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Hypertensive mediated organ damage evolution in resistant hypertension patients after adding spironolactone
Evolución de la lesión orgánica mediada por hipertensión en pacientes con hipertensión arterial resistente tras añadir espironolactona
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"etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Susana" "apellidos" => "Vázquez" "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" ] ] ] 2 => array:3 [ "nombre" => "Marta" "apellidos" => "Crespo" "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" ] ] ] 3 => array:3 [ "nombre" => "Julio" "apellidos" => "Pascual" "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" ] ] ] 4 => array:3 [ "nombre" => "Anna" "apellidos" => "Oliveras" "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" => "Servicio de Nefrología, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Institut Hospital del Mar d’ Investigacions Mèdiques, Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evolución de la lesión orgánica mediada por hipertensión en pacientes con hipertensión arterial resistente tras añadir espironolactona" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1064 "Ancho" => 2917 "Tamanyo" => 164056 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Correlation between reduction in albuminuria and reduction in DBP after 12 months of spironolactone treatment in patients with initial A2 or A3 albuminuria (A) and initial A1 albuminuria (B).</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">DBP: diastolic blood pressure; Dif_Alb: difference between final and initial albuminuria; Dif_cDBP: difference between final and initial clinical DBP.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Resistant hypertension (RHTN) is a major public health problem for primary care doctors and specialists today. Its prevalence is estimated to be between 10%–20% of the treated hypertensive population<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> and these patients have a higher risk of experiencing major cardiovascular events causing morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The Clinical Practice Guidelines of the European Society of Hypertension and the European Society of Cardiology recommend using spironolactone, an aldosterone receptor antagonist, as the fourth drug in patients with RHTN.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The antihypertensive efficacy of spironolactone in patients with RHTN has been widely confirmed in the control of clinical blood pressure (BP), self-measured BP monitoring at home and in 24-h ambulatory blood pressure monitoring (24<span class="elsevierStyleHsp" style=""></span>h ABPM).<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> However, few studies detail the variation in the circadian pattern of BP following the introduction of spironolactone. In addition, spironolactone has a beneficial effect on the reduction of myocardial fibrosis and ventricular remodelling in patients with heart failure (HF),<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–10</span></a> and in the reduction of proteinuria in patients with hypertension and pathological albuminuria or diabetic nephropathy.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–13</span></a> The scientific evidence for cardiac benefits after spironolactone primarily focuses on HF patients.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–10</span></a> In particular, studies in hypertensive patients are limited to reporting a reduction in left ventricular mass.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,15</span></a> Studies focusing on patients with RHTN and providing more echocardiographic data are scarce or have smaller samples.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> This study aimed to evaluate the evolution of hypertension-mediated organ damage (HMOD) at the cardiac and renal levels in patients with RHTN after spironolactone was added to antihypertensive therapy.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Population</span><p id="par0015" class="elsevierStylePara elsevierViewall">This was a retrospective observational study of patients diagnosed with RHTN who had spironolactone added to their antihypertensive therapy (starting dose 12.5–25<span class="elsevierStyleHsp" style=""></span>mg/day), seen at the Hypertension and Vascular Risk Unit of the Nephrology Service of Hospital del Mar [del Mar Hospital], Barcelona, from April 2016 to September 2018, with subsequent follow-up until January 2020. The study was approved by the local Institutional Ethics Committee in accordance with the Declaration of Helsinki.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The specific objectives were: (i) to evaluate the effect of spironolactone on HMOD, according to echocardiographic parameters and albuminuria, 12 months after its addition to antihypertensive treatment; (ii) to evaluate the efficacy of spironolactone in the control of clinical BP and 24<span class="elsevierStyleHsp" style=""></span>h ABPM, as well as changes in the circadian pattern of BP; (iii) to analyse whether there are associations between changes in BP and changes in HMOD after adding spironolactone.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Patients aged 18 years or older, diagnosed with RHTN, defined according to the guidelines from the European Society of Hypertension<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> as BP<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>140/90<span class="elsevierStyleHsp" style=""></span>mmHg despite receiving treatment with at least three antihypertensive drugs of different therapeutic classes, including a diuretic, were included. The diagnosis of RHTN was confirmed by 24<span class="elsevierStyleHsp" style=""></span>h ABPM (24<span class="elsevierStyleHsp" style=""></span>h BP<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>130/80<span class="elsevierStyleHsp" style=""></span>mmHg).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Studied variables</span><p id="par0030" class="elsevierStylePara elsevierViewall">Clinical and laboratory data were evaluated at baseline and 12 months after the start of spironolactone. Demographic and medical history data were collected, including age, sex, body mass index and abdominal circumference, presence or absence of concomitant pathologies (cardiovascular disease [ischaemic heart disease, cerebrovascular disease, and peripheral vascular disease], type 2 diabetes mellitus [T2DM], dyslipidaemia, chronic kidney disease [CKD], and obstructive sleep apnoea syndrome); and laboratory parameters (estimated glomerular filtration rate [eGFR],<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> potassium and glycated haemoglobin [HbA1c] in plasma and urinary albumin excretion [UAE] measured by urine albumin–creatinine ratio), before spironolactone was started and after 12 months of treatment. Albuminuria grades were defined as: A1 as EUA lower than 30<span class="elsevierStyleHsp" style=""></span>mg/g, A2 as EUA 30–300<span class="elsevierStyleHsp" style=""></span>mg/g and A3 as EUA higher than 300<span class="elsevierStyleHsp" style=""></span>mg/g.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Echocardiographic parameters</span><p id="par0035" class="elsevierStylePara elsevierViewall">The following parameters were analysed by transthoracic echocardiogram validated with 2.0–4.0<span class="elsevierStyleHsp" style=""></span>MHz transducers using a Vivid E9 system (GE Healthcare) in two-dimensional mode and colour Doppler, with the patient supine and non-tilted: posterior wall (PW) thickness, interventricular septal (IVS) thickness, left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter, left ventricular remodelling index (LVRI<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>PW/LVEDD), left atrial diameter, relationship of early ventricular filling wave to atrial contraction (E/A), and left ventricular filling pressure (LVFP) index (E/e’). These determinations were performed at baseline and after approximately 12 months of spironolactone treatment. In addition, left ventricle (LV) geometric patterns were also assessed.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Albuminuria</span><p id="par0040" class="elsevierStylePara elsevierViewall">Albuminuria was evaluated by immunonephelometry and expressed by the urine albumin–creatinine ratio determined in first morning urine. Biochemical parameters were obtained with autoanalysers using standard methods. Again, these determinations were performed before starting spironolactone treatment and at 12 months.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Blood pressure</span><p id="par0045" class="elsevierStylePara elsevierViewall">Clinical BP was determined using a validated semi-automatic device (Omron® 705IT) with a suitably-sized cuff for the brachial circumference of each subject. At each visit, three BP measurements spaced 1–2<span class="elsevierStyleHsp" style=""></span>min apart, were performed after five minutes of rest with the patient seated, and the final value was the mean of the three measurements.</p><p id="par0050" class="elsevierStylePara elsevierViewall">BP by 24<span class="elsevierStyleHsp" style=""></span>h ABPM was determined by a validated semi-automatic device (Spacelabs 90207-5Q) with a suitably-sized cuff for each patient. BP monitoring was started between 8<span class="elsevierStyleHsp" style=""></span>am and 10<span class="elsevierStyleHsp" style=""></span>am on a weekday, with systolic BP (SBP) and diastolic BP (DBP) values obtained every 20<span class="elsevierStyleHsp" style=""></span>min during the waking and sleeping periods. These periods were defined according to the times reported by the patients that they woke up and went to sleep on the day of the test. A minimum of 80% valid readings was required to consider the record good quality and to be accepted as valid.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Data were collected on antihypertensive drugs prescribed at baseline and 12 months after starting spironolactone. Treatment adherence was evaluated by self-reported patient data, with a systematic review at each visit.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Statistical measures of central tendency and arithmetic mean (95% confidence interval [95% CI]) were used for continuous variables and frequency distribution for discrete variables. The median (25th and 75th percentiles) was used for continuous variables that did not follow a normal distribution. The variation of the parameters of interest at 12 months of follow-up was studied using linear mixed models. The Wilcoxon test was used to evaluate the change in albuminuria, a parameter of non-normal distribution. Correlations between the SBP and DBP difference in time and changes in HMOD were evaluated using Pearson’s correlation coefficient.</p><p id="par0065" class="elsevierStylePara elsevierViewall">All analyses were adjusted for age, sex, body mass index, T2DM and estimated glomerular filtration rate. A p value <0.05 was considered statistically significant. The program used for the statistical analysis was STATA 15.1 (StataCorp, CollegeStation, TX, USA).</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 58 patients were included, with a mean age of 67 years; the majority were Caucasian males with a high prevalence of dyslipidaemia and obesity (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Before spironolactone was started, patients received an average of 3.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.2 antihypertensive drugs: 100% a diuretic (71.3% thiazide and 28.7% loop); 94.2% a renin–angiotensin–aldosterone system blocker (84.5% ARB and 15.5% ACE inhibitor); 87.9% a calcium channel blocker; 60.7% a beta-blocker; 35.4% an alpha-blocker; 10.2% a sympatholytic (clonidine or moxonidine); 3.4% a direct renin inhibitor (aliskiren); and 2.4% an arterial vasodilator (hydralazine).</p><p id="par0080" class="elsevierStylePara elsevierViewall">The initial daily dose of spironolactone (median [IQR 25–75]) was 25<span class="elsevierStyleHsp" style=""></span>mg (12.5–25) and 25<span class="elsevierStyleHsp" style=""></span>mg (12.5–37.5) at 12 months.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Regarding renal safety, a significant potassium elevation of 0.36<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.02<span class="elsevierStyleHsp" style=""></span>mmol/l and a reduction in estimated glomerular filtration rate at −6.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.0<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> was detected at 12 months of treatment, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 in both cases.</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Changes in hypertension-mediated organ damage</span><p id="par0090" class="elsevierStylePara elsevierViewall">Albuminuria decreased from an initial median (IQR 25–75) of 27.0<span class="elsevierStyleHsp" style=""></span>mg/g (7.5–255.4) to 11.3<span class="elsevierStyleHsp" style=""></span>mg/g (3.1–37.8) at 12 months, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.009. In patients who had A2 or A3 albuminuria at baseline, this reduction was especially pronounced: from 371.2<span class="elsevierStyleHsp" style=""></span>mg/g (139.5–797.4) initially, to 68.4<span class="elsevierStyleHsp" style=""></span>mg/g (26.5–186.5) finally, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02. The decrease in albuminuria was not correlated with a weight change in patients (body mass index variation of +0.3<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> after 12 months of follow-up, correlation r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.20; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.2), nor with HbA1c variation in patients with T2DM (HbA1c variation of −0.05% after 12 months, correlation r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.14, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.5). No patients were diagnosed with new T2DM onset during the study.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Regarding echocardiographic parameters (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), a reduction in PW thickness (mean [95% CI]) of −1.0<span class="elsevierStyleHsp" style=""></span>mm (−1.4 to −0.6), p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001, IVS thickness of −0.6<span class="elsevierStyleHsp" style=""></span>mm (−1.1 to −0.1), p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01, LVMI of −14.7<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> (−24.9 to −4.4), p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.006, and LVRI of −0.04 (−0.08 to −0.004), p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03 was observed. No statistically significant changes were found in the variation of LVEF, LVEDD, left ventricular end-systolic diameter, left atrial diameter, E/A, or E/e’. In addition, the proportion of patients with pathological LVMI (>95<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> in women or >115<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> in men) decreased from 72.4% at baseline to 56.9% after 12 months of spironolactone treatment (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). With regard to LV geometric patterns (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), the concentric hypertrophy pattern was initially predominant, present in 60.7% of patients, and prevalence decreased to 32.1% after 12 months of treatment (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). The echocardiographic normal LV pattern was in the majority at 12 months of spironolactone treatment (37.5% of patients), whereas it was 21.4% before treatment. Overall, 21.4% of patients experienced an improvement in their baseline LV geometric pattern, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Blood pressure changes</span><p id="par0100" class="elsevierStylePara elsevierViewall">With regard to clinical BP, a significant reduction in SBP from 152.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16.0<span class="elsevierStyleHsp" style=""></span>mmHg to 139.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.4<span class="elsevierStyleHsp" style=""></span>mmHg and DBP from 83.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.4<span class="elsevierStyleHsp" style=""></span>mmHg to 78.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.7<span class="elsevierStyleHsp" style=""></span>mmHg was observed at 12 months after the addition of spironolactone, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 in both cases. Sixty-point-four per cent of patients with insufficient control of clinical BP before starting spironolactone achieved adequate control (SBP<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>140<span class="elsevierStyleHsp" style=""></span>mmHg and DBP<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>90<span class="elsevierStyleHsp" style=""></span>mmHg) after 12 months of treatment. This percentage was higher when the BP changes were analysed according to the 24<span class="elsevierStyleHsp" style=""></span>h ABPM (the initial and final 24<span class="elsevierStyleHsp" style=""></span>h ABPM was available for 36 of the 58 patients). Thus, <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the results obtained in the 24<span class="elsevierStyleHsp" style=""></span>h ABPM records, with a decrease in SBP and DBP in both the daytime and night-time periods. Blood pressure normalised in 66.7% of patients (SBP 24<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>130<span class="elsevierStyleHsp" style=""></span>mmHg and DBP 24<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>80<span class="elsevierStyleHsp" style=""></span>mmHg) after 12 months of treatment. Regarding the circadian patterns of the 24<span class="elsevierStyleHsp" style=""></span>h ABPM (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), the non-dipping pattern predominated initially, present in 47.6% of patients. After 12 months of treatment, the predominant pattern was the dipping pattern (52.4%), and the riser pattern disappeared, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001. Thirty-eight point one per cent of patients experienced a favourable change in their circadian BP pattern (understood as a change from riser to non-dipping, from riser to dipping, or from non-dipping to dipping), p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Four patients (6.9%) initially had A2 or A3 albuminuria, concentric left ventricular hypertrophy and a riser pattern in 24<span class="elsevierStyleHsp" style=""></span>h ABPM. Three of them improved in the three parameters of HMOD after 12 months with spironolactone, and the fourth showed improvement exclusively in the level of albuminuria.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Association between BP changes and HMOD changes</span><p id="par0110" class="elsevierStylePara elsevierViewall">The reduction in albuminuria correlated with the decrease in clinical DBP obtained after the introduction of spironolactone: r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.46; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02. When the patients with A1 albuminuria and those with A2 or A3 albuminuria were analysed separately (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>), a correlation with DBP with greater statistical power was found: r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.50 in the group with baseline A1 albuminuria (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04) and r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.88 in the group with baseline A2 or A3 albuminuria (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). We found no correlations between a reduction in albuminuria and a decrease in clinical SBP. Nor did we find correlations between echocardiographic changes (PW thickness, IVS thickness, LVMI, and LVRI) and the decrease in clinical SBP or DBP. In patients with A2 or A3 albuminuria at baseline, the reduction in albuminuria correlated with a reduction in PW thickness after the introduction of spironolactone (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.40; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04), but no correlation was found between reduced albuminuria and changes in IVS thickness, LVMI, or LVRI.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">The main finding of this study is the confirmation that spironolactone use in patients with RHTN reduces HMOD at the cardiac and renal levels. The echocardiographic benefits have been reproduced in the literature mainly in patients with HF,<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,10</span></a> although the data are more limited in patients without HF. Edwards et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> observed a reduction in left ventricular mass in patients with CKD, and Pitt et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> also demonstrated a reduction in left ventricular hypertrophy in hypertensive patients with eplerenone 200<span class="elsevierStyleHsp" style=""></span>mg/day, but studies focusing on patients with RHTN treated with spironolactone are scarce. Gaddam et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> observed a reduction in left ventricular mass, IVS thickness, and LVEDD in patients with RHTN after six months of treatment with 25–50<span class="elsevierStyleHsp" style=""></span>mg/day of spironolactone, although the cohort analysed was of a reduced sample size (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11) and follow up was six months. All previous studies focused on reducing the percentage of patients with left ventricular hypertrophy, without providing other data regarding changes in echocardiographic parameters. In contrast, our study analyses the changes in each echocardiographic parameter. In a novel way, the different LV geometric patterns and the changes experienced after spironolactone treatment are shown (thus, 21.4% of patients showed an improvement concerning the initial LV geometric pattern).</p><p id="par0120" class="elsevierStylePara elsevierViewall">With regard to the antiproteinuric action, the beneficial effect of spironolactone is similar to that observed mainly in patients with diabetes or CKD and hypertension.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–13</span></a> Our study found an improvement in albuminuria after 12 months of spironolactone treatment in patients with RHTN, in whom the prevalence of T2DM and CKD were 48% and 27%, respectively, which is lower than in the studies reported. We ruled out that the improvement in albuminuria was related to weight loss in patients during the study or a significant improvement in HbA1c in diabetic patients. In addition, we found a correlation between the decrease in DBP achieved after introducing spironolactone and the reduction in albuminuria, suggesting that the antiproteinuric effect of spironolactone should be related to antihypertensive efficacy. On the contrary, the improvement in echocardiographic parameters did not correlate with the decrease in BP, so it could be an intrinsic effect of the drug itself or occur through other mechanisms not analysed here, such as changes in the renin–angiotensin–aldosterone axis. These data would be consistent with previously published information on the cardiological and renal benefits obtained from using angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers,<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a> which are drugs that also interfere with the renin–angiotensin–aldosterone system.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In all of the studies mentioned above, the reduction of HMOD was achieved with an initial dose of spironolactone of 25–50<span class="elsevierStyleHsp" style=""></span>mg/day and a subsequent dose escalation to 50–100<span class="elsevierStyleHsp" style=""></span>mg/day. In our study, the initial dose of spironolactone was 12.5–25<span class="elsevierStyleHsp" style=""></span>mg/day and the final median dose was 25<span class="elsevierStyleHsp" style=""></span>mg/day, with the cardiovascular and renal protective benefits of spironolactone being achieved at doses that appeared to be lower than in previous studies.</p><p id="par0130" class="elsevierStylePara elsevierViewall">The antihypertensive efficacy of spironolactone observed in this study is comparable to that of previous studies.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> In relation to the 24<span class="elsevierStyleHsp" style=""></span>h ABPM records, a reduction of SBP and DBP in both periods, daytime and night-time, has been reported<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> previously, but few studies detail how the circadian pattern of BP varies after spironolactone is added. Our study provides data on these changes, with the conversion of 100% of patients with a riser pattern to circadian profiles with lower cardiovascular risk after 12 months of treatment, as well as a significant improvement in the circadian pattern according to the initial 24<span class="elsevierStyleHsp" style=""></span>h ABPM in 38.1% of patients. These findings contribute to an improvement in the cardiovascular risk profile of these patients.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The study’s main limitations include the fact that this is a retrospective, single-centre observational study. In addition, the sample is limited by the requirement for an initial echocardiogram and another echocardiogram after 12 months of spironolactone treatment, which is not always performed in all patients at our centre for whom this drug is added. Therefore, fewer patients than those receiving spironolactone in actual clinical practice could be analysed.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In conclusion, spironolactone is a drug that is effective in the reduction of HMOD, that is, hypertensive heart disease and albuminuria, as well as in the improvement of the circadian pattern of BP in patients with RHTN, which contributes to the improvement of the cardiovascular risk profile of these patients.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Key concepts</span><p id="par0170" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0145" class="elsevierStylePara elsevierViewall">In RHTN, adding spironolactone reduces HMOD.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0150" class="elsevierStylePara elsevierViewall">Spironolactone is effective in reducing hypertensive heart disease and albuminuria.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0155" class="elsevierStylePara elsevierViewall">The use of spironolactone was related to an improvement in the 24<span class="elsevierStyleHsp" style=""></span>h ABPM circadian pattern.</p></li></ul></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This study has received partial funding from the <span class="elsevierStyleGrantSponsor" id="gs0005">ISCIII</span> [Instituto de Salud Carlos III (San Carlos III Institute)] project — <span class="elsevierStyleGrantSponsor" id="gs0010">RETICS</span> [Redes Temáticas de Investigación Cooperativa en Salud (Thematic Networks for Cooperative Health Research)] Sub-programme, and RETICS and <span class="elsevierStyleGrantSponsor" id="gs0015">REDinREN</span> [Renal Research Network] funds RD16/0009/0013.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that they have no potential conflicts of interest related to the content of this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1957597" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1684671" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1957598" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1684670" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Population" ] 1 => array:3 [ "identificador" => "sec0020" "titulo" => "Studied variables" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Echocardiographic parameters" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Albuminuria" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Blood pressure" ] ] ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Changes in hypertension-mediated organ damage" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Blood pressure changes" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Association between BP changes and HMOD changes" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Key concepts" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-03-05" "fechaAceptado" => "2021-12-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1684671" "palabras" => array:5 [ 0 => "Spironolactone" 1 => "Resistant hypertension" 2 => "24-h ambulatory blood pressure monitoring" 3 => "Albuminuria" 4 => "Echocardiography" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1684670" "palabras" => array:5 [ 0 => "Espironolactona" 1 => "Hipertensión arterial resistente" 2 => "Presión arterial ambulatoria de 24<span class="elsevierStyleHsp" style=""></span>h" 3 => "Albuminuria" 4 => "Ecocardiograma" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Resistant hypertension (RH) represents an important multi-organic impact and increases the morbi-mortality. We aimed to evaluate the evolution of hypertensive mediated organ damage in patients with RH after adding spironolactone.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Retrospective study of 58 patients with RH who started spironolactone (12.5–25<span class="elsevierStyleHsp" style=""></span>mg daily). Office blood pressure, 24-h ambulatory blood pressure monitoring (24<span class="elsevierStyleHsp" style=""></span>h-ABPM), urine albumin-to-creatinine ratio and echocardiographic parameters were analyzed prior to initiation of spironolactone and after 12 months of treatment.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Thirty-six percent of patients were women and mean age was 67.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.1 years. We observed a decrease in urine albumin-to-creatinine ratio (median [RIQ<span class="elsevierStyleInf">25–75</span>]) of 27.0 (7.5–255.4) to 11.3 (3.1–37.8)<span class="elsevierStyleHsp" style=""></span>mg/g, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.009. This was more relevant in patients with albuminuria grade A2 and A3: 371.2 (139.5–797.4) to 68.4 (26.5–186.5)<span class="elsevierStyleHsp" style=""></span>mg/g, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02. The echocardiographic changes were: posterior wall thickness: −1.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.4<span class="elsevierStyleHsp" style=""></span>mm (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), interventricular septal thickness: −0.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5<span class="elsevierStyleHsp" style=""></span>mm (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01), left ventricular (LV) mass index: −14.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.2<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.006), LV remodeling index: −0.04<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.036 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03), without statistically significant changes in LV ejection fraction, LV end-diastolic diameter, LV end-systolic diameter, left atrial diameter, relationship between early ventricular filling wave and atrial contraction and LV filling pressure index.</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Systolic/diastolic office blood pressure decreased −12.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.9/−4.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.0<span class="elsevierStyleHsp" style=""></span>mmHg, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001. In 24<span class="elsevierStyleHsp" style=""></span>h-ABPM, systolic and diastolic BP had a significant decrease in diurnal and nocturnal periods and 38.1% of patients presented a favorable change in the circadian pattern, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Adding spironolactone to patients with RH contributes to improve hypertensive mediated organ damage by reducing albuminuria levels and echocardiographic parameters of hypertensive heart disease.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">La hipertensión arterial resistente (HTAR) supone un importante impacto a nivel multiorgánico e incrementa la morbimortalidad. Este trabajo evalúa la evolución de la lesión orgánica mediada por hipertensión en pacientes con HTAR tras añadir espironolactona.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de 58 pacientes con HTAR a quienes se añadió espironolactona (12,5–25<span class="elsevierStyleHsp" style=""></span>mg/día). Se obtuvieron parámetros de presión arterial clínica y MAPA-24<span class="elsevierStyleHsp" style=""></span>h, cociente albúmina/creatinina y datos ecocardiográficos previos a iniciar espironolactona y tras 12 meses de tratamiento.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">El 36,2% de los pacientes eran mujeres y la edad media de 67,3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10,1 años. Se objetivó un descenso en albuminuria (mediana [RIC<span class="elsevierStyleInf">25–75</span>]) de 27,0 (7,5–255,4) a 11,3 (3,1–37,8)<span class="elsevierStyleHsp" style=""></span>mg/g (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,009), siendo más marcado en pacientes con albuminuria grado A2 y A3: de 371,2 (139,5–797,4) a 68,4 (26,5–186,5)<span class="elsevierStyleHsp" style=""></span>mg/g, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,02.. A nivel ecocardiográfico se evidenció: pared posterior: −1,0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0,4<span class="elsevierStyleHsp" style=""></span>mm (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001), tabique interventricular: −0,6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0,5<span class="elsevierStyleHsp" style=""></span>mm (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,01), índice de masa del ventrículo izquierdo (VI): −14,7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10,2 g/m2 (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,006), índice de remodelado del VI: −0,04<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0,036 (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,03), sin cambios estadísticamente significativos en fracción de eyección VI, diámetro diastólico VI, diámetro sistólico VI, diámetro de aurícula izquierda, relación entre onda de llenado ventricular temprano y contracción auricular ni en índice de presión llenado VI.</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">La presión arterial clínica sistólica/diastólica presentó un descenso de −12,5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4,9/−4,9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3,0<span class="elsevierStyleHsp" style=""></span>mmHg, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001. En los MAPA-24<span class="elsevierStyleHsp" style=""></span>h se observó un descenso significativo de presión arterial sistólica y diastólica en los períodos diurno y nocturno, y un cambio favorable en el patrón circadiano en el 38,1% de los pacientes, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Añadir espironolactona en HTAR contribuye a la reducción de la lesión orgánica mediada por hipertensión a nivel de albuminuria y de parámetros ecocardiográficos de cardiopatía hipertensiva.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1083 "Ancho" => 2167 "Tamanyo" => 92328 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Left ventricular geometric pattern variation after 12 months of spironolactone treatment.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">LV: left ventricle.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1339 "Ancho" => 2167 "Tamanyo" => 94563 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Circadian pattern blood pressure variation after 12 months of spironolactone treatment.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1064 "Ancho" => 2917 "Tamanyo" => 164056 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Correlation between reduction in albuminuria and reduction in DBP after 12 months of spironolactone treatment in patients with initial A2 or A3 albuminuria (A) and initial A1 albuminuria (B).</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">DBP: diastolic blood pressure; Dif_Alb: difference between final and initial albuminuria; Dif_cDBP: difference between final and initial clinical DBP.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A2 albuminuria: urinary albumin excretion 30–300<span class="elsevierStyleHsp" style=""></span>mg/g; A3 albuminuria: urinary albumin excretion >300<span class="elsevierStyleHsp" style=""></span>mg/g; BMI: body mass index; CKD: chronic kidney disease; OSAS: obstructive sleep apnoea syndrome; SD: standard deviation.</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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RHTN (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>58) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, years (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD) \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">67.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male, N (%) \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">37 (63.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Caucasian, N (%) \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">54 (93.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI, kg/m<span class="elsevierStyleSup">2</span> (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD) \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">31.6 (4.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abdominal circumference, cm (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD) \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">111.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type 2 diabetes mellitus, N (%) \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">28 (48.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyslipidaemia, N (%) \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">41 (70.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CKD stage 1, N (%) \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">18 (31.0%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CKD stage 2, N (%) \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">24 (41.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CKD stage 3A, N (%) \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">8 (13.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CKD stage 3B, N (%) \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">8 (13.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total albuminuria, mg/g, median (IQR<span class="elsevierStyleInf">25–75</span>) \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">27.0 (7.5–255.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A2 albuminuria, N (%) \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">10 (17.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A3 albuminuria, N (%) \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">10 (17.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OSAS, N (%) \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">23 (39.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ischaemic heart disease, N (%) \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">9 (15.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular disease, N (%) \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">7 (12.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripheral vascular disease, N (%) \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">4 (6.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3258155.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of patients with resistant hypertension.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">E/A: relationship of early ventricular filling wave to atrial contraction; E/e’: left ventricular filling pressure index; IVS thickness: interventricular septal thickness; LAD: left atrial diameter; LVEDD: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LVESD: left ventricular end-systolic diameter; LVMI: left ventricular mass index; LVRI: left ventricular remodelling index; PW thickness: posterior wall thickness.</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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PW thickness (mm) \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">12.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.0 \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">11.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.7 \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"><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="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IVS thickness (mm) \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">13.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.1 \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">12.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8 \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">0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LVEF (%) \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">63.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.0 \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">62.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.5 \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">0.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LVEDD (mm) \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">48.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.3 \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">47.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.1 \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">0.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LVESD (mm) \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">29.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.1 \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">28.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.5 \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">0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LVMI (g/m<span class="elsevierStyleSup">2</span>) \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">133.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>37.9 \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">118.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>39.3 \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">0.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LVRI \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">0.53<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.10 \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">0.49<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.10 \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">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LAD (mm) \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">39.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.8 \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">41.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.8 \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">0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">E/A \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">0.88<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.22 \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">0.91<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.36 \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">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">E/e’ \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">9.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.5 \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">9.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.4 \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">0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3258157.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Change in echocardiographic parameters after 12 months of spironolactone treatment.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">24<span class="elsevierStyleHsp" style=""></span>h ABPM: 24-h ambulatory blood pressure monitoring; DBP: diastolic blood pressure; SBP: systolic blood pressure.</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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">BP \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SBP-24<span class="elsevierStyleHsp" style=""></span>h (mmHg) \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">147.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.3 \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">135.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.4 \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"><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="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DBP-24<span class="elsevierStyleHsp" style=""></span>h (mmHg) \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">77.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.1 \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">71.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.7 \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">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="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Daytime SBP (mmHg) \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">150.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.7 \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">138.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18.2 \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">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="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Daytime DBP (mmHg) \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">80.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.2 \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">74.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.5 \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">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="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Night-time SBP (mmHg) \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">140.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.6 \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">128.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16.8 \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">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Night-time DBP (mmHg) \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">71.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.2 \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">65.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.2 \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">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3258156.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Blood pressure variation by 24<span class="elsevierStyleHsp" style=""></span>h ABPM after 12 months of spironolactone treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of resistant hypertension in the United States, 2003-2008" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S.D. 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