Study of the effect of chronic kidney disease on the incidence of cardiovascular events in a native Spanish population

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Se comparan pacientes en 4 grupos (sin enfermedad renal crónica [ERC], con filtrado glomerular [FG]<60ml con excreción urinaria de albúmina [EUA] normal, con albuminuria elevada y FG normal, y con FG descendido y albuminuria elevada). La diferencia es significativa (p<0,001, log-rank)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Bárbara Cancho, Nicolás Roberto Robles, Francisco Javier Felix-Redondo, Luis Lozano, Daniel Fernandez-Berges" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Bárbara" "apellidos" => "Cancho" ] 1 => array:2 [ "nombre" => "Nicolás Roberto" "apellidos" => "Robles" ] 2 => array:2 [ "nombre" => "Francisco Javier" "apellidos" => "Felix-Redondo" ] 3 => array:2 [ "nombre" => "Luis" "apellidos" => "Lozano" ] 4 => array:2 [ "nombre" => "Daniel" "apellidos" => "Fernandez-Berges" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S238702062100615X" "doi" => "10.1016/j.medcle.2020.10.019" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702062100615X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320308745?idApp=UINPBA00004N" "url" => "/00257753/0000015700000012/v1_202112010528/S0025775320308745/v1_202112010528/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020621006173" "issn" => "23870206" "doi" => "10.1016/j.medcle.2020.10.020" "estado" => "S300" "fechaPublicacion" => "2021-12-24" "aid" => "5536" "copyright" => "Elsevier España, S.L.U." 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Fernandez-Berges" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Bárbara" "apellidos" => "Cancho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Nicolás Roberto" "apellidos" => "Robles" "email" => array:1 [ 0 => "nrrobles@yahoo.es" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Francisco Javier" "apellidos" => "Felix-Redondo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "Luis" "apellidos" => "Lozano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 4 => array:3 [ "nombre" => "Daniel" "apellidos" => "Fernandez-Berges" 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"aff0025" ] 5 => array:3 [ "entidad" => "Unidad de Investigación Don Benito-Villanueva de la Serena, Programa de Investigación en Enfermedades Cardiovasculares, FundeSalud, Villanueva de la Serena, Badajoz, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Grupo de Investigadores Multidisciplinar de Extremadura (GRIMEX), Villanueva de la Serena, Badajoz, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Badajoz, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efecto de la enfermedad renal crónica sobre la incidencia de episodios cardiovasculares en población española" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1042 "Ancho" => 1675 "Tamanyo" => 110649 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Life survival. Patients are compared in 4 groups (without chronic kidney disease [CKD], with glomerular filtration rate [GFR] < 60 ml with normal urinary albumin excretion [UAE], with elevated albuminuria and normal GFR, and with decreased GFR and elevated albuminuria). The difference is significant (p < 0.001, log-rank)." ] ] ] "textoCompleto" => "IntroductionThe prevalence of cardiovascular disease (CVD) is several times higher in patients with chronic kidney disease (CKD) than in the general population.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> This CVD risk increases progressively as CKD progresses to end-stage renal disease. Ultimately, CVD accounts for approximately 50% of end-stage renal disease mortality.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> In addition to the traditional known risk factors for CVD, such as age, hypertension, diabetes mellitus, and hyperlipidemia, CKD patients have other non-traditional risk factors. These factors include anaemia, albuminuria, bone and mineral disorders, inflammation and, more recently, increased fibroblast growth factor 23.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> It has also been shown that CKD per se is a risk factor for the development of cardiovascular events.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> However, there are strong similarities between the risk markers for CKD and CVD.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Populations in southern Europe, such as Spain, where coronary heart disease incidence and mortality is low, have shown a prevalence of traditional cardiovascular risk factors close to the prevalence observed in countries characterised by much higher CVD incidence and mortality. In this sense, the high prevalence of cardiovascular risk factors in the Spanish population contrasts with the low incidence of CVD.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>The prevalence of CKD in Spain is very similar to the range of previously published studies in Europe. In this population, a high prevalence of traditional risk factors, overweight and obesity, hypertension, diabetes, dyslipidaemia, and smoking were significantly associated with CKD.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> This study attempted to prospectively assess the influence of CKD (defined as a low estimated glomerular filtration rate [GFR] and/or elevated albuminuria) on the incidence of acute cardiovascular events and mortality. To our knowledge, this is the first prospective study on this topic in the Spanish population.Design and methodsProspective observational study in the general population. A sample of 3,521 subjects between the ages of 25 and 79 who lived in the Don Benito-Villanueva de la Serena area (Badajoz, Spain) was randomly selected from the Health System database. 2831 people were included in the survey (participation rate 80.5%). The characteristics of the sample have been previously published. After a median follow-up of 81 (interquartile range [IQR] 75–89) months, data could be collected from 2669 subjects. The mean age was 50.6 ± 14.5 years, median 49 (IQR 39–62), and 54.6% (n = 1458) were women. Only Caucasian patients were included in the study. All subjects with a low estimated GFR at baseline were included (n = 98). These were older than those with a GFR > 60 ml/min/1.73 m2 (n = 2.571). Compared to this group, those with a reduced estimated GFR also had a higher prevalence of previous CVD, albuminuria, diabetes and hypertension. Overall, 94.6% (95% CI 88.0–97.7; n = 93) of the sample of patients with decreased GFR were in CKD stage III (72% stage IIIa; 22.4% stage IIIb). No patients undergoing renal replacement therapy were found within the sample. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the cardiovascular risk factors.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Serum creatinine (analysed by IDMS method), urea and packed cell volume were analysed after an overnight fast. GFR was estimated from serum creatinine using the CKD-EPI formula adjusted for sex. For statistical comparisons, chronic renal failure (CRF) was defined as a GFR < 60 ml/min estimated by the CKD-EPI formula.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Albuminuria was measured in a first morning urine specimen. Microalbuminuria was diagnosed when the albumin/creatinine ratio was greater than 30 mg/g. Macroalbuminuria was defined as an albumin excretion greater than 300 mg/g. Only 115 patients showed increased albuminuria; of these, 87.6% (95% CI 80.6–92.6; n = 101) showed microalbuminuria and the remainder (n = 14) macroalbuminuria.Primary objectives included death from any cause and cardiovascular events up to 31st December 2015. Deaths were identified from the Health Department's regional databases. A cardiovascular event was defined as coronary artery disease, heart failure, stroke, or peripheral artery disease. The methodology is defined in the attached file (additional material).Kaplan–Meier survival analysis was used to estimate survival before the first major cardiovascular event and cardiovascular death. All statistical tests were two-tailed. P values < 0.05 were considered significant. The analysis was carried out with the SPSS® 21.0 statistical package (SPSS Inc., Chicago, IL, USA). The Cox proportional hazards model was used to evaluate the independent effect of estimated GFR and albuminuria on the results. All variables known to be associated with estimated GFR or results were included in the final models, along with any variables associated with reduced estimated GFR (i.e., less than 60 ml/min/1.73 m2) in univariate analyses with a p < 0.01 according to the model used by Go et al.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Age was included as a dichotomous variable (younger or older than 65 years), as was the presence of increased albuminuria (>30 mg/g). Covariates were included as dichotomous variables.ResultsAn extensive description of the sample has been published in a separate report.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>During follow-up, 2 subjects reached end-stage renal failure. Survival free of cardiovascular events was 78.8% at 3 years and 76.8% at 5 years of follow-up for patients with a reduced estimated GFR. For patients with an estimated GFR greater than 60 ml/min, survival was 99.1% at 3 years and 98.5% at 5 years of follow-up. The overall comparison of both groups was statistically significant using the log-rank test (Mantel-Cox) (p < 0.001), as well as the Breslow test (p < 0.001). <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the Kaplan–Meier survival curves for the decreased GFR group and the preserved GFR group.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Survival for cardiovascular death was 90.9% at 3 years and 88.6% at 5 years of follow-up for patients with a reduced estimated GFR. For patients with an estimated GFR greater than 60 ml/min, survival was 99.5% at 3 years and 99.3% at 5 years of follow-up. The overall comparison of both groups was statistically significant using the log-rank test (Mantel–Cox) (p < 0.001), as well as the Breslow test (p < 0.001). <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a><a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the Kaplan–Meier survival curves for cardiovascular death.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>The Cox regression analysis is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. After adjusting for age, sex, diabetes, hypertension, dyslipidaemia, and smoking, the hazard ratio (HR) of cardiovascular events was 1.36 (95% CI 0.97–1.91) for CRF (p = 0.079). The increase in albuminuria was independently associated with a higher cardiovascular risk (HR 2.38; 95% CI 1.51–3.74; p < 0.001), as well as a higher cardiovascular mortality (HR 4.78; 95% CI 2.50–9.11; p < 0.001). For patients with albuminuria between 30 and 300 mg, the HR for cardiovascular events was 2.09 (95% CI 1.34–3.50; p = 0.005) and 3.80 (95% CI 1, 81−7.96; p < 0.001) for cardiovascular mortality.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Regarding the intensity of albuminuria, life survival was 99.5% at 3 years and 99.4% at 5 years of follow-up for those patients with normal range albuminuria. For patients with albuminuria above 30 mg/g and below 300 mg/g, survival was 90.2% at 3 years and 88.3% at 5 years of follow-up. For those with macroalbuminuria, survival was 42.2% at 3 and 5 years of follow-up. The overall comparison of all groups was statistically significant using the log-rank test (Mantel-Cox) (p < 0.001), as well as the Breslow test (p < 0.001). The event-free survival was 98.9% at 3 years and 98.3% at 5 years of follow-up for patients with normal albuminuria. For patients with albuminuria in the 30−300 mg/g range, survival was 84.9% at 3 years and 80.2% at 5 years. For those with albuminuria > 300 mg/g, the event-free survival was 31.7% at 3 and 5 years of follow-up. The overall comparison of all groups was statistically significant using the log-rank test (Mantel-Cox) (p < 0.001), as well as the Breslow test (p < 0.001). Kaplan–Meier survival curves can be seen in <a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>.<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>The combined effect of increased albuminuria and decreased GFR on the incidence of cardiovascular events is shown in <a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>. The event-free survival was 99.0% at 3 years and 98.4% at 5 years of follow-up for patients without CKD. For those with GFR < 60 ml/min and normal albuminuria, event-free survival was 81.2 at 3 and 5 years of follow-up. For patients with albuminuria greater than 30 mg/g and normal GFR, the event-free survival was 81.25% at 3 years and 78.3% at 5 years. For those with increased albuminuria and decreased GFR, event-free survival was 59.1% at 3 and 5 years of follow-up. The overall comparison of all groups was statistically significant using the log-rank (Mantel-Cox) (p < 0.001) and Breslow (p < 0.001) tests.<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Survival to cardiovascular death was 99.6% at 3 years and 99.4% at 5 years of follow-up for those patients without CKD. For patients with decreased GFR and normal urinary albumin excretion, survival was 94.5% at 3 and 5 years of follow-up. For those with increased albuminuria and normal GFR, survival was 89.5% at 3 years and 87% at 5 years of follow-up. Finally, for patients with decreased GFR and increased albuminuria, survival was 66.5% at 3 years and after 5 years of follow-up (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a><a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). The overall comparison of all groups was statistically significant using the log-rank test (Mantel-Cox) (p < 0.001), as well as the Breslow test (p < 0.001).<elsevierMultimedia ident="fig0030"></elsevierMultimedia>DiscussionCVD is the most common cause of death in patients with CKD, who should be considered in the group of patients with the highest risk of CVD.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Traditional and non-traditional risk factors have been linked to the high prevalence of CVD associated with CKD. The effect can be seen in the early stages of CKD, from GFR below 60 ml/min, accelerating vascular damage through the cumulative effects of functional and metabolic disorders, such as increased insulin resistance, stimulation of adhesion molecules, inhibition of nitric oxide synthesis, endothelial dysfunction and atherosclerosis.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Proinflammatory cytokines and impaired erythropoietin synthesis are associated with the development of anaemia, which contributes significantly to the development of left ventricular hypertrophy, a major cause of mortality.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> We found that, in the native Spanish population, an increase in albuminuria was independently associated with an increased risk of CVD. In contrast, the decrease in GFR did not show a significant relationship with CVD, although the result was close to the limits of statistical significance. Therefore, it could be suspected that, in this case, the sample was statistically insufficient. On the other hand, the correlation of the prevalence of CKD with classic cardiovascular risk factors could be due to the aetiology of kidney disease, in most cases, vascular nephropathy or non-proteinuric diabetic nephropathy.The CVD incidence rate in Spain and other southern European countries is unexpectedly low given the known high prevalence of cardiovascular risk factors. The functions based on the classical prevalence of risk factors and the episode rates used in the Framingham tables seem to overestimate the real individual risk in Spanish patients. However, these diseases continue to be the main cause of death in the Spanish population.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The reasons for this paradox remain unclear. It has been suggested that regional factors, such as lifestyle and the interaction between genes and environmental factors, may confer some protection.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> In any case, the low rate of major cardiovascular events observed is consistent with our knowledge of the special characteristics of cardiovascular risk in Spain and southern Europe. In this sense, the weight of CKD as a cardiovascular risk factor may be lower in the Spanish population than in other countries, since the prevalence of kidney disease found in the first phase of our study was low.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>Microalbuminuria has long been recognised as a hallmark of diabetic nephropathy and a predictor of cardiovascular events in people with diabetes mellitus.<a class="elsevierStyleCrossRefs" href="#bib0075">15,16</a> However, recent evidence indicates that increases in urinary albumin excretion even within the normal range, and thus below the specific cut-off for the definition of microalbuminuria, may predict renal and cardiovascular risk in adults with diabetes as well as in the general population.<a class="elsevierStyleCrossRefs" href="#bib0085">17,18</a> Therefore, it has been suggested that increases in albumin excretion may be a continuous marker of CVD. How are albuminuria and CVD linked? Obviously, a very small urinary albumin concentration is unlikely to be a direct cause. However, albuminuria is associated with other risk factors that may be causal or related to causal processes, such as diabetes mellitus, dyslipidaemia, hypertension or, as in our study, CRF.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> However, albuminuria showed an independent relationship with cardiovascular events. Albuminuria also reveals increased renal endothelial permeability and can be an easy-to-measure marker of diffuse endothelial dysfunction and underlying macrovascular and microvascular disease.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Our results reinforce the need to measure urinary albumin excretion in hypertensive and diabetic patients as a highly sensitive and specific marker of cardiovascular risk and, most interestingly, cardiovascular mortality.Our study has several strengths and limitations. As a prospective study, we have information on smoking or alcohol consumption, diet, physical activity, other possible unmeasured confounders (e.g., body mass index) or severity of certain conditions (such as blood pressure level or severity of diabetes), at least at baseline. Conversely, given that our study was conducted among native adults in southwestern Spain, our results may not be fully transferable to people in other geographic regions, especially those with a higher prevalence of foreign nationals.Several conclusions can be drawn from our study. In the native Spanish population, CKD was significantly associated with an increased cardiovascular risk. Increased urinary albumin excretion showed a greater prognostic value for cardiovascular morbidity and mortality than decreased glomerular filtration. However, regression analysis only confirmed the independent association with elevated albumin excretion. Our findings highlight the clinical and public health importance of systematically measuring urinary albumin excretion. Further prospective studies across Spain are needed to confirm these findings.FundingThis research was funded by a grant from the Carlos III Health Institute (PI14/00691).Conflict of interestsThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1632672" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aims" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1456829" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1632673" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Diseño y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1456828" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Design and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-07-09" "fechaAceptado" => "2020-10-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1456829" "palabras" => array:3 [ 0 => "Chronic kidney disease" 1 => "Urinary albumin excretion" 2 => "Cardiovascular disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1456828" "palabras" => array:3 [ 0 => "Enfermedad renal crónica" 1 => "Excreción urinaria de albúmina" 2 => "Enfermedad cardiovascular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "AimsTo evaluate the relationship between chronic kidney disease and the patient's cardiovascular risk measured through the incidence of major adverse cardiovascular events in a sample of Spanish population. Design and methodsThe sample consisted of 2668 subjects. Mean age was 50.6 ± 14.5 years and 54.6% were female. In all, 3.5% of subjects had a glomerular filtration rate (GFR) below 60 ml/min and 4.3% a urinary albumin excretion (UAE) above 30 mg/g. GFR was estimated from serum creatinine using the CKD-EPI equation. UAE was measured in first morning urine sample as mg/g of creatinine. We examined the multivariable association between the estimated GFR and the risks of cardiovascular events and death. The median follow-up was 81 (75–89) months. ResultsIn CKD patients the hazard ratio (HR) was 1.36 (95% CI 0.97–1.91) (P = .079) for cardiovascular events and 1.62 (95% CI 0.53–4.91) (P = .396) for cardiovascular mortality. Increased UAE was also associated with higher cardiovascular risk (HR 2.38; 95% CI 1.51–3.74; P < .001) as well as increased cardiovascular mortality (HR 4.78; 95% CI 2.50k9.11; P < ..001). For patients with UAE between 30 and 300 mg/g HR for cardiovascular events was 2.09 (95% CI 1.34–3.50; P = .005) and 3.80 (95% CI 1.81–7.96; P < .001) for cardiovascular mortality. ConclusionsAn independent association was found between reduced GFR and cardiovascular event incidence and mortality. Increased UAE showed a higher prognostic value than decreased GFR. Our findings highlight the clinical and public health importance of routinely measuring UAE." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aims" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivosEvaluar prospectivamente la correlación entre enfermedad renal crónica y el riesgo cardiovascular medido por la aparición de episodios cardiovasculares en la población española. Diseño y métodosLa muestra incluyó 2.668 personas con una edad media de 50,6 ± 14,5 años, siendo el 54,6% mujeres. En total, el 3,5% de los sujetos tenían una tasa de filtrado glomerular (TFG) <60 ml/min y el 4,3% una albuminuria >30 mg/g. La TFG fue estimada a partir de la creatinina usando la ecuación CKD-EPI. La excreción urinaria de albúmina fue medida como mg/g de creatinina en una muestra de orina de primera hora de la mañana. Se estudió mediante análisis de regresión de Cox la asociación entre TFG y excreción urinaria de albúmina con la morbimortalidad cardiovascular. La mediana de seguimiento fue de 81 (75–89) meses. ResultadosLa hazard ratio (HR) para episodios cardiovasculares fue de 1,36 (IC 95% 0,97–1,91) (p = 0,079) para pacientes con TFG disminuida y la HR para mortalidad cardiovascular fue de 1,62 (IC 95% 0,53–4,91) (p = 0,396). Por otra parte, una excreción urinaria de albúmina elevada se asociaba a un mayor riesgo cardiovascular (HR 2,38; IC 95% 1,51–3,74; p < 0,001), así como a una mortalidad cardiovascular incrementada (HR 4,78; IC 95% 2,50–9,11; p < 0,001). Para los pacientes con excreción urinaria de albúmina entre 30 y 300 mg/g, la HR para episodios cardiovasculares fue de 2,09 (IC 95% 1,34–3,50; p = 0,005) y de 3,80 (IC 95% 1,81–7,96; p < 0,001) para mortalidad cardiovascular. ConclusionesSe observó una asociación independiente entre TFG disminuida y la incidencia de episodios cardiovasculares y la mortalidad, en la población estudiada. La excreción urinaria de albúmina mostró un valor pronóstico mayor que el descenso de la TFG sobre ambos parámetros. Nuestros resultados subrayan la importancia de la medición sistemática de la excreción urinaria de albúmina." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Diseño y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Cancho B, Robles NR, Felix-Redondo FJ, Lozano L, Fernandez-Berges D. Efecto de la enfermedad renal crónica sobre la incidencia de episodios cardiovasculares en población española. Med Clin (Barc). 2021;157:569–574." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following is Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0040" ] ] ] ] "multimedia" => array:10 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1058 "Ancho" => 1675 "Tamanyo" => 95870 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Cardiovascular event-free survival. Patients with glomerular filtration rate (GFR) < 60 ml/min and those with preserved GFR are compared. The difference is significant (p < 0.001, log-rank)." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1072 "Ancho" => 1675 "Tamanyo" => 83707 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Life survival. Patients with glomerular filtration rate (GFR) < 60 ml/min and those with preserved GFR are compared. The difference is significant (p < 0.001, log-rank)." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1050 "Ancho" => 1675 "Tamanyo" => 115469 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Cardiovascular event-free survival. Patients are compared according to the intensity of urinary albumin excretion (UAE). The difference is significant (p < 0.001, log-rank)." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1087 "Ancho" => 1675 "Tamanyo" => 104365 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Life survival. Patients are compared according to the intensity of urinary albumin excretion (UAE). The difference is significant (p < 0.001, log-rank)." ] ] 4 => array:8 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1019 "Ancho" => 1675 "Tamanyo" => 120613 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Cardiovascular event-free survival. Patients are compared in 4 groups (without chronic kidney disease [CKD], with glomerular filtration rate [GFR] < 60 ml with normal urinary albumin excretion [UAE], with elevated albuminuria and normal GFR, and with decreased GFR and elevated albuminuria). The difference is significant (p < 0.001, log-rank)." ] ] 5 => array:8 [ "identificador" => "fig0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1042 "Ancho" => 1675 "Tamanyo" => 110649 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Life survival. Patients are compared in 4 groups (without chronic kidney disease [CKD], with glomerular filtration rate [GFR] < 60 ml with normal urinary albumin excretion [UAE], with elevated albuminuria and normal GFR, and with decreased GFR and elevated albuminuria). The difference is significant (p < 0.001, log-rank)." ] ] 6 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "All values are expressed as a percentage." "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">GFR ≥ 60 ml/min \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">GFR 45−60 ml/min \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">GFR < 45 ml/min \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 > 50 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">44.6<a class="elsevierStyleCrossRef" href="#tblfn0005">*</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">92.1 \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">92.3 \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">Hypertension \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">34.1<a class="elsevierStyleCrossRef" href="#tblfn0005">*</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">78.9 \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">92.3 \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">Diabetes mellitus \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">10.5<a class="elsevierStyleCrossRef" href="#tblfn0005">*</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">26.3 \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">46.2 \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">Dyslipidaemia \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">30.9<a class="elsevierStyleCrossRef" href="#tblfn0005">*</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">51.3 \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">60.5 \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">Smoking \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">32.9<a class="elsevierStyleCrossRef" href="#tblfn0005">*</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">10.5 \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">7.7 \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">BMI ≥ 30 \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">33.2<a class="elsevierStyleCrossRef" href="#tblfn0005">*</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">60.5 \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">50 \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">Previous cardiovascular disease \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">1.2<a class="elsevierStyleCrossRef" href="#tblfn0005">*</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">1.3 \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">7.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2782139.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p < 0.05, χ2 test." ] ] ] "descripcion" => array:1 [ "en" => "Prevalence of cardiovascular risk factors." ] ] 7 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><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"> \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"> \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95% CI</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"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><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">Exp (B) \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">Lower limit \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">Upper limit \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">Sex \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">0.578 \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">0.402 \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">0.831 \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">0.003 \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">Smoking \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">1.686 \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">1.081 \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">2.630 \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">0.021 \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">Hypertension \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">2.142 \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">1.314 \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">3.493 \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">Diabetes mellitus \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">1.632 \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">1.124 \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">2.369 \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">0.010 \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 \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">2.150 \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">1.500 \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">3.081 \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">GFR < 60 ml/min \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">1.358 \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">0.966 \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">1.910 \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">0.079 \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 \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">1.067 \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">1.048 \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">1.086 \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">Albuminuria \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">2.379 \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">1.510 \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">3.748 \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 => "xTab2782140.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Cox regression analysis for cardiovascular events." ] ] 8 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0045" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><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"> \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"> \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95% CI</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"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><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">Exp (B) \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">Lower limit \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">Upper limit \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">Sex \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">0.713 \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">0.369 \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">1.377 \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">0.314 \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">Smoking \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">2.331 \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">1.042 \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">5.213 \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">0.039 \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">Hypertension \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">2.665 \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">0.906 \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">7.839 \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">0.075 \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">Diabetes mellitus \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">1.762 \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">0.951 \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">3.266 \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">0.072 \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 \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">2.458 \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">1.283 \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">4.711 \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">0.007 \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">GFR < 60 ml/min \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">1.158 \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">0.658 \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">2.038 \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">0.610 \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 \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">1.127 \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">1.083 \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">1.172 \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">Albuminuria \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">4.781 \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">2.508 \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">9.114 \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 => "xTab2782141.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Cox regression analysis for cardiovascular death." ] ] 9 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 228955 ] ] ] "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" => "Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.S. 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Original article

Study of the effect of chronic kidney disease on the incidence of cardiovascular events in a native Spanish population

Efecto de la enfermedad renal crónica sobre la incidencia de episodios cardiovasculares en población española

Bárbara Canchoa, Nicolás Roberto Roblesa,b,c,

Corresponding author

nrrobles@yahoo.es

Corresponding author.

, Francisco Javier Felix-Redondod, Luis Lozanoe, Daniel Fernandez-Bergesf,g,h

a Hospital Universitario de Badajoz, Badajoz, Spain

b Cátedra de Riesgo Vascular, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain

c Red de Investigación Renal, Instituto de Salud Carlos III (RENINRED), Madrid, Spain

d Centro de Salud Villanueva de la Serena-Norte, Villanueva de la Serena, Badajoz, Spain

e Centro de Salud Merida, Mérida, Badajoz, Spain

f Unidad de Investigación Don Benito-Villanueva de la Serena, Programa de Investigación en Enfermedades Cardiovasculares, FundeSalud, Villanueva de la Serena, Badajoz, Spain

g Grupo de Investigadores Multidisciplinar de Extremadura (GRIMEX), Villanueva de la Serena, Badajoz, Spain

h Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Badajoz, Spain

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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Life survival&#46; Patients are compared in 4 groups &#40;without chronic kidney disease &#91;CKD&#93;&#44; with glomerular filtration rate &#91;GFR&#93;&#8239;&#60;&#8239;60&#8239;ml with normal urinary albumin excretion &#91;UAE&#93;&#44; with elevated albuminuria and normal GFR&#44; and with decreased GFR and elevated albuminuria&#41;&#46; The difference is significant &#40;p&#8239;&#60;&#8239;0&#46;001&#44; log-rank&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The prevalence of cardiovascular disease &#40;CVD&#41; is several times higher in patients with chronic kidney disease &#40;CKD&#41; than in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This CVD risk increases progressively as CKD progresses to end-stage renal disease&#46; Ultimately&#44; CVD accounts for approximately 50&#37; of end-stage renal disease mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In addition to the traditional known risk factors for CVD&#44; such as age&#44; hypertension&#44; diabetes mellitus&#44; and hyperlipidemia&#44; CKD patients have other non-traditional risk factors&#46; These factors include anaemia&#44; albuminuria&#44; bone and mineral disorders&#44; inflammation and&#44; more recently&#44; increased fibroblast growth factor 23&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It has also been shown that CKD <span class="elsevierStyleItalic">per se</span> is a risk factor for the development of cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However&#44; there are strong similarities between the risk markers for CKD and CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Populations in southern Europe&#44; such as Spain&#44; where coronary heart disease incidence and mortality is low&#44; have shown a prevalence of traditional cardiovascular risk factors close to the prevalence observed in countries characterised by much higher CVD incidence and mortality&#46; In this sense&#44; the high prevalence of cardiovascular risk factors in the Spanish population contrasts with the low incidence of CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The prevalence of CKD in Spain is very similar to the range of previously published studies in Europe&#46; In this population&#44; a high prevalence of traditional risk factors&#44; overweight and obesity&#44; hypertension&#44; diabetes&#44; dyslipidaemia&#44; and smoking were significantly associated with CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> This study attempted to prospectively assess the influence of CKD &#40;defined as a low estimated glomerular filtration rate &#91;GFR&#93; and&#47;or elevated albuminuria&#41; on the incidence of acute cardiovascular events and mortality&#46; To our knowledge&#44; this is the first prospective study on this topic in the Spanish population&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Design and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">Prospective observational study in the general population&#46; A sample of 3&#44;521 subjects between the ages of 25 and 79 who lived in the Don Benito-Villanueva de la Serena area &#40;Badajoz&#44; Spain&#41; was randomly selected from the Health System database&#46; 2831 people were included in the survey &#40;participation rate 80&#46;5&#37;&#41;&#46; The characteristics of the sample have been previously published&#46; After a median follow-up of 81 &#40;interquartile range &#91;IQR&#93; 75&#8211;89&#41; months&#44; data could be collected from 2669 subjects&#46; The mean age was 50&#46;6&#8239;&#177;&#8239;14&#46;5 years&#44; median 49 &#40;IQR 39&#8211;62&#41;&#44; and 54&#46;6&#37; &#40;n&#8239;&#61;&#8239;1458&#41; were women&#46; Only Caucasian patients were included in the study&#46; All subjects with a low estimated GFR at baseline were included &#40;n&#8239;&#61;&#8239;98&#41;&#46; These were older than those with a GFR&#8239;&#62;&#8239;60&#8239;ml&#47;min&#47;1&#46;73&#8239;m<span class="elsevierStyleSup">2</span> &#40;n&#8239;&#61;&#8239;2&#46;571&#41;&#46; Compared to this group&#44; those with a reduced estimated GFR also had a higher prevalence of previous CVD&#44; albuminuria&#44; diabetes and hypertension&#46; Overall&#44; 94&#46;6&#37; &#40;95&#37; CI 88&#46;0&#8211;97&#46;7&#59; n&#8239;&#61;&#8239;93&#41; of the sample of patients with decreased GFR were in CKD stage <span class="elsevierStyleSmallCaps">III</span> &#40;72&#37; stage <span class="elsevierStyleSmallCaps">III</span>a&#59; 22&#46;4&#37; stage <span class="elsevierStyleSmallCaps">III</span>b&#41;&#46; No patients undergoing renal replacement therapy were found within the sample&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the cardiovascular risk factors&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Serum creatinine &#40;analysed by IDMS method&#41;&#44; urea and packed cell volume were analysed after an overnight fast&#46; GFR was estimated from serum creatinine using the CKD-EPI formula adjusted for sex&#46; For statistical comparisons&#44; chronic renal failure &#40;CRF&#41; was defined as a GFR&#8239;&#60;&#8239;60&#8239;ml&#47;min estimated by the CKD-EPI formula&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Albuminuria was measured in a first morning urine specimen&#46; Microalbuminuria was diagnosed when the albumin&#47;creatinine ratio was greater than 30&#8239;mg&#47;g&#46; Macroalbuminuria was defined as an albumin excretion greater than 300&#8239;mg&#47;g&#46; Only 115 patients showed increased albuminuria&#59; of these&#44; 87&#46;6&#37; &#40;95&#37; CI 80&#46;6&#8211;92&#46;6&#59; n&#8239;&#61;&#8239;101&#41; showed microalbuminuria and the remainder &#40;n&#8239;&#61;&#8239;14&#41; macroalbuminuria&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Primary objectives included death from any cause and cardiovascular events up to 31st December 2015&#46; Deaths were identified from the Health Department&#39;s regional databases&#46; A cardiovascular event was defined as coronary artery disease&#44; heart failure&#44; stroke&#44; or peripheral artery disease&#46; The methodology is defined in the attached file &#40;additional material&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Kaplan&#8211;Meier survival analysis was used to estimate survival before the first major cardiovascular event and cardiovascular death&#46; All statistical tests were two-tailed&#46; P values&#8239;&#60;&#8239;0&#46;05 were considered significant&#46; The analysis was carried out with the SPSS&#174; 21&#46;0 statistical package &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#46; The Cox proportional hazards model was used to evaluate the independent effect of estimated GFR and albuminuria on the results&#46; All variables known to be associated with estimated GFR or results were included in the final models&#44; along with any variables associated with reduced estimated GFR &#40;i&#46;e&#46;&#44; less than 60&#8239;ml&#47;min&#47;1&#46;73&#8239;m<span class="elsevierStyleSup">2</span>&#41; in univariate analyses with a p&#8239;&#60;&#8239;0&#46;01 according to the model used by Go et al&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Age was included as a dichotomous variable &#40;younger or older than 65 years&#41;&#44; as was the presence of increased albuminuria &#40;&#62;30&#8239;mg&#47;g&#41;&#46; Covariates were included as dichotomous variables&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">An extensive description of the sample has been published in a separate report&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">During follow-up&#44; 2 subjects reached end-stage renal failure&#46; Survival free of cardiovascular events was 78&#46;8&#37; at 3 years and 76&#46;8&#37; at 5 years of follow-up for patients with a reduced estimated GFR&#46; For patients with an estimated GFR greater than 60&#8239;ml&#47;min&#44; survival was 99&#46;1&#37; at 3 years and 98&#46;5&#37; at 5 years of follow-up&#46; The overall comparison of both groups was statistically significant using the log-rank test &#40;Mantel-Cox&#41; &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#44; as well as the Breslow test &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the Kaplan&#8211;Meier survival curves for the decreased GFR group and the preserved GFR group&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Survival for cardiovascular death was 90&#46;9&#37; at 3 years and 88&#46;6&#37; at 5 years of follow-up for patients with a reduced estimated GFR&#46; For patients with an estimated GFR greater than 60&#8239;ml&#47;min&#44; survival was 99&#46;5&#37; at 3 years and 99&#46;3&#37; at 5 years of follow-up&#46; The overall comparison of both groups was statistically significant using the log-rank test &#40;Mantel&#8211;Cox&#41; &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#44; as well as the Breslow test &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows the Kaplan&#8211;Meier survival curves for cardiovascular death&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The Cox regression analysis is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; After adjusting for age&#44; sex&#44; diabetes&#44; hypertension&#44; dyslipidaemia&#44; and smoking&#44; the <span class="elsevierStyleItalic">hazard ratio</span> &#40;HR&#41; of cardiovascular events was 1&#46;36 &#40;95&#37; CI 0&#46;97&#8211;1&#46;91&#41; for CRF &#40;p&#8239;&#61;&#8239;0&#46;079&#41;&#46; The increase in albuminuria was independently associated with a higher cardiovascular risk &#40;HR 2&#46;38&#59; 95&#37; CI 1&#46;51&#8211;3&#46;74&#59; p&#8239;&#60;&#8239;0&#46;001&#41;&#44; as well as a higher cardiovascular mortality &#40;HR 4&#46;78&#59; 95&#37; CI 2&#46;50&#8211;9&#46;11&#59; p&#8239;&#60;&#8239;0&#46;001&#41;&#46; For patients with albuminuria between 30 and 300&#8239;mg&#44; the HR for cardiovascular events was 2&#46;09 &#40;95&#37; CI 1&#46;34&#8211;3&#46;50&#59; p&#8239;&#61;&#8239;0&#46;005&#41; and 3&#46;80 &#40;95&#37; CI 1&#44; 81&#8722;7&#46;96&#59; p&#8239;&#60;&#8239;0&#46;001&#41; for cardiovascular mortality&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Regarding the intensity of albuminuria&#44; life survival was 99&#46;5&#37; at 3 years and 99&#46;4&#37; at 5 years of follow-up for those patients with normal range albuminuria&#46; For patients with albuminuria above 30&#8239;mg&#47;g and below 300&#8239;mg&#47;g&#44; survival was 90&#46;2&#37; at 3 years and 88&#46;3&#37; at 5 years of follow-up&#46; For those with macroalbuminuria&#44; survival was 42&#46;2&#37; at 3 and 5 years of follow-up&#46; The overall comparison of all groups was statistically significant using the log-rank test &#40;Mantel-Cox&#41; &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#44; as well as the Breslow test &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#46; The event-free survival was 98&#46;9&#37; at 3 years and 98&#46;3&#37; at 5 years of follow-up for patients with normal albuminuria&#46; For patients with albuminuria in the 30&#8722;300&#8239;mg&#47;g range&#44; survival was 84&#46;9&#37; at 3 years and 80&#46;2&#37; at 5 years&#46; For those with albuminuria&#8239;&#62;&#8239;300&#8239;mg&#47;g&#44; the event-free survival was 31&#46;7&#37; at 3 and 5 years of follow-up&#46; The overall comparison of all groups was statistically significant using the log-rank test &#40;Mantel-Cox&#41; &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#44; as well as the Breslow test &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#46; Kaplan&#8211;Meier survival curves can be seen in <a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The combined effect of increased albuminuria and decreased GFR on the incidence of cardiovascular events is shown in <a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#46; The event-free survival was 99&#46;0&#37; at 3 years and 98&#46;4&#37; at 5 years of follow-up for patients without CKD&#46; For those with GFR&#8239;&#60;&#8239;60&#8239;ml&#47;min and normal albuminuria&#44; event-free survival was 81&#46;2 at 3 and 5 years of follow-up&#46; For patients with albuminuria greater than 30&#8239;mg&#47;g and normal GFR&#44; the event-free survival was 81&#46;25&#37; at 3 years and 78&#46;3&#37; at 5 years&#46; For those with increased albuminuria and decreased GFR&#44; event-free survival was 59&#46;1&#37; at 3 and 5 years of follow-up&#46; The overall comparison of all groups was statistically significant using the log-rank &#40;Mantel-Cox&#41; &#40;p&#8239;&#60;&#8239;0&#46;001&#41; and Breslow &#40;p&#8239;&#60;&#8239;0&#46;001&#41; tests&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Survival to cardiovascular death was 99&#46;6&#37; at 3 years and 99&#46;4&#37; at 5 years of follow-up for those patients without CKD&#46; For patients with decreased GFR and normal urinary albumin excretion&#44; survival was 94&#46;5&#37; at 3 and 5 years of follow-up&#46; For those with increased albuminuria and normal GFR&#44; survival was 89&#46;5&#37; at 3 years and 87&#37; at 5 years of follow-up&#46; Finally&#44; for patients with decreased GFR and increased albuminuria&#44; survival was 66&#46;5&#37; at 3 years and after 5 years of follow-up &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a><a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; The overall comparison of all groups was statistically significant using the log-rank test &#40;Mantel-Cox&#41; &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#44; as well as the Breslow test &#40;p&#8239;&#60;&#8239;0&#46;001&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">CVD is the most common cause of death in patients with CKD&#44; who should be considered in the group of patients with the highest risk of CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Traditional and non-traditional risk factors have been linked to the high prevalence of CVD associated with CKD&#46; The effect can be seen in the early stages of CKD&#44; from GFR below 60&#8239;ml&#47;min&#44; accelerating vascular damage through the cumulative effects of functional and metabolic disorders&#44; such as increased insulin resistance&#44; stimulation of adhesion molecules&#44; inhibition of nitric oxide synthesis&#44; endothelial dysfunction and atherosclerosis&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Proinflammatory cytokines and impaired erythropoietin synthesis are associated with the development of anaemia&#44; which contributes significantly to the development of left ventricular hypertrophy&#44; a major cause of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> We found that&#44; in the native Spanish population&#44; an increase in albuminuria was independently associated with an increased risk of CVD&#46; In contrast&#44; the decrease in GFR did not show a significant relationship with CVD&#44; although the result was close to the limits of statistical significance&#46; Therefore&#44; it could be suspected that&#44; in this case&#44; the sample was statistically insufficient&#46; On the other hand&#44; the correlation of the prevalence of CKD with classic cardiovascular risk factors could be due to the aetiology of kidney disease&#44; in most cases&#44; vascular nephropathy or non-proteinuric diabetic nephropathy&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The CVD incidence rate in Spain and other southern European countries is unexpectedly low given the known high prevalence of cardiovascular risk factors&#46; The functions based on the classical prevalence of risk factors and the episode rates used in the Framingham tables seem to overestimate the real individual risk in Spanish patients&#46; However&#44; these diseases continue to be the main cause of death in the Spanish population&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The reasons for this paradox remain unclear&#46; It has been suggested that regional factors&#44; such as lifestyle and the interaction between genes and environmental factors&#44; may confer some protection&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In any case&#44; the low rate of major cardiovascular events observed is consistent with our knowledge of the special characteristics of cardiovascular risk in Spain and southern Europe&#46; In this sense&#44; the weight of CKD as a cardiovascular risk factor may be lower in the Spanish population than in other countries&#44; since the prevalence of kidney disease found in the first phase of our study was low&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Microalbuminuria has long been recognised as a hallmark of diabetic nephropathy and a predictor of cardiovascular events in people with diabetes mellitus&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> However&#44; recent evidence indicates that increases in urinary albumin excretion even within the normal range&#44; and thus below the specific cut-off for the definition of microalbuminuria&#44; may predict renal and cardiovascular risk in adults with diabetes as well as in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> Therefore&#44; it has been suggested that increases in albumin excretion may be a continuous marker of CVD&#46; How are albuminuria and CVD linked&#63; Obviously&#44; a very small urinary albumin concentration is unlikely to be a direct cause&#46; However&#44; albuminuria is associated with other risk factors that may be causal or related to causal processes&#44; such as diabetes mellitus&#44; dyslipidaemia&#44; hypertension or&#44; as in our study&#44; CRF&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> However&#44; albuminuria showed an independent relationship with cardiovascular events&#46; Albuminuria also reveals increased renal endothelial permeability and can be an easy-to-measure marker of diffuse endothelial dysfunction and underlying macrovascular and microvascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Our results reinforce the need to measure urinary albumin excretion in hypertensive and diabetic patients as a highly sensitive and specific marker of cardiovascular risk and&#44; most interestingly&#44; cardiovascular mortality&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Our study has several strengths and limitations&#46; As a prospective study&#44; we have information on smoking or alcohol consumption&#44; diet&#44; physical activity&#44; other possible unmeasured confounders &#40;e&#46;g&#46;&#44; body mass index&#41; or severity of certain conditions &#40;such as blood pressure level or severity of diabetes&#41;&#44; at least at baseline&#46; Conversely&#44; given that our study was conducted among native adults in southwestern Spain&#44; our results may not be fully transferable to people in other geographic regions&#44; especially those with a higher prevalence of foreign nationals&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Several conclusions can be drawn from our study&#46; In the native Spanish population&#44; CKD was significantly associated with an increased cardiovascular risk&#46; Increased urinary albumin excretion showed a greater prognostic value for cardiovascular morbidity and mortality than decreased glomerular filtration&#46; However&#44; regression analysis only confirmed the independent association with elevated albumin excretion&#46; Our findings highlight the clinical and public health importance of systematically measuring urinary albumin excretion&#46; Further prospective studies across Spain are needed to confirm these findings&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0100" class="elsevierStylePara elsevierViewall">This research was funded by a grant from the <span class="elsevierStyleGrantSponsor" id="gs0005">Carlos III Health Institute</span> &#40;PI14&#47;00691&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Aims</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">To evaluate the relationship between chronic kidney disease and the patient&#39;s cardiovascular risk measured through the incidence of major adverse cardiovascular events in a sample of Spanish population&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design and methods</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The sample consisted of 2668 subjects&#46; Mean age was 50&#46;6&#8239;&#177;&#8239;14&#46;5 years and 54&#46;6&#37; were female&#46; In all&#44; 3&#46;5&#37; of subjects had a glomerular filtration rate &#40;GFR&#41; below 60&#8239;ml&#47;min and 4&#46;3&#37; a urinary albumin excretion &#40;UAE&#41; above 30&#8239;mg&#47;g&#46; GFR was estimated from serum creatinine using the CKD-EPI equation&#46; UAE was measured in first morning urine sample as mg&#47;g of creatinine&#46; We examined the multivariable association between the estimated GFR and the risks of cardiovascular events and death&#46; The median follow-up was 81 &#40;75&#8211;89&#41; months&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">In CKD patients the hazard ratio &#40;HR&#41; was 1&#46;36 &#40;95&#37; CI 0&#46;97&#8211;1&#46;91&#41; &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;079&#41; for cardiovascular events and 1&#46;62 &#40;95&#37; CI 0&#46;53&#8211;4&#46;91&#41; &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;396&#41; for cardiovascular mortality&#46; Increased UAE was also associated with higher cardiovascular risk &#40;HR 2&#46;38&#59; 95&#37; CI 1&#46;51&#8211;3&#46;74&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41; as well as increased cardiovascular mortality &#40;HR 4&#46;78&#59; 95&#37; CI 2&#46;50k9&#46;11&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;&#46;001&#41;&#46; For patients with UAE between 30 and 300&#8239;mg&#47;g HR for cardiovascular events was 2&#46;09 &#40;95&#37; CI 1&#46;34&#8211;3&#46;50&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;005&#41; and 3&#46;80 &#40;95&#37; CI 1&#46;81&#8211;7&#46;96&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;001&#41; for cardiovascular mortality&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">An independent association was found between reduced GFR and cardiovascular event incidence and mortality&#46; Increased UAE showed a higher prognostic value than decreased GFR&#46; Our findings highlight the clinical and public health importance of routinely measuring UAE&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Aims"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Design and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Evaluar prospectivamente la correlaci&#243;n entre enfermedad renal cr&#243;nica y el riesgo cardiovascular medido por la aparici&#243;n de episodios cardiovasculares en la poblaci&#243;n espa&#241;ola&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Dise&#241;o y m&#233;todos</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La muestra incluy&#243; 2&#46;668 personas con una edad media de 50&#44;6&#8239;&#177;&#8239;14&#44;5 a&#241;os&#44; siendo el 54&#44;6&#37; mujeres&#46; En total&#44; el 3&#44;5&#37; de los sujetos ten&#237;an una tasa de filtrado glomerular &#40;TFG&#41;&#8239;&#60;60&#8239;ml&#47;min y el 4&#44;3&#37; una albuminuria&#8239;&#62;30&#8239;mg&#47;g&#46; La TFG fue estimada a partir de la creatinina usando la ecuaci&#243;n CKD-EPI&#46; La excreci&#243;n urinaria de alb&#250;mina fue medida como mg&#47;g de creatinina en una muestra de orina de primera hora de la ma&#241;ana&#46; Se estudi&#243; mediante an&#225;lisis de regresi&#243;n de Cox la asociaci&#243;n entre TFG y excreci&#243;n urinaria de alb&#250;mina con la morbimortalidad cardiovascular&#46; La mediana de seguimiento fue de 81 &#40;75&#8211;89&#41; meses&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">La <span class="elsevierStyleItalic">hazard ratio</span> &#40;HR&#41; para episodios cardiovasculares fue de 1&#44;36 &#40;IC 95&#37; 0&#44;97&#8211;1&#44;91&#41; &#40;p&#8239;&#61;&#8239;0&#44;079&#41; para pacientes con TFG disminuida y la HR para mortalidad cardiovascular fue de 1&#44;62 &#40;IC 95&#37; 0&#44;53&#8211;4&#44;91&#41; &#40;p&#8239;&#61;&#8239;0&#44;396&#41;&#46; Por otra parte&#44; una excreci&#243;n urinaria de alb&#250;mina elevada se asociaba a un mayor riesgo cardiovascular &#40;HR 2&#44;38&#59; IC 95&#37; 1&#44;51&#8211;3&#44;74&#59; p&#8239;&#60;&#8239;0&#44;001&#41;&#44; as&#237; como a una mortalidad cardiovascular incrementada &#40;HR 4&#44;78&#59; IC 95&#37; 2&#44;50&#8211;9&#44;11&#59; p&#8239;&#60;&#8239;0&#44;001&#41;&#46; Para los pacientes con excreci&#243;n urinaria de alb&#250;mina entre 30 y 300&#8239;mg&#47;g&#44; la HR para episodios cardiovasculares fue de 2&#44;09 &#40;IC 95&#37; 1&#44;34&#8211;3&#44;50&#59; p&#8239;&#61;&#8239;0&#44;005&#41; y de 3&#44;80 &#40;IC 95&#37; 1&#44;81&#8211;7&#44;96&#59; p&#8239;&#60;&#8239;0&#44;001&#41; para mortalidad cardiovascular&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Se observ&#243; una asociaci&#243;n independiente entre TFG disminuida y la incidencia de episodios cardiovasculares y la mortalidad&#44; en la poblaci&#243;n estudiada&#46; La excreci&#243;n urinaria de alb&#250;mina mostr&#243; un valor pron&#243;stico mayor que el descenso de la TFG sobre ambos par&#225;metros&#46; Nuestros resultados subrayan la importancia de la medici&#243;n sistem&#225;tica de la excreci&#243;n urinaria de alb&#250;mina&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivos"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Dise&#241;o y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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    "NotaPie" => array:1 [
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Cancho B&#44; Robles NR&#44; Felix-Redondo FJ&#44; Lozano L&#44; Fernandez-Berges D&#46; Efecto de la enfermedad renal cr&#243;nica sobre la incidencia de episodios cardiovasculares en poblaci&#243;n espa&#241;ola&#46; Med Clin &#40;Barc&#41;&#46; 2021&#59;157&#58;569&#8211;574&#46;</p>"
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        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0115" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0040"
          ]
        ]
      ]
    ]
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      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1058
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular event-free survival&#46; Patients with glomerular filtration rate &#40;GFR&#41;&#8239;&#60;&#8239;60&#8239;ml&#47;min and those with preserved GFR are compared&#46; The difference is significant &#40;p&#8239;&#60;&#8239;0&#46;001&#44; log-rank&#41;&#46;</p>"
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      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1072
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            "Tamanyo" => 83707
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Life survival&#46; Patients with glomerular filtration rate &#40;GFR&#41;&#8239;&#60;&#8239;60&#8239;ml&#47;min and those with preserved GFR are compared&#46; The difference is significant &#40;p&#8239;&#60;&#8239;0&#46;001&#44; log-rank&#41;&#46;</p>"
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        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1050
            "Ancho" => 1675
            "Tamanyo" => 115469
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Fig&#46; "
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular event-free survival&#46; Patients are compared according to the intensity of urinary albumin excretion &#40;UAE&#41;&#46; The difference is significant &#40;p&#8239;&#60;&#8239;0&#46;001&#44; log-rank&#41;&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1087
            "Ancho" => 1675
            "Tamanyo" => 104365
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Fig&#46; "
            "rol" => "short"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Life survival&#46; Patients are compared according to the intensity of urinary albumin excretion &#40;UAE&#41;&#46; The difference is significant &#40;p&#8239;&#60;&#8239;0&#46;001&#44; log-rank&#41;&#46;</p>"
        ]
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      4 => array:8 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1019
            "Ancho" => 1675
            "Tamanyo" => 120613
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular event-free survival&#46; Patients are compared in 4 groups &#40;without chronic kidney disease &#91;CKD&#93;&#44; with glomerular filtration rate &#91;GFR&#93;&#8239;&#60;&#8239;60&#8239;ml with normal urinary albumin excretion &#91;UAE&#93;&#44; with elevated albuminuria and normal GFR&#44; and with decreased GFR and elevated albuminuria&#41;&#46; The difference is significant &#40;p&#8239;&#60;&#8239;0&#46;001&#44; log-rank&#41;&#46;</p>"
        ]
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      5 => array:8 [
        "identificador" => "fig0030"
        "etiqueta" => "Fig&#46; 6"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr6.jpeg"
            "Alto" => 1042
            "Ancho" => 1675
            "Tamanyo" => 110649
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0030"
            "detalle" => "Fig&#46; "
            "rol" => "short"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Life survival&#46; Patients are compared in 4 groups &#40;without chronic kidney disease &#91;CKD&#93;&#44; with glomerular filtration rate &#91;GFR&#93;&#8239;&#60;&#8239;60&#8239;ml with normal urinary albumin excretion &#91;UAE&#93;&#44; with elevated albuminuria and normal GFR&#44; and with decreased GFR and elevated albuminuria&#41;&#46; The difference is significant &#40;p&#8239;&#60;&#8239;0&#46;001&#44; log-rank&#41;&#46;</p>"
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      6 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at0035"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">All values are expressed as a percentage&#46;</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">&nbsp;\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">GFR&#8239;&#8805;&#8239;60&#8239;ml&#47;min&nbsp;\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">GFR 45&#8722;60&#8239;ml&#47;min&nbsp;\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">GFR&#8239;&#60;&#8239;45&#8239;ml&#47;min&nbsp;\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&#8239;&#62;&#8239;50 years&nbsp;\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">44&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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">92&#46;1&nbsp;\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">92&#46;3&nbsp;\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">Hypertension&nbsp;\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">34&#46;1<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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">78&#46;9&nbsp;\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">92&#46;3&nbsp;\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">Diabetes mellitus&nbsp;\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&#46;5<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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&#46;3&nbsp;\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&#46;2&nbsp;\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&nbsp;\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">30&#46;9<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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">51&#46;3&nbsp;\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">60&#46;5&nbsp;\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">Smoking&nbsp;\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">32&#46;9<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;5&nbsp;\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&#46;7&nbsp;\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&#8239;&#8805;&#8239;30&nbsp;\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">33&#46;2<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">60&#46;5&nbsp;\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&nbsp;\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">Previous cardiovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;2<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \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&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Upper limit&nbsp;\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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;402&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;831&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;686&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;081&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#46;021&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;314&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;002&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;632&nbsp;\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
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                  \t\t\t\t">1&#46;124&nbsp;\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
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                  \t\t\t\t">2&#46;369&nbsp;\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
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                  \t\t\t\t">0&#46;010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Dyslipidaemia&nbsp;\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
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                  \t\t\t\t">2&#46;150&nbsp;\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&#46;500&nbsp;\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&#46;081&nbsp;\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">&#60;0&#46;001&nbsp;\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">GFR&#8239;&#60;&#8239;60&#8239;ml&#47;min&nbsp;\t\t\t\t\t\t\n
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                  \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&#46;358&nbsp;\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&#46;966&nbsp;\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&#46;910&nbsp;\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&#46;079&nbsp;\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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;067&nbsp;\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&#46;048&nbsp;\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
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                  \t\t\t\t">1&#46;086&nbsp;\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
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Albuminuria&nbsp;\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">2&#46;379&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;510&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;748&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><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">&nbsp;\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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Exp &#40;B&#41;&nbsp;\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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lower limit&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Upper limit&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;713&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;369&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;377&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;314&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Smoking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;331&nbsp;\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
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                  \t\t\t\t">1&#46;042&nbsp;\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
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                  \t\t\t\t">5&#46;213&nbsp;\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
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                  \t\t\t\t">0&#46;039&nbsp;\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
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                  \t\t\t\t">Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;665&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;906&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7&#46;839&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;075&nbsp;\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
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                  \t\t\t\t">Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;762&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;951&nbsp;\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
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                  \t\t\t\t">3&#46;266&nbsp;\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
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                  \t\t\t\t">0&#46;072&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Dyslipidaemia&nbsp;\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
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                  \t\t\t\t">2&#46;458&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;283&nbsp;\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
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                  \t\t\t\t">4&#46;711&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;007&nbsp;\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
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                  \t\t\t\t">GFR&#8239;&#60;&#8239;60&#8239;ml&#47;min&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;038&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;610&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Albuminuria&nbsp;\t\t\t\t\t\t\n
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