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Primary aldosteronism: Aldosterone/renin ratio cut-off points
Hiperaldosteronismo primario: puntos de corte del cociente aldosterona/renina
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PA: primary aldosteronism; AHT: arterial hypertension.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Primary aldosteronism (PA) is the most common cause of secondary arterial hypertension of endocrine origin, affecting 6–12% of all hypertensive patients, with a higher prevalence in individuals with treatment resistant hypertension (20%). At equal blood pressure levels, these patients suffer a higher frequency of cardiovascular events than those with essential (primary) hypertension.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The screening method of choice for the diagnosis of PA is the plasma aldosterone (A)/renin (R) ratio. The latter can be measured as plasma renin activity (PRA), which is the capacity to convert angiotensinogen into angiotensin, or as immunoreactive plasma renin concentration (RC), giving rise to the aldosterone/plasma renin ratio (ARR) and the aldosterone/renin concentration ratio (ARC).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> The measurement of PRA is based on a radioimmunoassay (RIA), which is a complex, laborious manual and operator-dependent technique that makes any comparison of results between laboratories difficult. Automated methods for quantifying renin concentration are currently available that are easy to implement in the clinical laboratory, with better reproducibility and shorter processing times, but with poorer sensitivity at low values, as has been reported in the literature.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The lack of uniformity in the diagnostic protocols and laboratory methods used in the determination of A and R implies substantial variability in the cut-off values of ARR and ARC. Differences in pre-analytical conditions and in patient selection, as well as variations in R and A, geographical location and ethnic origin, explain the important variety of ARR cut-off values, ranging from 7.2 to 100.1<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h),<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> though most authors speak of values between 20 and 40<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> A multicenter study conducted by the Argentinean Society of Endocrinology (Sociedad Argentina de Endocrinología [SAEM])<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> determined cut-off values of 36<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for ARR and 2.39<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μIU/ml) for ARC. The method for measuring A was RIA DPC (Diagnostic Product Corporation, CA, USA) and that for measuring RC was IRMA DSL (Diagnostic Systems Laboratories Inc., TX, USA). The methodology currently used in our department and in other reference centers differs from that described in the SAEM study. New reference values are therefore needed.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The objectives of the present study were to:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0025" class="elsevierStylePara elsevierViewall">Optimize the ARR and ARC cut-off points for the screening of PA with the methodology currently being used at our hospital.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0030" class="elsevierStylePara elsevierViewall">Evaluate the correlation and diagnostic sensitivity of ARR and ARC for the screening of PA.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0035" class="elsevierStylePara elsevierViewall">Determine the prevalence of PA in our hypertensive patient population using as the detection value that described in the SAEM study.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a></p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">A prospective, cross-sectional study was conducted at a hospital in Buenos Aires (Argentina) in the period 2015–2017, with the evaluation of 345 subjects of both sexes. The study comprised 136 healthy controls and 209 patients diagnosed with arterial hypertension. The following exclusion criteria were applied: (1) individuals under 18<span class="elsevierStyleHsp" style=""></span>years of age; (2) pregnant women; (3) patients with endocrine disorders (thyroid dysfunction without adequate treatment, diabetes mellitus, hyperparathyroidism, adrenal insufficiency, pheochromocytoma, Cushing's syndrome); (4) patients with cardiological contraindications to modifying antihypertensive medication interfering with biochemical parameters (beta-blockers, angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], diuretics) or to receiving a normal sodium diet; and (5) patients with kidney, heart or liver failure.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The included subjects were clinically evaluated, with the recording of anthropometric parameters (weight, height, the body mass index [BMI], and blood pressure). Blood pressure was measured using Omron HEM-7200 oscillometric tensiometers. The blood pressure values were obtained according to the guidelines of the European Society of Hypertension,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a> the average of three recordings on each arm being calculated: at baseline, and after 3 and 5<span class="elsevierStyleHsp" style=""></span>min.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Biochemical measurements were requested for the assessment of the renin–angiotensin–aldosterone system (RAAS). Patients with a history of arterial hypertension (AHT) receiving antihypertensive treatment were evaluated by the AHT department to determine the feasibility of switching their medication to drugs that would not interfere with the measurement of A and R. Beta-blockers, ACEIs and ARBs were discontinued for two weeks, and diuretics for 4–6<span class="elsevierStyleHsp" style=""></span>weeks, with a switch being made to calcium antagonists (amlodipine) in the absence of cardiological contraindications. Potassium supplementing was prescribed when necessary. The patients were instructed to follow a normal sodium diet during the two weeks before the study, and an ion profile was requested before blood sampling. The measurements were made under conditions of normokalemia.</p><p id="par0055" class="elsevierStylePara elsevierViewall">All the included subjects gave their informed consent to their participation in the study.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Laboratory methods</span><p id="par0060" class="elsevierStylePara elsevierViewall">Sampling was performed in the morning between 8:00 am and 9:00 am, under 2<span class="elsevierStyleHsp" style=""></span>h post-walking conditions, in a tube with EDTA-K2. After centrifugation, the plasma samples were aliquoted and stored immediately at −20<span class="elsevierStyleHsp" style=""></span>°C until processing. Each aliquot was thawed a single time. We determined A with a solid phase competitive RIA (RIAZENco, Zentech S.A., Belgium), PRA using a solid phase RIA (DiaSorin Inc., USA), and RC with a chemiluminescent technique on an automated platform (LIAISON, DiaSorin, Saluggia, Italy). The following reference ranges were adopted in accordance with the specifications of the manufacturer: A 3.8–30<span class="elsevierStyleHsp" style=""></span>ng/dl, PRA 1.3–3.9<span class="elsevierStyleHsp" style=""></span>ng/ml/h and RC 4.4–46.4<span class="elsevierStyleHsp" style=""></span>μIU/ml.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study design</span><p id="par0065" class="elsevierStylePara elsevierViewall">The following was calculated for the screening of aldosteronism: ARR based on the A (ng/dl)/PRA (ng/ml/h) ratio and ARC using the A (ng/dl)/RC (μIU/ml) ratio. Suspected PA was based on ARR values >36<span class="elsevierStyleHsp" style=""></span>ng/dl/(ng/ml/h) associated with aldosterone measurements of ≥15<span class="elsevierStyleHsp" style=""></span>ng/ml (cut-off points established in a previous national study),<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> consistent with current guidelines<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> and the international literature.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In cases of pathological ARR, the diagnosis of PA was confirmed by captopril and/or saline overload testing to demonstrate the lack of suppression of aldosterone production.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> The current literature does not identify any concrete confirmatory test as the gold standard. In our department we use the captopril test for greater patient safety, though saline overload is performed in some cases in which captopril is not available, depending on the clinical condition of the patient.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In the saline overload test<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> we administered 2<span class="elsevierStyleHsp" style=""></span>l of physiological saline solution (0.9%) via the intravenous route as a 4<span class="elsevierStyleHsp" style=""></span>h infusion. The blood samples for the determinations of PRA and A were collected at the start of the test and at 4<span class="elsevierStyleHsp" style=""></span>h, with strict blood pressure control. The test is considered positive if the A values persist >10<span class="elsevierStyleHsp" style=""></span>ng/ml.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In the captopril test<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a> the A and PRA levels were measured at baseline and 1<span class="elsevierStyleHsp" style=""></span>h after 50<span class="elsevierStyleHsp" style=""></span>mg of captopril were administered via the oral route. Under normal conditions, the action of this drug (an ACEI) causes a decrease in A levels and an increase in PRA. The test is considered positive if the A values decrease less than 30% versus the baseline value and PRA remains suppressed. Four patients underwent both tests.</p><p id="par0085" class="elsevierStylePara elsevierViewall">All patients diagnosed with PA based on a pathological confirmation test were subjected to abdominal CAT and selective adrenal vein catheterization were indicated and feasible (33.3% of the patients).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The IBM SPSS version 21 statistical package was used. Differences between the groups with nonparametric data distribution were analyzed using the Mann–Whitney <span class="elsevierStyleItalic">U</span>-test, the Kruskal–Wallis test and the Spearman correlation method, and the receiver operating characteristic (ROC) curves were calculated to define the cut-off values for ARR and ARC.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Correlations between ARR and ARC were assessed using the presumptive diagnostic concordance (PDC) as parameter.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a> The latter was calculated as the percentage of samples that, based on the laboratory data, are equally classified as under or above the cut-off point established by the literature.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0100" class="elsevierStylePara elsevierViewall">A total of 345 subjects (136 controls and 209 hypertensive patients) participated in the study. Of these, 23 were lost to follow-up without having completed the requested tests, and were thus excluded. A total of 322 patients were included in the final analysis (119 controls and 203 hypertensive subjects). In this group of hypertensive patients, 12 cases of PA were diagnosed (5.9% of the total hypertensive subjects). <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the characteristics of the study population.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">There were no significant differences in age or clinical characteristics (weight, the BMI) between the groups. The blood pressure values were higher in the hypertensive patients than in the controls, and higher in patients with PA than in subjects with primary hypertension or the controls. The values corresponding to blood glucose, ion profile and lipid profile were similar in all three groups. In patients with PA, the serum potassium levels were lower than in the other two groups, but statistical significance was not reached (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.06) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The results corresponding to the renin–angiotensin–aldosterone system (RAAS) are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. On comparing the control group with the hypertensive patients, significant differences in A and PRA values were detected. Hypertensive patients had higher A values (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0001) and lower PRA (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03), with no significant differences in RC or in the ARR and ARC ratios (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). It should be noted that despite the differences found between the controls and the hypertensive patients, the individual values of the measurements in both groups were within the normal range.</p><p id="par0115" class="elsevierStylePara elsevierViewall">All of the controls showed normal ARR and ARC ratios. Among the hypertensive patients, we identified 39 pathological ratios, and confirmatory tests were performed in these cases. In this group, 27 cases corresponded to primary hypertension, while in 12 cases the diagnosis of PA was confirmed.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In the first group we performed 25 captopril and two saline overload tests, all of which proved negative.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Twelve patients had a diagnosis of PA. In this group we performed 7 captopril tests and one saline overload test, while four patients underwent both tests. In the latter the tests were made to confirm the results, which in all cases proved consistent.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Venous catheterization was performed in one-third of the patients (4 cases) in different hospital centers (because this is not available at our institution), with no selectivity being found. For this reason, and based on the clinical and imaging findings, 6 patients underwent unilateral adrenalectomy. The pathology study confirmed the presence of three aldosterone-producing adenomas (APAs), one adrenal carcinoma, a patient with multiple cortical adenomas, and one case reported as normal adrenal gland (after surgery the patient temporarily normalized her aldosterone levels, but hypertension persisted). Four patients were put under medical treatment, with suspected idiopathic bilateral hyperplasia. Two patients presented CAT images consistent with adenoma, but catheterization could not be performed (one patient rejected the procedure and the other had a medical contraindication due to a history of coronary disease). Medical treatment was therefore prescribed.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The patients with PA had a median aldosterone value of 52 (range 23–127) ng/dl, ARR 177.5 (50–653) (ng/dl)/(ng/ml/h) and ARC 8.7 (2.4–115) (ng/dl)/(μIU/ml), which proved significantly higher than in the other two groups.</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Determination of cut-off points using current methodology</span><p id="par0140" class="elsevierStylePara elsevierViewall">We retrospectively calculated ROC curves for ARR (area under the curve [AUC]<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.987, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001, 95% confidence interval [95%CI]: 0.972–1.000) and ARC (AUC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.975, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001, 95%CI: 0.954–0.996). The optimum cut-off value, considering the best specificity and sensitivity, in a presumed diagnosis of PA was 48.9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for ARR (sensitivity 100% and specificity 93.6%) and 2.3<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μIU/ml) for ARC (100% sensitivity and 90.9% specificity) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">For this ARR value, the positive predictive value (PPV) was 37.50% (95%CI: 19.16–55.84%) and the negative predictive value (NPV) 100% (95%CI: 99.83–100%), with Youden's index (<span class="elsevierStyleItalic">J</span>) 0.94 (95%CI: 0.91–0.96). With regard to ARC, the PPV was 31.43% (95%CI: 14.62–48.24%) and the NPV 100% (95%CI: 99.82–100%), with <span class="elsevierStyleItalic">J</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.92 (95%CI: 0.89–0.95).</p><p id="par0150" class="elsevierStylePara elsevierViewall">In all patients with ARR between 36 and 48.9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) the confirmatory tests proved negative.</p><p id="par0155" class="elsevierStylePara elsevierViewall">In our study, on considering the total population (controls, primary AHT and PA), the PDC between ARR and ARC was 96.6%.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Moreover, a good correlation was observed between ARR and ARC in both the overall population (<span class="elsevierStyleItalic">ρ</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.83; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) and in the control group (<span class="elsevierStyleItalic">ρ</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.74; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001), the patients with primary AHT (<span class="elsevierStyleItalic">ρ</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.85; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001), and in those with PA (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.89; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">In the present study we defined cut-off values of 48.9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for ARR (sensitivity 100% and specificity 93.6%) and 2.3 (ng/dl)/(μIU/ml) for ARC (100% sensitivity and 90.9% specificity), determining a 5.9% prevalence of PA in our population. This is consistent with the figures reported in the current literature.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The early detection of PA in hypertensive patients is essential in order to resolve the disease, and moreover allows for the reversal of organ damage secondary to excess aldosterone. The A/R ratio is widely used as a screening test for PA in hypertensive patients, but high sensitivity measurements should be obtained for this purpose. The ranges of the published guidelines are broad and variable; it is thus suggested that each population should have its own reference value. According to the guidelines of the Endocrine Society,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> the range is 20–40<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for ARR and 2.4–4.9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μIU/ml) for ARC. The Taiwanese Society<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a> advocates equal ARR values and a range of 2.4–7.7<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μIU/ml) for ARC. In 2009, the Japanese Society of Endocrinology<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a> recommended an ARR cut-off point<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for suspected PA, while the PAPY (PA Prevalence in Hypertensives) study<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">12</span></a> used an ARR value<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h).</p><p id="par0175" class="elsevierStylePara elsevierViewall">In the multicenter SAEM study,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> cut-off values of 36<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) were set for ARR and of 2.39<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μIU/dl) for ARC.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Following the diagnosis of the PA population with confirmatory tests, we retrospectively evaluated the cut-off points to optimize them according to our methodology, defining new cut-off values of 48.9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for ARR and 2.3<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μIU/ml) for ARC. We consider that the difference between the SAEM cut-off points and our own results is mainly due to the change in methodology as a consequence of technological development, though it cannot be discarded that the difference may be due in part to the different populations involved. Rossi et al.,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> using the same methodology, established cut-off values of 38.7<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for ARR and 2–3<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(mU/l) for ARC, with high specificity and sensitivity. These figures are very close to our own.</p><p id="par0185" class="elsevierStylePara elsevierViewall">It should be noted that by updating the cut-off values, unnecessary confirmatory tests can be avoided. In this population, on comparing the ARR cut-off point from the study of the SAEM<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> with our own value, 18% of the confirmatory tests would have been avoided.</p><p id="par0190" class="elsevierStylePara elsevierViewall">The technique for the determination of RC used in the present study (chemiluminescence; LIAISON, DiaSorin) is easier to implement in the clinical laboratory (due to its better reproducibility, the shorter processing time and independence of the substrate-angiotensinogen). As a result, it has been used on a routine basis and for a number of years by international reference centers with extensive experience in the field.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">7,13,14</span></a> Rossi et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> found a high level of correlation (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.92, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001) between the PRA and RC measures, with ARC being superior to ARR for the detection of PA in a population of hypertensive subjects. Unger et al.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">15</span></a> likewise found a very good correlation (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.91, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) between the two renin measurement methods in a population of adrenal incidentaloma patients without any suspension of the hypertensive medication, showing the clinical superiority of RC due to the technical benefits of this determination. Glinicki et al.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a> moreover recorded very good correlations between ARR and ARC in both the supine position and after two hours in the standing position, the values being similar to those reported by Ferrari et al.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a> In our study, ARR and ARC showed a very good correlation in both the global population and in the analyzed subgroups, with a presumptive diagnostic concordance (PDC) of 96.6%. Both areas under the curve were comparable, with similar sensitivity and specificity in the detection of PA. Thus, and considering the technical benefits described above and their stability in the face of the different clinical situations reported by the authors, we believe that ARC is a useful tool in clinical practice, being equivalent or superior to ARR.</p><p id="par0195" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first study conducted in Argentina with this RC and ARC methodology. The strengths of our study are that: (1) all patients were recruited and studied at the same site, thus ensuring the uniformity of the diagnostic protocol; and (2) all patients were evaluated with both renin measurement methods.</p><p id="par0200" class="elsevierStylePara elsevierViewall">Our study also has weaknesses: (1) there were relatively few male hypertensive patients; (2) confirmatory tests were not performed in all evaluated patients (only in patients with pathological ARR and ARC ratios); and (3) a pathological diagnosis was not available in 100% of the patients with PA.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0205" class="elsevierStylePara elsevierViewall">We have determined new cut-off values of 48.9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) for ARR and 2.3<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μIU/ml) for ARC in PA screening in our population, with the identification of a PA prevalence of 5.9% after diagnostic confirmation. To our knowledge, this is the first study conducted in our country with automated methodology for measuring renin (chemiluminescence; LIAISON, DiaSorin), which is also used by international reference centers for the management of this disorder. In our experience, ARR and ARC offered a very good sensitivity and concordance as screening methods.</p><p id="par0210" class="elsevierStylePara elsevierViewall">The study needs to be expanded with a greater number of patients in order to confirm the results obtained, and to assess their impact upon the diagnosis and treatment of patients with secondary hypertension.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0215" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1226546" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1140147" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1226547" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1140146" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Laboratory methods" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study design" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Determination of cut-off points using current methodology" ] ] ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-05-03" "fechaAceptado" => "2018-11-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1140147" "palabras" => array:3 [ 0 => "Primary aldosteronism" 1 => "Aldosterone" 2 => "Renin" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1140146" "palabras" => array:3 [ 0 => "Hiperaldosteronismo primario" 1 => "Aldosterona" 2 => "Renina" ] ] ] ] "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="spar0005" class="elsevierStyleSimplePara elsevierViewall">Primary aldosteronism (PA) is the most common cause of endocrine hypertension, with a prevalence rate of 6–12% in hypertensive patients. Aldosterone/renin ratio (ARR) is the screening test of choice for PA. Because of the variable cut-off points of ARR, reference values related to the populations and methods considered are recommended.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(i) To optimize the ARR cut-off points for PA screening with current methods; (ii) to assess the correlation and diagnostic sensitivity of the plasma aldosterone concentration/plasma renin activity (ARR) ratio and the aldosterone concentration/renin concentration (ARC) ratios for PA screening, and (iii) to determine the prevalence of PA in our population.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Plasma aldosterone concentration and plasma renin activity levels were measured using radioimmunoassays (RIAZENco Zentech and RIA DiaSorin respectively), while a chemiluminescence assay (Liaison Diasorin) was used to test renin concentration. ARR and ARC ratios were calculated in 345 subjects (136 healthy subjects and 209 hypertensive patients).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Prevalence of PA was 5.9% after diagnostic confirmation. ROC curve analysis suggested an ARR threshold of 48.9<span class="elsevierStyleHsp" style=""></span>(ng/dL)/(ng/mL/h) (100% sensitivity, 93.6% specificity) and an ARC threshold of 2.3<span class="elsevierStyleHsp" style=""></span>(ng/dL)/(μIU/mL) (100% sensitivity, 90.9% specificity). Good correlation was seen between ARR and ARC (<span class="elsevierStyleItalic">ρ</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.83, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.0001), with a presumptive diagnostic concordance of 96.6%.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">New cut-off values of ARR and ARC for screening of PA, with high sensitivity and good diagnostic concordance, were determined in the study population. It is important to have valid normal ranges to avoid diagnostic errors.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El hiperaldosteronismo primario (HAP) es la causa más frecuente de hipertensión endocrina, con una prevalencia del 6-12% en pacientes hipertensos. El cociente aldosterona/renina es el método de cribado de elección. Dada la variabilidad de sus puntos de corte, se sugiere contar con valores de referencia propios.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">1) Optimizar los puntos de corte del cociente aldosterona/renina para el cribado de hiperaldosteronismo con la metodología actual; 2) evaluar la correlación y la sensibilidad diagnóstica de los cocientes aldosterona/actividad de renina plasmática (RAA) y aldosterona/concentración de renina (RAC) para el cribado de hiperaldosteronismo, y 3) determinar la prevalencia de hiperaldosteronismo en nuestra población.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materiales y métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se determinaron los niveles de aldosterona (RIA competitivo en fase sólida RIAZENco Zentech), actividad de renina plasmática (RIA en fase sólida DiaSorin) y concentración de renina (quimioluminiscencia Liaison DiaSorin) en 345 sujetos (136 controles y 209 hipertensos). Se calcularon los cocientes RAA y RAC.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La prevalencia de HAP, tras confirmación diagnóstica, fue del 5,9% de los hipertensos. El valor de corte para sospecha de HAP determinado por curvas ROC fue 48,9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng/ml/h) para RAA (sensibilidad 100% y especificidad 93,6%) y 2,3<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(μUI/ml) para RAC (sensibilidad 100% y especificidad 90,9%). Se observó buena correlación entre RAA y RAC (ρ<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,83; p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,0001), con una concordancia diagnóstica presuntiva del 96,6%.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Hemos determinado en nuestra población nuevos valores de corte de RAA y RAC para el cribado de HAP, con buena sensibilidad y concordancia como métodos de cribado. Es importante contar con rangos de normalidad propios para evitar errores diagnósticos.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Eugenio Russmann ML, Delfino L, Fierro F, Santoro S, Peréz M, Caruso G, et al. Hiperaldosteronismo primario: puntos de corte del cociente aldosterona/renina. Endocrinol Diabetes Nutr. 2019;66:361–367.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1246 "Ancho" => 2333 "Tamanyo" => 100540 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Study population. PA: primary aldosteronism; AHT: arterial hypertension.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1808 "Ancho" => 2205 "Tamanyo" => 87069 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic curves.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2624 "Ancho" => 1571 "Tamanyo" => 165136 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Correlation between ARR–ARC, diagnostic concordance. The dotted lines correspond to the cut-off points for ARR: 48.9<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(ng(ml/h) and ARC: 2.3<span class="elsevierStyleHsp" style=""></span>(ng/dl)/(mU/l).</p>" ] ] 3 => 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="spar0075" class="elsevierStyleSimplePara elsevierViewall">PRA: plasma renin activity; RC: renin concentration; F: female; PA: primary aldosteronism; AHT: arterial hypertension; BMI: body mass index, weight/height<span class="elsevierStyleSup">2</span>; M: male; NS: nonsignificant; DBP: diastolic blood pressure; SBP: systolic blood pressure; ARR: aldosterone/plasma renin activity ratio; ARC: aldosterone/renin concentration ratio.</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Values are given as the mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation (SD) and the renin–angiotensin–aldosterone system (RAAS) measurements as the median and range.</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="" 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">Control \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">AHT \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"><span class="elsevierStyleItalic">p</span> (control vs. AHT) \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">PA \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"><span class="elsevierStyleItalic">p</span> (control and AHT vs. PA) \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"><span class="elsevierStyleItalic">n</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">119 \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">191 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">Sex (F/M) \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">65/54 \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">145/46 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">5/7 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">Age (years) \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">43.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13 \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">46.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13 \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">NS \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">46.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13 \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">NS \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">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">112<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">141<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15 \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><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">161<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15 \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 (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">74<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">83<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">0.001 \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">100<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">Weight (kg) \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">73<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16 \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">75<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>21 \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">NS \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">79<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15 \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">NS \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>) \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">26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">28<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">NS \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<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">NS \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">Glycemia (mg/dl) \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">94<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">111<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">NS \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">106<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12 \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">NS \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">Potassemia (mmol/l) \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">3.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.1 \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">4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.1 \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">NS \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">3.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">NS \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 cholesterol (mg/dl) \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">181<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17 \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">177<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18 \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">NS \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">195<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>55 \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">NS \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">HDL-cholesterol (mg/dl) \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<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">40<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">NS \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">50<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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">NS \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">Triglycerides (mg/dl) \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">99<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12 \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">115<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12 \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">NS \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">188<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>100 \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">NS \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">Aldosterone (ng/dl) \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">17.4 (2.8–70) \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">21.6 (2.5–97) \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">0.0001 \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">52 (23–127) \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">PRA (ng/ml/h) \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">1.4 (0.2–5) \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">1.6 (0.2–50) \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><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 (0.2–0.7) \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">RC (mIU/ml) \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">22.3 (5.2–88) \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">28.6 (0.6–501) \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">NS \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">3.7 (0.9–15) \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">ARR (A/PRA) \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 (2.2–34.5) \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">12 (0.2–101) \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">NS \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">177.5 (50–635) \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">ARC (A/RC) \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">0.7 (0.1–2.1) \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">0.8 (0.02–25) \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">NS \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">8.7 (2.4–115) \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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2095791.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the subjects included in the study.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0090" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 22 | 3 | 25 |
| 2024 October | 198 | 20 | 218 |
| 2024 September | 266 | 21 | 287 |
| 2024 August | 215 | 18 | 233 |
| 2024 July | 268 | 20 | 288 |
| 2024 June | 178 | 26 | 204 |
| 2024 May | 223 | 14 | 237 |
| 2024 April | 246 | 20 | 266 |
| 2024 March | 232 | 8 | 240 |
| 2024 February | 218 | 5 | 223 |
| 2024 January | 210 | 11 | 221 |
| 2023 December | 197 | 8 | 205 |
| 2023 November | 241 | 5 | 246 |
| 2023 October | 213 | 10 | 223 |
| 2023 September | 154 | 12 | 166 |
| 2023 August | 124 | 7 | 131 |
| 2023 July | 166 | 9 | 175 |
| 2023 June | 135 | 9 | 144 |
| 2023 May | 170 | 18 | 188 |
| 2023 April | 179 | 20 | 199 |
| 2023 March | 172 | 13 | 185 |
| 2023 February | 99 | 15 | 114 |
| 2023 January | 85 | 10 | 95 |
| 2022 December | 106 | 32 | 138 |
| 2022 November | 97 | 30 | 127 |
| 2022 October | 76 | 17 | 93 |
| 2022 September | 88 | 45 | 133 |
| 2022 August | 95 | 56 | 151 |
| 2022 July | 63 | 12 | 75 |
| 2022 June | 96 | 43 | 139 |
| 2022 May | 81 | 27 | 108 |
| 2022 April | 86 | 29 | 115 |
| 2022 March | 123 | 23 | 146 |
| 2022 February | 93 | 18 | 111 |
| 2022 January | 130 | 19 | 149 |
| 2021 December | 134 | 26 | 160 |
| 2021 November | 174 | 27 | 201 |
| 2021 October | 166 | 33 | 199 |
| 2021 September | 121 | 17 | 138 |
| 2021 August | 152 | 30 | 182 |
| 2021 July | 141 | 15 | 156 |
| 2021 June | 118 | 20 | 138 |
| 2021 May | 103 | 22 | 125 |
| 2021 April | 491 | 58 | 549 |
| 2021 March | 289 | 35 | 324 |
| 2021 February | 148 | 18 | 166 |
| 2021 January | 156 | 19 | 175 |
| 2020 December | 151 | 18 | 169 |
| 2020 November | 106 | 14 | 120 |
| 2020 October | 66 | 5 | 71 |
| 2020 September | 75 | 20 | 95 |
| 2020 August | 68 | 27 | 95 |
| 2020 July | 66 | 17 | 83 |
| 2020 June | 83 | 20 | 103 |
| 2020 May | 36 | 19 | 55 |
| 2020 April | 38 | 13 | 51 |
| 2020 March | 28 | 11 | 39 |
| 2020 February | 30 | 13 | 43 |
| 2020 January | 27 | 5 | 32 |
| 2019 December | 25 | 20 | 45 |
| 2019 November | 1 | 0 | 1 |
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