Valvular calcifications at the start of dialysis predict the onset of cardiovascular events in the course of follow-up

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Patients were divided in three groups according with the concomitant therapies, and there were significant statistical differences between groups (p <0 001 patients who were not receiving renin angiotensin system ras inhibitors or allopurinol n="30)" presented lower 25 8209 oh d3 d levels than those and plus p <0 001 highest 25 8209 oh d3 levels 11 7 3 p="0.005)" were found in patients receiving ras inhibitors plus allopurinol without statins lowest 5 1 82 who only</0> </0>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Claudia Yuste, Borja Quiroga, Soledad García de Vinuesa, Maria Angeles Goicoechea, Daniel Barraca, Ursula Verdalles, Jose Luño" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Claudia" "apellidos" => "Yuste" ] 1 => array:2 [ "nombre" => "Borja" "apellidos" => "Quiroga" ] 2 => array:2 [ "nombre" => "Soledad" "apellidos" => "García de Vinuesa" ] 3 => array:2 [ "nombre" => "Maria Angeles" "apellidos" => "Goicoechea" ] 4 => array:2 [ "nombre" => "Daniel" "apellidos" => "Barraca" ] 5 => array:2 [ "nombre" => "Ursula" "apellidos" => "Verdalles" ] 6 => array:2 [ "nombre" => "Jose" "apellidos" => "Luño" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251415123112?idApp=UINPBA000064" "url" => "/20132514/0000003500000002/v0_201504231604/X2013251415123112/v0_201504231605/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "titulo" => "Valvular calcifications at the start of dialysis predict the onset of cardiovascular events in the course of follow-up" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "157" "paginaFinal" => "163" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Carmen Sánchez-Perales, Eduardo Vázquez Ruiz de Castroviejo, Mª José García-Cortés, Mª del Mar Biechy, Jose Manuel Gil-Cunquero, Josefa Borrego-Hinojosa, Pilar Pérez del Barrio, Francisco Borrego-Utiel, Antonio Liébana" "autores" => array:9 [ 0 => array:3 [ "nombre" => "Carmen" "apellidos" => "Sánchez-Perales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 1 => array:3 [ "nombre" => "Eduardo" "apellidos" => "Vázquez Ruiz de Castroviejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 2 => array:3 [ "nombre" => "Mª José" "apellidos" => "García-Cortés" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Mª del Mar" "apellidos" => "Biechy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 4 => array:3 [ "nombre" => "Jose Manuel" "apellidos" => "Gil-Cunquero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 5 => array:3 [ "nombre" => "Josefa" "apellidos" => "Borrego-Hinojosa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 6 => array:3 [ "nombre" => "Pilar" "apellidos" => "Pérez del Barrio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 7 => array:3 [ "nombre" => "Francisco" "apellidos" => "Borrego-Utiel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 8 => array:3 [ "nombre" => "Antonio" "apellidos" => "Liébana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Nephrology, Complejo Hospitalario de Jaén [Hospital Complex of Jaén], Jaén " "etiqueta" => "a" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Cardiology, Complejo Hospitalario de Jaén, Jaén" "etiqueta" => "b" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Las calcificaciones valvulares al inicio de diálisis predicen la aparición de eventos cardiovasculares en la evolución" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "498v35n02-90412312fig5.jpg" "Alto" => 904 "Ancho" => 2000 "Tamanyo" => 111002 ] ] "descripcion" => array:1 [ "en" => "– Event-free survival (MI, stroke and/or death from cardiovascular causes); Kaplan-Meier Curves A: all patients; B: patients with no diagnosis of coronary artery disease, stroke or AF at the start of dialysis; VC: valvular calcification" ] ] ] "textoCompleto" => "Introduction The presence of cardiac valvular calcifications (VC) in chronic kidney disease (CKD) is considered a frequent fact. Population studies have confirmed an association between CKD and mitral or aortic VC from initial stages of decreased glomerular filtration1,2. Nevertheless, most publications derive from studies of prevalent peritoneal dialysis and haemodialysis patients, in which the prevalence of VC is greater than 30% of patients3,4,5. In these studies, VC correlates with the time on replacement therapy, inflammation, malnutrition and atherosclerotic heart disease6,7,8,9,10. VC has been a predictor for mortality from cardiovascular causes and from any other cause3 in some studies, although not in all of them11. VC and atherosclerosis are frequently observed in a same patient on dialysis, and the association between them has been demonstrated7,12. Based on this association, VC has been considered one of the manifestations of atherosclerosis7,13. However, all patients with VC do not have atherosclerosis. This suggests that, although both processes share pathogenic mechanisms, their pathogenesis and possibly the risk they involve are not identical14. There are few studies about VC in patients with advanced stages of CKD at the onset of replacement therapy15,16. The purpose of this study was to analyse the presence of VC in patients who started dialysis for the first time and its relationship with the occurrence of events and cardiovascular mortality during follow-up.Methods We included patients diagnosed with stage 5 CKD, who started haemodialysis or peritoneal dialysis for the first time between November 2003 and September 2007 in our hospital centre. Patients who started treatment in another centre or had undergone prior renal transplantation were excluded. The observational period ranged from the first day of dialysis to termination due to transplantation, death, patient transfer outside our health area of influence, or the end of the study 31 December 2012. In the first month of dialysis, the following variables were assessed and included for analysis: demographic characteristics; anthropometric measurements; pulse pressure; history of hypertension and/or antihypertensive treatment (HTN); diabetes with indication of drug treatment at any time of follow-up; active smoking habit or cessation in the last 10 years; coronary artery disease documented by a history of myocardial infarction (MI) or compatible coronary angiographic test; ischaemic or haemorrhagic stroke, documented by a neurologist and/or imaging test report; atrial fibrillation (AF) in any of its forms documented in a prior medical record or by an ECG finding; and, analytical variables, such as haemoglobin, mineral metabolism (calcium, phosphorous, PTH), urea, creatinine, troponin I, albumin, C-reactive protein (CRP), cholesterol and fractions, triglycerides and glycosylated haemoglobin. VC was studied with colour Doppler echocardiography by a single observer. It was defined as increased echo-refringence with a thickness > 1 mm at the level of the mitral or aortic annulus or leaf let. Three grades were established according to the calcification area: mild, when there were only small, isolated areas; moderate, when there were multiple areas; and severe, when calcification was extensive and diffuse. It was analysed whether the calcification was limited to only one valve, mitral or aortic, or involved both. The endpoint of our study was the occurrence of one or several of the following events in the course of follow-up: MI, stroke or death from cardiovascular causes (defined as death due to heart failure), pulmonary thromboembolism, sudden death, mesenteric ischaemia or peripheral arterial ischaemia.Statistical Analysis The Student’s t-test or the nonparametric Mann-Whitney test was used for the comparison of means. For the comparison of qualitative variables, the Pearson’s Chi-square test was used. For the analysis of the association between VC and the risk factors that were present at the start of treatment, a logistic regression multivariate analysis was performed, and the odds ratio (OR) and 95% confidence interval were obtained. The predictive power of variables for the occurrence of the endpoint of our study was analysed through a Cox proportional-hazard regression analysis. The prognostic variable was the occurrence of the endpoint defined in the Methods section. Predictive variables were the presence of VC, and other variables with significant association in the univariate analysis or of special significance. The hazard ratio (HR) and 95% confidence interval were obtained. Event-free survival was analysed with the Kaplan-Meier method, and the Mantel-Haenszel test (log-rank) was used to compare survival curves. For hypothesis contrast tests, a value of p < 0.05 was considered statistically significant. The analyses were carried out with the statistical package SPSS 15.0 for Windows.Results Following the exclusion criteria, 48 patients were not included; another 29 patients were not included since they could not participate in the entire initial study. The total number of enrolled patients was 256. Mean age was 65.1 ± 15.9 years, median age was 69.9, and 146 patients (57%) were male. Nephropathies induced by renal failure included the following: glomerulonephritis 17.2%; interstitial nephropathies 15.2%; nephrosclerosis 15.6%; polycystic kidney disease 6.3%; other familial diseases 1.2%; systemic diseases 5.1%; diabetes 18.4%; unidentified diseases 18.8%; other 2.3%. Diabetes caused nephropathy or was a concomitant disease in 73 (28.5%) patients. They study included 213 (83%) patients receiving haemo-dialysis and 43 (17%) patients in peritoneal dialysis, with a mean age of 66.8 ± 14.8 and 56.5 ± 18.5 years, respectively (p = 0.004). Patients were monitored for 42.1 ± 30 months (range: 0.23–109.4), with a follow-up of 898.1 patient-years.Prevalence of Valvular Calcification At the beginning of the dialysis programme, valvular calcification (VC) was present in 128 patients, which accounts for a prevalence of 50%. The grades were: 90 mild (35.1%); 30 moderate (11.7%); and 8 severe (3.1%). Calcification was present in the mitral valve in 39 (15.2%) patients, the aortic valve in 20 (7.8%), and in both valves in 69 (27%) patients. Those patients who had valvular calcification were an average of 18 years older and were mostly women, diabetic patients, and had a history of cardiovascular events and diagnosis of atrial fibrillation. A higher proportion of patients included in the haemodialysis programme had valvular calcification. Creatinine, albumin and phosphorous levels were lower, while pulse pressure and body mass index were higher (Table 1). They also had greater left ventricular mass and left atrial dimension and greater diastolic dysfunction (Table 2).<img alt="Table 1 – Characteristics of patients with VC at the start of dialysis" src="498v35n02-90412312fig1.jpg"></img><img alt="Table 2 – Echocardiographic parameters" src="498v35n02-90412312fig2.jpg"></img> Frequency of HT and smoking habit, calcium levels, iPTH, anaemia or dyslipidemia, and systolic function assessed by echocardiography were not different from those observed in patients who did not have valvular calcification. In the multivariate logistic regression analysis, we included factors with statistical significance in the univariate analysis and other factors of potential involvement in the valvular calcification process: total cholesterol, HDL and LDL fractions, triglycerides, CRP, and left ventricular ejection fraction (LVEF). In this analysis, the factors independently related to the presence of VC were older age and lower albumin level (Table 3).<img alt="Table 3 – Factors associated with the presence of VC at the start of dialysis. Logistic Regression Analysis" src="498v35n02-90412312fig3.jpg"></img>Occurrence of endpoint During follow-up, 68 patients presented endpoint events of the study: MI, stroke, and/or death from cardiovascular causes. The distribution was as follows: • Patients who died from cardiovascular causes: 50. Causes included: 8 MI; 7 stroke, of which 5 were haemorrhagic and 2 ischaemic, and 1 patient also had MI; 13 sudden death; 9 heart failure, cardiogenic shock or malignant arrhythmia; 8 mesenteric ischaemia; 2 pulmonary thromboembolism; 3 arterial ischaemia/lower limb amputation. • Patients who had cardiovascular events: 18, of which 10 were MI, 7 were strokes, and 1 patient had MI and stroke. Twelve of these patients died in the follow-up due to non-cardiovascular causes, one received a renal transplant, and five were alive at the end of the study. The 68 patients who experienced an endpoint event were older than the 188 patients who did not. Most were diabetic patients and patients with a history of AF, MI and/or stroke. In the echocardiographic test, they showed greater left ventricular mass and left atrial dilation with less left ventricular ejection fraction. Valvular calcification was more frequent in these patients (Table 4).<img alt="Table 4 – Patients who had the event (MI, stroke and/or death from cardiovascular causes)" src="498v35n02-90412312fig4.jpg"></img> In the Kaplan-Meier analysis, the event-free survival was shorter in patients with valvular calcification. This difference was maintained when the analysis was performed in the 192 (75%) patients with no prior diagnosis of coronary artery disease, stroke or AF (Figure 1).<img alt="Figure 1 – Event-free survival (MI, stroke and/or death from cardiovascular causes); Kaplan-Meier Curves A: all patients; B: patients with no diagnosis of coronary artery disease, stroke or AF at the start of dialysis; VC: valvular calcification" src="498v35n02-90412312fig5.jpg"></img>Figure 1 – Event-free survival (MI, stroke and/or death from cardiovascular causes); Kaplan-Meier Curves A: all patients; B: patients with no diagnosis of coronary artery disease, stroke or AF at the start of dialysis; VC: valvular calcification The occurrence of endpoint events increased according to the VC grade. In the absence of calcification, 13.2% of patients presented an event, 37% with mild or moderate grade and 75% of patients with severe grade (Figure 2).<img alt="Figure 2 – Event occurrence (MI, stroke and/or death from cardiovascular causes) by VC grade. VC: absent vs. mild-moderate, p = 0.000; absent vs. severe, p = 0.000; mild-moderate vs. severe, p = 0.036" src="498v35n02-90412312fig6.jpg"></img>Figure 2 – Event occurrence (MI, stroke and/or death from cardiovascular causes) by VC grade. VC: absent vs. mild-moderate, p = 0.000; absent vs. severe, p = 0.000; mild-moderate vs. severe, p = 0.036 In the Cox regression analysis, we included variables with statistical significance in the univariate analysis and others that were potentially associated with cardiovascular morbidity-mortality, such as sex, haemoglobin, phosphorous, CRP and dialysis technique. The factors independently associated with the occurrence of the endpoint of the study were the presence of VC at the start of dialysis, older age, and prior diagnoses of AF, coronary artery disease, and/or stroke (Table 5).<img alt="Table 5 – Predictive factors for event occurrence (MI, stroke and/or death from cardiovascular causes). Cox Regression Analysis" src="498v35n02-90412312fig7.jpg"></img> To assess whether VC severity increased the risk for endpoint events, the same analysis was performed for the calcification grades. For mild-moderate grade VC, the results were the following: HR 1.780 (95% CI 0.953–3.346, p = 0.07). Results for severe grade VC were: HR 4.517 (95% CI: 1.827– 11.809, p = 0.02).Discussion The results of this study show that there is a high prevalence of VC in patients who start dialysis and that the presence of VC is associated with the occurrence of cardiovascular events and mortality in the course of follow-up. In the last decade, the scientific literature has shown that the frequency of VC (aortic, mitral, or both) in CKD is high. In the Framingham study, CKD (11% of patients with glomerular filtration rate < 40 mL/min) increased the risk of mitral valve calcification by 60%, although not aortic calcification1. Another study did not find an association between glomerular filtration rate < 60 mL/min and aortic valve calcification, but it did find an association with mitral valve calcification in diabetic patients only2. Most of the information about VC is from prevalent dialysis population studies, with a prevalence ranging from 30 to 70% of patients on both peritoneal dialysis3,2 and haemodialysis4,5,11. However, studies of patients who initiate dialysis are less frequent. A recent published study of incident dialysis patients in Japan showed a VC prevalence of 57.7%, for an age slightly younger than that of our study15. In another publication, the prevalence of VC at the start of dialysis was 35.6% for patients 15 years younger than our patients16. In our study, older age and lower levels of albumin (an inflammatory and malnutrition marker) were independently associated with the presence of VC. Age is an important factor associated with VC3,6, along with inflammatory markers. In prevalent dialysis patients, an association was demonstrated between VC and inflammatory markers, such as β2 microglobulin, cytokines, CRP and others like fetuin A5,15,9,8. In the baseline assessment, patients with VC had a higher incidence of history of cardiovascular events, AF and diabetes, along with higher blood pressure and pulse pressure as well as structural alterations such as left ventricular hypertrophy and greater diastolic dysfunction. In studies of patients with VC on dialysis, cardiovascular disease and structural cardiac alterations have not always been assessed. In prevalent patients, VC has been associated with coronary artery disease10, a history of cardiovascular events and left ventricular hypertrophy11, and carotid intima-media thickness13. In the Japanese study of events during dialysis, cardiovascular events and structural cardiac alterations were not analysed15. In another study, patients with prior coronary artery events were excluded16. VC was not associated with alterations in bone-mineral metabolism, which is similar to other studies of incident dialysis patients15,6; some studies of prevalent patients have shown an association between VC and some biochemical alterations in calcium/phosphorous metabolism17,18. A possible explanation is the better phosphorous control in incident patients with residual renal function, which does not exclude the involvement of bone-mineral metabolism alterations in the genesis of VC. The pathogenesis of VC and vascular calcification is not clear, although they share mechanisms; in patients on dialysis, a correlation between VC and vascular calcification has been shown19. CKD involves alterations in calcium/phosphorous metabolism and bone remodelling, inflammation and imbalance between inducers and inhibitors of calcification. The final result is the phenotypical change of cells in valvular and vascular structures to osteoblasts20,21. Both in experimental studies22 and clinical studies23, an inverse correlation has been shown between vascular and valvular calcification with the loss of bone mineralization, and, in patients on dialysis, it has been shown that the presence of VC is associated with a greater progression of coronary calcification, measured by multi-slice CT16. In the ADVANCE study, patients treated with the calcimimetic cinacalcet showed less increase in the progression of aortic valve calcification, which indicates the involvement of mineral metabolism disorders in VC24. Another matter is the importance of VC as a predictive factor for cardiovascular risk in patients on dialysis. In studies of prevalent haemodialysis patients, VC was a predictor variable for all-cause mortality4. In prevalent peritoneal dialysis patients, it was a predictor for cardiovascular mortality and mortality from any cause; this is similar to the risk posed by the history of atherosclerotic events, which establishes it as a cardiovascular disease marker3. In other studies, VC was not a predictor of mortality in the multivariate analysis adjusted for age and inflammatory markers16 or adjusted for prior cardiovascular events11. A study of asymptomatic prevalent dialysis patients (69% haemodialysis) at high risk for cardiovascular disease, segmental alterations in myocardial contractility and LVEF < 40% demonstrated an association between VC and the presence of inducible myocardial ischaemia; this suggests that VC may be a marker for silent myocardial ischaemia risk in this population25. In this study, VC was a predictor variable for the occurrence of MI, stroke and/or death from cardiovascular causes. There were more severe VC events than mild-moderate events (Figure 2). In the multivariate analysis adjusted for all the included variables, the mild-moderate grade was observed at the limit of statistical significance as a predictor variable for endpoint events. The availability of simple tools is important to assess cardiovascular risk. In studies conducted in our institution, the history of cardiovascular events recorded in medical records, data from exploratory tests and electrocardiograms were useful to predict cardiovascular risk in our population on dialysis26,27,28,29. Echocardiography is a safe, low-cost, widely available technique and a simple tool that adds value to the results of this study. In summary, at the start of a dialysis programme, a high proportion of patients have VC. This fact doubles the risk of MI, stroke and/or death from cardiovascular causes during the course of dialysis. The magnitude of this risk is similar to that of cardiovascular disease or the presence of AF before the start of dialysis.<hr></hr> Sent for Review: 22 June 2014 Accepted on: 21 Oct. 2014<a href="http://dx.doi.org/10.3265/Nefrologia.pre2014.Oct.12640" class="elsevierStyleCrossRefs">http://dx.doi.org/10.3265/Nefrologia.pre2014.Oct.12640</a> * Corresponding author. Carmen Sánchez-Perales, Nephrology, Complejo Hospitalario de Jaén, Navas de Tolosa 4 y 6.P1, 6º D, 23003, Jaén E-mail:<a href="mailto:mcsanchezp@senefro.org" class="elsevierStyleCrossRefs">mcsanchezp@senefro.org</a>" "pdfFichero" => "498v35n02a90412312pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec503488" "palabras" => array:3 [ 0 => "Calcificación valvular" 1 => "Diálisis" 2 => "Factores de riesgo cardiovascular" ] ] ] "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec503487" "palabras" => array:3 [ 0 => "Valvular calcification" 1 => "Dialysis" 2 => "Cardiovascular risk factors" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => " La calcificación valvular (CV) en la enfermedad renal crónica es frecuente, aunque la mayor parte de la información procede de pacientes prevalentes en diálisis. Son pocos los estudios que analicen la CV en los pacientes que inician diálisis. Objetivo: Analizar la presencia de CV al inicio de diálisis y su relación con eventos y/o muerte cardiovascular en la evolución. Métodos: Incluimos en el estudio los pacientes incidentes en diálisis entre nov/03 y sept/07. En el 1º mes de tratamiento analizamos la presencia de CV mediante Ecocardiograma-doppler, junto a factores demográficos y de riesgo cardiovascular, enfermedad coronaria, accidente cerebrovascular (ACV), fibrilación auricular (FA) y parámetros de electro y ecocardiográficos dimensionales y funcionales cardiacos. Los valores bioquímicos analizados fueron: hemoglobina, metabolismo calcio/fósforo/iPTH, colesterol y fracciones, triglicéridos, troponina I, albúmina, PCR y hemoglobina glicosilada. Analizamos la asociación de la CV con la presentación de infarto de miocardio (IAM), ACV y/o muerte cardiovascular hasta el trasplante, muerte, o fin del estudio (dic/2012). Resultados: De 256 pacientes incluidos (83% hemodiálisis, 17% diálisis peritoneal), 128 (50%) presentaban CV (mitral: 39, aórtica: 20, ambas: 69). En el análisis multivariante la CV se asoció a mayor edad (OR: 1,110; IC 95%: 1,073-1,148; p = 0,000) y menor albúmina (OR: 0,29; IC 95%: 0,14-0,61; p = 0,001). En un seguimiento de 42,1 ± 30,2 meses (898,1 pacientesaño), 68 pacientes presentaron IAM, ACV y/o murieron por causa cardiovascular. En el análisis de regresión de Cox, la mayor edad (HR: 1,028; IC 95%: 1,002-1,055; p = 0,037), la enfermedad coronaria y/o ACV (HR: 1,979; IC95%: 1,111-3,527; p = 0,021), la FA (HR: 2,474; IC 95%: 1,331-4,602; p = 0,004) y la presencia de CV antes de entrar en diálisis (HR: 1,996; IC 95%: 1,077-3,700; p = 0,028), fueron predictores independientes de la presentación de los eventos analizados. Conclusiones: La prevalencia de CV en el momento de iniciar diálisis es alta y su presencia predice la presentación de eventos y/o muerte cardiovascular en la evolución." ] "en" => array:1 [ "resumen" => " Valvular calcification (VC) in chronic kidney disease is frequent, although most information derives from prevalent dialysis patients. There are few studies that analyse VC in patients who start dialysis. Objective: To analyse the presence of VC at the start of dialysis and its relationship with events and/or death from cardiovascular causes in the course of follow-up. Methods: In the study, we included patients who started dialysis between November 2003 and September 2007. In the first month of treatment, we assessed the presence of VC by Doppler echocardiography, along with demographic factors and risk factors for cardiovascular disease, coronary artery disease, stroke, atrial fibrillation (AF), and cardiac dimensional and functional electrocardiographic and echocardiographic parameters. The biochemistry values assessed were: haemoglobin, calcium/phosphorous/iPTH metabolism, cholesterol and fractions, triglycerides, troponin I, albumin, CRP and glycosylated haemoglobin. We analysed the association between VC and the presence of myocardial infarction (MI), stroke and/or death from cardiovascular causes up to transplantation, death or the end of the study (December 2012). Results: Of 256 enrolled patients (83% haemodialysis, 17% peritoneal dialysis), 128 (50%) had VC (mitral: 39, aortic: 20, both: 69). In the multivariate analysis, VC was associated with older age (OR: 1.110; 95% CI: 1.073–1.148; p = 0.000) and lower albumin levels (OR: 0.29; 95% CI: 0.14–0.61; p = 0.001). In a follow-up lasting 42.1 ± 30.2 months (898.1 patient-years), 68 patients suffered MI, stroke and/or died from cardiovascular causes. In the Cox regression analysis, older age (HR: 1.028; 95% CI: 1.002–1.055; p = 0.037), coronary artery disease and/or stroke (HR: 1.979; 95% CI: 1.111–3.527; p = 0.021), AF (HR: 2.474; 95% CI: 1.331–4.602; p = 0.004), and the presence of VC at the start of dialysis (HR: 1.996; 95% CI: 1.077–3.700; p = 0.028) were the predictor variables for the occurrence of the analysed events. Conclusions: The prevalence of VC at the start of dialysis is high and its presence predicts the occurrence of events and/or cardiovascular death in the course of follow-up." ] ] "multimedia" => array:7 [ 0 => array:8 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "498v35n02-90412312fig1.jpg" "imagenAlto" => 1083 "imagenAncho" => 1033 "imagenTamanyo" => 192238 ] ] ] ] ] "descripcion" => array:1 [ "en" => "– Characteristics of patients with VC at the start of dialysis" ] ] 1 => array:8 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "498v35n02-90412312fig2.jpg" "imagenAlto" => 583 "imagenAncho" => 1029 "imagenTamanyo" => 95708 ] ] ] ] ] "descripcion" => array:1 [ "en" => "– Echocardiographic parameters" ] ] 2 => array:8 [ "identificador" => "tbl3" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "498v35n02-90412312fig3.jpg" "imagenAlto" => 358 "imagenAncho" => 1041 "imagenTamanyo" => 64614 ] ] ] ] ] "descripcion" => array:1 [ "en" => "– Factors associated with the presence of VC at the start of dialysis. Logistic Regression Analysis" ] ] 3 => array:8 [ "identificador" => "tbl4" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "498v35n02-90412312fig4.jpg" "imagenAlto" => 912 "imagenAncho" => 1041 "imagenTamanyo" => 153084 ] ] ] ] ] "descripcion" => array:1 [ "en" => "– Patients who had the event (MI, stroke and/or death from cardiovascular causes)" ] ] 4 => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "498v35n02-90412312fig5.jpg" "Alto" => 904 "Ancho" => 2000 "Tamanyo" => 111002 ] ] "descripcion" => array:1 [ "en" => "– Event-free survival (MI, stroke and/or death from cardiovascular causes); Kaplan-Meier Curves A: all patients; B: patients with no diagnosis of coronary artery disease, stroke or AF at the start of dialysis; VC: valvular calcification" ] ] 5 => array:8 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "498v35n02-90412312fig6.jpg" "Alto" => 770 "Ancho" => 1025 "Tamanyo" => 65016 ] ] "descripcion" => array:1 [ "en" => "– Event occurrence (MI, stroke and/or death from cardiovascular causes) by VC grade. VC: absent vs. mild-moderate, p = 0.000; absent vs. severe, p = 0.000; mild-moderate vs. severe, p = 0.036" ] ] 6 => array:8 [ "identificador" => "tbl5" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "498v35n02-90412312fig7.jpg" "imagenAlto" => 525 "imagenAncho" => 1033 "imagenTamanyo" => 88172 ] ] ] ] ] "descripcion" => array:1 [ "en" => "– Predictive factors for event occurrence (MI, stroke and/or death from cardiovascular causes). Cox Regression Analysis" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Cross-sectional association of kidney function with valvular and annular calcification: the Framingham heart study. J Am Soc Nephrol. 2006;17:521-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16382018" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Cross-sectional association of kidney function with valvular and annular calcification: the Framingham heart study." 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Las calcificaciones valvulares al inicio de diálisis predicen la aparición de eventos cardiovasculares en la evolución

Carmen Sánchez-Peralesa, Eduardo Vázquez Ruiz de Castroviejob, Mª José García-Cortésa, Mª del Mar Biechya, Jose Manuel Gil-Cunqueroa, Josefa Borrego-Hinojosaa, Pilar Pérez del Barrioa, Francisco Borrego-Utiela, Antonio Liébanaa

a Nephrology, Complejo Hospitalario de Jaén [Hospital Complex of Jaén], Jaén

b Cardiology, Complejo Hospitalario de Jaén, Jaén

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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction </span></p><p class="elsevierStylePara"> The presence of cardiac valvular calcifications &#40;VC&#41; in chronic kidney disease &#40;CKD&#41; is considered a frequent fact&#46; Population studies have confirmed an association between CKD and mitral or aortic VC from initial stages of decreased glomerular filtration1&#44;2&#46; Nevertheless&#44; most publications derive from studies of prevalent peritoneal dialysis and haemodialysis patients&#44; in which the prevalence of VC is greater than 30&#37; of patients3&#44;4&#44;5&#46; In these studies&#44; VC correlates with the time on replacement therapy&#44; inflammation&#44; malnutrition and atherosclerotic heart disease6&#44;7&#44;8&#44;9&#44;10&#46; VC has been a predictor for mortality from cardiovascular causes and from any other cause3 in some studies&#44; although not in all of them11&#46;</p><p class="elsevierStylePara"> VC and atherosclerosis are frequently observed in a same patient on dialysis&#44; and the association between them has been demonstrated<span class="elsevierStyleSup">7&#44;12</span>&#46; Based on this association&#44; VC has been considered one of the manifestations of atherosclerosis<span class="elsevierStyleSup">7&#44;13</span>&#46; However&#44; all patients with VC do not have atherosclerosis&#46; This suggests that&#44; although both processes share pathogenic mechanisms&#44; their pathogenesis and possibly the risk they involve are not identical<span class="elsevierStyleSup">14</span>&#46;</p><p class="elsevierStylePara"> There are few studies about VC in patients with advanced stages of CKD at the onset of replacement therapy<span class="elsevierStyleSup">15&#44;16</span>&#46;</p><p class="elsevierStylePara"> The purpose of this study was to analyse the presence of VC in patients who started dialysis for the first time and its relationship with the occurrence of events and cardiovascular mortality during follow-up&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Methods </span></p><p class="elsevierStylePara"> We included patients diagnosed with stage 5 CKD&#44; who started haemodialysis or peritoneal dialysis for the first time between November 2003 and September 2007 in our hospital centre&#46; Patients who started treatment in another centre or had undergone prior renal transplantation were excluded&#46; The observational period ranged from the first day of dialysis to termination due to transplantation&#44; death&#44; patient transfer outside our health area of influence&#44; or the end of the study 31 December 2012&#46;</p><p class="elsevierStylePara"> In the first month of dialysis&#44; the following variables were assessed and included for analysis&#58; demographic characteristics&#59; anthropometric measurements&#59; pulse pressure&#59; history of hypertension and&#47;or antihypertensive treatment &#40;HTN&#41;&#59; diabetes with indication of drug treatment at any time of follow-up&#59; active smoking habit or cessation in the last 10 years&#59; coronary artery disease documented by a history of myocardial infarction &#40;MI&#41; or compatible coronary angiographic test&#59; ischaemic or haemorrhagic stroke&#44; documented by a neurologist and&#47;or imaging test report&#59; atrial fibrillation &#40;AF&#41; in any of its forms documented in a prior medical record or by an ECG finding&#59; and&#44; analytical variables&#44; such as haemoglobin&#44; mineral metabolism &#40;calcium&#44; phosphorous&#44; PTH&#41;&#44; urea&#44; creatinine&#44; troponin I&#44; albumin&#44; C-reactive protein &#40;CRP&#41;&#44; cholesterol and fractions&#44; triglycerides and glycosylated haemoglobin&#46;</p><p class="elsevierStylePara"> VC was studied with colour Doppler echocardiography by a single observer&#46; It was defined as increased echo-refringence with a thickness &#62; 1 mm at the level of the mitral or aortic annulus or leaf let&#46; Three grades were established according to the calcification area&#58; mild&#44; when there were only small&#44; isolated areas&#59; moderate&#44; when there were multiple areas&#59; and severe&#44; when calcification was extensive and diffuse&#46; It was analysed whether the calcification was limited to only one valve&#44; mitral or aortic&#44; or involved both&#46;</p><p class="elsevierStylePara"> The endpoint of our study was the occurrence of one or several of the following events in the course of follow-up&#58; MI&#44; stroke or death from cardiovascular causes &#40;defined as death due to heart failure&#41;&#44; pulmonary thromboembolism&#44; sudden death&#44; mesenteric ischaemia or peripheral arterial ischaemia&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Statistical Analysis </span></span></p><p class="elsevierStylePara"> The Student&#8217;s <span class="elsevierStyleItalic">t</span>-test or the nonparametric Mann-Whitney test was used for the comparison of means&#46; For the comparison of qualitative variables&#44; the Pearson&#8217;s Chi-square test was used&#46; For the analysis of the association between VC and the risk factors that were present at the start of treatment&#44; a logistic regression multivariate analysis was performed&#44; and the odds ratio &#40;OR&#41; and 95&#37; confidence interval were obtained&#46; The predictive power of variables for the occurrence of the endpoint of our study was analysed through a Cox proportional-hazard regression analysis&#46; The prognostic variable was the occurrence of the endpoint defined in the Methods section&#46; Predictive variables were the presence of VC&#44; and other variables with significant association in the univariate analysis or of special significance&#46; The hazard ratio &#40;HR&#41; and 95&#37; confidence interval were obtained&#46;</p><p class="elsevierStylePara"> Event-free survival was analysed with the Kaplan-Meier method&#44; and the Mantel-Haenszel test &#40;log-rank&#41; was used to compare survival curves&#46; For hypothesis contrast tests&#44; a value of <span class="elsevierStyleItalic">p</span> &#60; 0&#46;05 was considered statistically significant&#46; The analyses were carried out with the statistical package SPSS 15&#46;0 for Windows&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Results </span></span></p><p class="elsevierStylePara"> Following the exclusion criteria&#44; 48 patients were not included&#59; another 29 patients were not included since they could not participate in the entire initial study&#46; The total number of enrolled patients was 256&#46; Mean age was 65&#46;1 &#177; 15&#46;9 years&#44; median age was 69&#46;9&#44; and 146 patients &#40;57&#37;&#41; were male&#46; Nephropathies induced by renal failure included the following&#58; glomerulonephritis 17&#46;2&#37;&#59; interstitial nephropathies 15&#46;2&#37;&#59; nephrosclerosis 15&#46;6&#37;&#59; polycystic kidney disease 6&#46;3&#37;&#59; other familial diseases 1&#46;2&#37;&#59; systemic diseases 5&#46;1&#37;&#59; diabetes 18&#46;4&#37;&#59; unidentified diseases 18&#46;8&#37;&#59; other 2&#46;3&#37;&#46; Diabetes caused nephropathy or was a concomitant disease in 73 &#40;28&#46;5&#37;&#41; patients&#46;</p><p class="elsevierStylePara"> They study included 213 &#40;83&#37;&#41; patients receiving haemo-dialysis and 43 &#40;17&#37;&#41; patients in peritoneal dialysis&#44; with a mean age of 66&#46;8 &#177; 14&#46;8 and 56&#46;5 &#177; 18&#46;5 years&#44; respectively &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;004&#41;&#46; Patients were monitored for 42&#46;1 &#177; 30 months &#40;range&#58; 0&#46;23&#8211;109&#46;4&#41;&#44; with a follow-up of 898&#46;1 patient-years&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Prevalence of Valvular Calcification </span></span></p><p class="elsevierStylePara"> At the beginning of the dialysis programme&#44; valvular calcification &#40;VC&#41; was present in 128 patients&#44; which accounts for a prevalence of 50&#37;&#46; The grades were&#58; 90 mild &#40;35&#46;1&#37;&#41;&#59; 30 moderate &#40;11&#46;7&#37;&#41;&#59; and 8 severe &#40;3&#46;1&#37;&#41;&#46; Calcification was present in the mitral valve in 39 &#40;15&#46;2&#37;&#41; patients&#44; the aortic valve in 20 &#40;7&#46;8&#37;&#41;&#44; and in both valves in 69 &#40;27&#37;&#41; patients&#46;</p><p class="elsevierStylePara"> Those patients who had valvular calcification were an average of 18 years older and were mostly women&#44; diabetic patients&#44; and had a history of cardiovascular events and diagnosis of atrial fibrillation&#46; A higher proportion of patients included in the haemodialysis programme had valvular calcification&#46; Creatinine&#44; albumin and phosphorous levels were lower&#44; while pulse pressure and body mass index were higher &#40;Table 1&#41;&#46; They also had greater left ventricular mass and left atrial dimension and greater diastolic dysfunction &#40;Table 2&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 1 – Characteristics of patients with VC at the start of dialysis" src="498v35n02-90412312fig1.jpg"></img></p><p class="elsevierStylePara"><img alt="Table 2 – Echocardiographic parameters" src="498v35n02-90412312fig2.jpg"></img></p><p class="elsevierStylePara"> Frequency of HT and smoking habit&#44; calcium levels&#44; iPTH&#44; anaemia or dyslipidemia&#44; and systolic function assessed by echocardiography were not different from those observed in patients who did not have valvular calcification&#46;</p><p class="elsevierStylePara"> In the multivariate logistic regression analysis&#44; we included factors with statistical significance in the univariate analysis and other factors of potential involvement in the valvular calcification process&#58; total cholesterol&#44; HDL and LDL fractions&#44; triglycerides&#44; CRP&#44; and left ventricular ejection fraction &#40;LVEF&#41;&#46; In this analysis&#44; the factors independently related to the presence of VC were older age and lower albumin level &#40;Table 3&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 3 – Factors associated with the presence of VC at the start of dialysis&#46; Logistic Regression Analysis" src="498v35n02-90412312fig3.jpg"></img></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Occurrence of endpoint </span></span></p><p class="elsevierStylePara"> During follow-up&#44; 68 patients presented endpoint events of the study&#58; MI&#44; stroke&#44; and&#47;or death from cardiovascular causes&#46; The distribution was as follows&#58;</p><p class="elsevierStylePara"> &#8226; Patients who died from cardiovascular causes&#58; 50&#46; Causes included&#58; 8 MI&#59; 7 stroke&#44; of which 5 were haemorrhagic and 2 ischaemic&#44; and 1 patient also had MI&#59; 13 sudden death&#59; 9 heart failure&#44; cardiogenic shock or malignant arrhythmia&#59; 8 mesenteric ischaemia&#59; 2 pulmonary thromboembolism&#59; 3 arterial ischaemia&#47;lower limb amputation&#46;</p><p class="elsevierStylePara"> &#8226; Patients who had cardiovascular events&#58; 18&#44; of which 10 were MI&#44; 7 were strokes&#44; and 1 patient had MI and stroke&#46; Twelve of these patients died in the follow-up due to non-cardiovascular causes&#44; one received a renal transplant&#44; and five were alive at the end of the study&#46;</p><p class="elsevierStylePara"> The 68 patients who experienced an endpoint event were older than the 188 patients who did not&#46; Most were diabetic patients and patients with a history of AF&#44; MI and&#47;or stroke&#46; In the echocardiographic test&#44; they showed greater left ventricular mass and left atrial dilation with less left ventricular ejection fraction&#46; Valvular calcification was more frequent in these patients &#40;Table 4&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 4 – Patients who had the event &#40;MI&#44; stroke and&#47;or death from cardiovascular causes&#41;" src="498v35n02-90412312fig4.jpg"></img></p><p class="elsevierStylePara"> In the Kaplan-Meier analysis&#44; the event-free survival was shorter in patients with valvular calcification&#46; This difference was maintained when the analysis was performed in the 192 &#40;75&#37;&#41; patients with no prior diagnosis of coronary artery disease&#44; stroke or AF &#40;Figure 1&#41;&#46;</p><p class="elsevierStylePara"><img alt="Figure 1 – Event-free survival &#40;MI&#44; stroke and&#47;or death from cardiovascular causes&#41;&#59; Kaplan-Meier Curves A&#58; all patients&#59; B&#58; patients with no diagnosis of coronary artery disease&#44; stroke or AF at the start of dialysis&#59; VC&#58; valvular calcification" src="498v35n02-90412312fig5.jpg"></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Figure 1 &#8211; Event-free survival &#40;MI&#44; stroke and&#47;or death from cardiovascular causes&#41;&#59; Kaplan-Meier Curves A&#58; all patients&#59; B&#58; patients with no diagnosis of coronary artery disease&#44; stroke or AF at the start of dialysis&#59; VC&#58; valvular calcification</span></p><p class="elsevierStylePara"> The occurrence of endpoint events increased according to the VC grade&#46; In the absence of calcification&#44; 13&#46;2&#37; of patients presented an event&#44; 37&#37; with mild or moderate grade and 75&#37; of patients with severe grade &#40;Figure 2&#41;&#46;</p><p class="elsevierStylePara"><img alt="Figure 2 – Event occurrence &#40;MI&#44; stroke and&#47;or death from cardiovascular causes&#41; by VC grade&#46; VC&#58; absent vs&#46; mild-moderate&#44; p &#61; 0&#46;000&#59; absent vs&#46; severe&#44; p &#61; 0&#46;000&#59; mild-moderate vs&#46; severe&#44; p &#61; 0&#46;036" src="498v35n02-90412312fig6.jpg"></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Figure 2 &#8211; Event occurrence &#40;MI&#44; stroke and&#47;or death from cardiovascular causes&#41; by VC grade&#46; VC&#58; absent vs&#46; mild-moderate&#44; </span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">p</span></span><span class="elsevierStyleBold"> &#61; 0&#46;000&#59; absent vs&#46; severe&#44; </span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">p</span></span><span class="elsevierStyleBold"> &#61; 0&#46;000&#59; mild-moderate vs&#46; severe&#44; </span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">p</span></span><span class="elsevierStyleBold"> &#61; 0&#46;036</span></p><p class="elsevierStylePara"> In the Cox regression analysis&#44; we included variables with statistical significance in the univariate analysis and others that were potentially associated with cardiovascular morbidity-mortality&#44; such as sex&#44; haemoglobin&#44; phosphorous&#44; CRP and dialysis technique&#46; The factors independently associated with the occurrence of the endpoint of the study were the presence of VC at the start of dialysis&#44; older age&#44; and prior diagnoses of AF&#44; coronary artery disease&#44; and&#47;or stroke &#40;Table&#160;5&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 5 – Predictive factors for event occurrence &#40;MI&#44;&#160;stroke and&#47;or death from cardiovascular causes&#41;&#46; Cox Regression Analysis" src="498v35n02-90412312fig7.jpg"></img></p><p class="elsevierStylePara"> To assess whether VC severity increased the risk for endpoint events&#44; the same analysis was performed for the calcification grades&#46; For mild-moderate grade VC&#44; the results were the following&#58; HR 1&#46;780 &#40;95&#37; CI 0&#46;953&#8211;3&#46;346&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;07&#41;&#46; Results for severe grade VC were&#58; HR 4&#46;517 &#40;95&#37; CI&#58; 1&#46;827&#8211; 11&#46;809&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;02&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Discussion </span></p><p class="elsevierStylePara"> The results of this study show that there is a high prevalence of VC in patients who start dialysis and that the presence of VC is associated with the occurrence of cardiovascular events and mortality in the course of follow-up&#46; In the last decade&#44; the scientific literature has shown that the frequency of VC &#40;aortic&#44; mitral&#44; or both&#41; in CKD is high&#46; In the Framingham study&#44; CKD &#40;11&#37; of patients with glomerular filtration rate &#60; 40 mL&#47;min&#41; increased the risk of mitral valve calcification by 60&#37;&#44; although not aortic calcification<span class="elsevierStyleSup">1</span>&#46; Another study did not find an association between glomerular filtration rate &#60; 60 mL&#47;min and aortic valve calcification&#44; but it did find an association with mitral valve calcification in diabetic patients only<span class="elsevierStyleSup">2</span>&#46; Most of the information about VC is from prevalent dialysis population studies&#44; with a prevalence ranging from 30 to 70&#37; of patients on both peritoneal dialysis<span class="elsevierStyleSup">3&#44;2</span> and haemodialysis<span class="elsevierStyleSup">4&#44;5&#44;11</span>&#46; However&#44; studies of patients who initiate dialysis are less frequent&#46; A recent published study of incident dialysis patients in Japan showed a VC prevalence of 57&#46;7&#37;&#44; for an age slightly younger than that of our study<span class="elsevierStyleSup">15</span>&#46; In another publication&#44; the prevalence of VC at the start of dialysis was 35&#46;6&#37; for patients 15 years younger than our patients<span class="elsevierStyleSup">16</span>&#46;</p><p class="elsevierStylePara"> In our study&#44; older age and lower levels of albumin &#40;an inflammatory and malnutrition marker&#41; were independently associated with the presence of VC&#46; Age is an important factor associated with VC<span class="elsevierStyleSup">3&#44;6</span>&#44; along with inflammatory markers&#46; In prevalent dialysis patients&#44; an association was demonstrated between VC and inflammatory markers&#44; such as &#946;2 microglobulin&#44; cytokines&#44; CRP and others like fetuin A<span class="elsevierStyleSup">5&#44;15&#44;9&#44;8</span>&#46;</p><p class="elsevierStylePara"> In the baseline assessment&#44; patients with VC had a higher incidence of history of cardiovascular events&#44; AF and diabetes&#44; along with higher blood pressure and pulse pressure as well as structural alterations such as left ventricular hypertrophy and greater diastolic dysfunction&#46; In studies of patients with VC on dialysis&#44; cardiovascular disease and structural cardiac alterations have not always been assessed&#46; In prevalent patients&#44; VC has been associated with coronary artery disease<span class="elsevierStyleSup">10</span>&#44; a history of cardiovascular events and left ventricular hypertrophy<span class="elsevierStyleSup">11</span>&#44; and carotid intima-media thickness<span class="elsevierStyleSup">13</span>&#46; In the Japanese study of events during dialysis&#44; cardiovascular events and structural cardiac alterations were not analysed<span class="elsevierStyleSup">15</span>&#46; In another study&#44; patients with prior coronary artery events were excluded<span class="elsevierStyleSup">16</span>&#46;</p><p class="elsevierStylePara"> VC was not associated with alterations in bone-mineral metabolism&#44; which is similar to other studies of incident dialysis patients<span class="elsevierStyleSup">15&#44;6</span>&#59; some studies of prevalent patients have shown an association between VC and some biochemical alterations in calcium&#47;phosphorous metabolism<span class="elsevierStyleSup">17&#44;18</span>&#46; A possible explanation is the better phosphorous control in incident patients with residual renal function&#44; which does not exclude the involvement of bone-mineral metabolism alterations in the genesis of VC&#46; The pathogenesis of VC and vascular calcification is not clear&#44; although they share mechanisms&#59; in patients on dialysis&#44; a correlation between VC and vascular calcification has been shown<span class="elsevierStyleSup">19</span>&#46; CKD involves alterations in calcium&#47;phosphorous metabolism and bone remodelling&#44; inflammation and imbalance between inducers and inhibitors of calcification&#46; The final result is the phenotypical change of cells in valvular and vascular structures to osteoblasts<span class="elsevierStyleSup">20&#44;21</span>&#46;</p><p class="elsevierStylePara"> Both in experimental studies<span class="elsevierStyleSup">22</span> and clinical studies23&#44; an inverse correlation has been shown between vascular and valvular calcification with the loss of bone mineralization&#44; and&#44; in patients on dialysis&#44; it has been shown that the presence of VC is associated with a greater progression of coronary calcification&#44; measured by multi-slice CT<span class="elsevierStyleSup">16</span>&#46; In the ADVANCE study&#44; patients treated with the calcimimetic cinacalcet showed less increase in the progression of aortic valve calcification&#44; which indicates the involvement of mineral metabolism disorders in VC<span class="elsevierStyleSup">24</span>&#46;</p><p class="elsevierStylePara"> Another matter is the importance of VC as a predictive factor for cardiovascular risk in patients on dialysis&#46; In studies of prevalent haemodialysis patients&#44; VC was a predictor variable for all-cause mortality<span class="elsevierStyleSup">4</span>&#46; In prevalent peritoneal dialysis patients&#44; it was a predictor for cardiovascular mortality and mortality from any cause&#59; this is similar to the risk posed by the history of atherosclerotic events&#44; which establishes it as a cardiovascular disease marker<span class="elsevierStyleSup">3</span>&#46; In other studies&#44; VC was not a predictor of mortality in the multivariate analysis adjusted for age and inflammatory markers<span class="elsevierStyleSup">16</span> or adjusted for prior cardiovascular events<span class="elsevierStyleSup">11</span>&#46; A study of asymptomatic prevalent dialysis patients &#40;69&#37; haemodialysis&#41; at high risk for cardiovascular disease&#44; segmental alterations in myocardial contractility and LVEF &#60; 40&#37; demonstrated an association between VC and the presence of inducible myocardial ischaemia&#59; this suggests that VC may be a marker for silent myocardial ischaemia risk in this population<span class="elsevierStyleSup">25</span>&#46;</p><p class="elsevierStylePara"> In this study&#44; VC was a predictor variable for the occurrence of MI&#44; stroke and&#47;or death from cardiovascular causes&#46; There were more severe VC events than mild-moderate events &#40;Figure 2&#41;&#46; In the multivariate analysis adjusted for all the included variables&#44; the mild-moderate grade was observed at the limit of statistical significance as a predictor variable for endpoint events&#46;</p><p class="elsevierStylePara"> The availability of simple tools is important to assess cardiovascular risk&#46; In studies conducted in our institution&#44; the history of cardiovascular events recorded in medical records&#44; data from exploratory tests and electrocardiograms were useful to predict cardiovascular risk in our population on dialysis<span class="elsevierStyleSup">26&#44;27&#44;28&#44;29</span>&#46; Echocardiography is a safe&#44; low-cost&#44; widely available technique and a simple tool that adds value to the results of this study&#46;</p><p class="elsevierStylePara"> In summary&#44; at the start of a dialysis programme&#44; a high proportion of patients have VC&#46; This fact doubles the risk of MI&#44; stroke and&#47;or death from cardiovascular causes during the course of dialysis&#46; The magnitude of this risk is similar to that of cardiovascular disease or the presence of AF before the start of dialysis&#46;</p><hr></hr><p class="elsevierStylePara"> Sent for Review&#58; 22 June 2014 <br></br> Accepted on&#58; 21 Oct&#46; 2014</p><p class="elsevierStylePara"><a href="http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;3265&#47;Nefrologia&#46;pre2014&#46;Oct&#46;12640" class="elsevierStyleCrossRefs">http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;3265&#47;Nefrologia&#46;pre2014&#46;Oct&#46;12640</a></p><p class="elsevierStylePara"> &#42; <span class="elsevierStyleItalic">Corresponding author</span>&#46;<br></br> Carmen S&#225;nchez-Perales&#44; <br></br> Nephrology&#44; Complejo Hospitalario de Ja&#233;n&#44; <br></br> Navas de Tolosa 4 y 6&#46;P1&#44; 6&#186; D&#44; 23003&#44; Ja&#233;n <br></br><span class="elsevierStyleItalic">E-mail&#58;</span><a href="mailto&#58;mcsanchezp&#64;senefro&#46;org" class="elsevierStyleCrossRefs">mcsanchezp&#64;senefro&#46;org</a></p>"
    "pdfFichero" => "498v35n02a90412312pdf001.pdf"
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          "palabras" => array:3 [
            0 => "Calcificaci&#243;n valvular"
            1 => "Di&#225;lisis"
            2 => "Factores de riesgo cardiovascular"
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            0 => "Valvular calcification"
            1 => "Dialysis"
            2 => "Cardiovascular risk factors"
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        "resumen" => "<p class="elsevierStylePara"> La calcificaci&#243;n valvular &#40;CV&#41; en la enfermedad renal cr&#243;nica es frecuente&#44; aunque la mayor parte de la informaci&#243;n procede de pacientes prevalentes en di&#225;lisis&#46; Son pocos los estudios que analicen la CV en los pacientes que inician di&#225;lisis&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Objetivo&#58;</span> Analizar la presencia de CV al inicio de di&#225;lisis y su relaci&#243;n con eventos y&#47;o muerte cardiovascular en la evoluci&#243;n&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">M&#233;todos&#58;</span> Incluimos en el estudio los pacientes incidentes en di&#225;lisis entre nov&#47;03 y sept&#47;07&#46; En el 1&#186; mes de tratamiento analizamos la presencia de CV mediante Ecocardiograma-doppler&#44; junto a factores demogr&#225;ficos y de riesgo cardiovascular&#44; enfermedad coronaria&#44; accidente cerebrovascular &#40;ACV&#41;&#44; fibrilaci&#243;n auricular &#40;FA&#41; y par&#225;metros de electro y ecocardiogr&#225;ficos dimensionales y funcionales cardiacos&#46; Los valores bioqu&#237;micos analizados fueron&#58; hemoglobina&#44; metabolismo calcio&#47;f&#243;sforo&#47;iPTH&#44; colesterol y fracciones&#44; triglic&#233;ridos&#44; troponina I&#44; alb&#250;mina&#44; PCR y hemoglobina glicosilada&#46; Analizamos la asociaci&#243;n de la CV con la presentaci&#243;n de infarto de miocardio &#40;IAM&#41;&#44; ACV y&#47;o muerte cardiovascular hasta el trasplante&#44; muerte&#44; o fin del estudio &#40;dic&#47;2012&#41;&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Resultados&#58;</span> De 256 pacientes incluidos &#40;83&#37; hemodi&#225;lisis&#44; 17&#37; di&#225;lisis peritoneal&#41;&#44; 128 &#40;50&#37;&#41; presentaban CV &#40;mitral&#58; 39&#44; a&#243;rtica&#58; 20&#44; ambas&#58; 69&#41;&#46; En el an&#225;lisis multivariante la CV se asoci&#243; a mayor edad &#40;OR&#58; 1&#44;110&#59; IC 95&#37;&#58; 1&#44;073-1&#44;148&#59; p &#61; 0&#44;000&#41; y menor alb&#250;mina &#40;OR&#58; 0&#44;29&#59; IC 95&#37;&#58; 0&#44;14-0&#44;61&#59; p &#61; 0&#44;001&#41;&#46; En un seguimiento de 42&#44;1 &#177; 30&#44;2 meses &#40;898&#44;1 pacientesa&#241;o&#41;&#44; 68 pacientes presentaron IAM&#44; ACV y&#47;o murieron por causa cardiovascular&#46; En el an&#225;lisis de regresi&#243;n de Cox&#44; la mayor edad &#40;HR&#58; 1&#44;028&#59; IC 95&#37;&#58; 1&#44;002-1&#44;055&#59; p &#61; 0&#44;037&#41;&#44; la enfermedad coronaria y&#47;o ACV &#40;HR&#58; 1&#44;979&#59; IC95&#37;&#58; 1&#44;111-3&#44;527&#59; p &#61; 0&#44;021&#41;&#44; la FA &#40;HR&#58; 2&#44;474&#59; IC 95&#37;&#58; 1&#44;331-4&#44;602&#59; p &#61; 0&#44;004&#41; y la presencia de CV antes de entrar en di&#225;lisis &#40;HR&#58; 1&#44;996&#59; IC 95&#37;&#58; 1&#44;077-3&#44;700&#59; p &#61; 0&#44;028&#41;&#44; fueron predictores independientes de la presentaci&#243;n de los eventos analizados&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Conclusiones&#58;</span> La prevalencia de CV en el momento de iniciar di&#225;lisis es alta y su presencia predice la presentaci&#243;n de eventos y&#47;o muerte cardiovascular en la evoluci&#243;n&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"> Valvular calcification &#40;VC&#41; in chronic kidney disease is frequent&#44; although most information derives from prevalent dialysis patients&#46; There are few studies that analyse VC in patients who start dialysis&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Objective&#58;</span> To analyse the presence of VC at the start of dialysis and its relationship with events and&#47;or death from cardiovascular causes in the course of follow-up&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Methods&#58; </span>In the study&#44; we included patients who started dialysis between November 2003 and September 2007&#46; In the first month of treatment&#44; we assessed the presence of VC by Doppler echocardiography&#44; along with demographic factors and risk factors for cardiovascular disease&#44; coronary artery disease&#44; stroke&#44; atrial fibrillation &#40;AF&#41;&#44; and cardiac dimensional and functional electrocardiographic and echocardiographic parameters&#46; The biochemistry values assessed were&#58; haemoglobin&#44; calcium&#47;phosphorous&#47;iPTH metabolism&#44; cholesterol and fractions&#44; triglycerides&#44; troponin I&#44; albumin&#44; CRP and glycosylated haemoglobin&#46; We analysed the association between VC and the presence of myocardial infarction &#40;MI&#41;&#44; stroke and&#47;or death from cardiovascular causes up to transplantation&#44; death or the end of the study &#40;December 2012&#41;&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Results&#58; </span>Of 256 enrolled patients &#40;83&#37; haemodialysis&#44; 17&#37; peritoneal dialysis&#41;&#44; 128 &#40;50&#37;&#41; had VC &#40;mitral&#58; 39&#44; aortic&#58; 20&#44; both&#58; 69&#41;&#46; In the multivariate analysis&#44; VC was associated with older age &#40;OR&#58; 1&#46;110&#59; 95&#37; CI&#58; 1&#46;073&#8211;1&#46;148&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;000&#41; and lower albumin levels &#40;OR&#58; 0&#46;29&#59; 95&#37; CI&#58; 0&#46;14&#8211;0&#46;61&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;001&#41;&#46; In a follow-up lasting 42&#46;1 &#177; 30&#46;2 months &#40;898&#46;1 patient-years&#41;&#44; 68 patients suffered MI&#44; stroke and&#47;or died from cardiovascular causes&#46; In the Cox regression analysis&#44; older age &#40;HR&#58; 1&#46;028&#59; 95&#37; CI&#58; 1&#46;002&#8211;1&#46;055&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;037&#41;&#44; coronary artery disease and&#47;or stroke &#40;HR&#58; 1&#46;979&#59; 95&#37; CI&#58; 1&#46;111&#8211;3&#46;527&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;021&#41;&#44; AF &#40;HR&#58; 2&#46;474&#59; 95&#37; CI&#58; 1&#46;331&#8211;4&#46;602&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;004&#41;&#44; and the presence of VC at the start of dialysis &#40;HR&#58; 1&#46;996&#59; 95&#37; CI&#58; 1&#46;077&#8211;3&#46;700&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;028&#41; were the predictor variables for the occurrence of the analysed events&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Conclusions&#58;</span> The prevalence of VC at the start of dialysis is high and its presence predicts the occurrence of events and&#47;or cardiovascular death in the course of follow-up&#46;</p>"
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                  "referenciaCompleta" => "Cross-sectional association of kidney function with valvular and annular calcification: the Framingham heart study. J Am Soc Nephrol. 2006;17:521-7.  <a href="http://www.ncbi.nlm.nih.gov/pubmed/16382018" target="_blank">[Pubmed]</a>"
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Article information

ISSN: 20132514
Original language: English

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	4	7	11
2024 October	40	28	68
2024 September	39	24	63
2024 August	44	40	84
2024 July	34	23	57
2024 June	60	30	90
2024 May	82	26	108
2024 April	60	24	84
2024 March	52	22	74
2024 February	46	30	76
2024 January	42	21	63
2023 December	38	23	61
2023 November	40	28	68
2023 October	47	22	69
2023 September	31	14	45
2023 August	55	26	81
2023 July	29	42	71
2023 June	59	32	91
2023 May	65	25	90
2023 April	31	8	39
2023 March	32	13	45
2023 February	18	17	35
2023 January	29	31	60
2022 December	52	31	83
2022 November	28	31	59
2022 October	34	19	53
2022 September	47	35	82
2022 August	35	44	79
2022 July	31	32	63
2022 June	42	28	70
2022 May	36	35	71
2022 April	32	34	66
2022 March	39	41	80
2022 February	37	37	74
2022 January	33	27	60
2021 December	31	40	71
2021 November	24	29	53
2021 October	39	49	88
2021 September	28	33	61
2021 August	34	34	68
2021 July	31	32	63
2021 June	28	13	41
2021 May	34	30	64
2021 April	71	58	129
2021 March	40	27	67
2021 February	31	15	46
2021 January	42	15	57
2020 December	32	12	44
2020 November	26	10	36
2020 October	17	15	32
2020 September	26	9	35
2020 August	41	17	58
2020 July	40	7	47
2020 June	27	10	37
2020 May	54	6	60
2020 April	31	14	45
2020 March	35	13	48
2020 February	44	22	66
2020 January	42	15	57
2019 December	36	23	59
2019 November	38	25	63
2019 October	31	13	44
2019 September	43	24	67
2019 August	24	12	36
2019 July	38	21	59
2019 June	39	16	55
2019 May	48	28	76
2019 April	77	23	100
2019 March	39	19	58
2019 February	20	9	29
2019 January	47	22	69
2018 December	74	39	113
2018 November	97	15	112
2018 October	79	10	89
2018 September	67	14	81
2018 August	41	14	55
2018 July	45	16	61
2018 June	35	11	46
2018 May	45	14	59
2018 April	41	10	51
2018 March	24	5	29
2018 February	27	5	32
2018 January	24	4	28
2017 December	38	8	46
2017 November	65	12	77
2017 October	50	2	52
2017 September	62	12	74
2017 August	76	6	82
2017 July	71	13	84
2017 June	77	9	86
2017 May	68	6	74
2017 April	38	5	43
2017 March	65	4	69
2017 February	53	9	62
2017 January	40	6	46
2016 December	124	17	141
2016 November	138	10	148
2016 October	171	26	197
2016 September	183	7	190
2016 August	340	0	340
2016 July	262	0	262
2016 June	184	0	184
2016 May	180	0	180
2016 April	167	0	167
2016 March	181	0	181
2016 February	232	0	232
2016 January	192	0	192
2015 December	201	1	202
2015 November	132	1	133
2015 October	131	5	136
2015 September	136	4	140
2015 August	153	9	162
2015 July	271	0	271
2015 June	172	0	172
2015 May	295	24	319
2015 April	33	0	33

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