Predictive value of white blood cell subtypes for long-term outcome following myocardial infarction

IntroductionElevation of total white blood cells (WBC) count is associated with higher mortality in patients with acute coronary syndromes. However, it is unknown which specific subset of leukocytes best correlates with increased risk of adverse outcome.Methods and resultsWe prospectively studied the predictive value of WBC subtypes for long-term outcome in 1037 patients with acute myocardial infarction (AMI). Total WBC, neutrophil, monocyte and lymphocyte counts, and high-sensitivity C-reactive protein (CRP) were obtained in each patient. The median duration of follow up was 23 months (range, 6–42 months). Analyzed separately, baseline total WBC (HR 2.2, 95% CI 1.5–3.3; P < 0.0001), neutrophil (HR 2.7, 95% CI 1.8–4.1; P < 0.0001) and monocyte (HR 1.9, 95% CI 1.3–2.8; P = 0.001) counts in the upper quartile, and lymphocyte count in the lower quartile (HR 1.5, 95% CI 1.1–2.3; P = 0.03), were all independent predictors of mortality. Comparing nested models, adding other WBC data failed to improve model based on neutrophil count. In contrast, adding neutrophil count to the models based on total WBC (P = 0.01), on monocyte count (P < 0.0001) or on lymphocyte count (P < 0.0001) improved the prediction of the models. Neutrophil count in the upper quartile (≥9800 μL^?1) remained a strong independent predictor of mortality after adjustment for left ventricular systolic function and for CRP (HR 2.2, 95% CI 1.6–3.0; P < 0.0001).ConclusionOf all WBC subtypes, elevated neutrophil count best correlates with mortality in patients with AMI. Neutrophil count provides additive prognostic information when combined with CRP.     

Gender differences in epicardial and tissue-level reperfusion in patients undergoing primary angioplasty for acute myocardial infarction

ObjectivePregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients.MethodBlood samples were drawn at study entry. Serum PAPP-A values ≥4 mIU/L were considered elevated. Mortality and non-fatal myocardial infarction was prospectively registered. The primary outcome was the composite outcome of myocardial infarction and all-cause mortality, secondary outcomes were all-cause mortality and myocardial infarction.ResultsPatients (n = 4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62–2.45, p < 0.0005), all-cause mortality (HR 2.42, 1.92–3.06, p < 0.0005), and myocardial infarction (HR 1.40, 1.01–1.94, p = 0.046). After Holm's correction, the latter significance disappeared. After adjustment for risk factors and medication at entry, elevated PAPP-A remained significantly related to the composite outcome (HR 1.51, 1.22–1.86, p < 0.0005) and all-cause mortality (HR 1.68, 1.32–2.13, p < 0.0005).ConclusionIn patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death.     

Probucol therapy improves long-term (>10-year) survival after complete revascularization: a propensity analysis

ObjectiveProbucol has anti-atherosclerotic properties and has been shown to reduce post-angioplasty coronary restenosis. However, the effect of probucol therapy on long-term (>10 years) outcome following coronary revascularization is less well established. Accordingly, we sought to determine if probucol therapy at the time of complete coronary revascularization reduces mortality in patients with coronary artery disease (CAD).MethodsWe collected data from 1694 consecutive patients who underwent complete revascularization (PCI and/or bypass surgery). Mortality data were compared between patients administered probucol and those not administered probucol at the time of revascularization. A propensity score (PS) was calculated to evaluate the effects of variables related to decisions regarding probucol administration. The association of probucol use and mortality was assessed using 3 Cox regression models, namely, conventional adjustment, covariate adjustment using PS, and matching patients in the probucol and no-probucol groups using PS.ResultsIn the pre-match patients, 231 patients were administered probucol (13.6%). During follow-up [10.2 (SD, 3.2) years], 352 patients died (including 113 patients who died of cardiac-related issues). Probucol use was associated with significant decrease in all-cause death (hazard ratio [HR], 0.65; P = 0.036 [conventional adjustment model] and HR, 0.57; P = 0.008 [PS adjusted model]). In post-match patients (N = 450, 225 matched pair), the risk of all-cause mortality was significantly lower in the probucol group than in the no-probucol group (HR, 0.45; P = 0.002).ConclusionIn CAD patients who had undergone complete revascularization, probucol therapy was associated with a significantly reduced risk of all-cause mortality.     

Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study

ObjectiveSerum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD.MethodsWe measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded.ResultsDuring an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p = 0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p < 0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p = 0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p < 0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09, p = 0.06).ConclusionsHigher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD.     

Serum copper as a marker of inflammation in prediction of short term outcome in high risk patients with chronic heart failure

BackgroundOxidative process and inflammation are regarded as important factors in the pathogenesis of chronic heart failure. Our study was aimed at investigating the prognostic value of serum copper levels in high risk subjects with chronic heart failure.MethodsSerum copper levels and other prognostic indicators were determined in the group of 60 patients with chronic heart failure due to ischemic heart disease: 30 consecutive subjects with acute decompensation of chronic heart failure (acute group A) and 30 patients with chronic stable heart failure (group B). Patients were followed prospectively 12 months. Primary end-point was the mean time to death and/or heart failure hospital admission.ResultsThe mean time to death was in the group A 279.4 ± 18.9 days and 351.7 ± 13.6 days in the group B (p < 0.0001). Cox proportional hazard model revealed that the time to death for all subjects (n = 60) was affected by cardiothoracic ratio (p < 0.001). The time to combined end-point death or hospital admission was affected by serum copper concentration (p < 0.0001).ConclusionSerum copper levels predicted short term outcome in high risk patients with chronic heart failure.     

Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction

ObjectiveWe aimed to investigate the relationship of each white blood cells (WBC) subtype with neurologic severity and outcome in acute stroke.MethodsWe included 779 patients with first-ever acute cerebral infarction within 72 h after symptom onset. We investigated the association between counts for WBC subtypes in peripheral blood at admission and (1) initial stroke severity; (2) early change in stroke severity within one week; and (3) functional outcome at three months.ResultsHigher total WBC and neutrophil counts were associated with more severe stroke at admission (p < 0.001). In contrast, lower lymphocyte counts were associated with a lesser improvement during the first week after admission (p < 0.05) and with poor functional outcome at three months (OR = 0.706 per 1000 lymphocyte counts/mm³, p = 0.020).ConclusionsOur study merits further investigation on the role of each WBC subtype in ischemic injury and different prognostic value of WBC subtypes measured at admission in acute stroke.     

The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: an observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes

AimsTo elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance.MethodsContinuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden.ResultsIn 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p = 0.032), although average risk versus non-glargine was non-significantly higher (HR 1.37, 95% CI 0.78–2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p = 0.35) and the mean risk was similar for glargine and non-glargine (p = 0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p = 0.037) and breast cancer (p = 0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59–0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78–1.14) compared to the general population and did not change with longer diabetes duration (p = 0.68 and p = 0.53 respectively).ConclusionsAnalysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research.     

Prognostic impact of peakVO2-changes in stable CHF on chronic beta-blocker treatment

BackgroundPeak oxygen uptake (pVO2) is used for risk stratification in chronic heart failure (CHF), but little is known about the prognostic impact of pVO2-changes in patients on chronic beta-blocker (BBL) therapy. We therefore prospectively evaluated individual pVO2-changes at a 6-month interval in patients all receiving BBL.Methods194 patients with stable CHF on stable medication were included (V1) and underwent clinical evaluation and exercise testing. Testing was repeated (V2) at 5.7 ± 1.5 months after V1 and patients were followed > 12 months after V2. Death or hospitalisation due to cardiac reasons was the predefined EP (EPP, end-point positive; n = 62; EPN, end-point negative; n = 113).ResultsInitial characteristics did not differ between EPP and EPN. Multivariate cox regression analysis revealed that change of pVO2 (EPP: − 0.6 ± 2.6 ml/kg min; EPN: + 2.5 ± 3.3 ml/kg min; p < 0.001) was independent to pVO2, LVEF, NTproBNP and NYHA at V2 for prediction of the combined end-point during follow-up. An increase of pVO2 by 10% was identified as an adequate cut-off value for risk stratification and ROC-analysis showed the significant incremental prognostic value of the determination of pVO2 changes in combination with pVO2.ConclusionsSerial measurements of pVO2 yield additional information for risk stratification in clinically homogenous CHF patients receiving BBL. This is the first study demonstrating this fact within a narrow predefined interval with all patients on BBL.     

Soluble TWEAK plasma levels predict expansion of human abdominal aortic aneurysms

ObjectivesDiminished soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) concentrations are associated with cardiovascular diseases. We have analyzed sTWEAK levels and its relation with expansion rate in subjects with abdominal aortic aneurysm (AAA).MethodssTWEAK levels were measured by ELISA.ResultssTWEAK concentrations were diminished in small AAA (≤5 cm; 353 ± 12 pg/mL; n = 25, p = 0.03) and large AAA (>5 cm; 315 ± 21 pg/mL; n = 18, p = 0.004) compared with healthy subjects (411 ± 22 pg/mL; n = 27). Moreover, sTWEAK concentrations were negatively associated with AAA size (r = ?0.4; p = 0.008). sTWEAK was also negatively associated with AAA expansion rate with 5 years of follow-up (n = 79, r = ?0.263; p = 0.031). Multivariate regression analysis revealed that sTWEAK levels were independently associated with AAA growth rate (β = ?0.208; p = 0.046).ConclusionssTWEAK plasma levels were decreased in subjects with AAA and were independently related with AAA expansion rate indicating that this protein could be a novel diagnostic and prognostic biomarker of AAA.     

Glycemic Status and Incident Heart Failure in Elderly Without History of Diabetes Mellitus: The Health, Aging, and Body Composition Study

BackgroundIt is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).Methods and ResultsThe association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A_1c [HbA_1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new-onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health, Aging, and Body Composition Study (median age, 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate was 10.7 cases per 1000 person-years with FG <100 mg/dL, 13.1 with FG 100–125 mg/dL, and 26.6 with FG ≥126 mg/dL (P = .002; P = .003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate [HR], and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10 mg/dL, 1.10; 95% CI, 1.02–1.18; P = .009); the addition of OGTT, fasting insulin, HbA_1c, HOMA-IR, or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n = 69), FG showed a strong association in adjusted models (HR per 10 mg/dL, 1.15; 95% CI, 1.03–1.29; P = .01). In comparison, when only HF with LVEF >40%, was considered (n = 71), the association was weaker (HR per 10 mg/dL, 1.05; 95% CI; 0.94–1.18; P = .41).ConclusionsFasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.     

The relation of serum gamma-glutamyl transferase levels with coronary lesion complexity and long-term outcome in patients with stable coronary artery disease

BackgroundRelation of serum gamma-glutamyl transferase (GGT) levels with extent, severity, and complexity of coronary artery disease has not been adequately studied. Therefore, we evaluated the relationship between GGT levels and coronary complexity, severity and extent assessed by SYNTAX score and long-term adverse events.MethodsWe enrolled 442 consecutive patients with stable angina pectoris who underwent coronary angiography. Baseline serum GGT levels were measured and SYNTAX score was calculated from the study population. Median follow-up duration was 363 days. Endpoints were all cause mortality and any revascularization.ResultsGGT levels demonstrated an increase from low SYNTAX tertile to high tertile. In multivariate analysis serum GGT, diabetes mellitus, HDL-cholesterol, eGFR and ejection fraction were found to be independent predictors of high SYNTAX score. The survival analysis showed that long-term revascularization rates were comparable between the GGT groups (for 36 U/l cut point) of the overall population (7.7% vs 8.6% logrank, p = 0.577), whereas long-term all cause mortality rate was higher in the GGT ≥ 36 U/l group (3.6% vs 11.6% logrank, p = 0.001). In Cox proportional hazards regression model, GGT ≥ 36 U/l group was found to be an independent predictor of long-term all cause mortality in the unadjusted (HR 2.54, 95% CI 1.17–5.48, p = 0.018) and age- and gender-adjusted (HR 2.58, 95% CI 1.19–5.58, p = 0.016) models.ConclusionSerum GGT level was independently associated with coronary complexity and long-term mortality in patients with stable coronary artery disease.     

Prognostic value of a new cardiopulmonary exercise testing parameter in chronic heart failure: oxygen uptake efficiency at peak exercise - comparison with oxygen uptake efficiency slope

IntroductionA growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O₂ consumption (VO₂) and minute ventilation (VE) in patients with chronic heart failure (CHF).ObjectiveTo evaluate the prognostic value of a new CPET parameter — peak oxygen uptake efficiency (POUE) — and to compare it with OUES in patients with CHF.MethodsWe prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy — 153 male, aged 53.3 ± 13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7 ± 8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone — who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverterdefibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up.Peak VO₂, percentage of predicted peak VO₂, VE/VCO₂ slope, OUES and POUE were analyzed. OUES was calculated using the formula VO₂ (l/min) = OUES (log₁₀VE) + b. POUE was calculated as pVO₂ (l/min) / log₁₀peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE.ResultspVO₂: 20.5 ± 5.9; percentage of predicted peak VO₂: 68.6 ± 18.2; VE/VCO₂ slope: 30.6 ± 8.3; OUES: 1.85 ± 0.61; POUE: 0.88 ± 0.27. During a mean follow-up of 33.1 ± 14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37).ConclusionPOUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.     

B-type natriuretic peptide and assessment of jeopardised myocardium in acute myocardial infarction

BackgroundB-type natriuretic peptide (BNP) is used as prognostic marker in acute coronary syndromes. It is unknown whether BNP reflects the amount of jeopardised myocardium in the initial phase of acute ST-elevation myocardial infarction (STEMI).MethodsPatients admitted for percutaneous coronary intervention in the acute phase of STEMI were studied. Samples for BNP were taken at the time of coronary intervention and were correlated with the amount of jeopardised myocardium. This was defined on coronary angiography as the vascular region distal to the infarct-related lesion and was expressed by a vascular score. The extend of epicardial injury on ECG was evaluated by: summation of STsegment elevation in the infarct-related leads, number of leads with ≥ 1 mm ST-segment elevation and number of leads with ≥ 1 mm ST-segment depression/elevation.ResultsA total of 113 patients (median age (25th, 75th percentile) 61 (54, 69)) were studied. Median BNP was 27 pg/ml (12, 62) and was assessed 225 min (150, 315) after onset of pain. There was no significant relation between BNP and vascular score (r = 0.026, p = 0.8). The only independent variable of BNP was time delay between onset of pain and sample collection. Stepwise regression identified the extent of ST-segment elevation as independent predictor of the vascular score.ConclusionAt initial presentation of STEMI, BNP measurement does not allow a correct prediction of jeopardised myocardium. In contrast, ST-segment analysis, in particularly the extent of ST-segment elevation, provides useful information about the extent of jeopardised myocardium.     

Which leukocyte subsets predict cardiovascular mortality? From the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study

ObjectiveWhite blood cells are known to predict cardiovascular mortality, but form a highly heterogeneous population. It is therefore possible that specific subtypes disproportionally contribute to the prediction of cardiovascular outcomes. Therefore, we compared leukocyte subsets alone and in conjunction with an established inflammatory marker, C-reactive protein, for predicting death due to cardiovascular disease in a high-risk population.MethodsPatients, 3316, (mean [SD] age, 62 [10] years) scheduled for coronary angiography were prospectively followed up. Neutrophil, monocyte and lymphocyte counts were determined. Neutrophil and monocyte subsets were further analysed on the basis of surface expression of CD11b, CD18, CD31, CD40 and CD58. Lymphocytes were further subdivided into CD3, CD4, CD8, and CD19 subsets. The association between each marker and subsequent cardiovascular mortality was assessed using multivariable Cox regression models.ResultsDuring a median follow-up period of 7.8 years, 745 (22.5%) patients died, of which 484 were due to cardiovascular events. After entering conventional risk factors and removing patients with a current infection, neutrophil count (HR [95% CI] = 1.90 [1.39, 2.60], P < 0.001) and the neutrophil/lymphocyte ratio (HR [95% CI] = 1.68 [1.24, 2.27], P = 0.003) emerged as independent predictors of cardiovascular mortality. After mutual adjustment, neutrophil count (HR [95% CI] = 1.87 [1.35, 2.50], P < 0.001) out-performed C-reactive protein (HR [95% CI] 1.32 [0.99, 1.78], P = 0.06) as a predictor of cardiovascular mortality.ConclusionsDue to its predictive potential and inexpensive determination, assessment of high neutrophil counts may represent an important marker, possibly improving cardiovascular mortality risk prediction.     

Five-year survival and prognostic factors in a cohort of hospitalized nonagenarians

BackgroundThe number of hospitalized nonagenarians is increasing. Only a few studies have evaluated long-term predictors of survival in these patients. The aim of this study was to determine the 5-year outcome of a cohort of hospitalized nonagenarians, and to identify predictors of long-term survival.MethodsIn 124 consecutive medical hospitalized patients older than 89 years, and followed up during 5 years, the following variables were prospectively recorded: sociodemographic characteristics, main diagnoses, Charlson comorbidity index, Barthel index, Lawton–Brody test, Mini-Mental State Examination, Short Portable Mental Status Questionnaire of Pfeiffer, Mini Nutritional Assessment, albumin levels, and the 5-year survival.ResultsOut of the 124 patients, 109 died (87.9%) during the follow-up. The probability of being alive at 1, 3 and 5 years was 45%, 22% and 12%, respectively. A worse 5-year survival was significantly related to the diagnoses of pneumonia (p = 0.037), heart failure (p = 0.045), higher Charlson index (p = 0.026), poorer functional status measured by the Barthel index (p = 0.003), and the Lawton–Brody test (p = 0.007), cognitive impairment measured by the Pfeiffer test (p = 0.011), and lower levels of albumin (p = 0.028). In the multivariate analysis, the Charlson index (p < 0.001), and the Barthel index (p = 0.003) were independently related to 5-year survival. These two variables were also 5-year survival prognostic factors in the subgroup of discharged patients. A prognostic index using these two variables was created: PI = (0.2 × Charlson index + 0.6 × Barthel index) × 0.92.ConclusionsIn hospitalized nonagenarian patients, poor scores in the Barthel Index and a higher comorbidity evaluated by the Charlson index are independently related to 5-year survival.     

Prognostic value of serum cystatin C and N-terminal pro b-type natriuretic peptide in patients with acute heart failure

BackgroundCystatin C (CysC) is a good prognostic marker in heart failure. However, there is not much information of CysC combined with other biomarkers in acute heart failure (AHF).AimTo assess prognostic value of CysC and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients hospitalized for AHF with no apparent deterioration of renal function.DesignProspective, multicenter, observational study.MethodsCysC and NTpro-BNP were measured in patients consecutively admitted with a diagnosis of AHF. Patients with, NTpro-BNP concentration above 900 pg/mL and serum creatinine below 1.3 mg/dL, were included for statistical analysis. End-point of the study was all-cause mortality during a 12-month follow-up.Results526 patients with AHF and NTpro-BNP concentration above 900 pg/mL were included in the study. From this group, 367 patients (69.8%) had serum creatinine below 1.3 mg/dL. Receiver operating characteristic (ROC) curves were used to determine the best cut-off value for CysC. Patients with a concentration of CsyC above 1.25 mg/dL had a 37.8% mortality rate, vs. 13.6% for those below cut-off (p < 0.001). After Cox proportional hazard model, age, CysC, low total cholesterol and HF with preserved ejection fraction remained significantly associated with all-cause mortality during one-year follow-up.ConclusionsIn AHF and normal or slightly impaired renal function, performance of CysC may be superior to NT-proBNP. Hence, CysC may be the preferred biomarker in the assessment of patients with AHF and slightly impaired renal function.     

Hypoglycemia-associated mortality is not drug-associated but linked to comorbidities

ObjectiveAlthough tight glucose control is used widely in hospitalized patients, there is concern that medication-induced hypoglycemia may worsen patient outcomes. We sought to determine if the mortality risk associated with hypoglycemia in hospitalized noncritically ill patients is linked to glucose-lowering medications (drug-associated hypoglycemia) or merely an association mediated by comorbidities (spontaneous hypoglycemia).MethodsA retrospective cohort of patients admitted to the general wards of an academic center during 2007 was studied. The in-hospital mortality risk of a hypoglycemic group (at least 1 blood glucose ≤ 70 mg/dL) was compared with that of a normoglycemic group using survival analysis. Stratification by subgroups of patients with spontaneous and drug-associated hypoglycemia was performed.ResultsAmong 31,970 patients, 3349 (10.5%) had at least 1 episode of hypoglycemia. Patients with hypoglycemia were older, had more comorbidities, and received more antidiabetic agents. Hypoglycemia was associated with increased in-hospital mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.33-2.09; P < .001). However, this greater risk was limited to patients with spontaneous hypoglycemia (HR, 2.62; 95% CI, 1.97-3.47; P < .001) and not to patients with drug-associated hypoglycemia (HR, 1.06; 95% CI, 0.74-1.52; P = .749). After adjustment for patient comorbidities, the association between spontaneous hypoglycemia and mortality was eliminated (HR, 1.11; 95% CI, 0.76-1.64; P = .582).ConclusionDrug-associated hypoglycemia was not associated with increased mortality risk in patients admitted to the general wards. The association between spontaneous hypoglycemia and mortality was eliminated after adjustment for comorbidities, suggesting that hypoglycemia may be a marker of disease burden rather than a direct cause of death.     

A study in three European IBD cohorts confirms that the ATG16L1 c.898A > G (p.Thr300Ala) variant is a susceptibility factor for Crohn’s disease

Background and aimsA recent study reported that a nonsynonymous SNP rs2241880 (c.898A > G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A > G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands.MethodsIn total, we included 910 European IBD patients and compared the ATG16L1 c.898A > G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n = 310; ulcerative colitis [UC] n = 179), Hungary (CD n = 147; UC n = 117), and the Netherlands (CD n = 157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics.ResultsWe found a highly significant association of c.898A > G to CD. The association was significant (p = 0.0005) for the total CD cohort but also for the individual populations from Germany (p = 0.02) and Netherlands (p = 0.02) whereas in the Hungarian CD patients a clear trend was observed (p = 0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A > G and UC. No statistical interactions were observed between ATG16L1 c.898A > G and CARD15 variants. Furthermore no association to a CD subphenotype was detected.ConclusionsWe confirm that ATG16L1 variant c898A > G confers a risk variant for CD but is not associated with a distinct CD phenotype.     

Predictors of Acute Renal Dysfunction After Ventricular Assist Device Placement

BackgroundAcute renal dysfunction (ARD) is a frequent complication after ventricular assist device (VAD) implantation. The purpose was to identify predictors associated with ARD after VAD implantation.Methods and ResultsARD was defined using the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, end-stage kidney disease (RIFLE) criteria. Patients who developed ARD during VAD support (ARD, n = 24) were compared with patients who did not (NoARD, n = 29). Patients with ARD before implant were excluded. Patient characteristics pre-VAD implant, incidence of complications during support and survival were analyzed. Baseline characteristics were similar. The ARD group had longer cardiopulmonary bypass (CPB) time, greater need for reoperation and higher risk of bleeding (>1 L) intraoperatively (P < .05). The ARD group had a higher incidence of infections (17% vs. 50%, OR 5, 95%CI 1.3-17), liver injury (58% vs. 17%, OR 7, 95%CI 2-24), ventricular arrhythmias (42% vs. 14%, OR 4, 95%CI 1.1-16), and right ventricular failure (73% vs. 30%, OR 7, 95%CI 2-24). Need for dialysis was associated with higher pre-VAD creatinine and worse outcomes. Survival was significantly lower in the ARD group (HR 8.5, 95%CI 2-29).ConclusionsAcute renal dysfunction is a common and serious complication post-VAD implantation and is associated with reduced survival. Longer CPB time, higher intraoperative blood loss, and reoperation are associated factors with the development of this disease.