Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension

Background and objectives

Left ventricular hypertrophy (LVH) and abnormal left ventricular (LV) geometry predict adverse outcomes in the general and hypertensive populations, but findings in CKD are still inconclusive.

Design, setting, participants, & measurements

We enrolled 445 patients with hypertension and CKD stages 2–5 in two academic nephrology clinics in 1999–2003 who underwent both echocardiography and ambulatory BP monitoring. LVH (LV mass >100 g/m² [women] and >131 g/m² [men]) and relative wall thickness (RWT) were used to define LV geometry: no LVH and RWT≤0.45 (normal), no LVH and RWT>0.45 (remodeling), LVH and RWT≤0.45 (eccentric), and LVH and RWT>0.45 (concentric). We evaluated the prognostic role of LVH and LV geometry on cardiovascular (CV; composite of fatal and nonfatal events) and renal outcomes (composite of ESRD and all-cause death).

Results

Age was 64.1±13.8 years old; 19% had diabetes, and 22% had CV disease. eGFR was 39.9±20.2 ml/min per 1.73 m². LVH was detected in 249 patients (56.0%); of these, 125 had concentric LVH, and 124 had eccentric pattern, whereas 71 patients had concentric remodeling. Age, women, anemia, and nocturnal hypertension were independently associated with both concentric and eccentric LVH, whereas diabetes and history of CV disease associated with eccentric LVH only, and CKD stages 4 and 5 associated with concentric LVH only. During follow-up (median, 5.9 years; range, 0.04–15.3), 188 renal deaths (112 ESRD) and 103 CV events (61 fatal) occurred. Using multivariable Cox analysis, concentric and eccentric LVH was associated with higher risk of CV outcomes (hazard ratio [HR], 2.59; 95% confidence interval [95% CI], 1.39 to 4.84 and HR, 2.79; 95% CI, 1.47 to 5.26, respectively). Similarly, greater risk of renal end point was detected in concentric (HR, 2.33; 95% CI, 1.44 to 3.80) and eccentric (HR, 2.30; 95% CI, 1.42 to 3.74) LVH. Sensitivity analysis using LVH and RWT separately showed that LVH but not RWT was associated with higher cardiorenal risk.

Conclusions

In patients with CKD, LVH is a strong predictor of the risk of poor CV and renal outcomes independent from LV geometry.     

Episiotomy healing assessment: Redness,Oedema, Ecchymosis,Discharge, Approximation (REEDA) scale reliability

OBJECTIVE:

to analyse the Redness, Oedema, Ecchymosis, Discharge, Approximation (REEDA) scale reliability when evaluating perineal healing after a normal delivery with a right mediolateral episiotomy.

METHOD:

observational study based on data from a clinical trial conducted with 54 randomly selected women, who had their perineal healing assessed at four time points, from 6 hours to 10 days after delivery, by nurses trained in the use of this scale. The kappa coefficient was used in the reliability analysis of the REEDA scale.

RESULTS:

the results indicate good agreement in the evaluation of the discharge item (0.75< Kappa ≥0.88), marginal and good agreement in the first three assessments of oedema (0.16< Kappa ≥0.46), marginal agreement in the evaluation of ecchymosis (0.25< Kappa ≥0.42) and good agreement regarding redness (0.46< Kappa ≥0.66). For the item coaptation, the agreement decreased from excellent in the first assessment to good in the last assessment. In the fourth evaluation, the assessment of all items displayed excellent or good agreement among the evaluators.

CONCLUSION:

the difference in the scores among the evaluators when applying the scale indicates that this tool must be improved to allow an accurate assessment of the episiotomy healing process.     

Circadian disrupting exposures and breast cancer risk: a meta-analysis

Purpose

Shift work, short sleep duration, employment as a flight attendant, and exposure to light at night, all potential causes of circadian disruption, have been inconsistently associated with breast cancer (BrCA) risk. The aim of this meta-analysis is to quantitatively evaluate the combined and independent effects of exposure to different sources of circadian disruption on BrCA risk in women.

Methods

Relevant studies published through January 2014 were identified by searching the PubMed database. The pooled relative risks (RRs) and corresponding 95 % confidence intervals (CIs) were estimated using fixed- or random effects models as indicated by heterogeneity tests. Generalized least squares trend test was used to assess dose–response relationships.

Results

A total of 28 studies, 15 on shift work, 7 on short sleep duration, 3 on flight attendants, and 6 on light at night were included in the analysis. The combined analysis suggested a significantly positive association between circadian disruption and BrCA risk (RR = 1.14; 95 % CI 1.08–1.21). Separate analyses showed that the RR for BrCA was 1.19 (95 % CI 1.08–1.32) for shift work, 1.120 (95 % CI 1.119–1.121) for exposure to light at night, 1.56 (95 % CI 1.10–2.21) for employment as a flight attendant, and 0.96 (95 % CI 0.86–1.06) for short sleep duration. A dose–response analysis showed that each 10-year increment of shift work was associated with 16 % higher risk of BrCA (95 % CI 1.06–1.27) based on selected case–control studies. No significant dose–response effects of exposure to light at night and sleep deficiency were found on BrCA risk.

Conclusions

Our meta-analysis demonstrates that circadian disruption is associated with an increased BrCA risk in women. This association varied by specific sources of circadian disrupting exposures, and a dose–response relationship remains uncertain. Therefore, future rigorous prospective studies are needed to confirm these relationships.

     

Better Adherence to the Mediterranean Diet Could Mitigate the Adverse Consequences of Obesity on Cardiovascular Disease: The SUN Prospective Cohort

Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or ≥6 points in the Trichopoulou’s Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93–2.25) for ≥25 – <30 kg/m² of BMI and 2.00 (1.04–3.83) for ≥30 kg/m² of BMI, compared to a BMI < 25 kg/m². In contrast, these estimates were 0.77 (0.35–1.67) and 1.15 (0.39–3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity.     

Do Fructose-Containing Sugars Lead to Adverse Health Consequences? Results of Recent Systematic Reviews and Meta-analyses

Sugars have replaced fat as the dominant public health nutrition concern. A fructose-centric view of cardiometabolic disease has emerged whereby fructose-containing sugars are thought to have deleterious effects on body weight, fasting and postprandial blood lipids, glycemia, blood pressure, uric acid, and markers of nonalcoholic fatty liver disease. Long-term prospective cohort studies have not supported these associations when assessing the relation between total fructose-containing sugars at any amount of intake and incident cardiometabolic disease. Conversely, a consistent signal for harm has been reported for sugary beverages when comparing the highest with the lowest intakes. These associations, however, do not hold at moderate intakes, which are more reflective of real-world intakes, are subject to important collinearity effects, and have small risk estimates with modest population-attributable risk fractions. Higher-level evidence from controlled feeding trials shows that fructose-containing sugars in either liquid or solid form have adverse cardiometabolic effects only when they supplement diets with excess calories compared with the same diets without the excess calories. In the absence of harm when fructose-containing sugars are exchanged for other sources of carbohydrate under energy-matched conditions, excess calories appear to be the dominant consideration. Like with the earlier fat story, it is difficult to separate the contribution of fructose-containing sugars from that of other sources of excess calories in the epidemic of obesity and cardiometabolic disease. Attention needs to remain focused on reducing the overconsumption of all caloric foods associated with obesity and cardiometabolic disease, including sugary beverages and foods, and promoting greater physical activity.     

Synthesis of heterometallic metal–organic frameworks and their performance as electrocatalyst for CO2 reduction

Herein we report the solventless synthesis and doping of the benchmark HKUST-1(Cu) as a facile route to afford heterometallic metal–organic frameworks (MOFs) having proficient behavior as electrocatalytic materials in the reduction of carbon dioxide. Zn(ii), Ru(iii) and Pd(ii) were selected as doping metals (M_D) with the aim of partially replacing the Cu(ii) atoms of the pristine structure to afford HKUST-1(Cu,M_D) type materials. Apart from the high yield and good crystallinity of the obtained materials, the extremely high reagent concentration that the reaction conditions imply makes it feasible to control dopant loading in all cases. Prepared samples were processed as electrodes and assembled in a continuous flow filter-press electrochemical cell. Faraday efficiency to methanol and ethanol at Ru(iii)-based electrodes resulted in activity as high as 47.2%, although the activity of the material decayed with time. The interplay of the dopant metal and copper(ii), and the long-term performance are also discussed.

The solventless synthesis of heterometallic metal–organic frameworks and their proficient behavior as electrocatalysts in the CO₂ reduction to alcohols is presented.     

Association of Polyphenols from Oranges and Apples with Specific Intestinal Microorganisms in Systemic Lupus Erythematosus Patients

Our group has recently shown the existence of a gut microbial dysbiosis in systemic lupus erythematosus (SLE), supporting previous evidence involving intestinal bacteria in the initiation and amplification of autoimmune diseases. While several studies have addressed the use of dietary fibres to modify intestinal microbiota, information about other correlated components, such as polyphenols, is scarce. The aim of this work was to identify dietary components able to influence this altered microbiota in 20 SLE women and 20 age-matched controls. Food intake was recorded by means of a food frequency questionnaire. The intake of fibres was calculated from Marlett tables, and Phenol-Explorer was used for polyphenol consumption. Results showed positive associations between flavone intake and Blautia, flavanones and Lactobacillus, and dihydrochalcones and Bifidobacterium in the SLE group. Regarding the controls, dihydroflavonols were directly associated with Faecalibacterium, whereas flavonol intake was inversely associated with Bifidobacterium. From the food sources of these polyphenols related to microbiota, orange intake was directly associated with Lactobacillus and apple with Bifidobacterium in SLE, whilst red wine was the best contributor to Faecalibacterium variation. The association between common foods and particular microbial genera, reported to be decreased in SLE, could be of great importance for these patients.     

miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis

Neutrophil extracellular traps (NET) induce a procoagulant response linking inflammation and thrombosis. Low levels of miR-146a, a brake of inflammatory response, are involved in higher risk of cardiovascular events, but the mechanisms explaining how miR-146a exerts its function remain largely undefined. The aim of this study was to explore the impact of miR-146a deficiency in NETosis both in sterile and non-sterile models in vivo, and to investigate the underlying mechanism. Two models of inflammation were used: (i) Ldlr^-/- mice transplanted with bone marrow from miR-146a^-/- or wild-type mice were fed a high-fat diet, generating an atherosclerosis model; and (ii) an acute inflammation model was generated by injecting lipopolysaccharide (1 mg/kg) into miR-146a^-/- and wildtype mice. miR-146a deficiency increased NETosis in both models. Accordingly, miR-146a^-/- mice showed significantly reduced carotid occlusion time and elevated levels of NET in thrombi following FeCl3-induced thrombosis. Infusion of DNAse I abolished arterial thrombosis in both WT and miR-146a^-/- mice. Interestingly, miR-146a-deficient mice have aged, hyperreactive and pro-inflammatory neutrophils in their circulation which are more prone to form NET independently of the stimulus. Furthermore, we demonstrated that patients with community-acquired pneumonia with reduced miR-146a levels associated with the T variant of the functional rs2431697 had an increased risk of cardiovascular events due, in part, to an increased generation of NET.