Eduardo Núñez

Usefulness of the Neutrophil to Lymphocyte Ratio in Predicting Long-Term Mortality in ST Segment Elevation Myocardial Infarction

Neutrophil to lymphocyte ratio (N/L) has been associated with poor outcomes in patients who underwent cardiac angiography. Nevertheless, its role for risk stratification in acute coronary syndromes, specifically in patients with ST-segment elevation myocardial infarction (STEMI), has not been elucidated. We sought to determine the association of N/L maximum value (N/L max) with mortality in the setting of STEMI and to compare its predictive ability with total white blood cell maximum count (WBC max). We analyzed 515 consecutive patients admitted with STEMI to a single university center. White blood cells (WBC) and differential count were measured at admission and daily for the first 96 hours afterward. Patients with cancer, inflammatory diseases, or premature death were excluded, and 470 patients were included in the final analysis. The association between N/L max and WBC max with mortality was assessed by Cox regression analysis. During follow-up, we registered 106 deaths (22.6%). A positive trend between mortality and N/L max quintiles was observed; 6.4%, 12.4%, 11.7%, 34%, and 47.9% of deaths occurred from quintiles 1 to 5 (p <0.001), respectively. In a multivariable setting, after adjusting for standard risk factors, patients in the fourth (Q4 vs Q1) and fifth quintile (Q5 vs Q1) showed the highest mortality risk (hazard ratio 2.58, 95% confidence interal 1.06 to 6.32, p = 0.038 and hazard ratio 4.20, 95% confidence interal 1.73 to 10.21, p = 0.001, respectively). When WBC max and cells subtypes were entered together, N/L max remained as the only WBC parameter; furthermore, the model with N/L max showed the most discriminative ability. In conclusion, N/L max is a useful marker to predict subsequent mortality in patients admitted for STEMI, with a superior discriminative ability than total WBC max.

Improvement in risk stratification with the combination of the tumour marker antigen carbohydrate 125 and brain natriuretic peptide in patients with acute heart failure

AIMnElevated brain natriuretic peptide (BNP) and tumour marker antigen carbohydrate 125 (CA125) levels have shown to be associated with higher risk for adverse outcomes in patients with acute heart failure (AHF). Nevertheless, no attempt has been made to explore the utility of combining these two biomarkers. We sought to assess whether CA125 adds prognostic value to BNP in predicting 6-month all-cause mortality in patients with AHF.nnnMETHODS AND RESULTSnWe analysed 1111 consecutive patients admitted for AHF. Antigen carbohydrate 125 (U/mL) and BNP (pg/mL) were measured at a median of 72 +/- 12 h after instauration of treatment. Antigen carbohydrate 125 and BNP were dichotomized based on proposed prognostic cutpoints, and a variable with four categories was formed (BNP-CA125): C1 = BNP < 350 and CA125 < 60 (n = 394); C2 = BNP > or = 350 and CA125 < 60 (n = 165); C3 = BNP < 350 and CA125 > or = 60 (n = 331); and C4 = BNP > or = 350 and CA125 > or = 60 (n = 221). The independent association between BNP-CA125 and mortality was assessed with the Cox regression analysis, and their added predictive ability tested by the integrated discrimination improvement (IDI) index. At 6 months, 181 deaths (16.3%) were identified. The cumulative rate of mortality was lower for patients in C1 (7.8%), intermediate for C2 and C3 (17.8% and 16.9%, respectively), and higher for C4 (37.2%), and P-value for trend <0.001. After adjusting for established risk factors, the highest risk was observed when both biomarkers were elevated (C4 vs. C1: HR = 4.05, 95% CI = 2.54-6.45; P < 0.001) and intermediate when only one of them was elevated: (C2 vs. C1: HR = 1.71, 95% CI = 1.00-2.93; P = 0.050) and (C3 vs. C1: HR = 2.10, 95% CI = 1.30-3.39; P = 0.002). Moreover, when CA125 was added to the clinical model + BNP, a 10.4% (P < 0.0001) improvement in the IDI (on the relative scale) was found.nnnCONCLUSIONnIn patients admitted with AHF, CA125 added prognostic value beyond the information provided by BNP, and thus, their combination enables better 6-month risk stratification.

Frailty and other geriatric conditions for risk stratification of older patients with acute coronary syndrome.

BACKGROUNDnGeriatric conditions may predict outcomes beyond age and standard risk factors. Our aim was to investigate a wide spectrum of geriatric conditions in survivors after an acute coronary syndrome.nnnMETHODSnA total of 342 patients older than 65 years were included. At hospital discharge, 5 geriatric conditions were evaluated: frailty (Fried and Green scores), physical disability (Barthel index), instrumental disability (Lawton-Brody scale), cognitive impairment (Pfeiffer questionnaire), and comorbidity (Charlson and simple comorbidity indexes). The outcomes were postdischarge mortality and the composite of death/myocardial infarction during a 30-month median follow-up.nnnRESULTSnSeventy-four (22%) patients died and 105 (31%) suffered from the composite end point. Through univariable analysis, all individual geriatric indexes were associated with outcomes, mainly mortality. Of all of them, frailty using the Green score had the strongest discriminative accuracy (area under the receiver operating characteristic curve 0.76 for mortality). After full adjustment including clinical and geriatric data, the Green score was the only independent predictive geriatric condition (per point; mortality: hazard ratio 1.25, 95% CI 1.15-1.36, P = .0001; composite end point: hazard ratio 1.16, 95% CI 1.09-1.24, P = .0001). A Green score ≥ 5 points was the strongest mortality predictor. The addition of the Green score to the clinical model improved discrimination (area under the receiver operating characteristic curve 0.823 vs 0.846) and significantly reclassified mortality risk (net reclassification improvement 26.3, 95% CI 1.4-43.5; integrated discrimination improvement 4.0, 95% CI 0.8-9.0). The incremental predictive information was even greater over the GRACE score.nnnCONCLUSIONSnFrailty captures most of the prognostic information provided by geriatric conditions after acute coronary syndromes. The Green score performed better than the other geriatric indexes.

Estrategias para la elaboración de modelos estadísticos de regresión

Multivariable regression models are widely used in health science research, mainly for two purposes: prediction and effect estimation. Various strategies have been recommended when building a regression model: a) use the right statistical method that matches the structure of the data; b) ensure an appropriate sample size by limiting the number of variables according to the number of events; c) prevent or correct for model overfitting; d) be aware of the problems associated with automatic variable selection procedures (such as stepwise), and e) always assess the performance of the final model in regard to calibration and discrimination measures. If resources allow, validate the prediction model on external data.

Continuous ambulatory peritoneal dialysis as a therapeutic alternative in patients with advanced congestive heart failure

Continuous ambulatory peritoneal dialysis (CAPD) has been proposed as an additional therapeutic resource for patients with advanced congestive heart failure (CHF). The objective of this study was to determine the therapeutic role of CAPD, in terms of surrogate endpoints, in the management of patients with advanced CHF and renal dysfunction.

Differential prognostic effect of systolic blood pressure on mortality according to left‐ventricular function in patients with acute heart failure

To evaluate the relationship between systolic blood pressure (SBP) and long‐term mortality in patients with acute heart failure (AHF) stratified by ejection fraction (LVEF): reduced (≤40%) vs. preserved (≥50%).

Influence of Comorbid Conditions on One-Year Outcomes in Non–ST-Segment Elevation Acute Coronary Syndrome

OBJECTIVEnTo investigate comorbid conditions with prognostic influence in non-ST-segment elevation acute coronary syndrome (NSTEACS).nnnPATIENTS AND METHODSnThe study group consisted of a derivation cohort of 1017 patients (admitted from October 1, 2002, through October 1, 2008) and an external validation cohort of 652 patients (admitted from February 1, 2006, through September 30, 2009). Comorbid conditions, including risk factors and components of the Charlson comorbidity index (ChCI) and coronary artery disease-specific index, were recorded. The main outcome was one-year mortality.nnnRESULTSnDuring follow-up, 103 patients died. After adjusting for variables associated with NSTEACS characteristics (base model), 5 comorbid conditions predicted mortality: severe or mild renal failure (hazard ratio [HR], 2.9 and HR, 1.6, respectively), dementia (HR, 3.1), peripheral artery disease (HR, 2.0), previous heart failure (HR, 2.6), and previous myocardial infarction (HR, 1.4). A simple comorbidity index (SCI) was developed using these variables, (per point: HR, 1.6; 95% confidence interval, 1.4-1.8; P = .0001). Adding the SCI, Charlson comorbidity index, or coronary artery disease-specific index to the base model resulted in a gain of 6.58%, 5.00%, and 4.04%, respectively, in discriminative ability (P = .001), without significant differences among the 3 indices. In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEACS. The strength of the association between SCI and mortality rate was similar in the external validation cohort (HR, 1.3; 95% confidence interval, 1.1-1.6; P = .001).nnnCONCLUSIONnRenal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEACS. A simple index using these variables proved to be as accurate as the more complex comorbidity indices for risk stratification. In-hospital management of patients with comorbid conditions merits further investigation.

Hyperuricemia in acute heart failure. More than a simple spectator

BACKGROUNDnHyperuricemia is a prevalent condition in chronic heart failure (CHF), describing increased oxidative stress and inflammation. Although there is evidence that serum uric acid (UA) predicts mortality in CHF, its role as a prognostic biomarker in acute heart failure (AHF) has not yet been well assessed. The aim of this study was to determine if UA levels predict all-cause mortality. Additionally, as a secondary endpoint we sought the clinical predictors of UA serum level in this population.nnnMETHODSnWe analyzed 560 consecutive patients with AHF admitted in a single university center. UA (mg/dl) was measured during early hospitalization. Patient survival status was followed up after discharge (median follow-up: 330 days). The independent association of UA level with all-cause mortality was analyzed using Cox regression analysis.nnnRESULTSnDuring follow-up 165 (29.5%) deaths were identified. Patients with UA levels above the median value (>or=7.7 mg/dl) exhibited higher mortality rates (21.1 vs. 37.9%; p<0.001). In multivariable analysis, after adjusting for recognized prognostic factors and potential confounders, UA>or=7.7 mg/dl and per change in 1 mg/dl of UA was associated with an increased risk of mortality (HR 1.45, CI 95%=1.03-2.44; p=0.03 and HR 1.08, CI 95%=1.01-1.15; p=0.03, respectively).nnnCONCLUSIONnUA serum levels is an independent predictor of all-cause mortality in an unselected patients admitted with AHF.

Antigen carbohydrate 125 and brain natriuretic peptide serial measurements for risk stratification following an episode of acute heart failure

BACKGROUNDnThe prognostic utility of combining serial measurements of brain natriuretic peptide (BNP) and antigen carbohydrate 125 (CA125) is largely unknown. The aim of this work is to assess the prognostic utility of serial measurements of BNP, CA125, and their optimal combination for predicting long-term mortality, following a hospitalization for acute heart failure (AHF).nnnMETHODS AND RESULTSnWe analyzed 293 consecutive patients admitted with AHF where CA125 and BNP were measured at discharge (T1) and at the first ambulatory visit (T2: median 31 days after discharge). Biomarkers were evaluated as snapshot determinations or as serial changes in absolute, relative or categorical changes and related to subsequent mortality with Cox regression analysis. The incremental prognostic value added by each biomarker was evaluated by the integrated discrimination improvement (IDI) index. During a median follow-up of 18 months, 91 deaths (31.1%) were identified. From the different metrics tested, the categorical changes in CA125 (Normalization: decreasing to≤35 U/ml at T2; Decreasing but not normalization: decreasing but T2>35 U/ml; small-increase: increasing but T2≤35 U/ml and; high-increase: increasing and T2>35 U/ml) showed the best discriminative accuracy. For BNP none of the serial changes metrics tested were superior to a single determination at T2 (BNP≥100 pg/ml). Adding these two biomarkers characterization to the clinical model, resulted in a 9.21% (p<0.001) gain in IDI index.nnnCONCLUSIONSnIn patients discharged for AHF, CA125 modeled as a pre-post categorical change, and BNP as a single determination at T2, resulted in the best marker combination for predicting all-cause mortality.

Effects of inspiratory muscle training in patients with heart failure with preserved ejection fraction.

Background Heart failure with preserved ejection fraction (HFpEF) is remarkably common in elderly people with highly prevalent comorbid conditions. Despite its increasing in prevalence, there is no evidence-based effective therapy for HFpEF. We sought to evaluate whether inspiratory muscle training (IMT) improves exercise capacity, as well as left ventricular diastolic function, biomarker profile and quality of life (QoL) in patients with advanced HFpEF and nonreduced maximal inspiratory pressure (MIP). Design and methods A total of 26 patients with HFpEF (median (interquartile range) age, peak exercise oxygen uptake (peak VO2) and left ventricular ejection fraction of 73 years (66–76), 10u2009ml/min/kg (7.6–10.5) and 72% (65–77), respectively) were randomized to receive a 12-week programme of IMT plus standard care vs. standard care alone. The primary endpoint of the study was evaluated by positive changes in cardiopulmonary exercise parameters and distance walked in 6 minutes (6MWT). Secondary endpoints were changes in QoL, echocardiogram parameters of diastolic function, and prognostic biomarkers. Results The IMT group improved significantly their MIP (pu2009<u20090.001), peak VO2 (pu2009<u20090.001), exercise oxygen uptake at anaerobic threshold (pu2009=u20090.001), ventilatory efficiency (pu2009=u20090.007), metabolic equivalents (pu2009<u20090,001), 6MWT (pu2009<u20090.001), and QoL (pu2009=u20090.037) as compared to the control group. No changes on diastolic function parameters or biomarkers levels were observed between both groups. Conclusions In HFpEF patients with low aerobic capacity and non-reduced MIP, IMT was associated with marked improvement in exercise capacity and QoL.