? Clin Invest Arterioscler. 2017;29:46–50.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">IVUS: intravascular ultrasonography; STE-ACS: ST-segment elevation acute coronary syndrome.</p>" "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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Population (n) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Duration (months) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug and dose (mg) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Atheroma plaque volume change vs baseline \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">REVERSAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stable angina (654) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Atorvastatin 80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+0.2% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ASTEROID \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stable angina (349) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rosuvastatin 40<br>Atorvastatin 80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.79% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001)<br>−0.99% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SATURN \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stable angina (1039) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rosuvastatin 40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.22% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IBIS-4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">STE-ACS (103) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rosuvastatin 40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.90% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.007) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">STABLE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Coronary lesion (225) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rosuvastatin 40<br>Rosuvastatin 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.018) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1344479.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Summary of studies with IVUS that determine the impact of an “aggressive” lipid-lowering strategy on atherosclerotic plaque regression.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0170" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of acute coronary syndromes and their implications for therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 2 | 10 |
| 2024 October | 48 | 4 | 52 |
| 2024 September | 37 | 5 | 42 |
| 2024 August | 56 | 3 | 59 |
| 2024 July | 47 | 7 | 54 |
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| 2023 September | 46 | 4 | 50 |
| 2023 August | 20 | 2 | 22 |
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| 2023 June | 56 | 4 | 60 |
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| 2023 April | 66 | 1 | 67 |
| 2023 March | 35 | 2 | 37 |
| 2023 February | 26 | 2 | 28 |
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| 2022 December | 13 | 2 | 15 |
| 2022 November | 13 | 7 | 20 |
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| 2018 April | 10 | 5 | 15 |
| 2018 March | 15 | 0 | 15 |
| 2018 February | 6 | 0 | 6 |
| 2018 January | 11 | 0 | 11 |
| 2017 March | 4 | 1 | 5 |
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