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5?mmol/L before start of the three most recent hemodialysis sessions. MI was diagnosed when at least two of three criteria were met: typical symptoms; elevated levels of cardiac enzymes; diagnostic changes in the electrocardiogram. Stroke was defined as a neurologic deficit lasting longer than 24?h. Computed tomographic or magnetic resonance imaging was available in all but 16 cases. The 4D study endpoints were centrally adjudicated by three members of the endpoint committee blinded to study treatment and according to pre-defined criteria. For the present analysis, combined cardiovascular events (CVE), sudden death, MI, stroke, all-cause mortality and deaths due to EPZ5676 molecular weight infection were all chosen as separate outcome measures. The categorization of these events was based on the primary judgment of the endpoint committee during the 4D Study. Continuous variables were expressed as mean with standard deviation or median with interquartile ranges, as appropriate. Categorical variables were expressed as percentages. The study population was divided into quartiles according to the PAPP-A concentration at baseline: ��13.4?mIU/L (quartile 1), 13.5�C17.0?mIU/L (quartile 2), 17.1�C20.9?mIU/L (quartile 3), >20.9?mIU/L (quartile 4). The Cox MAPK proportional hazards regression model was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the clinical outcomes of combined cardiovascular events (CVE), sudden death, MI, stroke, all-cause death and death due to infection. The first quartile of PAPP-A served as the reference group. PAPP-A was furthermore analyzed LY2109761 in vitro as a continuous variable. In the continuous analyses, the hazard ratios and 95% CI are given per standard deviation of PAPP-A concentrations. All Cox regression analyses were adjusted for potential confounders including age, sex, smoking status, body mass index, atorvastatin treatment, systolic blood pressure, dialysis vintage, coronary artery disease, and levels of hemoglobin, HbA1c, albumin, phosphate, creatinine and total cholesterol in the multivariate analyses. Kaplan�CMeier analyses were performed for the outcomes mentioned above. To compare the curves of the four groups, the log-rank test was computed. Furthermore, we investigated PAPP-A in relation to conventional cardiovascular risk factors including age, sex, smoking status, systolic blood pressure, LDL-cholesterol and HbA1c status. We used Cox regression and ROC analyses to evaluate the models with a) conventional cardiovascular risk factors only and b) the addition of PAPP-A to conventional cardiovascular risk factors, respectively. All p-values reported are two-sided and a p-value