Very Long-Term Prognostic Role of Admission BNP in Non-ST Segment Elevation Acute Coronary Syndrome

Background

BNP has been extensively evaluated to determine short- and intermediate-term prognosis in patients with acute coronary syndrome, but its role in long-term mortality is not known.

Objective

To determine the very long-term prognostic role of B-type natriuretic peptide (BNP) for all-cause mortality in patients with non-ST segment elevation acute coronary syndrome (NSTEACS).

Methods

A cohort of 224 consecutive patients with NSTEACS, prospectively seen in the Emergency Department, had BNP measured on arrival to establish prognosis, and underwent a median 9.34-year follow-up for all-cause mortality.

Results

Unstable angina was diagnosed in 52.2%, and non-ST segment elevation myocardial infarction, in 47.8%. Median admission BNP was 81.9 pg/mL (IQ range = 22.2; 225) and mortality rate was correlated with increasing BNP quartiles: 14.3; 16.1; 48.2; and 73.2% (p < 0.0001). ROC curve disclosed 100 pg/mL as the best BNP cut-off value for mortality prediction (area under the curve = 0.789, 95% CI= 0.723-0.854), being a strong predictor of late mortality: BNP < 100 = 17.3% vs. BNP ≥ 100 = 65.0%, RR = 3.76 (95% CI = 2.49-5.63, p < 0.001). On logistic regression analysis, age >72 years (OR = 3.79, 95% CI = 1.62-8.86, p = 0.002), BNP ≥ 100 pg/mL (OR = 6.24, 95% CI = 2.95-13.23, p < 0.001) and estimated glomerular filtration rate (OR = 0.98, 95% CI = 0.97-0.99, p = 0.049) were independent late-mortality predictors.

Conclusions

BNP measured at hospital admission in patients with NSTEACS is a strong, independent predictor of very long-term all-cause mortality. This study allows raising the hypothesis that BNP should be measured in all patients with NSTEACS at the index event for long-term risk stratification.     

Association of Fluid Overload with Cardiovascular Morbidity and All-Cause Mortality in Stages 4 and 5 CKD

Background and objectives

Fluid overload is a common characteristic associated with renal progression in CKD. Additionally, fluid overload is an independent predictor of all-cause or cardiovascular mortality in patients on dialysis, but its influence on patients not on dialysis is uncertain. The aim of the study was to assess the relationship between the severity of fluid status and clinical outcomes in an advanced CKD cohort.

Design, setting, participants, & measurements

In total, 478 predialysis patients with stages 4 and 5 CKD in the integrated CKD care program were enrolled from January of 2011 to December of 2011 and followed-up until August of 2013. The clinical outcomes included cardiovascular morbidity and all-cause mortality. The relative hydration status (overhydration/extracellular water) was used as the presentation of the severity of fluid status and measured using a body composition monitor. Overhydration/extracellular water >7% was defined as fluid overload.

Results

Over a median follow-up period of 23.2 (12.6–26.4) months, 66 (13.8%) patients reached all-cause mortality or cardiovascular morbidity. The adjusted hazard ratio of the combined outcome of all-cause mortality or cardiovascular morbidity for every 1% higher overhydration/extracellular water was 1.08 (95% confidence interval, 1.04 to 1.12; P<0.001). The adjusted overhydration/extracellular water for the combined outcome of all-cause mortality or cardiovascular morbidity in participants with overhydration/extracellular water ≥7% compared with those with overhydration/extracellular water <7% was 1.93 (95% confidence interval, 1.01 to 3.69; P=0.04). In subgroup analysis, higher overhydration/extracellular water was consistently associated with increased risk for the combined outcome independent of diabetes, cardiovascular disease, and serum albumin. There was no significant interaction between all subgroups.

Conclusions

These findings suggest that fluid overload is an independent risk factor of the combined outcome of all-cause mortality or cardiovascular morbidity in patients with advanced CKD.     

Association of Height with Mortality in Patients Undergoing Maintenance Hemodialysis

Background and objectives

Body mass index (BMI), determined as kilograms in body weight divided by the square of the height in meters (m²), is inversely associated with mortality in patients undergoing maintenance hemodialysis (MHD). It is commonly inferred that differences in the weight component of the BMI equation are responsible for this negative correlation. However, there are almost no data on the relationship between height and mortality in these patients. This study was conducted to examine the association between height and mortality in MHD patients and to evaluate the contribution of height to the BMI-mortality relationship.

Design, setting, participants, & measurements

A prospective study conducted from July 1, 2001, through June 30, 2006, enrolled a nationally representative cohort of 117,644 MHD patients receiving treatment in DaVita, Inc. outpatient dialysis facilities with (1) known height and weight, (2) age ≥18 years, (3) dialysis vintage ≥90 days, and (4) nonoutlying BMI values (≥12 to ≤60 kg/m²). The end date of follow-up was June 30, 2007, and median follow-up was 852 days (interquartile range, 504–1367 days). Mortality hazard ratios were computed within sex-standardized deciles of height and weight, and outcomes included all-cause mortality and cardiovascular, gastrointestinal, cancer, and infection mortality. Hazard models were unadjusted, adjusted for case-mix variables, or adjusted for case-mix variables plus laboratory variables.

Results

Mean age was 61±15 years; 45% of patients were women and 57% had diabetes. In adjusted models, height, also adjusted for weight, was directly associated with all-cause mortality and cardiovascular, infection, and cancer mortality. Compared with the median height decile, mortality risk in the highest height decile was 1.18 (95% confidence interval, 1.14 to 1.23) in fully adjusted analyses (P<0.001). Receiver-operating characteristic curves indicated that in adjusted analyses the contribution of height to the relationship between BMI and mortality was almost identical to that of weight.

Conclusions

In MHD patients, height is positively associated with mortality risk and contributes similarly to weight with regard to the negative BMI-mortality relationship.     

Age-Specific Association of Reduced Estimated Glomerular Filtration Rate and Albuminuria with All-Cause Mortality

Summary

Background and objectives

It has been suggested that reduced estimated GFR (eGFR) among older adults does not necessarily reflect a pathologic phenomenon.

Design, setting, participants, & measurements

We examined the association between eGFR and albumin-to-creatinine ratio (ACR) and all-cause mortality stratified by age (45 to 59.9, 60 to 69.9, 70 to 79.9, and ≥80 years) among 24,350 U.S. adults in the population-based REasons for Geographic and Racial Differences in Stroke (REGARDS) study. A spot urine sample was used to calculate ACR, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. All-cause mortality was assessed over a median follow-up of 4.5 years.

Results

Among participants ≥80 years of age (n = 1669), the age, race, gender, and geographic region of residence adjusted hazard ratios (95% confidence intervals) for mortality associated with eGFR levels of 45 to 59.9 and <45 ml/min per 1.73 m², versus ≥60 ml/min per 1.73 m², were 1.6 (1.3 – 2.1) and 2.2 (1.7 – 2.9), respectively. Also, among participants ≥80 years of age, the hazard ratios for mortality associated with ACR levels of 10 to 29.9, 30 to 299.9, and ≥300 mg/g, versus <10 mg/g, were 1.7 (1.3 – 2.1), 2.5 (1.9 – 3.3), and 5.1 (3.6 – 7.4), respectively. These associations were present after further multivariable adjustment and within the younger age groupings studied.

Conclusions

These data suggest that reduced eGFR and albuminuria confer an increased risk for mortality in all age groups, including adults ≥80 years of age.     

eGFR and Outcomes in Patients with Acute Decompensated Heart Failure with or without Elevated BUN

Background and objectives

In patients with heart failure, the association of renal dysfunction and BUN levels with outcomes is unclear. The aim of our study was to investigate the association between the eGFR at discharge and outcomes in patients with heart failure with or without an elevated BUN level at discharge.

Design, setting, participants, & measurements

Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes Registry, 4449 patients discharged alive after hospitalization for acute decompensated heart failure were investigated to assess the association of eGFR in the context of serum BUN level at discharge with all-cause mortality. The enrolled patients were divided into four groups on the basis of the discharge levels of eGFR (<45 or ≥45 ml/min per 1.73 m²) and BUN (≥25 or <25 mg/dl). The median follow-up period after discharge was 517 (381–776) days.

Results

The all–cause mortality rate after discharge was 19.1%. After adjustment for multiple comorbidities, an eGFR<45 ml/min per 1.73 m² was associated with a significantly higher risk of all-cause mortality in patients with a BUN≥25 mg/dl (hazard ratio, 1.58; 95% confidence interval, 1.33 to 1.88; P<0.001) but not in patients with a BUN<25 mg/dl (hazard ratio, 0.97; 95% confidence interval, 0.76 to 1.26; P=0.84) relative to those with an eGFR≥45 ml/min per 1.73 m² and a BUN<25 mg/dl. Among patients with an eGFR≥45 ml/min per 1.73 m², a BUN≥25 mg/dl was associated with a significantly higher risk of all-cause mortality than a BUN<25 mg/dl (hazard ratio, 1.34; 95% confidence interval, 1.04 to 1.73; P=0.02).

Conclusions

We showed that elevation of BUN at discharge significantly modified the relation between eGFR at discharge and the risk of all-cause mortality after discharge, suggesting that the association between eGFR and outcomes may be largely dependent on concomitant elevation of BUN.     

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

Background

Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice.

Objective

We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF).

Methods

Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up.

Results

105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03).

Conclusions

In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.     

The association between obesity and outcomes in critically ill patients

BACKGROUND:

Obesity rates are increasing worldwide, particularly in North America. The impact of obesity on the outcome of critically ill patients is unclear.

METHODS:

A prospective observational cohort study of consecutive patients admitted to a tertiary critical care unit in Canada between January 10, 2008 and March 31, 2009 was conducted. Exclusion criteria were age <18 years, admission <24 h, planned cardiac surgery, pregnancy, significant ascites, unclosed surgical abdomen and brain death on admission. Height, weight and abdominal circumference were measured at the time of intensive care unit (ICU) admission. Coprimary end points were ICU mortality and a composite of ICU mortality, reintubation, ventilator-associated pneumonia, line sepsis and ICU readmission. Subjects were stratified as obese or nonobese, using two separate metrics: body mass index (BMI) ≥30 kg/m² and a novel measurement of 75th percentile for waist-to-height ratio (WHR).

RESULTS:

Among 449 subjects with a BMI ≥18.5 kg/m², both BMI and WHR were available for comparative analysis in 348 (77.5%). Neither measure of obesity was associated with the primary end points. BMI ≥30 kg/m² was associated with a lower odds of six-month mortality than the BMI <30 kg/m² group (adjusted OR 0.59 [95% CI 0.36 to 0.97]; P=0.04) but longer intubation times (adjusted RR 1.56 [95% CI 1.17 to 2.07]; P=0.003) and longer ICU length of stay (adjusted RR 1.67 [95% CI 1.21 to 2.31]; P=0.002). Conversely, measurement of 75th percentile for WHR was associated only with decreased ICU readmission (OR 0.23 [95% CI 0.07 to 0.79]; P=0.02).

CONCLUSIONS:

Obesity was not necessarily associated with worse outcomes in critically ill patients.     

Glycemic Control and Survival in Peritoneal Dialysis Patients with Diabetes Mellitus

Summary

Background and objectives

The optimal target for glycemic control has not been established for diabetic peritoneal dialysis (PD) patients.

Design, setting, participants, & measurements

We examined mortality-predictability of hemoglobin A1c random serum glucose in a contemporary cohort of diabetic PD patients treated in DaVita dialysis clinics July 2001 through June 2006 with follow-up through June 2007.

Results

We identified 2798 diabetic PD patients with A1c data. Serum glucose correlated with A1C (r = 0.51). Adjusted all-cause death hazard ratio and 95% confidence interval for baseline A1c increments of 7.0 to 7.9%, 8.0 to 8.9%, 9.0 to 9.9%, and ≥10%, compared with 6.0 to 6.9% (reference), were 1.13 (0.97 to 1.32), 1.05 (0.88 to 1.27), 1.06 (0.84 to 1.34), and 1.48 (1.18 to 1.86); and for time-averaged A1c values were 1.10 (0.96 to 1.27), 1.28 (1.07 to 1.53), 1.34 (1.05 to 1.70), and 1.81 (1.33 to 2.46), respectively. The A1c-mortality association was modified by hemoglobin level such that higher all-cause mortality was evident only in nonanemic patients. Similar but non-significant trends in cardiovascular death risk was found across A1c increments. Adjusted all-cause death HR for time-averaged blood glucose 150 to 199, 200 to 249, 250 to 299, and ≥300 mg/dl, compared with 60 to 99 mg/dl (reference), were 1.02 (0.70 to 1.47), 1.12 (0.77 to 1.63), 1.45 (0.97 to 2.18), and 2.10 (1.37 to 3.20), respectively.

Conclusions

Poor glycemic control appears associated incrementally with higher mortality in PD patients. Moderate to severe hyperglycemia is associated with higher death risk especially in certain subgroups.     

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure

Introduction

Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF.

Objective

The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure.

Methods

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome.

Results

A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): −2.65 to −0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993).

Conclusion

Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed.     

Intravenous Iron Exposure and Mortality in Patients on Hemodialysis

Background and objectives

Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined.

Design, setting, participants, & measurements

The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding.

Results

Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150–350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0–150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46).

Conclusions

Among patients on incident dialysis, receipt of ≤1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.     

Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria Donors

Background and objectives

The quality and age of donor organs are known to have a major effect on patient and graft outcomes, but it is uncertain whether this association is uniform for all recipients. We aimed to determine whether the use of expanded criteria deceased donor (ECD) kidneys for transplantation compared with standard criteria deceased donor (SCD) kidneys has a different association with survival in younger (age <60 years old) compared with older (age ≥60 years old) recipients.

Design, setting, participants, & measurements

Using data from the Australian and New Zealand Dialysis and Transplant Registry (1997–2009), we compared the risk of all-cause mortality and death with functioning graft among younger and older recipients who had received either an SCD or an ECD kidney using the adjusted Cox proportional hazard models.

Results

In total, 3822 patients were transplanted between 1997 and 2009. Over a follow-up period of 21,249 person-years (a median duration of 5.3 years [interquartile range, 2.22–8.6 years]), 567 recipients (n=385 for those age <60 years old; n=182 for those age ≥60 years old) died. Recipient age was an effect modifier between donor types, all-cause mortality, and death with functioning graft (P values for interaction were 0.05 and 0.04, respectively). In younger recipients, there was an excess risk of all-cause mortality (adjusted hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.23 to 1.97) and death with functioning graft (adjusted HR, 1.72; 95% CI, 1.28 to 2.29) after transplantation with ECD kidneys compared with SCD kidneys, but there was no statistically significant association among older recipients (adjusted HR, 1.11; 95% CI, 0.80 to 1.54 and adjusted HR, 1.30; 95% CI, 0.89 to 1.89, respectively). This excess risk was largely caused by death from cardiovascular disease.

Conclusions

There was an excess risk of all-cause mortality and death with functioning graft when younger recipients were transplanted with ECD kidneys compared with SCD kidneys. These findings suggest that caution is needed in allocating ECD kidneys to younger recipients.     

Alkaline Phosphatase and Mortality in Patients on Peritoneal Dialysis

Background and objectives

Elevated total serum alkaline phosphatase levels have been associated with higher mortality in the general population, CKD patients, and hemodialysis patients. However, in peritoneal dialysis patients, this association has received little attention. The aim of this study was to evaluate the association between alkaline phosphatase and all-cause and cardiovascular mortality in peritoneal dialysis patients.

Design, setting, participants, & measurements

In this single center retrospective cohort study, 1021 incident peritoneal dialysis patients from January 1, 2006, to December 31, 2010 with baseline serum alkaline phosphatase values were enrolled. Collected baseline data included demographic characteristics and clinical and laboratory measurements. All patients were followed until December 31, 2012. The associations of total serum alkaline phosphatase levels with all-cause and cardiovascular mortality were assessed using multivariable-adjusted Cox models.

Results

Of 1021 patients, mean age was 47.5 (±15.5) years, 59.1% of patients were men, and 22.8% of patients were diabetic. The median serum alkaline phosphatase level was 64 U/L (interquartile range=52–82 U/L). During a median 31-month (interquartile range=19–45 months) follow-up period, 203 patients died, of which 109 deaths were caused by cardiovascular disease. After adjusting for demographics, comorbid conditions, liver function, and bone metabolism parameters, the highest alkaline phosphatase quartile was significantly associated with a hazard ratio for all-cause mortality of 1.70 (95% confidence interval, 1.06 to 2.74, P=0.03) and a hazard ratio for cardiovascular mortality of 1.94 (95% confidence interval, 1.02 to 3.72, P=0.04). Each 10 U/L higher baseline alkaline phosphatase level was associated with 4% (95% confidence interval, 1.00 to 1.08, P=0.04) and 7% (95% confidence interval, 1.02 to 1.11, P=0.003) higher risk of all-cause and cardiovascular mortality, respectively.

Conclusion

Higher total serum alkaline phosphatase levels at the commencement of peritoneal dialysis were independently associated with all-cause and cardiovascular mortality in peritoneal dialysis patients.     

Uric Acid Levels and All-Cause and Cardiovascular Mortality in the Hemodialysis Population

Summary

Background and objectives

Hyperuricemia is associated with hypertension, coronary artery disease, and chronic kidney disease. However, there are no specific data on the relationship of uric acid to cardiovascular disease in the chronic hemodialysis setting.

Design, setting, participants, & measurements

Data from 5827 patients on chronic hemodialysis from six countries affiliated with the Dialysis Outcomes and Practice Patterns Study (DOPPS) were analyzed. All laboratory data were based upon the initial cross-section of patients in DOPPS I and II. Cox regression was used to calculate the hazard ratio (HR) of all-cause and cardiovascular (CV) mortality with adjustments for case-mix including 14 classes of comorbidity.

Results

There were no clinically significant differences in baseline characteristics between those who had measured uric acid (n = 4637) and those who did not (n = 1190). Uric acid level was associated with lower all-cause mortality (HR: 0.95, 95% confidence interval [CI]: 0.90 to 1.00 per 1 mg/dl higher uric acid level) and CV mortality (HR: 0.92, 95% CI: 0.86 to 0.99). When analyzed as a dichotomous variable, the adjusted HR at uric acid ≤8.2 mg/dl compared with >8.2 mg/dl was 1.24 (95% CI: 1.03 to 1.49) for all-cause mortality and 1.54 (95% CI: 1.15 to 2.07) for CV mortality.

Conclusions

Higher uric acid levels were associated with lower risk of all-cause and CV mortality in the hemodialysis population. These results are in contrast to the association of hyperuricemia with higher cardiovascular risk in the general population and should be the subject of further research.     

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

Background and objectives

Novel markers may help to improve risk prediction in CKD. One potential candidate is tissue advanced glycation end product accumulation, a marker of cumulative metabolic stress, which can be assessed by a simple noninvasive measurement of skin autofluorescence. Skin autofluorescence correlates with higher risk of cardiovascular events and mortality in people with diabetes or people requiring RRT, but its role in earlier CKD has not been studied.

Design, setting, participants, & measurements

A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling for biochemistry, and measurement of skin autofluorescence. Kaplan–Meier plots and multivariate Cox proportional hazards models were used to investigate associations between skin autofluorescence (categorical in quartiles) and all-cause mortality.

Results

In total, 1707 participants had skin autofluorescence measured; 170 (10%) participants died after a median of 3.6 years of follow-up. The most common cause of death was cardiovascular disease (41%). Higher skin autofluorescence was associated significantly with poorer survival (all-cause mortality, P<0.001) on Kaplan–Meier analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed that the highest quartile of skin autofluorescence was associated with all-cause mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P<0.001 and hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively, compared with the lowest quartile). This association was not maintained after additional adjustment to include cardiovascular disease, diabetes, smoking, body mass index, eGFR, albuminuria, and hemoglobin.

Conclusions

Skin autofluorescence was not independently associated with all-cause mortality in this study. Additional research is needed to clarify whether it has a role in risk prediction in CKD.     

Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure

Background

Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.

Objective

We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.

Methods

Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.

Results

Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58–4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67–8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23–8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).

Conclusion

These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.     

Presence and Outcomes of Kidney Disease in Patients with Pulmonary Hypertension

Background and objectives

Pulmonary hypertension is associated with higher mortality rates. The associations of nondialysis-dependent CKD and all-cause mortality in patients with pulmonary hypertension were studied.

Design, setting, participants, & measurements

The study population included those patients who underwent right heart catheterization for confirmation of pulmonary hypertension between 1996 and January 2011. Pulmonary hypertension was defined as the presence of mean pulmonary artery pressure≥25 mmHg at rest measured by right heart catheterization. CKD was defined as the presence of two measurements of eGFR<60 ml/min per 1.73 m² 90 days apart. The risk factors associated with CKD as well as the association between CKD and death in those patients with pulmonary hypertension using logistic regression and Cox proportional hazard models were examined.

Results

Of 1088 patients with pulmonary hypertension, 388 (36%) patients had CKD: 340 patients had stage 3 CKD, and 48 (4%) patients had stage 4 CKD. In the multivariable analysis, older age, higher hemoglobin, and higher mean right atrial pressures were independently associated with CKD. During a median follow-up of 3.2 years (interquartile range=1.5–5.6 years), 559 patients died. After adjusting for relevant covariates, presence of stage 3 CKD (hazard ratio, 1.37; 95% confidence interval, 1.14 to 1.66) and stage 4 CKD (hazard ratio, 2.69; 95% confidence interval, 1.88 to 3.86) was associated with all-cause mortality in those patients with pulmonary hypertension. When eGFR was examined as a continuous measure, a 5 ml/min per 1.73 m² lower eGFR was associated with a 5% (95% confidence interval, 1.03 to 1.07) higher hazard for death. This higher risk with CKD was similar irrespective of demographics, left ventricular function, and pulmonary capillary wedge pressure.

Conclusion

In a clinical population referred for right heart catheterization, presence of CKD was associated with higher all-cause mortality in those patients with pulmonary hypertension. Mechanisms that may underlie these associations warrant additional studies.     

DISCORDANCE BETWEEN BODY MASS INDEX AND ANTHROPOMETRIC MEASUREMENTS AMONG HIV-1-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY AND WITH LIPOATROPHY/LIPOHYPERTROPHY SYNDROME

Introduction:

Highly Active Antiretroviral Therapy (HAART) has improved and extended the lives of thousands of people living with HIV/AIDS around the world. However, this treatment can lead to the development of adverse reactions such as lipoatrophy/lipohypertrophy syndrome (LLS) and its associated risks.

Objective:

This study was designed to assess the prevalence of self-reported lipodystrophy and nutritional status by anthropometric measurements in patients with HIV/AIDS.

Methods:

An observational study of 227 adult patients in the Secondary Immunodeficiencies Outpatient Department of Dermatology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo (3002 ADEE-HCFMUSP). The sample was divided into three groups; Group 1 = 92 patients on HAART and with self-reported lipodystrophy, Group 2 = 70 patients on HAART without self-reported lipodystrophy and Group 3 = 65 patients not taking HAART. The nutritional status of individuals in the study sample was determined by body mass index (BMI) and percentage of body fat (% BF). The cardiovascular risk and diseases associated with abdominal obesity were determined by waist/hip ratio (WHR) and waist circumference (WC).

Results:

The prevalence of self-reported lipoatrophy/lipohypertrophy syndrome was 33% among women and 59% among men. Anthropometry showed depletion of fat mass in the evaluation of the triceps (TSF) in the treatment groups with HAART and was statistically independent of gender; for men p = 0.001, and for women p = 0.007. Similar results were found in the measurement of skin folds of the upper and lower body (p = 0.001 and p = 0.003 respectively). In assessing the nutritional status of groups by BMI and % BF, excess weight and body fat were more prevalent among women compared to men (p = 0.726). The WHR and WC revealed risks for cardiovascular and other diseases associated with abdominal obesity for women on HAART and with self-reported LLS (p = 0.005) and (p = 0.011).

Conclusions:

Anthropometric measurements were useful in the confirmation of the prevalence of LLS. BMI alone does not appear to be a good parameter for assessing the nutritional status of HIV-infected patients on HAART and with LLS. Other anthropometric measurements are needed to evaluate patients with the lipoatrophy/lipohypertrophy syndrome.     

Determining respiratory system resistance and reactance by impulse oscillometry in obese individuals

Objective:

To evaluate peripheral respiratory system resistance and reactance (Rrs and Xrs, respectively) in obese individuals.

Methods:

We recruited 99 individuals, dividing them into four groups by body mass index (BMI): < 30.0 kg/m² (control, n = 31); 30.0-39.9 kg/m² (obesity, n = 13); 40.0-49.9 kg/m² (severe obesity, n = 28); and ≥ 50.0 kg/m² (morbid obesity, n = 13). Using impulse oscillometry, we measured total Rrs, central Rrs, and Xrs. Peripheral Rrs was calculated as the difference between total Rrs and central Rrs. All subjects also underwent spirometry.

Results:

Of the 99 individuals recruited, 14 were excluded because they failed to perform forced expiratory maneuvers correctly during spirometry. The individuals in the severe obesity and morbid obesity groups showed higher peripheral Rrs and lower Xrs in comparison with those in the two other groups.

Conclusions:

Having a BMI ≥ 40 kg/m² was associated with a significant increase in peripheral Rrs and with a decrease in Xrs.     

Peri-operative risk factors for delayed gastric emptying after a pancreaticoduodenectomy

Background

Delayed gastric emptying (DGE) is a frequent cause of morbidity, prolonged hospital stay and readmission after a pancreaticoduodenectomy (PD). We sought to evaluate predictive peri-operative factors for DGE after a PD.

Methods

Four hundred and sixteen consecutive patients who underwent a PD at our tertiary referral centre were identified. Univariate and multivariate (MV) logistic regression models were used to assess peri-operative factors associated with the development of clinically significant DGE and a post-operative pancreatic fistula (POPF).

Results

DGE occurred in 24% of patients (n = 98) with Grades B and C occurring at 13.5% (n = 55) and 10.5% (n = 43), respectively. Using MV regression, a body mass index (BMI) ≥35 [odds ratio (OR) = 3.19], operating room (OR) length >5.5 h (OR = 2.72) and prophylactic octreotide use (OR = 2.04) were independently associated with an increased risk of DGE. DGE patients had a significantly longer median hospital stay (12 versus 7 days), higher 90-day readmission rates (32% versus 18%) and an increased incidence of a pancreatic fistula (59% versus 27%). When controlling for POPF, only OR length >5.5 h (OR 2.73) remained significantly associated with DGE.

Conclusions

DGE remains a significant cause of morbidity, increased hospital stay and readmission after PD. Our findings suggest patients with a BMI ≥35 or longer OR times have a higher risk of DGE either independently or through the development of POPF. These patients should be considered for possible enteral feeding tube placement along with limited octreotide use to decrease the potential risk and consequences of DGE.     

Associations of Posthemodialysis Weights above and below Target Weight with All-Cause and Cardiovascular Mortality

Background and objectives

Fluid removal via ultrafiltration is a primary function of hemodialysis, and inadequate volume control is associated with significant morbidity and mortality among chronic dialysis patients. Treatment-to-treatment fluid removal goals are typically calculated on the basis of interdialytic weight gain and prescribed target weight. The clinical effect of frequent missed target weights is unclear. This study was designed to evaluate the associations of postdialysis weights above and below the prescribed target weight (separately) and outcomes.

Design, setting, participants, & measurements

Data were taken from a national cohort of 10,785 prevalent, thrice-weekly, in-center hemodialysis patients dialyzing from 2005 to 2008 (median time at risk, 2.1 [25th percentile, 75th percentile] years) at a single dialysis organization. Patients were characterized as having an above target weight miss if their postdialysis weight was >2 kg above target weight in at least 30% of baseline treatments (14.6% of cohort), or they were characterized as control otherwise. Below target weight miss characterization was analogous for patients with postdialysis weight >2 kg below target weight (6.6% of cohort). Coprimary endpoints were all-cause and cardiovascular mortality.

Results

Above target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.28; 95% confidence interval, 1.15 to 1.43); and below target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05 to 1.40). Both above and below target weight misses were also significantly associated with greater cardiovascular mortality. Secondary analyses demonstrated dose-response relationships between target weight misses and mortality. Results from sensitivity analyses considering the difference in postdialysis and target weights as a proportion of body weight were analogous to the primary results.

Conclusions

Postdialysis weights >2 kg above and below target weight are associated with higher all-cause and cardiovascular mortality. Consistent target weight achievement is a viable target for improving fluid management.