Red Cell Distribution Width in Relation to Incidence of Stroke and Carotid Atherosclerosis: A Population-Based Cohort Study

BackgroundIncreased red cell distribution width (RDW) has been related to poor prognosis in patients with cardiovascular disease, and is a predictor of cardiovascular mortality in the general population. The purpose of the present study was to investigate if RDW is associated with increased incidence of stroke and its subtypes in individuals from the general population.MethodsRed cell distribution width was measured in 26,879 participants (16,561 women and 10,318 men aged 45–73 years) without history of coronary events or stroke, from the population-based Malmö Diet and Cancer Study. Incidences of total stroke and stroke subtypes over a mean follow-up of 15.2 years were calculated in relation to sex-specific quartiles of RDW. The presence of carotid plaque and intima–media thickness, as assessed by ultrasound, was studied in relation to RDW in a randomly selected subcohort (n = 5,309).ResultsIncidences of total stroke (n = 1,869) and cerebral infarction (n = 1,544) were both increased in individuals with high RDW. Hazard ratios (HRs) in the highest compared to the lowest quartile were 1.31 for total stroke (95% confidence interval [CI]: 1.11–1.54, p for trend = 0.004) and 1.32 for cerebral infarction (95% CI: 1.10–1.58, p for trend = 0.004) after adjustment for stroke risk factors and hematological parameters. The adjusted HR for intracerebral hemorrhage (n = 230) was 1.44 (95% CI: 0.90–2.30) and the HR for subarachnoid hemorrhage (n = 75) was 0.94 (95% CI: 0.43–2.07), in the highest compared to the lowest quartile of RDW. Red cell distribution width was positively associated with intima–media thickness of the common carotid artery (p for trend = 0.011).ConclusionsRed cell distribution width in the highest quartile was associated with increased incidence of total stroke and cerebral infarction. There was no significant association between RDW and incidence of intracerebral or subarachnoid hemorrhage.     

Association between NAD+ levels and anaemia among women in community‐based study

Nicotinamide adenine dinucleotide (NAD⁺) level is the protective factor of cardiovascular diseases (CVDs). In addition, anaemia is a risk factor of adverse cardiovascular outcomes in women. However, there are limited data about the association between NAD⁺ and anaemia. The aim of this study was to evaluate association of NAD⁺ with anaemia among women. A total of 727 females from Jidong community were included in the current analysis. NAD⁺ levels were tested by the cycling assay and HPLC assay using whole blood samples. Anaemia was determined by haemoglobin (Hb) concentration, and the subtypes of anaemia were further defined according to mean corpuscular volume (MCV) in blood. Multivariable logistic analysis was used to analyse the association between NAD⁺ levels and anaemia or its subtypes. The mean age of recruited subjects was 42.7 years. The proportion of anaemia by NAD⁺ levels quartiles were 19.7% (35/178), 4.8% (9/189), 3.4% (6/178) and 2.7% (5/182). Haematological parameters including haemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red blood count (RBC) increased over NAD⁺ quartiles. Red cell volume distribution width (RDW) decreased over NAD⁺ quartiles. Compared with the lowest quartile of NAD⁺ levels (<27.6μM), the adjusted odds ratios with 95% confidence intervals of the top quartile were 0.15 (0.06–0.41) for anaemia, 0.05 (0.01–0.36) for microcytic anaemia and 0.37 (0.10–1.36) for normocytic anaemia respectively. Higher NAD⁺ levels were significantly associated with lower prevalence of anaemia among women, especially microcytic anaemia and normocytic anaemia. Haematological parameters might serve as a predictor of the blood NAD⁺ levels.     

Associations between Renal Hyperfiltration and Serum Alkaline Phosphatase

Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008–2011) was performed. Renal hyperfiltration was defined as exceeding the age- and sex-specific 97.5^th percentile. We divided participants into 4 groups according to their estimated glomerular filtration rate (eGFR): >120, 90–119, 60–89, and <60 mL/min/1.73 m². The participants with eGFR >120 mL/min/1.73 m² showed the highest risk for MS, in the highest ALP quartiles (3.848, 95% CI, 1.876–7.892), compared to the lowest quartile. Similarly, the highest risk for DM, in the highest ALP quartiles, was observed in participants with eGFR >120 ml/min/1.73 m² (2.166, 95% CI, 1.084–4.329). ALP quartiles were significantly associated with albuminuria in participants with eGFR ≥ 60 ml/min/1.73m². The highest ALP quartile had a 1.631-fold risk elevation for albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005). After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for renal hyperfiltration (95% CI, 1.204–2.192, P = 0.002). In addition, hyperfiltration was significantly associated with hemoglobin, triglyceride, white blood cell count, DM, smoking, and alcohol consumption (P<0.05). The relationship between serum ALP and metabolic disorders is stronger in participants with an upper-normal range of eGFR. Higher ALP levels are significantly associated with renal hyperfiltration in Korean general population.     

The prognostic value of red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in radiotherapy for oropharyngeal cancer

BackgroundRed cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are known inflammatory indices. Elevated values are found in many cancers and may be associated with a poor prognosis. The article aimed to assess the impact of RDW, NLR, and PLR on overall survival (OS) of patients with oropharyngeal cancer treated with radiotherapy (RT).Materials and methodsThis retrospective study includes 208 patients treated for oropharyngeal cancer with definitive RT or RT combined with neoadjuvant or concurrent systemic therapy, at one institution between 2004 and 2014. The receiver operating characteristic (ROC) method, log-rank testing, and Cox proportional hazards regression model were used for the analysis.ResultsThe OS was significantly higher in RDW ≤ 13.8% (p = 0.001) and NLR ≤ 2.099 (p = 0.016) groups. The RDW index was characterized by the highest discriminatory ability [area under the curve (AUC) = 0.59, 95% confidence interval (CI): 0.51–0.67], closely followed by NLR (AUC = 0.58, 95% CI: 0.50–0.65). In the univariate Cox regression analysis, RDW [hazard ratio (HR): 1.28, 95% CI: 1.12–1.47, p < 0.001] and NLR (HR: 1.11, 95% CI: 1.06–1.18, p < 0.001) were associated with an increased risk of death. In the multivariate analysis, among the analyzed indices, only NLR was significantly associated with survival (HR: 1.16, 95% CI: 1.03–1.29, p = 0.012).ConclusionsIn the study, only NLR proved to be an independent predictor of OS. However, its clinical value is limited due to the relatively low sensitivity and specificity.     

Red Blood Cell Distribution Width as a Pragmatic Marker for Outcome in Pediatric Critical Illness

Background

Red cell distribution width (RDW) is a routine laboratory measure associated with poor outcomes in adult critical illness.

Objective

We determined the utility of RDW as an early pragmatic biomarker for outcome in pediatric critical illness.

Methods

We used multivariable logistic regression to test the association of RDW on the first day of pediatric intensive care unit (PICU) admission with prolonged PICU length of stay (LOS) >48 hours and mortality. The area under the receiver operating characteristic curve (AUROC) for RDW was compared to the Pediatric Index of Mortality (PIM)-2 score.

Results

Over a 13-month period, 596 unique patients had RDW measured on the first day of PICU admission. Sepsis was an effect modifier for LOS >48 hours but not mortality. In sepsis, RDW was not associated with LOS >48 hours. For patients without sepsis, each 1% increase in RDW was associated with 1.17 (95% CI 1.06, 1.30) increased odds of LOS >48 hours. In all patients, RDW was independently associated with PICU mortality (OR 1.25, 95% CI 1.09, 1.43). The AUROC for RDW to predict LOS >48 hours and mortality was 0.61 (95% CI 0.56, 0.66) and 0.65 (95% CI 0.55, 0.75), respectively. Although the AUROC for mortality was comparable to PIM-2 (0.75, 95% CI 0.66, 0.83; p = 0.18), RDW did not increase the discriminative utility when added to PIM-2. Despite the moderate AUROC, RDW <13.4% (upper limit of lower quartile) had 53% risk of LOS >48 hours and 3.3% risk of mortality compared to patients with an RDW >15.7% (lower limit of upper quartile) who had 78% risk of LOS >48 hours and 12.9% risk of mortality (p<0.001 for both outcomes).

Conclusions

Elevated RDW was associated with outcome in pediatric critical illness and provided similar prognostic information as the more complex PIM-2 severity of illness score. Distinct RDW thresholds best discriminate low- versus high-risk patients.     

Relation between Red Cell Distribution Width and Fibroblast Growth Factor 23 Cleaving in Patients with Chronic Kidney Disease and Heart Failure

Objective

In chronic kidney disease (CKD), both anemia and deregulated phosphate metabolism are common and predictive of adverse outcome. Previous studies suggest that iron status influences phosphate metabolism by modulating proteolytic cleavage of FGF23 into C-terminal fragments. Red cell distribution width (RDW) was recently identified as a strong prognostic determinant for cardiovascular morbidity and mortality, independently of iron status. We assessed whether RDW is associated with FGF23 cleaving in CKD patients with heart failure.

Materials and Methods

The associations between RDW and either intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23, reflecting iFGF23 and C-terminal fragments together) and the iFGF23/cFGF23 ratio were analyzed in 52 patients with CKD (eGFR 34,9 ± 13.9 ml/min/1.73m²) and chronic heart failure (CHF). Associations between RDW and FGF23 forms were studied by linear regression analysis adjusted for parameters of renal function, iron metabolism, phosphate metabolism and inflammation.

Results

Median cFGF23 levels were 197.5 [110–408.5] RU/ml, median iFGF23 levels were 107.3 [65.1–162.2] pg/ml and median FGF23 ratio was 0.80 [0.37–0.86]. Mean RDW was 14.1 ± 1.2%. cFGF23 and RDW were associated (β = 1.63x10^-3, P <0.001), whereas iFGF23 and RDW were not (β = -1.38x10^-3, P = 0.336). The iFGF23/cFGF23 ratio was inversely associated with RDW. The difference between cFGF23 and iFGF23 (cFGF23- iFGF23) was positively associated with RDW (β = 1.74x10^-3, P< 0.001). The association between cFGF23 and RDW persisted upon multivariable linear regression analysis, adjusted for parameters of renal function, phosphate metabolism, iron metabolism and inflammation (β = 0.97x10^-3, P = 0.047).

Conclusion

RDW is associated with cFGF23 but not with iFGF23 levels in patients with CKD and CHF. This suggests a connection between RDW and FGF23 catabolism, independent of iron status and inflammation. Future studies are needed to unravel underlying mechanisms and whether these pertain to the link between RDW and outcome.     

Progressive Rise in Red Blood Cell Distribution Width Predicts Mortality and Cardiovascular Events in End-Stage Renal Disease Patients

Red blood cell distribution width (RDW) is a robust marker of adverse clinical outcomes in various populations. However, the clinical significance of a progressive rise in RDW is undetermined in end-stage renal disease (ESRD) patients. The purpose of this study was to determine the prognostic importance of a change in RDW in ESRD patients. Three hundred twenty-six incident dialysis patients were retrospectively analyzed. Temporal changes in RDW during 12 months after dialysis initiation were assessed by calculating the coefficients by linear regression. Patients were divided into two groups: an RDW-decreased group who had negative coefficient values (n = 177) and an RDW-increased group who had positive values (n = 149). The associations between rising RDW and mortality and cardiovascular (CV) events were investigated. During a median follow-up of 2.7 years (range, 1.0–7.7 years), 75 deaths (24.0%) and 60 non-fatal CV events (18.4%) occurred. The event-free survival rate for the composite of end-points was lower in the RDW-increased group (P = 0.004). After categorizing patients according to baseline RDW, the event-free survival rate was lowest in patients with a baseline RDW >14.9% and increased RDW, and highest in patients with a baseline RDW ≤14.9% and decreased RDW (P = 0.02). In multivariate analysis, rising RDW was independently associated with the composite of end-points (hazard ratio = 1.75, P = 0.007), whereas the baseline RDW was not. This study shows that a progressive rise in RDW independently predicted mortality and CV events in ESRD patients. Rising RDW could be an additive predictor for adverse CV outcomes ESRD patients.     

Red Cell Distribution Width and Other Red Blood Cell Parameters in Patients with Cancer: Association with Risk of Venous Thromboembolism and Mortality

Background

Cancer patients are at high risk of developing venous thromboembolism (VTE). Red cell distribution width (RDW) has been reported to be associated with arterial and venous thrombosis and mortality in several diseases. Here, we analyzed the association between RDW and other red blood cell (RBC) parameters with risk of VTE and mortality in patients with cancer.

Methods

RBC parameters were measured in 1840 patients with cancers of the brain, breast, lung, stomach, colon, pancreas, prostate, kidney; lymphoma, multiple myeloma and other tumor sites, that were included in the Vienna Cancer and Thrombosis Study (CATS), which is an ongoing prospective, observational cohort study of patients with newly diagnosed or progressive cancer after remission. Primary study outcome is occurrence of symptomatic VTE and secondary outcome is death during a maximum follow-up of 2 years.

Results

During a median follow-up of 706 days, 131 (7.1%) patients developed VTE and 702 (38.2%) died. High RDW (>16%) was not associated with a higher risk of VTE in the total study cohort; in competing risk analysis accounting for death as competing variable the univariable subhazard ratio (SHR) was 1.34 (95% confidence interval [CI]: 0.80–2.23, p = 0.269). There was also no significant association between other RBC parameters and risk of VTE. High RDW was associated with an increased risk of mortality in the total study population (hazard ratio [HR, 95% CI]: 1.72 [1.39–2.12], p<0.001), and this association prevailed after adjustment for age, sex, hemoglobin, leukocyte and platelet count (HR [95% CI]: 1.34 [1.06–1.70], p = 0.016).

Conclusions

RDW and other RBC parameters were not independently associated with risk of VTE in patients with cancer and might therefore not be of added value for estimating risk of VTE in patients with cancer. We could confirm that high RDW is an independent predictor of poor overall survival in cancer.     

Confirmation of the Reported Association of Clonal Chromosomal Mosaicism with an Increased Risk of Incident Hematologic Cancer

Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS). The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE) and the Women’s Health Initiative (WHI). We detected clonal mosaicism in 169 individuals (1.4%) and large clonal mosaic events (>2 mb) in 117 (1.0%) individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia), the carriers had a 5.5-fold increased risk (95% CI: 3.3–9.3; p-value = 7.5×10⁻¹¹) of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9–41.6; p-value = 7.3×10⁻¹⁴). Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications.     

Increased Arterial Diameters in the Posterior Cerebral Circulation in Men with Fabry Disease

A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males – females; normal – impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity.     

Leukoaraiosis,a Common Brain Magnetic Resonance Imaging Finding,as a Predictor of Traffic Crashes

Background

There are no reported studies on the relationship between traffic crashes and brain tissue changes in healthy drivers. The relationship between traffic crashes and leukoaraiosis, a common magnetic resonance imaging finding, was investigated in this study.

Methods

A total of 3,930 automobile drivers (2,037 men and 1,893 women; age, 21–87 years) who underwent brain magnetic resonance imaging as part of total health check-ups and answered a road traffic questionnaire were examined to determine whether asymptomatic leukoaraiosis was associated with various types of traffic crashes. Multiple logistic regression analysis was performed to elucidate the relationship between leukoaraiosis and various types of traffic crashes.

Results

Subcortical leukoaraiosis was diagnosed in 28.52% of all subjects, whereas periventricular leukoaraiosis was diagnosed in 9.57% of all subjects. Adjusted odds ratios for involvement in all types of traffic crashes were not significant for subjects with periventricular leukoaraiosis; however, they were significant for subjects with multiple and large multiple subcortical leukoaraiosis. Adjusted odds ratios for involvement in crashes at crossroads were 1.09 (95% confidence interval [CI], 0.60–2.00) for subjects with single subcortical leukoaraiosis, 3.35 (95% CI, 2.36–4.77) for subjects with multiple subcortical leukoaraiosis, and 2.45 (95% CI, 2.36–4.98) for subjects with large multiple subcortical leukoaraiosis. Periventricular leukoaraiosis was not significantly associated with crossroad crashes. Involvement in crashes of any type, parking lot crashes, and rear-end collisions showed no significant association with either subcortical or periventricular leukoaraiosis.

Conclusions

Multiple subcortical leukoaraiosis, but not periventricular leukoaraiosis, is significantly associated with traffic crashes, in particular, crossroad crashes. This association is independent of sex, age, and driving exposure. To our knowledge, this is the first evidence describing the relationship between brain tissue changes and traffic crashes.     

Combined Value of Red Blood Cell Distribution Width and Global Registry of Acute Coronary Events Risk Score for Predicting Cardiovascular Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Global Registry of Acute Coronary Events (GRACE) risk score and red blood cell distribution width (RDW) content can both independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). We investigated the combined predictive value of RDW and GRACE risk score for cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI) for the first time. We enrolled 480 ACS patients. During a median follow-up time of 37.2 months, 70 (14.58%) patients experienced MACEs. Patients were divided into tertiles according to the baseline RDW content (11.30–12.90, 13.00–13.50, 13.60–16.40). GRACE score was positively correlated with RDW content. Multivariate Cox analysis showed that both GRACE score and RDW content were independent predictors of MACEs (hazard ratio 1.039; 95% confidence interval [CI] 1.024–1.055; p < 0.001; 1.699; 1.294–2.232; p < 0.001; respectively). Furthermore, Kaplan–Meier analysis demonstrated that the risk of MACEs increased with increasing RDW content (p < 0.001). For GRACE score alone, the area under the receiver operating characteristic (ROC) curve for MACEs was 0.749 (95% CI: 0.707–0.787). The area under the ROC curve for MACEs increased to 0.805 (0.766–0.839, p = 0.034) after adding RDW content. The incremental predictive value of combining RDW content and GRACE risk score was significantly improved, also shown by the net reclassification improvement (NRI = 0.352, p < 0.001) and integrated discrimination improvement (IDI = 0.023, p = 0.002). Combining the predictive value of RDW and GRACE risk score yielded a more accurate predictive value for long-term cardiovascular events in ACS patients who underwent PCI as compared to each measure alone.     

When to Start Antiretroviral Therapy in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa

Background

There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm³ or CD4 percentage (CD4%) <25%.

Methods and Findings

ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping.The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm³ (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm³ or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data.

Conclusions

The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm³ or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors'' Summary     

Higher Blood 25(OH)D Level May Reduce the Breast Cancer Risk: Evidence from a Chinese Population Based Case-Control Study and Meta-Analysis of the Observational Studies

Experimental data suggest a protective effect of vitamin D on breast cancer; however, epidemiologic results remain inclusive. With a Chinese population-based case-control study and meta-analysis of the observational studies, we here systematically evaluated the association of blood 25(OH)D level and breast cancer risk. With 593 breast cancer cases and 580 cancer-free controls from Shanghai, China, we found that 80% of the normal women had severe vitamin D deficiency (less than 20 ng/mL) and 15.2% had mild deficiency (20 to 30 ng/mL) and only 4.8% of women had sufficient vitamin D level (>30 ng/mL) while the proportion was 96.1%, 3.2% and 0.7% respectively for the breast cancer patients. Compared to those with the lowest quartile of plasma 25(OH)D level, women with highest quartile 25(OH)D level showed a significant decreased breast cancer risk (Q4 vs.Q1: OR = 0.10, 95% CI = 0.06–0.15) and every 1 ng/ml increment of plasma 25(OH)D level led to a 16% lower odds of breast cancer (OR = 0.84, 95% CI = 0.81–0.87; P<0.001). From the meta-analysis of the observational studies, we found that women with highest quantile of blood 25(OH)D level was associated with a significantly reduced breast cancer risk compared to those with lowest quantile of blood 25(OH)D level for the 11 nested case-control and retrospective studies (pooled OR = 0.86, 95% CI = 0.75–1.00) and 10 case-control studies (7 population based, OR = 0.35, 95% CI = 0.24–0.52; 3 hospital based, OR = 0.08, 95% CI = 0.02–0.33). These results suggest that vitamin D may have a chemo-preventive effect against breast cancer.     

Increased Red Blood Cell Distribution Width Associates with Cancer Stage and Prognosis in Patients with Lung Cancer

Background

Red cell distribution width (RDW), one of many routinely examined parameters, shows the heterogeneity in erythrocyte size. We investigated the association of RDW levels with clinical parameters and prognosis of lung cancer patients.

Methods

Clinical and laboratory data from 332 patients with lung cancer in a single institution were retrospectively studied by univariate analysis. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival.

Results

The RDW levels were divided into two groups: high RDW (>=15%), n=73 vs. low RDW, n=259 (<15%). Univariate analysis showed that there were significant associations of high RDW values with cancer stage, performance status, presence of other disease, white blood cell count, hemoglobin, mean corpuscular volume, platelet count, albumin level, C-reactive protein level, and cytokeratin 19 fragment level. Kruskal-Wallis tests revealed an association of RDW values with cancer stage in patients irrespective of comorbidity (patient with/without comorbidity: p<0.0001, patient without comorbidity: p<0.0001). Stages I-IV lung cancer patients with higher RDW values had poorer prognoses than those with lower RDW values (Wilcoxon test: p=0.002). In particular, the survival rates of stage I and II patients (n=141) were lower in the high RDW group (n=19) than in the low RDW group (n=122) (Wilcoxon test: p<0.001). Moreover, multivariate analysis showed higher RDW is a significant prognostic factor (p=0.040).

Conclusion

RDW is associated with several factors that reflect inflammation and malnutrition in lung cancer patients. Moreover, high levels of RDW are associated with poor survival. RDW might be used as a new and convenient marker to determine a patient’s general condition and to predict the mortality risk of lung cancer patients.     

Decreased Platelet Count in Patients Receiving Continuous Veno-Venous Hemofiltration: A Single-Center Retrospective Study

Background

A decreased platelet count may occur and portend a worse outcome in patients receiving continuous renal replacement therapy (CRRT). We aim to investigate the incidence of decreased platelet count and related risk factors in patients receiving CRRT.

Methods

In this retrospective study, we screened all patients receiving continuous veno-venous hemofiltration (CVVH) at Jinling Hospital between November 2008 and October 2012. The patients were included who received uninterrupted CVVH for more than 72 h and had records of blood test for 4 consecutive days after ruling out pre-existing conditions that may affect the platelet count. Platelet counts before and during CVVH, illness severity, CVVH settings, and outcomes were analyzed.

Results

The study included 125 patients. During the 3-day CVVH, 44.8% and 16% patients had a mild decline (20–49.9%) and severe decline (≥50%) in the platelet count,respectively; 37.6% and 16.0% patients had mild thrombocytopenia (platelet count 50.1–100×10⁹/L) and severe thrombocytopenia (platelet count ≤50×10⁹/L), respectively. Patients with a severe decline in the platelet count had a significantly lower survival rate than patients without a severe decline in the platelet count (35.0% versus 59.0%, P = 0.012), while patients with severe thrombocytopenia had a survival rate similar to those without severe thrombocytopenia (45.0% versus 57.1%, P = 0.308). Female gender, older age, and longer course of the disease were independent risk factors for a severe decline in the platelet count.

Conclusions

A decline in the platelet count and thrombocytopenia are quite common in patients receiving CVVH. The severity of the decline in the platelet count rather than the absolute count during CVVH may be associated with hospital mortality. Knowing the risk factors for a severe decline in the platelet count may allow physicians to prevent such an outcome.     

Association between Soluble (Pro)Renin Receptor Concentration in Cord Blood and Small for Gestational Age Birth: A Cross-Sectional Study

Objective

The (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth.

Methods

Participants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10^th percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births.

Results

Among 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2–65.1 ng/ml), 157 pairs in the third quartile (Q3: 65.1–73.1 ng/ml) and 156 pairs in the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08–0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020).

Conclusion

High s(P)RR concentration is associated with a lower SGA birth likelihood.     

Global DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the Breast Cancer Family Registry

Lower global DNA methylation is associated with genomic instability and it is one of the epigenetic mechanisms relevant to carcinogenesis. Emerging evidence for several cancers suggests that lower overall levels of global DNA methylation in blood are associated with different cancer types, although less is known about breast cancer. We examined global DNA methylation levels using a sibling design in 273 sisters affected with breast cancer and 335 unaffected sisters from the New York site of the Breast Cancer Family Registry. We measured global DNA methylation in total white blood cell (WBC) and granulocyte DNA by two different methods, the [³H]-methyl acceptance assay and the luminometric methylation assay (LUMA). Global methylation levels were only modestly correlated between sisters discordant for breast cancer (Spearman correlation coefficients ranged from -0.08 to 0.24 depending on assay and DNA source). Using conditional logistic regression models, women in the quartile with the lowest DNA methylation levels (as measured by the [³H]-methyl acceptance assay) had a 1.8-fold (95% CI = 1.0–3.3) higher relative association with breast cancer than women in the quartile with the highest DNA methylation levels. When we examined the association on a continuous scale, we also observed a positive association (odds ratio, OR = 1.3, 95% CI = 1.0–1.7, for a one unit change in the natural logarithm of the DPM/μg of DNA). We observed no association between measures by the LUMA assay and breast cancer risk. If replicated in prospective studies, this study suggests that global DNA methylation levels measured in WBC may be a potential biomarker of breast cancer risk even within families at higher risk of cancer.     

Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

Objectives

Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants.

Methods

suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register.

Results

For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1^st to the 4^th quartile (HR = 1.72, 95% CI: 1.11–2.69). For women, it increased by 108% from the 1^st to the 4^th quartile (HR = 2.08, 95% CI: 1.45–2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002).

Conclusions

High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression.     

Hypertension and Obesity in Adults Living in a High HIV Prevalence Rural Area in South Africa

Hypertension and excess body weight are major risk factors of cardiovascular morbidity and mortality in developing countries. In countries with a high HIV prevalence, it is unknown how increased antiretroviral treatment and care (ART) coverage has affected the prevalence of overweight, obesity, and hypertension. We conducted a health survey in 2010 based on the WHO STEPwise approach in 14,198 adult resident participants of a demographic surveillance area in rural South Africa to investigate factors associated with hypertension and excess weight including HIV infection and ART status. Women had a significantly higher median body mass index (BMI) than men (26.4 vs. 21.2 kg/m², p<0.001). The prevalence of obesity (BMI≥30 kg/m²) in women (31.3%, 95% confidence interval (CI) 30.2–32.4) was 6.5 times higher than in men (4.9%, 95% CI 4.1–5.7), whereas prevalence of hypertension (systolic or diastolic blood pressure≥140 or 90 mm Hg, respectively) was 1.4 times higher in women than in men (28.5% vs 20.8%, p<0.001). In multivariable regression analysis, both hypertension and obesity were significantly associated with sex, age, HIV and ART status. The BMI of women and men on ART was on average 3.8 (95% CI 3.2–3.8) and 1.7 (95% CI 0.9–2.5) kg/m² lower than of HIV-negative women and men, respectively. The BMI of HIV-infected women and men not on ART was on average 1.2 (95% CI 0.8–1.6) and 0.4 (95% CI -0.1–0.9) kg/m² lower than of HIV-negative women and men, respectively. Obesity was a bigger risk factor for hypertension in men (adjusted odds ratio (aOR) 2.99, 95% CI 2.00–4.48) than in women (aOR 1.64, 95% CI 1.39–1.92) and overweight (25≤BMI<30) was a significant risk factor for men only (aOR 1.53 95% CI 1.14–2.06). Our study suggests that, cardiovascular risk factors of hypertension and obesity differ substantially between women and men in rural South Africa.