Estimation of Missing Baseline Serum Creatinine for Acute Kidney Injury Diagnosis in Hospitalized Patients.

INTRODUCTION: In hospitalized patients, information on preadmission kidney function is often missing, impeding timely and accurate acute kidney injury (AKI) detection and affecting results of AKI-related studies. OBJECTIVE: In this study, we provided estimates of preadmission serum creatinine (SCr), based on a multivariate linear regression (Model 1) and random forest model (Model 2) built with different parametrizations. Their accuracy for AKI diagnosis was compared with the accuracy of commonly used surrogate methods: (i) SCr at hospital admission (first SCr) and (ii) SCr back-calculated from the assumed estimated glomerular filtration rate of 75 mL/min/1.73 m2 (eGFR 75). METHODS: From 44,670 unique adult admissions to a tertiary referral centre between 2013 and 2015, we analysed 8,540 patients with preadmission SCr available. To control for differences in characteristics of patients with and without SCr, we used an inverse probability weighting technique. RESULTS: Estimates of SCr were likely to be higher than true preadmission SCr in a low Cr concentration and undervalued in high concentrations although for Model 2 Complete-SCr these differences were smallest. The true cumulative incidence of AKI was 14.8%. Model 2 Complete-SCr had the best agreement for AKI diagnosis (kappa 0.811, 95% CI 0.787-0.835), while surrogate methods resulted in the lowest agreement: (kappa 0.553, 0.516-0.590) and (0.648, 0.620-0.676) for first SCr and eGFR 75, respectively. CONCLUSIONS: Multivariable imputation of preadmission SCr, taking into account elementary admission data, improved accuracy in AKI diagnosis over commonly used surrogate methods. Random forest-based models can serve as an effective tool in research.

Conversion methods for modified Jaffe reaction assays of serum creatinine.

BACKGROUND: Modifications in Jaffe serum creatinine (sCr) assays question the suitability of the results for direct comparison. METHODS: sCr in adult in-patients was routinely measured either by SRM 909-standardized/noncompensated (method A) or isotope dilution mass spectrometry traceable/compensated method (reference). We converted values by method A into values by the reference using a formula provided by the manufacturer [Beckman Coulter (BC)] and traditional equating methods. RESULTS: The BC-based conversion and linear equating resulted in underestimated sCr values, whereas equipercentile equating (EE) provided sCr with not significantly different distribution from the reference values. Proportions of patients with renal impairment did not differ between the reference and EE-converted sCr, as opposed to BC-recalculated values. Three percent of patients were classified into better renal function category when applying BC versus EE conversion. CONCLUSIONS: Equipercentile equation was a more accurate method for recalculation of sCr obtained from different Jaffe reaction assays than the linear equating or the BC linear formula. This study emphasizes the importance of the derivation sample specificity when applying research results to other real-world populations.

Patient and system delays in the treatment of acute coronary syndrome.

INTRODUCTION: Early reperfusion for patients with ST-segment elevation myocardial infarction (STEMI) is indicated by the European Society of Cardiology, while a timely invasive strategy is recommended for patients with high-risk and intermediate-risk non-ST-elevation acute coronary syndromes (NSTE-ACS). This study aims to assess patient and system delays according to diagnosis and risk profile, and to identify predictors of prolonged delay. METHODS: We assembled a cohort of patients (n=939) consecutively admitted to the cardiology department of two hospitals, one in the metropolitan area of Porto and one in the north-east region of Portugal, between August 2013 and December 2014. RESULTS: The proportion of patients with time from symptom onset to first medical contact (FMC) ≥120 min was highest among high-risk NSTE-ACS (57.7%), followed by intermediate-risk NSTE-ACS (52.1%) and STEMI (43.3%). Regardless of diagnosis and risk stratification, use of own transportation and inability to interpret cardiac symptoms correctly were associated with prolonged delays. Regarding system delays, we found that 78.0% of patients with STEMI and 65.8% of patients with high-risk NSTE-ACS were treated in a timeframe exceeding the recommended limits. Admission to a non-percutaneous coronary intervention-capable hospital, admission on weekends and complications at admission were associated with prolonged delays to treatment. CONCLUSIONS: Due to both patient and system delays, a large proportion of STEMI and high-risk NSTE-ACS patients still fail to have access to timely reperfusion.

Serum creatinine trajectories in real-world hospitalized patients: clinical context and short-term mortality.

Fluctuations in serum creatinine (SCr) during hospitalization may provide additional prognostic value beyond baseline renal function. This study aimed to identify groups of patients with distinct creatinine trajectories over hospital stay and assess them in terms of clinical characteristics and short-term mortality. This retrospective study included 35 853 unique adult admissions to a tertiary referral center between January 2012 and January 2016 with at least three SCr measurements within the first 9 days of stay. Individual SCr courses were determined using linear regression or linear-splines model and grouped into clusters. SCr trajectories were described as median SCr courses within clusters. Almost half of the patients presented with changing, mainly declining SCr concentration during hospitalization. In comparison to patients with an increase in SCr, those with a significant decline were younger, more often admitted via the emergency department, more often required a higher level of care, had fewer comorbidities and the more pronounced the fall in SCr, the greater the observed difference. Regardless of baseline renal function, an increase in SCr was related to the highest in-hospital mortality risk among compared clusters. Also, patients with normal renal function at admission followed by decreasing SCr were at higher risk of inpatient death, but lower 90-day postdischarge mortality than patients with a stable SCr. Acute changes in inpatient SCr convey important prognostic information and can only be interpreted by looking at their evolution over time. Recognizing underlying causes and providing adequate care is crucial for improving adverse prognosis.

Definition of baseline renal function in hospitalised patients with multiple preadmission measures of serum creatinine-A joint modelling approach.

AIM: With the use of a joint model (JM) we investigated how different definitions of baseline serum creatinine (SCr) would affect the association between an acute increase in inpatients' SCr and 30-day mortality and whether this effect depends on premorbid SCr trajectory. METHODS: This was a retrospective study including adult patients admitted to a tertiary acute-care hospital in Porto, Portugal, between January 1, 2013, and December 31, 2015, who had at least two preadmission ambulatory and two inpatients SCr measurements. The baseline SCr was defined as the lowest (-min), the most recent (-last) or the median (-medi) value over the preadmission period. The JM combined a linear mixed model for repeated inpatient SCr relative to baseline value and a Cox proportional survival model. Preadmission SCr courses were identified using linear regression and subsequently clustered based upon a patient-specific slope. Preadmission SCr trajectories were described as median SCr courses within clusters. RESULTS: SCr trajectories were: "Stable" (78.0% of patients), "Decreasing" (11.3%) and "Increasing" (10.7%). Overall, an increase in inpatient SCr by 50% relative to baseline SCr-min raised the risk of 30-day mortality by 74%; the estimate was not different from hazard ratio (HR) obtained for SCr-last (1.78) and SCr-medi (1.71). We found no differences in HR across preadmission trajectories. CONCLUSION: The increased risk of death associated with an abrupt rise in inpatient SCr depends neither on the definition of baseline SCr nor patients' SCr trajectory before hospitalisation. Preadmission SCr-medi value may be the least biased estimate of the baseline renal function.

Early prediction of treatment failure in severe community-acquired pneumonia: The PRoFeSs score.

PURPOSE: To identify a single/panel of biomarkers and to provide a point score that, after 48 h of treatment, could early predict treatment failure at fifth day of Intensive Care Unit (ICU) stay in severe community-acquired pneumonia (SCAP) patients. MATERIALS AND METHODS: Single-center, prospective cohort study of 107 ICU patients with SCAP. Primary outcome included death or absence of improvement in Sequential Organ Failure Assessment score by ≥2 points within 5 days of treatment. Biomarkers were evaluated within 12 h of first antibiotic dose (D1) and 48 h after the first assessment (D3). RESULTS: A model based on Charlson's score and a panel of biomarkers (procalcitonin on D1 and D3, B-natriuretic peptide on D1, D-dimer and lactate on D3) had good discrimination for primary outcome in both derivation (AUC 0.82) and validation (AUC 0.76) samples and was well calibrated (X2 = 0.98; df = 1; p = .32). A point score system (PRoFeSs score) built on the estimates of regression coefficients presented good discrimination (AUC 0.81; 95% Confidence Interval 0.72-0.89) for primary outcome. CONCLUSIONS: In SCAP, a combination of biomarkers measured at admission and 48 h later may early predict treatment failure. PRoFeSs score may recognize patients with poor short-term prognosis.

Quality of Care and 30-day Mortality of Women and Men With Acute Myocardial Infarction.

INTRODUCTION AND OBJECTIVES: Despite increased awareness of sex disparities in care and outcomes of acute myocardial infarction (AMI), there appears to have been no consistent attenuation of these differences over the last decade. We investigated differences by sex in management and 30-day mortality using the European Society of Cardiology Acute Cardiovascular Care Association quality indicators (QIs) for AMI. METHODS: Proportions and standard errors of the 20 Acute Cardiovascular Care Association QIs were calculated for 771 patients with AMI who were admitted to the cardiology departments of 2 tertiary hospitals in Portugal between August 2013 and December 2014. The association between the composite QI and 30-day mortality was derived from logistic regression. RESULTS: Significantly fewer eligible women than men received timely reperfusion, were discharged on dual antiplatelet therapy and high-intensity statins, and were referred to cardiac rehabilitation. Women were less likely to receive recommended interventions (59.6% vs 65.2%; P <.001) and also had higher mean GRACE 2.0 risk score-adjusted 30-day mortality (3.0% vs 1.7%; P <.001). An inverse association between the composite QI and crude 30-day mortality was observed for both sexes (OR, 0.08; 95%CI, 0.01-0.64 for the highest performance tertile vs the lowest). CONCLUSIONS: Performance in AMI management is worse for women than men and is associated with higher 30-day mortality, which is also worse for women. Evidence-based QIs have the potential to improve health care delivery and patient prognosis in the overall AMI population and may also bridge the disparity gap between women and men.

Prognostic Effect of Renal Function in Ambulatory Patients With Heart Failure and Reduced Ejection Fraction: The Kidney Is a Marker of Cardiac Function.

BACKGROUND: Chronic kidney disease is a frequent comorbidity in heart failure (HF), associated with increased mortality. The impact of temporal evolution of kidney function in HF prognosis is largely unknown. We evaluated the effect of renal function over time in all-cause mortality among ambulatory patients with HF. METHODS: We retrospectively analyzed data from 560 patients with HF with left ventricular systolic dysfunction followed for a median of 25.1 months at an outpatient clinic. Demographics and comorbidities were collected at baseline. Creatinine values were abstracted from records at each clinical visit. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and was categorized into 3 classes. Extended Cox models were performed to study the association between time-varying eGFR and death. RESULTS: Patients' mean age was 67.5 ± 13.9 years, 67.0% were men, 46.1% had ischemic etiology, the majority had moderate-to-severe left ventricular systolic dysfunction, and 45.9% had chronic kidney disease at baseline. The eGFR declined approximately 9.0 mL/min/1.73 m2 over 5 years. In crude analysis, time-varying eGFR had a significant dose-dependent association with death (hazard ratio [HR] = 1.34, 95% confidence interval [CI]: 1.03-1.75 for eGFR between 30 and 60 mL/min/1.73 m2; HR = 1.55, 95% CI: 1.11-2.17 for <30 mL/min/1.73 m2). The prognostic value of time-varying eGFR was totally explained by baseline comorbidities, indicators of HF severity and drugs (adjusted HR = 1.11, 95% CI: 0.83-1.48; HR = 1.19, 95% CI: 0.79-1.80, for eGFR 30-60 and <30 mL/min/m2, respectively). CONCLUSIONS: Time-varying kidney function is not independently related to poor prognosis in HF. Rather than directly affecting survival, renal impairment is probably a surrogate marker of HF severity.

Sex differences in presenting symptoms of acute coronary syndrome: the EPIHeart cohort study.

OBJECTIVES: Prompt diagnosis of acute coronary syndrome (ACS) remains a challenge, with presenting symptoms affecting the diagnosis algorithm and, consequently, management and outcomes. This study aimed to identify sex differences in presenting symptoms of ACS. DESIGN: Data were collected within a prospective cohort study (EPIHeart). SETTING: Patients with confirmed diagnosis of type 1 (primary spontaneous) ACS who were consecutively admitted to the Cardiology Department of two tertiary hospitals in Portugal between August 2013 and December 2014. PARTICIPANTS: Presenting symptoms of 873 patients (227 women) were obtained through a face-to-face interview. OUTCOME MEASURES: Typical pain was defined according to the definition of cardiology societies. Clusters of symptoms other than pain were identified by latent class analysis. Logistic regression was used to quantify differences in presentation of ACS symptoms by sex. RESULTS: Chest pain was reported by 82% of patients, with no differences in frequency or location between sexes. Women were more likely to feel pain with an intensity higher than 8/10 and this association was stronger for patients aged under 65 years (interaction P=0.028). Referred pain was also more likely in women, particularly pain referred to typical and atypical locations simultaneously. The multiple symptoms cluster, which was characterised by a high probability of presenting with all symptoms, was almost fourfold more prevalent in women (3.92, 95% CI 2.21 to 6.98). Presentation with this cluster was associated with a higher 30-day mortality rate adjusted for the GRACE V.2.0 risk score (4.9% vs 0.9% for the two other clusters, P<0.001). CONCLUSIONS: While there are no significant differences in the frequency or location of pain between sexes, women are more likely to feel pain of higher intensity and to present with referred pain and symptoms other than pain. Knowledge of these ACS presentation profiles is important for health policy decisions and clinical practice.

Inequalities in access to cardiac rehabilitation after an acute coronary syndrome: the EPiHeart cohort.

OBJECTIVES: To estimate cardiac rehabilitation (CR) referral and participation rates among patients with acute coronary syndrome (ACS) and to identify their determinants, in two Portuguese regions. DESIGN: Prospective cohort study. SETTING: Patients consecutively admitted to the cardiology department of two hospitals, one in the district of Porto and one in the north-east region (NER) of Portugal, were enrolled in the EPIHeart cohort and then followed up for 6 months. PARTICIPANTS: Between August 2013 and December 2014, 939 patients were included in the cohort, and 853 were re-evaluated at 6-month follow-up. OUTCOME MEASURES: Referral rate was defined as the proportion of eligible patients who were referred to a CR programme, whereas participation rate was defined as the proportion of eligible patients who completed a CR programme, as was recommended by their physicians. RESULTS: Patients referred were 32.3% and 10.7% of those eligible in Porto and NER, respectively. In both regions, referral to CR decreased with age and with longer travel times to CR centres and increased with education or social class. At follow-up, 128 patients from Porto (26.2% of those eligible and 81.0% of those referred) and 26 from NER (7.1% of those eligible and 66.7% of those referred) reported actually participating in a CR programme. In Porto, the main barriers to participation were the long time until a programme was available and lack of perceived benefit. Patients in NER identified distance to CR and costs as the main barriers. CONCLUSIONS: CR remains clearly underused in Portugal, with major inequalities in access between regions. Achieving equitable and greater use of CR requires a multilevel approach addressing barriers related to healthcare system, providers and patients in order to improve provision, referral and participation.

Sex-related inequalities in management of patients with acute coronary syndrome-results from the EURHOBOP study.

BACKGROUND: Real-world data from different levels of hospital specialisation would help to understand if differences in management between women and men with acute coronary syndrome (ACS) are still a priority target. We aimed to identify sex inequalities in management of patients with different types of ACS. METHODS: We analysed 1757 patients with a non-ST-elevation ACS (NSTEACS) and 1184 with ST elevation myocardial infarction (STEMI) or left bundle branch block (non-classifiable (NC) ACS (STEMI/NC ACS group), consecutively discharged from ten Portuguese hospitals with different specialisation levels, between 2008 and 2010. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between sex and the performance of coronary angiography, reperfusion and revascularisation. RESULTS: Among STEMI/NC ACS, men had higher probability of performing coronary angiography than women (adjusted OR = 1.64, 95% CI: 1.11-2.44), while among NSTEACS patients there was no significant difference by sex (adjusted OR = 1.26, 95% CI: 0.99-1.62). In patients who underwent coronary angiography, there was no difference in proportion of women and men submitted to revascularisation, regardless of the ACS type. Although men with STEMI/NC ACS were more likely to undergo reperfusion (crude OR = 2.17, 95% CI: 1.68-2.81), the effect became not significant after multivariable adjustment (adjusted OR = 1.33, 95% CI: 0.96-1.84). CONCLUSION: Women diagnosed with STEMI/NC, but not NSTEACS, had lower probability when compared with men to be submitted to coronary angiography. There was no difference in performance of reperfusion and revascularisation by sex.

Missed Opportunities in Symptomatic Patients before a First Acute Coronary Syndrome: The EPIHeart Cohort Study.

OBJECTIVES: The aim of this study was to assess the proportion of patients with a first episode of acute coronary syndrome (ACS) reporting preceding chest pain, having previously sought medical care and undergone the performance of exams, and to identify the determinants of seeking medical advice and undergoing electrocardiogram (ECG). METHODS: Within a cohort study, 690 patients with a first episode of ACS were evaluated. A questionnaire was applied to assess chest pain within the preceding 6 months of the event and health system resources utilization. Determinants were identified by logistic regression. RESULTS: Preceding chest pain was reported by 61% of patients, 43% of these sought medical help, of whom less than half underwent ECG, and in 39% pain was attributed to a problem of the heart. Patients with hypertension were more likely to seek medical care (adjusted odds ratio, OR, 2.13, 95% CI 1.29-3.51), and former smokers (OR 0.52, 95% CI 0.28-0.99) and patients of a higher social class (OR 0.16, 95% CI 0.05-0.48) were less likely to seek medical care. The performance of ECG was associated with male sex (OR 2.56, 95% CI 1.11-5.87), health subsystem coverage (OR 3.88, 95% CI 1.11-13.53), and living in the northeastern region (OR 9.07, 95% CI 4.07-20.24), whereas cognitive impairment (OR 0.37, 95% CI 0.15-0.92) and being employed (OR 0.36, 95% CI 0.14-0.97) were inversely associated. CONCLUSIONS: These results suggest there are opportunities to improve the diagnosis of myocardial ischemia before acute coronary events.

Prognostic Effect of the Dose of Loop Diuretic Over 5 Years in Chronic Heart Failure.

BACKGROUND: High diuretic doses in chronic heart failure (HF) are potentially deleterious. We assessed the effect of dynamic furosemide dose on all-cause mortality among HF ambulatory patients. METHODS AND RESULTS: A cohort of 560 ambulatory patients from an outpatient clinic specialized in HF, with median age 70 years, 67% male, and 89% with moderate-severely reduced ejection fraction, was retrospectively followed for up to 5 years. Dynamic furosamide exposure was categorized as low (0-59 mg/d), medium (60-119 mg/d), high (120-159 mg/d), and very high (≥160 mg/d). Extended Cox models were used to estimate the association between time-varying diuretic dose and mortality. A dose-dependent crude association between higher doses of furosemide and death (hazard ratio [HR] = 1.34, 95% confidence interval (CI): 1.06-2.16; HR = 2.09, 95% CI: 1.54-2.84, for high and very high dose, respectively) was totally explained by patients' characteristics and disease severity indicators (adjusted HR = 0.94, 95% CI: 0.63-1.38; HR = 1.10, 95% CI: 0.79-1.55, for high and very high dose, respectively). CONCLUSION: In this context, higher doses of diuretic did not impair survival, but rather indicated greater severity of the patient's condition.

Disability-adjusted life years lost due to ischemic heart disease in mainland Portugal, 2013.

INTRODUCTION AND OBJECTIVES: Estimates of the burden of ischemic heart disease (IHD), including geographic differences, should support health policy decisions. We set out to estimate the burden of IHD in mainland Portugal in 2013 by calculating disability-adjusted life years (DALYs) and to compare this burden between five regions. METHODS: Years of life lost (YLLs) were calculated by multiplying the number of IHD deaths in 2013 (Statistics Portugal) by the life expectancy at the age at which death occurred. Years lived with disability (YLDs) were computed as the number of cases of acute coronary syndrome, stable angina and ischemic heart failure multiplied by an average disability weight. Crude and age-standardized DALYs (direct method, Standard European Population) were calculated for mainland Portugal and for the Northern, Central, Lisbon, Alentejo and Algarve regions. RESULTS: In 2013, 95413 DALYs were lost in mainland Portugal due to IHD. YLLs accounted for 88.3% of the disease burden. Age-standardized DALY rates per 1000 population were higher in men than in women, across the entire country (8.9 in men; 3.4 in women) and within each region, ranging from 7.3 in the Northern and Central regions to 11.8 in the Algarve in men, and from 2.6 in the Northern region to 4.6 in Lisbon in women. CONCLUSIONS: Nearly 100000 DALYs were lost to IHD in Portugal, mostly through early mortality. This study enables accurate comparisons with other countries and between regions; however, it highlights the need for population-based studies to obtain specific data on morbidity.

Electronic Medical Record-Based Predictive Model for Acute Kidney Injury in an Acute Care Hospital.

Patients with acute kidney injury (AKI) are at risk for increased morbidity and mortality. Lack of specific treatment has meant that efforts have focused on early diagnosis and timely treatment. Advanced algorithms for clinical assistance including AKI prediction models have potential to provide accurate risk estimates. In this project, we aim to provide a clinical decision supporting system (CDSS) based on a self-learning predictive model for AKI in patients of an acute care hospital. Data of all in-patient episodes in adults admitted will be analysed using "data mining" techniques to build a prediction model. The subsequent machine-learning process including two algorithms for data stream and concept drift will refine the predictive ability of the model. Simulation studies on the model will be used to quantify the expected impact of several scenarios of change in factors that influence AKI incidence. The proposed dynamic CDSS will apply to future in-hospital AKI surveillance in clinical practice.

Trends in pharmacological therapy following an acute coronary syndrome in Portugal: a systematic review.

AIMS: To assess time trends in the use of main drug classes for secondary prevention, during hospitalization and at hospital discharge, following an acute coronary syndrome, in Portugal, using a systematic review. METHODS: We searched PubMed, from inception until 2012, to identify studies reporting the proportion of acute coronary syndrome patients treated with main pharmacological therapy. We used linear regression to quantify the annual variation in use of drugs, adjusting for the proportion of men in the sample and patients' mean age, and including a quadratic term of data collection year when relevant. RESULTS: In 25 eligible studies, including patients treated from 1993 to 2009, we observed an increase in the prescription of pharmacological treatments at hospital discharge. Extrapolating from these data, and assuming a mean patient age of 65 years and 70% of men, we estimate that in 2008, 95% of patients would have been discharged with aspirin, 92% with clopidogrel, 82% with ß-blockers, 80% with angiotensin-converting enzyme inhibitors and 91% with statins. Treatment during hospitalization followed a similar pattern, except for a steeper increase in angiotensin-converting enzyme inhibitors use, which was initially lower, but reached similar levels to those at discharge in recent years. CONCLUSION: In Portugal, there was an increase in the use of recommended pharmacological therapy for secondary prevention after an acute coronary syndrome over the last 15 years, during hospitalization and at hospital discharge.

Validity of the Seattle Heart Failure Model for prognosis in a population at low coronary heart disease risk.

AIM: Validation of the Seattle Heart Failure Model (SHFM) for predicting the risk of death in a population different than the derivation cohort. METHODS: In a retrospective analysis of a cohort of chronic heart failure patients with left ventricular systolic dysfunction, consecutively referred between 2000 and 2011, we computed the score, according to characteristics at referral. We compared the observed risk of death with that predicted by the model, using receiver operating characteristic (ROC) curves to assess discrimination and a goodness-of-fit test for the comparison of predicted and observed risks. RESULTS: In 565 patients, 68.5% were men, the median age was 70 years, 46.0% had ischemic cause, 89.7% moderate-severe left ventricular systolic dysfunction and 61.2% New York Heart Association class II. The risk of death increased progressively with the model's score, with an area under the ROC curve between 0.69 and 0.72 when considering different follow-up periods. The model underestimated the risk of death (observed vs. predicted: 12.2 vs. 10.4%, P < 0.001; 28.1 vs. 25.1%, P < 0.001; and 43.4 vs. 35.7%, P < 0.001 at 1, 3 and 5 years, respectively). Accurate predictions, with nonsignificant differences between observed and predicted risks in a goodness-of-fit test, were obtained after recalibration. CONCLUSION: In this study, the SHFM substantially underestimated the absolute risk of death in ambulatory chronic heart failure patients, mostly nonischemic and elderly. After adjustment for sample-specific circumstances, the recalibrated model demonstrated to be credible in clinical practice and may provide useful information to physicians.

Prognostic Value of Osteoprotegerin in Acute Heart Failure.

BACKGROUND: Osteoprotegerin (OPG) is promising as a predictor of adverse prognosis in patients with acute coronary syndromes and chronic heart failure. Its prognostic value in acute heart failure (AHF) is unknown. The aim of this study was to assess the prognostic value provided by serum OPG levels at discharge after an admission for AHF. METHODS: In a prospective study, we enrolled 338 patients consecutively admitted with AHF to the internal medicine department of a tertiary care university hospital in Porto, Portugal between March 2009 and December 2010. OPG was measured using a commercial enzyme-linked immunosorbent assay and was both analyzed as a continuous variable and categorized by quartiles. Patients were followed for up to 6 months after discharge to ascertain the occurrence of all-cause death or hospital readmission resulting from AHF. RESULTS: During follow-up, 119 patients died or were readmitted for AHF. A graded increase in the risk of the combined end point was observed across quartiles of OPG. At 6 months, the cumulative risk of the end point was 25% for the first quartile and 50% for the fourth quartile. The multivariable adjusted risk of death or hospitalization for AHF increased progressively across categories of OPG up to a statistically significant 2.44-fold increase in risk in the highest category (P for linear trend = 0.002, ie, by 5% per 10 pg/mL increase in OPG). CONCLUSIONS: Serum OPG was directly associated with a higher probability of death or readmission for AHF within 6 months, irrespective of other known prognostic markers. This was true both when the ejection fraction was preserved and when it was reduced.