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class="elsevierStyleTextfn">Original article</span>" "titulo" => "Risk of mortality associated to chronic kidney disease in patients with type 2 diabetes mellitus: A 13-year follow-up" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "487" "paginaFinal" => "492" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "José Antonio Gimeno-Orna, Yolanda Blasco-Lamarca, Belén Campos-Gutierrez, Edmundo Molinero-Herguedas, Luis Miguel Lou-Arnal, Blanca García-García" "autores" => array:6 [ 0 => array:4 [ "nombre" => "José Antonio" "apellidos" => "Gimeno-Orna" "email" => array:1 [ 0 => "jagimeno@salud.aragon.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Yolanda" "apellidos" => "Blasco-Lamarca" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Belén" "apellidos" => "Campos-Gutierrez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Edmundo" "apellidos" => "Molinero-Herguedas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Luis Miguel" "apellidos" => "Lou-Arnal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "Blanca" "apellidos" => "García-García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Comarcal de Alcañiz, Alcañiz, Teruel, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital Universitario de Burgos, Burgos, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Endocrinología, Hospital Royo Villanova, Zaragoza, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Riesgo de mortalidad asociado a enfermedad renal crónica en pacientes con diabetes tipo 2 durante un seguimiento de 13 años" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2398 "Ancho" => 3124 "Tamanyo" => 336627 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estimated probability using Kaplan–Meier survival curves according to the combined categories of GFR and UAE (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.0001).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The presence of diabetes mellitus (DM) increases patients’ cardiovascular risk and it is considered to be equivalent to coronary heart disease risk.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> However, not all patients with DM have the same cardiovascular risk.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> It is widely known that the presence of chronic kidney disease (CKD) increases the risk of overall mortality and cardiovascular mortality (CVM) in the general population. This increased risk is associated to both increased urinary albumin excretion (UAE) and reduced glomerular filtration rate (GFR). These two variables provide independent information.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients with diabetic nephropathy have CVM rates well above the very high risk<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">4</span></a> threshold that has been defined by the European Society of Cardiology (ESC) guidelines.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">5</span></a> Due to their prognostic significance, monitoring of both GFR and UAE is recommended in follow-up of patients with DM.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">6,7</span></a> Furthermore, it is recognised that in DM patients with CKD the approach to reduce the increased cardiovascular risk, should be multidisciplinary.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In the review by the Chronic Kidney Disease Prognosis Consortium,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">3</span></a> most of the studies included that assessed mortality risk in association with the presence of CKD were of less than 10 years’ duration and did not include populations from Spain.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The aims of our study, using long-term follow-up of a cohort of patients with type 2 DM, were:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0025" class="elsevierStylePara elsevierViewall">To describe mortality rates as a function of GFR, UAE, and the combination of the two variables.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0030" class="elsevierStylePara elsevierViewall">To ascertain that GFR and UAE offer independent information on patient mortality risk at long-term follow-up.</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0035" class="elsevierStylePara elsevierViewall">A prospective cohort study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0040" class="elsevierStylePara elsevierViewall">This is described in detail in previous articles.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">8,9</span></a> Between 1 June 1994 and 1 June 1998, we selected 463 patients with type 2 DM being followed as endocrinology outpatients at the <span class="elsevierStyleItalic">Hospital Comarcal de Alcañiz</span> (Alcañiz district hospital). This hospital has a referral population of 70,000 patients.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The inclusion criteria were: diabetes diagnosed using the World Health Organisation criteria valid at the time of diagnosis,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a> older than 35 years at the time of diagnosis, and absence of treatment with insulin for at least 1 year after diagnosis. Exclusion criteria were: severe somatic disease, pregnancy, uncontrolled hyperthyroidism or hypothyroidism, systemic corticoid treatment, or advanced renal failure (creatinine greater than 3<span class="elsevierStyleHsp" style=""></span>mg/dL). The study design was approved by the hospital ethics committee, and all participants gave their verbal consent before being enrolled.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Baseline examination</span><p id="par0050" class="elsevierStylePara elsevierViewall">On enrolment, patients were interviewed, noting their age, sex, known time with DM, smoking habits (active smoker, ex-smoker, or nonsmoker), DM treatment (diet, oral hypoglycaemics, or insulin) and any manifestation of existing vascular disease (ischaemic heart disease, lower limb ischaemia, or cerebrovascular disease). Physical examination included measurement of weight and height (and calculation of body mass index, defined as weight in kg/[height in metres] squared), and systolic and diastolic blood pressure, with classification of patients as hypertensive if systolic pressure was above 140<span class="elsevierStyleHsp" style=""></span>mmHg or diastolic above 90<span class="elsevierStyleHsp" style=""></span>mmHg or if they were on antihypertensive treatment. A venous blood sample was taken, after an overnight fasting (10<span class="elsevierStyleHsp" style=""></span>h) and before taking antidiabetic medication; biochemical measurements included: blood glucose, glycosylated haemoglobin (HbA1c), creatinine, total cholesterol, and triglycerides. A 24<span class="elsevierStyleHsp" style=""></span>h urine sample was collected, and after excluding urinary infection, UAE was measured, with samples classified as normoalbuminuria (<30<span class="elsevierStyleHsp" style=""></span>mg), microalbuminuria (30–300<span class="elsevierStyleHsp" style=""></span>mg), or macroalbuminuria or proteinuria (>300<span class="elsevierStyleHsp" style=""></span>mg). Biochemistry was measured with a Shimadzu CL 7200 auto-analyser. HbA1c was measured with a Cobas Mira Plus automatic analyser, with a normal range of 4.5–5.7%. UAE was measured using immunoturbidimetry on a Cobas Integra 700 analyser.</p><p id="par0055" class="elsevierStylePara elsevierViewall">GFR was calculated in mL/min per 1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> using the CKD-EPI formula:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><p id="par0060" class="elsevierStylePara elsevierViewall">If (woman and creatinine<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.7) GFR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>144<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>([creatinine/0.7]<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>−0.329)<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>(0.993<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>age).</p></li><li class="elsevierStyleListItem" id="lsti0020"><p id="par0065" class="elsevierStylePara elsevierViewall">If (woman and creatinine<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.7) GFR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>144<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>([creatinine/0.7]<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>−1.209)<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>(0.993<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>age).</p></li><li class="elsevierStyleListItem" id="lsti0025"><p id="par0070" class="elsevierStylePara elsevierViewall">If (man and creatinine<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.9) GFR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>141<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>([creatinine/0.9]<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>−0.411)<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>(0.993<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>age).</p></li><li class="elsevierStyleListItem" id="lsti0030"><p id="par0075" class="elsevierStylePara elsevierViewall">If (man and creatinine<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.9) GFR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>141<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>([creatinine/0.9]<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>−1.209)<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>(0.993<span class="elsevierStyleHsp" style=""></span>**<span class="elsevierStyleHsp" style=""></span>age).</p></li></ul></p><p id="par0080" class="elsevierStylePara elsevierViewall">GFR was categorised into 3 groups (≥60, 45–59, <45), as there were only 4 patients with a filtrate <30<span class="elsevierStyleHsp" style=""></span>mL/min per 1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Cohort follow-up</span><p id="par0085" class="elsevierStylePara elsevierViewall">All patients were prospectively followed up until their death or date of study closure on 31 August 2012. Causes of death were obtained from the hospital clinical notes or by contacting the general practitioner who signed the death certificate. Deaths were considered cardiovascular if they were sudden death, due to myocardial infarction, due to end stage heart failure, or due to cerebrovascular disease. In 4 patients (0.9%), it was not possible to determine their vital status and they were considered lost to follow-up.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical methods</span><p id="par0090" class="elsevierStylePara elsevierViewall">Quantitative variables are reported as mean and standard deviation (SD), and qualitative variables are reported as frequency distribution. Quantitative variables were compared using Student <span class="elsevierStyleItalic">t</span> test or the nonparametric Mann–Whitney test (time since onset of DM and triglycerides). For comparison of qualitative variables, a chi-square test was used.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The primary outcome variable was overall mortality. Patients were stratified into 9 categories according to their GFR and UAE. The category with GFR<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>60 and UAE<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30 was used as the reference category.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Patients were followed up from their inclusion in the study until leaving the study due to reaching the closing date, death, or being lost to follow-up. The rates of the different events are expressed per 1000 patient-year. Rates were compared between the different categories considered using Kaplan–Meier analysis and the log-rank test.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Subsequently, Cox-regression models were used, with calculation of hazard ratios (HR) and 95% confidence intervals (CI), to assess the risk conferred by the presence of the different categories of GFR and UAE, and their interaction. Univariate and multivariate models were used, adjusting for age, sex, smoking, presence of arterial hypertension, existing vascular disease, cholesterol and triglycerides (introduced in a logarithmic form), HbAlc, and time since onset of DM. The independent predictors of total mortality were determined using a sequential elimination procedure. The improved predictive power assumed by inclusion of GFR<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>UAE in the models was determined with Harrell's C statistic. Associations with a <span class="elsevierStyleItalic">P</span> value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05 were considered statistically significant. The software used was SPSS version 22.0.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0110" class="elsevierStylePara elsevierViewall">Of 463 patients, 453 were included; in 10 patients there was no information on GFR or UAE. Among patients included, 178 (39.3%) were men. Mean age was 64.9 years (SD 9.3 years) and the mean time since onset of DM was 10.4 years (SD 7.5 years). At the time of enrolment, 192 (42.4%) patients were on treatment with insulin and 98 (21.6%) had evidence of vascular disease.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Regarding GFR, 69.8% of patients had a GFR<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>, 23.4% had a GFR between 45 and 59<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>, and 6.8% had a GFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>45<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. The prevalence of normo- micro- and macroalbuminuria was 70.9%, 23.1%, and 6%, respectively.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Over a median 13-year follow-up (interquartile range 6.5 years; minimum 1 month, maximum 17 years) there was a total of 207 deaths (rate 39.5/1000), of which 74 were cardiovascular deaths (rate 14.1/1000). There was a significant linear trend in the progressive increase of overall mortality rates as GFR deteriorated and UAE increased (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Patient characteristics according to survival or non-survival during follow-up are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Compared with patients who survived, the patients who died were older and had a longer time since onset of DM, higher prevalence of initial insulin treatment, lower cholesterol levels, higher prevalence of macroangiopathy, lower GFR, and higher UAE.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the rates and HR for mortality according to the GFR and UAE levels. The interaction between GFR and UAE was not significant. In multivariate analysis, the variables that were independently associated with mortality risk, in order of predictive power, were age (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.092, <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>77.1, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.0001), UAE (HR<span class="elsevierStyleInf">30–300</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.02 and HR<span class="elsevierStyleInf">>300</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.3, <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11.6, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.003), presence of existing vascular disease (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.7, <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9.9, <span class="elsevierStyleItalic">P</span>=.002), active smoking (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.84, <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6.9, <span class="elsevierStyleItalic">P</span>=.032), GFR (HR<span class="elsevierStyleInf">45–59</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.34 and HR<span class="elsevierStyleInf"><45</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.84, <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6.4, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.041), and initial cholesterol levels (HR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.843, <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4.9, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.026).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Harrell's <span class="elsevierStyleItalic">C</span> statistic was 0.726 in the baseline mortality prediction model, composed of age, sex, smoking status, presence of arterial hypertension and existing vascular disease, cholesterol and triglycerides, HbAlc, and time since onset of DM. Inclusion of GFR and UAE improved the predictive power for mortality of the model (Harrell's <span class="elsevierStyleItalic">C</span> statistic 0.741, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.045 vs. previous model).</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">This prospective follow-up over a median of 13 years in a cohort of 453 patients with type 2 diabetes has allowed us to prove the prognostic significance of the simultaneous inclusion of GFR and UAE in predicting mortality risk.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The issue of diabetes as a risk of coronary heart disease has been widely debated.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">1,11,12</span></a> In one benchmark epidemiological study<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a> carried out by the Emerging Risk Factors Collaboration (ERFC), with more than 820,900 participants, the presence of DM approximately doubled the mortality risk, with total mortality rates of 29/1000 in men and 23/1000 in women and CVM rates of 13/1000 in men and 11/1000 in women with DM. In our study, the mortality rate was higher (39/1000), which could be explained by the older age of our patients compared with the previous study (65 vs. 58 years). However, CVM in our study was 14/1000, similar to that described in the ERFC data.</p><p id="par0150" class="elsevierStylePara elsevierViewall">One review<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">4</span></a> of clinical trials with at least 1000 patients with type 2 DM in each study demonstrated that mortality rate varied between studies, ranging from 2.8 to 84.2/1000 patient-years. Therefore, considering the high prevalence of the disease,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">14</span></a> it is a challenge to accurately identify those patients with DM that are at the most unfavourable extreme of the vascular risk spectrum. One consistent finding<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">4</span></a> is that the higher mortality rates are observed in trials that include patients with CKD. One study of 42,761 patients with type 2 diabetes followed over 4 years<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">15</span></a> demonstrated a synergistic interaction between low GFR and high UAE on mortality risk. In our study, as in the previously mentioned study, both GFR and UAE were independent predictive factors for mortality risk, and furthermore, they improved the predictive power of the models; the fact that the interaction term did not reach statistical significance could be due to the relatively low number of patients included. Besides age, other factors significantly associated with mortality risk in our patients, were similar to those described in the literature: presence of existing vascular disease,<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">1,16</span></a> low cholesterol levels (probably as a marker of weakness)<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">17</span></a> and active smoking.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">18</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">As in the general population, in patients with DM there is a progressive increase in mortality risk as GFR decreases and UAE increases.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">19</span></a> Our data support this fact in a prolonged follow-up of more than 10 years. The possible pathophysiological mechanisms that explain the association between CKD and mortality include the increased prevalence of HTN and left ventricular hypertrophy, the increased activity of both the sympathetic system and renin–aldosterone system, endothelial dysfunction, low grade inflammation, and high levels of asymmetric dimethylarginine.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">20</span></a> It must also be kept in mind that the changes over time in both GFR<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">21</span></a> and UAE<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">22</span></a> offer additional prognostic information.</p><p id="par0160" class="elsevierStylePara elsevierViewall">The greatest strength of our study was the long follow-up of patients, with only few losses, which allowed a reliable estimation of mortality rates during this period of time and reinforced the internal validity. The results are in agreement with those obtained in a previous data analysis with a shorter follow-up.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">23</span></a> Regarding noteworthy weaknesses, we must point out the limited number of subjects, with a low number of events in some categories, which makes the estimations less precise. Also, this study included patients with type 2 DM selected from hospital outpatient clinics, with a mean age of 65 years and a mean time since onset of DM of more than 10 years, which limits the external validity of the results. Finally, there were few patients with GFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>45, therefore the conclusions are primarily valid for stages 1–3A of CKD.</p><p id="par0165" class="elsevierStylePara elsevierViewall">We can conclude that GFR and UAE are independent predictors, without significant interaction, of mortality risk in patients with type 2 diabetes. We consider the systematic assessment of both parameters fundamental in the follow-up of patients with type 2 diabetes.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres604424" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec618578" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres604423" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec618579" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study population" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Baseline examination" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Cohort follow-up" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical methods" ] ] ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-03-04" "fechaAceptado" => "2015-05-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec618578" "palabras" => array:3 [ 0 => "Type 2 diabetes mellitus" 1 => "Chronic renal failure" 2 => "Mortality" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec618579" "palabras" => array:3 [ 0 => "Diabetes mellitus tipo 2" 1 => "Insuficiencia renal crónica" 2 => "Mortalidad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Our aim was to assess the usefulness of glomerular filtration rate (GFR) and urinary albumin excretion (UAE) to predict the risk of mortality in patients with type 2 diabetes mellitus.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This is a prospective cohort study in patients with type 2 diabetes mellitus. Clinical end-point was mortality rate. GFR was measured in ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and stratified in 3 categories (≥60; 45–59; <45); UAE was measured in mg/24<span class="elsevierStyleHsp" style=""></span>h and was also stratified in 3 categories (<30; 30–300; >300). Mortality rates were reported per 1000 patient-years. Cox regression models were used to predict mortality risk associated with combined GFR and UAE. The predictive power was estimated with C-Harrell statistic.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 453 patients (39.3% males), aged 64.9 (SD 9.3) years were included; mean diabetes duration was 10.4 (SD 7.5) years. Median follow-up was 13 years. Total mortality rate was 39.5/1000. The progressive increase in mortality in the successive categories of GFR and UAE was statistically significant (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001). In a multivariable analysis, UAE (HR30-300<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.02 and HR<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.83; <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11.6; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.003) and GFR (HR45-59<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.34 and HR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>45<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.84; <span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6.4; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.041) were independent predictors for mortality, with no significant interaction. Simultaneous inclusion of GFR and UAE improved the predictive power of models (C-Harrell 0.741 vs. 0.726; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.045).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">GFR and UAE are independent predictors for mortality in type 2 diabetic patients and do not show a statistically significant interaction.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Nuestro objetivo fue evaluar la influencia de la tasa de filtración glomerular (TFG) y de la excreción de albúmina urinaria (EAU) sobre el riesgo de mortalidad en pacientes con diabetes mellitus tipo 2 (DM2).</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohortes prospectivo con inclusión de pacientes con DM2. El punto final clínico fue mortalidad total. La TFG se midió en ml/min/1,73 m<span class="elsevierStyleSup">2</span> con estratificación en 3 categorías (≥60; 45-59; <45) y la EAU en mg/24<span class="elsevierStyleHsp" style=""></span>h con estratificación también en 3 categorías (<30; 30-300; >300).</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se evaluaron las tasas de mortalidad por cada 1.000 pacientes/año y, mediante regresión de Cox, el riesgo de mortalidad asociado con las categorías de TFG y EAU. El poder predictivo se midió con el estadístico C de Harrell.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se incluyó a 453 pacientes (39,3% varones, edad 64,9 [DE 9,3] años y evolución de DM2 10,4 [DE 7,5] años). Durante una mediana de 13 años de seguimiento, la tasa de mortalidad total fue de 39,5/1.000, con incremento progresivo ante descenso de la TFG y aumento de la EAU (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001). En análisis multivariante la EAU (HR<span class="elsevierStyleInf">30-300</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,02 y HR<span class="elsevierStyleInf">>300</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2,83; chi<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11,6; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,003) y la TFG (HR<span class="elsevierStyleInf">45-59</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,34 y HR<span class="elsevierStyleInf"><45</span>=<span class="elsevierStyleHsp" style=""></span>1,84; chi<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6,4; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,041) fueron predictores independientes de mortalidad sin interacción significativa. La inclusión de TFG y EAU mejoró la capacidad predictiva de los modelos (C de Harrell 0,741 vs. 0,726; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,045).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La TFG y la EAU son predictores independientes de mortalidad en pacientes con DM2, sin interacción significativa.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gimeno-Orna JA, Blasco-Lamarca Y, Campos-Gutierrez B, Molinero-Herguedas E, Lou-Arnal LM, García-García B. Riesgo de mortalidad asociado a enfermedad renal crónica en pacientes con diabetes tipo 2 durante un seguimiento de 13 años. Nefrologia. 2015;35:487–492.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2398 "Ancho" => 3124 "Tamanyo" => 336627 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estimated probability using Kaplan–Meier survival curves according to the combined categories of GFR and UAE (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.0001).</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">BMI, body mass index; CVD, cardiovascular disease; CVE, cerebrovascular event; CI, confidence interval; GFR, glomerular filtration rate in mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>; HR, hazard ratio; HTN, hypertension; LL, lower limbs; UAE, urinary albumin excretion.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total sample \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Did not die \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Died \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">GFR 45–59 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 (1.4–2.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">GFR <45 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.4 (2.9–6.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Microalbuminuria (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.5 (1.1–2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Macroalbuminuria (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.6 (2.3–5.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sex (% men) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.3(0.9–1.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Existing CVD (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 (1.4–2.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Ischaemic heart disease (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4(0.9–2.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">CVE (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.029 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9 (1.2–3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">LL ischaemia (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.8 (1.9–4.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Smoking (% active) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.2(0.8–1.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HTN (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.2 (0.9–1.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Treatment with insulin (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4 (0.7–3.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64.9 (9.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61.5 (9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69 (7.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1(1.07–1.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cholesterol (mmol/L)mg/dL: divide by 0.0259 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.66 (1.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.77 (1.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.53 (1.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.83 (0.73–0.95) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Triglycerides (mmol/L)mg/dL: divide by 0.0113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.54 (1.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.54 (0.91) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.55 (1.19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.022 (0.89–1.18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BMI (kg/m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.3 (4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.3 (4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.4 (4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1(0.97–1.03) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HbA1c (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.76 (1.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.7 (1.46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.8 (1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.025 (0.94–1.12) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Time since onset of DM (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.4 (7.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.4 (6.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.7 (8.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.026 (1.008–1.044) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab989881.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Patient characteristics according to survival during follow-up. The variables are reported as mean (SD) or frequency distribution.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CI, confidence interval; GFR, glomerular filtration rate in mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>; HR, hazard ratio; UAE, 24<span class="elsevierStyleHsp" style=""></span>h urinary albumin excretion.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">UAE<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">UAE 30–300 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">UAE<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>300 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">UAE<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">UAE 30–300 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col">UAE<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>300 \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Rate/1000 patient-years \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">GFR<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reference \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.5 (1–2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.2 (1.5–6.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">GFR 45–59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">115.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (1.4–2.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (1.7–5.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.7 (1.5–15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">GFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">114.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">141 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.1 (2.4–11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.6 (1.7–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.1 (3.7–13) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab989880.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mortality rates per 1000 patient-years and mortality risk according to the combined GFR and UAE categories.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0120" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mortality from coronary heart disease 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Year/Month | Html | Total | |
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2024 October | 55 | 34 | 89 |
2024 September | 63 | 31 | 94 |
2024 August | 88 | 59 | 147 |
2024 July | 121 | 30 | 151 |
2024 June | 93 | 38 | 131 |
2024 May | 88 | 40 | 128 |
2024 April | 69 | 35 | 104 |
2024 March | 50 | 48 | 98 |
2024 February | 53 | 50 | 103 |
2024 January | 40 | 43 | 83 |
2023 December | 69 | 24 | 93 |
2023 November | 73 | 40 | 113 |
2023 October | 72 | 90 | 162 |
2023 September | 52 | 118 | 170 |
2023 August | 65 | 38 | 103 |
2023 July | 54 | 36 | 90 |
2023 June | 85 | 28 | 113 |
2023 May | 84 | 38 | 122 |
2023 April | 93 | 28 | 121 |
2023 March | 109 | 29 | 138 |
2023 February | 92 | 22 | 114 |
2023 January | 62 | 45 | 107 |
2022 December | 63 | 38 | 101 |
2022 November | 86 | 38 | 124 |
2022 October | 75 | 78 | 153 |
2022 September | 57 | 34 | 91 |
2022 August | 64 | 39 | 103 |
2022 July | 64 | 65 | 129 |
2022 June | 94 | 40 | 134 |
2022 May | 61 | 37 | 98 |
2022 April | 112 | 55 | 167 |
2022 March | 102 | 57 | 159 |
2022 February | 226 | 53 | 279 |
2022 January | 99 | 45 | 144 |
2021 December | 106 | 40 | 146 |
2021 November | 70 | 44 | 114 |
2021 October | 103 | 36 | 139 |
2021 September | 79 | 39 | 118 |
2021 August | 49 | 39 | 88 |
2021 July | 49 | 27 | 76 |
2021 June | 31 | 12 | 43 |
2021 May | 35 | 38 | 73 |
2021 April | 71 | 28 | 99 |
2021 March | 58 | 27 | 85 |
2021 February | 64 | 26 | 90 |
2021 January | 53 | 15 | 68 |
2020 December | 54 | 22 | 76 |
2020 November | 68 | 24 | 92 |
2020 October | 34 | 15 | 49 |
2020 September | 37 | 17 | 54 |
2020 August | 45 | 15 | 60 |
2020 July | 59 | 18 | 77 |
2020 June | 52 | 24 | 76 |
2020 May | 61 | 17 | 78 |
2020 April | 41 | 23 | 64 |
2020 March | 54 | 23 | 77 |
2020 February | 60 | 28 | 88 |
2020 January | 54 | 20 | 74 |
2019 December | 75 | 31 | 106 |
2019 November | 82 | 28 | 110 |
2019 October | 57 | 23 | 80 |
2019 September | 59 | 20 | 79 |
2019 August | 70 | 28 | 98 |
2019 July | 45 | 24 | 69 |
2019 June | 51 | 36 | 87 |
2019 May | 51 | 25 | 76 |
2019 April | 84 | 45 | 129 |
2019 March | 49 | 25 | 74 |
2019 February | 34 | 17 | 51 |
2019 January | 48 | 28 | 76 |
2018 December | 202 | 47 | 249 |
2018 November | 437 | 22 | 459 |
2018 October | 436 | 21 | 457 |
2018 September | 146 | 24 | 170 |
2018 August | 110 | 24 | 134 |
2018 July | 66 | 16 | 82 |
2018 June | 55 | 16 | 71 |
2018 May | 86 | 13 | 99 |
2018 April | 51 | 9 | 60 |
2018 March | 118 | 10 | 128 |
2018 February | 44 | 5 | 49 |
2018 January | 28 | 6 | 34 |
2017 December | 36 | 10 | 46 |
2017 November | 50 | 7 | 57 |
2017 October | 37 | 8 | 45 |
2017 September | 36 | 10 | 46 |
2017 August | 53 | 6 | 59 |
2017 July | 69 | 9 | 78 |
2017 June | 81 | 8 | 89 |
2017 May | 73 | 19 | 92 |
2017 April | 59 | 29 | 88 |
2017 March | 51 | 11 | 62 |
2017 February | 49 | 8 | 57 |
2017 January | 29 | 16 | 45 |
2016 December | 71 | 7 | 78 |
2016 November | 68 | 25 | 93 |
2016 October | 74 | 17 | 91 |
2016 September | 138 | 4 | 142 |
2016 August | 176 | 4 | 180 |
2016 July | 155 | 8 | 163 |
2016 June | 121 | 0 | 121 |
2016 May | 136 | 0 | 136 |
2016 April | 114 | 0 | 114 |
2016 March | 85 | 0 | 85 |
2016 February | 139 | 0 | 139 |
2016 January | 101 | 0 | 101 |
2015 December | 124 | 0 | 124 |
2015 November | 111 | 0 | 111 |