Serum sclerostin is an independent predictor of mortality in hemodialysis patients

Background

Sclerostin (Scl) has recently emerged as a novel marker of bone remodeling and vascular calcification. However, whether high circulating Scl is also a risk factor for death is not well established. The purpose of this study was to test whether serum Scl would be associated with mortality.

Methods

we measured serum Scl in a hemodialysis patients’ cohort, which was followed during a ten-year period. Competing risk regression models were applied, as during the follow-up, patients were exposed to both events kidney transplant and death.

Results

Ninety-one patients aged 42.3?±?18.8 years (55% of male gender, 15% of diabetes) were included. During the follow-up, 32 patients underwent kidney transplant and 26 patients died. Non-survivals presented higher FGF23, higher Scl and lower creatinine. There was an association between all-cause mortality and higher Scl (HR =?2.2), higher age (HR =?1.04) and presence of diabetes (HR =?2.27), by competing risk analyses. Even including potential markers of mortality, as creatinine, FGF 23, and gender, Scl, age and diabetes remained significantly related to higher mortality.

Conclusion

Serum Scl is an independent predictor of mortality in dialysis patients. However, whether clinical interventions to modulate Scl would be able to improve these patients survival needs to be determined.

     

Hyponatraemia is an independent predictor of in-hospital mortality

BackgroundHyponatraemia increases morbidity and mortality, but the extent to which this condition influences mortality independently of other contributing factors is unclear.Materials and methodsAll hyponatremic patients admitted to the internal medicine department during a six month period were included. Medical records were reviewed and patients' demographics, underlying disease, cause of hyponatremia and in-hospital deaths were noted. Control group consisted of patients with normonatremia admitted to the same department during the same period matched 1:1 by sex, age and underlying disease. Difference in in-hospital mortality rate between the study and control groups was tested by chi-square test. Baseline demographics, underlying diseases, cause of hyponatremia and state of hyponatremia correction as possible risk factors for mortality were tested in a multivariate analysis.ResultsThe baseline cohort of all admitted patients consisted of 2171 patients. Hyponatraemia was found in 278 (13%) patients (160 females and 118 males). The three most common causes of hyponatremia included gastrointestinal loss (52 patients), decreased oral intake (47 patients), and dilution hyponatremia (45 patients). The in-hospital mortality rate in the hyponatremic group was significantly higher compared with the control group (22% vs 7%, respectively; OR 3.75, 95% CI 2.17–6.48, p < 0.0001). In a multivariate analysis age above 65 years, dilution hyponatremia, decreased oral intake as etiologic factors of hyponatremia, and unsuccessful hyponatremia correction were independent factors associated with increased mortality.ConclusionHyponatraemia represents independent factor associated with in-hospital mortality. Age above 65 years, failure to correct hyponatremia and some specific etiologic factors of hyponatremia are related to increased mortality.     

Thrombocytopenia is an independent predictor of mortality in pulmonary hypertension

BackgroundEstablished prognostic factors for pulmonary hypertension (PH) include brain natriuretic peptide, troponins and hemodynamic measures such as central venous pressure and cardiac output. The prognostic role of thrombocytopenia, however, has yet to be determined in patients with PH. The aim of this study was to evaluate effect of thrombocytopenia on mortality in patients with PH.Methods521 patients with severe PH, defined by a pulmonary artery systolic pressure >60 mm Hg on transthoracic echocardiography and a platelet count measured within one month after diagnosis were enrolled from three hospitals of Montefiore Medical Center. The cohort was divided into two groups: mild thrombocytopenia to a normal platelet count (platelet count 100,000–450,000 per uL); and moderate to severe thrombocytopenia (platelet count <100,000 per uL). Inpatient and social security death records were used to determine 1-year all-cause mortality.ResultsMean age was 70.3 ± 15.6 with 40% of patients being male. Overall mortality at 1 year was 30.7%, with increased mortality in PH patients with mild thrombocytopenia compared to those with moderate to severe thrombocytopenia (46.5% vs. 27.0%, p < 0.001). In multivariate analysis, moderate to severe thrombocytopenia remained an independent predictor of mortality (HR 1.798, 95% CI 1.240–2.607, p = 0.002).ConclusionsModerate to severe thrombocytopenia is an independent predictor of higher mortality in patients with severe PH. These findings may support the use of thrombocytopenia as a useful prognostic indicator in patients with severe PH.     

Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients

Although various studies reported that pulse pressure, an indirect index of arterial stiffening, was an independent risk factor for mortality, a direct relationship between arterial stiffness and all-cause and cardiovascular mortality remained to be established in patients with essential hypertension. A cohort of 1980 essential hypertensive patients who attended the outpatient hypertension clinic of Broussais Hospital between 1980 and 1996 and who had a measurement of arterial stiffness was studied. At entry, aortic stiffness was assessed from the measurement of carotid-femoral pulse-wave velocity (PWV). A logistic regression model was used to estimate the relative risk of all-cause and cardiovascular deaths. Selection of classic risk factors for adjustment of PWV was based on their influence on mortality in this cohort in univariate analysis. Mean age at entry was 50+/-13 years (mean+/-SD). During an average follow-up of 112+/-53 months, 107 fatal events occurred. Among them, 46 were of cardiovascular origin. PWV was significantly associated with all-cause and cardiovascular mortality in a univariate model of logistic regression analysis (odds ratio for 5 m/s PWV was 2.14 [95% confidence interval, 1.71 to 2.67, P<0.0001] and 2.35 [95% confidence interval, 1.76 to 3.14, P<0.0001], respectively). In multivariate models of logistic regression analysis, PWV was significantly associated with all-cause and cardiovascular mortality, independent of previous cardiovascular diseases, age, and diabetes. By contrast, pulse pressure was not significantly and independently associated to mortality. This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.     

A low level of CD4+CD28+ T cells is an independent predictor of high mortality in human immunodeficiency virus type 1-infected patients

This study investigated coexpression of CD28, CD45RA, and CD45RO on CD4(+) and CD8(+) cells in 107 human immunodeficiency virus (HIV) type 1-infected patients, who were followed-up prospectively and were not treated with highly active antiretroviral therapy, and 65 control subjects. The most important novel finding was that a 50% reduction in CD4(+)CD28(+) cells predicted increased mortality (relative hazards [HR], 1.6; 95% confidence interval [CI], 1.0-2.6; P=.04), even after adjusting for the CD4(+) cell counts, virus load, beta(2)-microglobulin and hemoglobin levels, and HIV disease stage. Patients with progressed HIV infection had decreased concentrations of all studied cell subsets. Concerning the proportions of cells, only CD4(+)CD28(+), CD4(+)CD45RA(+), and CD8(+)CD45RO(+) cells decreased with HIV progression. Low proportions of CD4(+)CD45RA(+), CD8(+)CD45RA(+), and CD8(+)CD45RO(+) cells predicted mortality only in univariate but not in multivariate Cox analyses. If our results are confirmed in other studies, coexpression of CD28 on CD4(+) cells may be a useful marker to evaluate HIV progression.     

Anemia is an independent predictor of mortality after percutaneous coronary intervention

OBJECTIVES: The aim of the present study was to assess whether anemia is a marker of increased risk during interventional procedure and poor midterm survival after percutaneous coronary intervention (PCI). BACKGROUND: Anemia is associated with increased risk of mortality in patients with heart failure and myocardial infarction (MI). METHODS: We examined the outcomes of 6,116 consecutive PCI patients based on the hemoglobin (Hb) value before the interventional procedure. Patients were divided into three groups based on the baseline Hb level (g/l): Hb <10 = severe anemia; Hb 10 to 12 = mild anemia; Hb >12 = no anemia. RESULTS: The presence of anemia is associated with higher 30-day major adverse cardiac events, post-PCI peak troponin and creatine kinase-MB fraction, and a longer length of stay. After controlling for multiple covariates, significant difference in one-year survival was noted in the anemic groups compared with no anemia group (adjusted hazard ratio for Hb 10 to 12: 1.5 [95% confidence interval 1.3 to 1.8]; for Hb <10: 1.8 [95% confidence interval 1.3 to 2.3]; p = 0.004.) This adverse effect of anemia on survival was noted in all three presenting clinical syndromes (stable angina, unstable angina, and MI). CONCLUSIONS: Anemia is an independent predictor of mortality after PCI and is associated with higher short-term adverse procedural events.     

The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure.

AIM: Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF. METHODS AND RESULTS: We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P=0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, low blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR=1.85 per %, P=0.008), elevated pro-BNP levels (HR=9.35 per log[pro-BNP], P=0.001), and low blood pressure (HR=0.96 per mmHg, P=0.041) remained as independent predictors of death. CONCLUSION: In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF.     

Renal insufficiency is an independent predictor of mortality after percutaneous coronary intervention

The present study was designed to evaluate whether the presence of renal disease during percutaneous coronary intervention (PCI) is associated with worse outcomes at 1 year in a multicenter study. The incidence of death, myocardial infarction, coronary artery bypass grafting, repeat PCI, and repeat revascularization were prospectively collected on 4,602 patients (6,542 lesions) in 2 waves of patients who underwent PCI in 17 centers between July 1997 and June 1999. Renal disease was defined as the presence of an increased creatinine level in a patient with a history or presence of renal failure treated with low protein diet or dialysis. Patients with renal disease (n = 192) were older and more likely to have diabetes, heart failure, reduced ejection fraction, known coronary disease, and multivessel disease than patients without renal disease (n = 4,410). Rates of stenting were equivalent (68.2% vs 73.0%, p = NS). Patients with renal disease had lower angiographic success (84.9% vs 92.8%, p <0.001) and higher mortality, both in-hospital (5.7% vs 1.2%, p <0.001) and at 1 year (19.7% vs 4.4%, p <0.0001). After adjusting for clinical, demographic, and angiographic differences, renal disease remained an independent predictor of in-hospital (odds ratio 3.81, 95% confidence interval 1.70 to 8.58) and 1-year (risk ratio 2.46, 95% confidence interval 1.64 to 3.68) mortality. Renal disease conferred additional mortality risk in established high-risk clinical subgroups. In conclusion, after adjusting for a higher frequency of co-morbidities, renal disease remains a strong and independent predictor of increased in-hospital and 1-year mortality after PCI and is additive to other clinical markers of worse outcome.     

Low CD4+ T cell nadir is an independent predictor of lower HIV-specific immune responses in chronically HIV-1-infected subjects receiving highly active antiretroviral therapy

The influence of CD4(+) T cell nadirs on human immunodeficiency virus (HIV)-specific immune responses in subjects with apparently normal CD4(+) T cell counts is not known. We evaluated the frequency of HIV-1-specific immune responses in a cohort of patients with complete viral suppression (HIV-1 RNA load, <50 copies/mL) who were receiving highly active antiretroviral therapy and had a wide range of CD4(+) T cell nadirs. We found positive associations between CD4(+) T cell nadirs and the magnitude of HIV-specific CD8(+) T cell responses (P=.02) and of T cell helper responses (P=.04). These data show the CD4(+) T cell nadir to be an independent predictor of HIV-specific CD4(+) and CD8(+) T cell responses in HIV-1-infected subjects with optimal suppression of viremia.     

Serum cholesterol is a significant and independent mortality predictor in liver cirrhosis patients

Background and Aim. Accurate assessment of cirrhotic patient’s prognosis is essential for decisions regarding the course of treatment. Therefore we aimed to confirm and quantify the predictive value of serum cholesterol and serum triglycerides in liver cirrhosis patients.Material and methods. We performed a retrospective observational cohort study on consecutive patients with liver cirrhosis (n = 191). Relevant clinical and laboratory variables were obtained from patients‘ charts and patients were followed for two months. Mortality was the main outcome.Results. Thirty-eight patients died in the follow-up period. Significant difference was observed in the level of total serum cholesterol between surviving and deceased patients (2.27 ± 1.02 mmol/L vs. 2.97 ± 1.00 mmol/L, P < 0.0001 respectively). Cholesterol was confirmed as a significant predictor of mortality in univariate logistic regression analysis, and independent predictor beside bilirubin, creatinine and MELD score in multivariate logistic regression analysis. Addition of serum cholesterol level to a prognostic model based on total bilirubin, creatinine and INR increased its accuracy by 4%. Adding cholesterol to the MELD score improved prediction accuracy by 3%. There was no significant difference in serum levels of triglycerides between surviving and deceased patients.Conclusion. Serum cholesterol is a routinely measured parameter, which has independent prognostic value in patients with liver cirrhosis.