Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

Background

The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population.

Objective

To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality.

Methods

Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed.

Results

GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016).

Conclusion

Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients.     

Systemic Inflammation Predicts All-Cause Mortality: A Glasgow Inflammation Outcome Study

Introduction

Markers of the systemic inflammatory response, including C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score), as well as neutrophil, lymphocyte and platelet counts have been shown to be prognostic of survival in patients with cancer. The aim of the present study was to examine the prognostic relationship between these markers of the systemic inflammatory response and all-cause, cancer, cardiovascular and cerebrovascular mortality in a large incidentally sampled cohort.

Methods

Patients (n = 160 481) who had an incidental blood sample taken between 2000 and 2008 were studied for the prognostic value of C-reactive protein (>10mg/l, albumin (>35mg/l), neutrophil (>7.5×10⁹/l) lymphocyte and platelet counts. Also, patients (n = 52 091) sampled following the introduction of high sensitivity C-reactive protein (>3mg/l) measurements were studied. A combination of these markers, to make cumulative inflammation-based scores, were investigated.

Results

In all patients (n = 160 481) C-reactive protein (>10mg/l) (HR 2.71, p<0.001), albumin (>35mg/l) (HR 3.68, p<0.001) and neutrophil counts (HR 2.18, p<0.001) were independently predictive of all-cause mortality. These associations were also observed in cancer, cardiovascular and cerebrovascular mortality before and after the introduction of high sensitivity C-reactive protein measurements (>3mg/l) (n = 52 091). A combination of high sensitivity C-reactive protein (>3mg/l), albumin and neutrophil count predicted all-cause (HR 7.37, p<0.001, AUC 0.723), cancer (HR 9.32, p<0.001, AUC 0.731), cardiovascular (HR 4.03, p<0.001, AUC 0.650) and cerebrovascular (HR 3.10, p<0.001, AUC 0.623) mortality.

Conclusion

The results of the present study showed that an inflammation-based prognostic score, combining high sensitivity C-reactive protein, albumin and neutrophil count is prognostic of all-cause mortality.     

Free Levels of Selected Organic Solutes and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Results from the Retained Organic Solutes and Clinical Outcomes (ROSCO) Investigators

Background and Objectives

Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney — p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine — with outcomes in hemodialysis patients.

Design, Setting, Participants and Measurements

We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/V_UREA.

Results

Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17–2.25; p=0.004) and first cardiovascular event (1.60; 1.23–2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18–1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05–3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12–2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses.

Conclusions

Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.     

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives

Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.

Methods

We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).

Results

Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67–0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74–0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70–0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66–0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76–0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74–0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71–0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77–0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74–0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.

Conclusion

Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.     

Nucleated Red Blood Cells as Predictors of All-Cause Mortality in Cardiac Intensive Care Unit Patients: A Prospective Cohort Study

Background

The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients.

Methods

NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality.

Results

We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4–11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45–10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63–6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01).

Conclusions

NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score.     

Sagittal Abdominal Diameter Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Incident Peritoneal Dialysis Patients

Backgrounds and Aims

Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients.

Methods

We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients.

Results

The mean SAD was 24.5±4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514–7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005–1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994–32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007–1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m²).

Conclusions

SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients.     

Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in South-East Asian Patients with End-Stage Renal Disease

Background

Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore.

Methods

Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005–2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease.

Results

After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67–2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30–2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (≤65 years old) without diabetes or cardiovascular disease.

Conclusion

ESRD patients who initiated dialysis with HD experienced better survival outcomes than those who initiated dialysis with PD in Singapore, although survival outcomes may not differ between the two dialysis modalities in young and healthier patients. These findings are potentially confounded by selection bias, as patients were not randomized to the two dialysis modalities in this cohort study.     

Diabetic Patients Could Do As Well as Non-Diabetic Patients without Inflammation on Peritoneal Dialysis

Background

Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients.

Methods

Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions.

Results

Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared.

Conclusion

Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD.     

Care Needs and Clinical Outcomes of Older People with Dementia: A Population-Based Propensity Score-Matched Cohort Study

Objective

To explore the healthcare resource utilization, psychotropic drug use and mortality of older people with dementia.

Design

A nationwide propensity score-matched cohort study.

Setting

National Health Insurance Research database.

Participants

A total of 32,649 elderly people with dementia and their propensity-score matched controls (n=32,649).

Measurements

Outpatient visits, inpatient care, psychotropic drug use, in-hospital mortality and all-cause mortality at 90 and 365 days.

Results

Compared to the non-dementia group, a higher proportion of patients with dementia used inpatient services (1 year after index date: 20.91% vs. 9.55%), and the dementia group had more outpatient visits (median [standard deviation]: 7.00 [8.87] vs. 3.00 [8.30]). Furthermore, dementia cases with acute admission had the highest psychotropic drug utilization both at baseline and at the post-index dates (difference-in-differences: all <0.001). Dementia was associated with an increased risk of all-cause mortality (90 days, Odds ratio (OR)=1.85 [95%CI 1.67-2.05], p<0.001; 365 days, OR=1.59 [1.50-1.69], p<0.001) and in-hospital mortality (90 days, OR=1.97 [1.71-2.27], p<0.001; 365 days, OR=1.82 [1.61-2.05], p<0.001) compared to matched controls.

Conclusions

When older people with dementia are admitted for acute illnesses, they may increase their use of psychotropic agents and their risk of death, particularly in-hospital mortality.     

Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients

Background

Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD patients.

Methods

A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all-cause, cardiovascular, or infection-related mortality and hospitalization.

Results

During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55–3.69, P<0.001), cardiovascular mortality (HR 2.14, 95% CI, 1.07–4.26, P = 0.031) and infection-related mortality (HR 3.07, 95% CI, 1.30–7.25, P = 0.011) using tertile 1 as the reference group after adjusting for clinical variables including liver diseases. The highest tertile also had a significantly higher risk for first hospitalization (HR 1.22, 95% CI, 1.00–1.48, P = 0.048) and cardiovascular hospitalization (HR 1.42, 95% CI, 1.06–1.92, P = 0.028).

Conclusions

Our data demonstrate that high serum GGT levels were an independent risk factor for all-cause, cardiovascular, and infection-related mortality, as well as cardiovascular hospitalization in HD patients. These findings suggest that serum GGT levels might be a useful biomarker to predict clinical outcomes in HD patients.     

Pre-Dialysis Visits to a Nephrology Department and Major Cardiovascular Events in Patients Undergoing Dialysis

Background and Objectives

Pre-dialysis care by a nephrology out-patient department (OPD) may affect the outcomes of patients who ultimately undergo maintenance dialysis. This study examined the effect of pre-dialysis care by a nephrology OPD on the incidence of one-year major cardiovascular events after initiation of dialysis.

Design, Setting Participants, & Measurements

The study consisted of Taiwanese patients with chronic kidney disease (CKD) who commenced dialysis from 2006 to 2008. The number of nephrology OPD visits during the critical care period (within 6 months of initiation of dialysis) and the early care period (6–36 months before initiation of dialysis) were analyzed. The primary outcome measure was one-year major cardiovascular events.

Results

A total of 1191 CKD patients who initiated dialysis from 2006 to 2008 were included. Binary logistic regression showed that patients with ≧3 visits during the critical care period and those with ≧11 visits during the early care period had fewer composite major cardiovascular events than those with 0 visits. Patients with early referral are less likely to experience composite major cardiovascular events than those with late referral, with aOR 0.574 (95% CI = 0.43–0.77, P<0.001). Patients with both ≧3 visits during critical care period and ≧11 visits during early care period were less likely to experience composite major cardiovascular events (aOR = 0.25, 95% CI = 0.16–0.39, P < 0.001).

Conclusions

Patients with adequate pre-dialysis nephrology OPD visits, not just early referral, may had fewer one-year composite major cardiovascular events after initiation of dialysis. This information may be important to medical care providers and public health policy makers in their efforts to improve the well-being of CKD patients.     

Serum Potassium Levels and Its Variability in Incident Peritoneal Dialysis Patients: Associations with Mortality

Background

Abnormal serum potassium is associated with an increased risk of mortality in dialysis patients. However, the impacts of serum potassium levels on short- and long-term mortality and association of potassium variability with death in peritoneal dialysis (PD) patients are uncertain.

Methods

We examined mortality-predictability of serum potassium at baseline and its variability in PD patients treated in our center January 2006 through December 2010 with follow-up through December 2012. The hazard ratios (HRs) were used to assess the relationship between baseline potassium levels and short-term (≤1 year) as well as long-term (>1 year) survival. Variability of serum potassium was defined as the coefficient of variation of serum potassium (CVSP) during the first year of PD.

Results

A total of 886 incident PD patients were enrolled, with 248 patients (27.9%) presented hypokalemia (serum potassium <3.5 mEq/L). During a median follow-up of 31 months (range: 0.5–81.0 months), adjusted all-cause mortality hazard ratio (HR) and 95% confidence interval (CI) for baseline serum potassium of <3.0, 3.0 to <3.5, 3.5 to <4.0, 4.5 to <5.0, and ≥5.0 mEq/L, compared with 4.0 to <4.5 (reference), were 1.79 (1.02–3.14), 1.15 (0.72–1.86), 1.31 (0.82–2.08), 1.33 (0.71–2.48), 1.28 (0.53–3.10), respectively. The increased risk of lower potassium with mortality was evident during the first year of follow-up, but vanished thereafter. Adjusted all-cause mortality HR for CVSP increments of 7.5% to <12.0%; 12.0% to <16.7% and ≥16.7%, compared with <7.5% (reference), were 1.35 (0.67–2.71), 2.00 (1.05–3.83) and 2.18 (1.18–4.05), respectively. Similar association was found between serum potassium levels and its variability and cardiovascular mortality.

Conclusions

A lower serum potassium level was associated with all-cause and cardiovascular mortality during the first year of follow-up in incident PD patients. In addition, higher variability of serum potassium levels conferred an increased risk of death in this population.     

Serum Levels of Monocyte Chemoattractant Protein-1 and All-Cause and Cardiovascular Mortality among Patients with Coronary Artery Disease

Background

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.

Methods

MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.

Results

During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.

Conclusions

Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.     

Association between Resistin Levels and All-Cause and Cardiovascular Mortality: A New Study and a Systematic Review and Meta-Analysis

Context

Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results.

Objective

To investigate the association between resistin and both all-cause and cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations.

Data Source and Study Selection

MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality.

Data Extraction

Performed independently by two investigators, using a standardized data extraction sheet.

Data Synthesis

In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45).

Conclusions

Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease.     

Impact of Body Mass Index on In-Hospital Complications in Patients Undergoing Percutaneous Coronary Intervention in a Japanese Real-World Multicenter Registry

Background

Obesity is associated with advanced cardiovascular disease. However, some studies have reported the “obesity paradox” after percutaneous coronary intervention (PCI). The relationship between body mass index (BMI) and clinical outcomes after PCI has not been thoroughly investigated, especially in Asian populations.

Methods

We studied 10,142 patients who underwent PCI at 15 Japanese hospitals participating in the JCD-KICS registry from September 2008 to April 2013. Patients were divided into four groups according to BMI: underweight, BMI <18.5 (n=462); normal, BMI ≥18.5 and <25.0 (n=5,945); overweight, BMI ≥25.0 and <30.0 (n=3,100); and obese, BMI ≥30.0 (n=635).

Results

Patients with a high BMI were significantly younger (p<0.001) and had a higher incidence of coronary risk factors such as hypertension (p<0.001), hyperlipidemia (p<0.001), diabetes mellitus (p<0.001), and current smoking (p<0.001), than those with a low BMI. Importantly, patients in the underweight group had the worst in-hospital outcomes, including overall complications (underweight, normal, overweight, and obese groups: 20.4%, 11.5%, 8.4%, and 10.2%, p<0.001), in-hospital mortality (5.8%, 2.1%, 1.2%, and 2.7%, p<0.001), cardiogenic shock (3.5%, 2.0%, 1.5%, and 1.6%, p=0.018), bleeding complications (10.0%, 4.5%, 2.6%, and 2.8%, p<0.001), and receiving blood transfusion (7.6%, 2.7%, 1.6%, and 1.7%, p<0.001). BMI was inversely associated with bleeding complications after adjustment by multivariate logistic regression analysis (odds ratio, 0.95; 95% confidence interval, 0.92–0.98; p=0.002). In subgroup multivariate analysis of patients without cardiogenic shock, BMI was inversely associated with overall complications (OR, 0.98; 95% CI, 0.95–0.99; p=0.033) and bleeding complications (OR, 0.95; 95% CI, 0.91–0.98; p=0.006). Furthermore, there was a trend that BMI was moderately associated with in-hospital mortality (OR, 0.94; 95% CI, 0.88–1.01; p=0.091).

Conclusions

Lean patients, rather than obese patients are at greater risk for in-hospital complications during and after PCI, particularly for bleeding complications.     

Iron Supplementation and Mortality in Incident Dialysis Patients: An Observational Study

Background

Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting.

Methods

In our observational single-center cohort study (INVOR study) we prospectively studied 235 incident dialysis patients. Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and all-cause mortality, cardiovascular and sepsis-related mortality. Furthermore, the time-dependent association of ferritin levels with mortality in patients with normal C-reactive protein (CRP) levels (<0.5 mg/dL) and elevated CRP levels (≧0.5 mg/dL) was evaluated by using non-linear P-splines to allow flexible modeling of the association.

Results

One hundred and ninety-one (81.3%) patients received intravenous iron, 13 (5.5%) patients oral iron, whereas 31 (13.2%) patients were never supplemented with iron throughout the observation period. Eighty-two (35%) patients died during a median follow-up of 34 months, 38 patients due to cardiovascular events and 21 patients from sepsis. Baseline CRP levels were not different between patients with and without iron supplementation. However, baseline serum ferritin levels were lower in patients receiving iron during follow up (median 93 vs 251 ng/mL, p<0.001). Iron supplementation was associated with a significantly reduced all-cause mortality [HR (95%CI): 0.22 (0.08–0.58); p = 0.002] and a reduced cardiovascular and sepsis-related mortality [HR (95%CI): 0.31 (0.09–1.04); p = 0.06]. Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality, whereas in patients with elevated CRP values ferritin levels>800 ng/mL were linked with increased mortality.

Conclusions

Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients. While serum ferritin levels up to 800 ng/mL appear to be safe, higher ferritin levels are associated with increased mortality in the setting of concomitant inflammation.     

Association of Pretreatment Anemia with Pathological Response and Survival of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Population-Based Study

Background

Anemia related to adjuvant chemotherapy might predict compromised survival in patients with breast cancer. The present population-based study was to investigate the correlation of pretreatment anemia with pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NCT).

Methods

From 1999 to 2011, a total of 655 patients with operable or locally advanced breast cancer who underwent NCT before definitive surgery were reviewed. The patients were subdivided into anemic (baseline hemoglobin (Hb)<12.0g/dL) and non-anemic (Hb≥12.0g/dL) groups. Comparison was made between anemic and non-anemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Logistic and Cox regression models were utilized to determine the predictive value of pretreatment anemia in outcomes of patients undergoing NCT.

Results

166 women (25.3%) were anemic before treatment. Patients in the anemic group were less likely to achieve pCR in NCT than their non-anemic counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs 66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs 94.4%, p<0.001) compared with those without. After adjustment for confounders, pretreatment anemia was demonstrated to correlate with elevated risk of relapse (hazard ratio (HR) 1.453, 95% CI 1.077–1.962, p = 0.015), cancer-specific mortality (HR 2.961, 95% CI 1.679–5.222, p<0.001) and all-cause mortality (HR 2.873, 95% CI 1.757–4.699, p<0.001).

Conclusions

Pretreatment anemia was associated with worse pathological response to NCT as well as survival status in breast cancer. Further studies are warranted to identify optimal interventions and improve the prognosis of this subgroup.     

Progression of Aortic Arch Calcification Over 1 Year Is an Independent Predictor of Mortality in Incident Peritoneal Dialysis Patients

Backgrounds and Aims

The presence and progression of vascular calcification have been demonstrated as important risk factors for mortality in dialysis patients. However, since the majority of subjects included in most previous studies were hemodialysis patients, limited information was available in peritoneal dialysis (PD) patients. Therefore, the aim of this study was to investigate the prevalence of aortic arch calcification (AoAC) and prognostic value of AoAC progression in PD patients.

Methods

We prospectively determined AoAC by chest X-ray at PD start and after 12 months, and evaluated the impact of AoAC progression on mortality in 415 incident PD patients.

Results

Of 415 patients, 169 patients (40.7%) had AoAC at baseline with a mean of 18.1±11.2%. The presence of baseline AoAC was an independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence interval (CI): 1.336–3.561, P = 0.002] and cardiovascular mortality (HR: 3.582, 95% CI: 1.577–8.132, P = 0.002). Among 363 patients with follow-up chest X-rays at 12 months after PD start, the proportion of patients with AoAC progression was significantly higher in patients with baseline AoAC (64.2 vs. 5.3%, P<0.001). Moreover, all-cause and cardiovascular death rates were significantly higher in the progression groups than in the non-progression group (P<0.001). Multivariate Cox analysis revealed that AoAC progression was an independent predictor for all-cause (HR: 2.625, 95% CI: 1.150–5.991, P = 0.022) and cardiovascular mortality (HR: 4.008, 95% CI: 1.079–14.890, P = 0.038) in patients with AoAC at baseline.

Conclusions

The presence and progression of AoAC assessed by chest X-ray were independently associated with unfavorable outcomes in incident PD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in these patients.     

Carotid Atherosclerotic Disease Predicts Cardiovascular Events in Hemodialysis Patients: A Prospective Study

Background

To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients.

Methods

Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed.

Results

83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02).

Conclusions

The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies.     

Female Gender and Differences in Outcome after Isolated Coronary Artery Bypass Graft Surgery: Does Age Play a Role?

Introduction

Female gender is a known risk factor for early and late mortality after coronary artery bypass graft surgery (CABG). Higher age of women at operation may influence outcome, since age per se is also an important risk factor. The purpose of our study was to analyze possible gender differences in outcome after isolated CABG in different age groups to delineate the impact of female gender and age.

Methods

All patients over 60 years of age undergoing isolated CABG at our department during 2001 and 2011 were included and categorized by age into sexagenarians (2266, 16.6% women), septuagenarians (2332, 25.4% women) and octogenarians (374, 32% women) and assessed by gender for 30-day and 180-day mortality.

Results

Thirty-day mortality was significantly higher in women only amongst septuagenarians (7.1 vs. 4.7%, p = 0.033). Same differences apply for 180-day mortality (12.3 vs. 8.2%, p = 0.033) and estimated one-year survival (81.6 ± 4.2 vs. 86.9 ± 2.2%, p = 0.001). Predictive factors for 30-day mortality of septuagenarian were logistic EuroSCORE (ES) (p = 0.003), perioperative myocardial infarction (MI) (p<0.001), pneumonia (p<0.001), abnormal LV-function (p<0.04) and use of LIMA graft (p<0.001), but not female gender. However, female gender was found to be an independent predictor for 180-day mortality (HR 1.632, p = 0.001) in addition to ES, use of LIMA graft, perioperative MI, pneumonia and abnormal LV function (HR 1.013, p = 0.004; HR 0.523, p<0.001; HR 2.710, p<0.001; HR 3.238, p<0.001; HR 2.013, p<0.001).

Conclusion

Women have a higher observed probability of early death after CABG in septuagenarians. However, female gender was not found to be an independent risk factor for 30-day, but for 180-day survival. Therefore, reduction of high impact risk factors such as perioperative MI and enhancement of LIMA use should be future goals. In view of our findings, decision for surgical revascularization should not be based on gender.