Supplemental Digital Content is available in the text. 2), height-adjusted weight (70.2±11.2 kg), waist circumference (93.3±10.6 cm), hip circumference (104.0±9.0 cm), waist:hip ratio (0.90±0.06), and waist:height ratio (0.60±0.07). Associations with blood pressure were linear with no threshold levels below which lower general or central adiposity was not associated with lower blood pressure. On average, each 1 SD higher measured adiposity marker was associated with a 3 mm Hg higher systolic blood pressure and 2 mm Hg higher diastolic blood pressure (SEs <0.1 mm Hg), but for the waist:hip ratio, associations were only approximately half as strong. General adiposity associations were independent of central adiposity, but central adiposity associations were substantially reduced by adjustment for general adiposity. Findings were similar for men and women. In Mexican adults, often overweight or obese, markers of general adiposity were stronger independent predictors of blood pressure than measured markers of central adiposity, with no threshold effects.Previous studies have reached differing conclusions about the importance of general versus central markers of adiposity to blood pressure, leading to suggestions that population-specific adiposity thresholds may be needed. We examined the relevance of adiposity to blood pressure among 111 911 men and women who, when recruited into the Mexico City Prospective Study, were aged 35 to 89 years, had no chronic disease, and were not taking antihypertensives. Linear regression was used to estimate the effects on systolic and diastolic blood pressure of 2 markers of general adiposity (body mass index and height-adjusted weight) and 4 markers of central adiposity , adjusted for relevant confounders. Mean (SD) adiposity levels were: body mass index (28.7±4.5 kg/m A recent study of 0.5 million mostly lean Chinese adults found that systolic blood pressure (SBP) increased by ≈8 mm Hg for each 5 kg/m2 higher BMI,13 somewhat greater than has been documented in Western populations.1 In addition to varying between populations, the relevance of adiposity to blood pressure may vary within a population over time, perhaps because of changing levels of other characteristics. Different markers of adiposity also differ in their relevance to blood pressure. For example, although some studies have found BMI to be more strongly related to blood pressure than waist circumference (WC) or the waist:hip ratio (WHR),14 others have found the opposite,17 whereas BMI and the waist:height ratio (WHtR) have been found to exhibit similar associations with blood pressure in some studies.18Adiposity and blood pressure are major modifiable risk factors for cardiovascular and other chronic diseases.19 recommended that further studies are needed to determine whether existing recommended adiposity cutoff points should be population specific and noted that there was little existing evidence among Hispanic populations. We report the relevance of several common markers of adiposity to blood pressure among 110 000 men and women from Mexico City who were free from disease and not taking antihypertensives when recruited into a prospective study at the start of the 21st century.21In 2008, a World Health Organization Expert Consultation on WC and WHR21; a summary is given below.The rationale and design of the Mexico City Prospective Study has been described in detail previously20 Weight (wearing light clothes), standing height, WC, and hip circumference (HC) were measured to the nearest 0.1 kg or 0.1 cm, respectively. Regularly calibrated electronic scales, fixed stadiometers, and nonstretchable tapes were used according to a standard protocol. WC was measured at the midpoint between the iliac crest and the lower rib, and HC was measured at the widest circumference over the gluteal muscles. Seated blood pressure was measured after 5 minutes of rest, using a manual sphygmomanometer and suitably sized cuff. Three blood pressure measurements were taken over about a 6-minute period, with the average of the 3 measures used in analyses.Between 1998 and 2004, 159 755 participants aged ≥35 years from the Coyoacán and Iztapalapa districts of Mexico City were visited in their homes and agreed to take part in a prospective cohort study. Trained nurses recorded data directly into a handheld electronic device, with subsequent automated checks for unusual values or data entry errors. Age, sex, socioeconomic status, lifestyle , disease history, and medication were recorded.Six adiposity variables, either directly measured or derived, were assessed, including 2 anthropometric markers of general adiposity (height-adjusted weight [HtaW] and BMI) and 4 anthropometric markers of central adiposity . BMI was calculated as weight in kilograms divided by the square of height in meters. HtaW was calculated in men using the equation HtaW=weight in kg+0.852×(164.8−height in cm) and in women using the equation HtaW=weight in kg+0.682×(151.8−height in cm), based on the coefficients of the sex-specific linear regression models of weight on height. To limit the effects of measurement errors, very extreme or implausible values of adiposity or blood pressure were excluded (see the Table footnote for exact exclusion criteria). In addition, to limit reverse causation, those taking blood pressure–lowering medication (regularly in the last year) and those previously diagnosed with diabetes mellitus, cancer, liver cirrhosis, vascular, respiratory, or chronic kidney diseases were also excluded, as were those aged ≥90 years, or with missing data on any confounder (see below).online-only Data Supplement for groupings used for covariates). Analyses were also either adjusted for sex or done separately in men and women. Mean-adjusted blood pressure estimates together with their 95% confidence intervals were plotted against the mean adiposity levels for each group. For visual comparability of the plots between the different markers of adiposity, each horizontal axis extends across 4SDs, from −2SD below to +2SD above the mean level observed in all participants. To separate the effects of general adiposity from any independent effects of central markers of adiposity (and vice versa), analyses of each marker were done before and after further adjustment for other markers. For example, HtaW and BMI associations were estimated before and after adjustment for WHR (or waist and hip considered separately), and WC and HC associations were estimated before and after adjustment for BMI . WHtR associations were adjusted for weight only . Subsequently, continuous analyses were done to estimate the mean difference in SBP and DBP associated with a 1 SD higher level of adiposity . Analyses were done using SAS version 9.3 and R version 2.11.1.For categorical analyses of each anthropometric adiposity marker, individuals were split into 10 equally sized groups . For each group, adjusted means of baseline SBP and diastolic blood pressure (DBP) were calculated using standard regression techniques, with adjustment for baseline age, residential district, education, smoking status, level of physical activity, and alcohol consumption , and the Mexican Ministry of Health . The funders had no input on the collection, analysis, or reporting of the data.Of the 159 755 recruited participants, 4892 were excluded because they were aged ≥90 years at recruitment, had extreme measured values for blood pressure or the adiposity markers, or had missing covariate data, and a further 42 952 were excluded because they had a previous diagnosis of chronic disease or were taking blood pressure–lowering medication. The remaining 111 911 participants included 38 338 men  and 73 573 women .2 in men and 29.2±4.9 kg/m2 in women. At every age, mean BMI and HC were lower, and mean WC was higher, among men, and consequently mean WHR was higher in men than in women at every age . The WHtR increased with age in both sexes and was, on average, slightly lower among men (0.58±0.06 versus 0.61±0.08). Mean SBP increased with age, from 123±12 mm Hg at ages 35 to 39 years to 134±18 mm Hg at ages 80 to 89 years in men and, even more steeply, from 117±12 mm Hg to 136±18 mm Hg in women. DBP was less strongly, and somewhat less monotonically, related to age.The age- and sex-specific mean (±SD) levels of each of the anthropometric measures, derived markers of adiposity and blood pressure, are shown in the Table. On average, across all ages, mean height was 165±7 cm in men and 152±6 cm in women, mean weight was 76±13 kg in men and 67±12 kg in women, and mean BMI was 27.8±4.1 kg/mr=0.25), but somewhat more strongly correlated in men (adjusted r=0.48).The correlations between the different adiposity markers are shown in Figures S1 and S2. In both men and women, weight, WC, and HC were all highly correlated (each pairwise age-adjusted correlation coefficient >0.80). By contrast, height was only weakly positively correlated with waist and HC in men, and nearly uncorrelated in women. BMI and WHR were weakly correlated with each other in women  among those from the poorer of the 2 studied districts , among the physically inactive and, particularly for women, among the less well educated. Anthropometric markers of adiposity were, however, largely unrelated to smoking status or alcohol consumption.The 2 markers of general adiposity, HtaW and BMI, were both positively, and linearly, associated with SBP, with each 1 SD higher level associated with about a 3-mm Hg higher SBP  were also positively, and linearly, related to SBP. However, although the strength of association for WC, HC, and WHtR was comparable with that seen for HtaW and BMI, the strength of association for the measured WHR was only about half as big . Again, the positive, linear associations between each marker of general adiposity and DBP were largely unaffected by adjustment for central adiposity, whereas the associations between the markers of central adiposity and DBP were greatly attenuated after adjustment for general adiposity.The relevance of BMI to both SBP and DBP was somewhat weaker at older ages  than at younger ages . Among the large numbers of participants who were aged <60 years at recruitment, however, the strength of association between BMI and blood pressure was virtually the same within each age range.2 higher BMI (or each 11 kg of weight-for-height) was associated with a 3 mm Hg higher SBP and a 2 mm Hg higher DBP. For a given amount of general adiposity, any marker of central adiposity, including the ratio of waist-to-hip circumference or of waist-to-height, was much less strongly related.In this study of 110 000 Mexican adults free from known chronic diseases and not taking antihypertensive medication at the time of assessment, the anthropometric markers of adiposity that were most predictive of blood pressure were the measures of general adiposity. Within the ranges studied, there was no evidence of any threshold level below which less adiposity was not associated with lower blood pressure. On average, each 4.5 kg/m2 higher BMI was associated with about a 5 mm Hg higher SBP,1 whereas a more contemporary study of 500 000 mostly lean Chinese adults found that 5 kg/m2 higher BMI was associated with an 8 mm Hg higher SBP.13 Our findings from this study of Mexican adults (with high levels of adiposity) give more modest estimates. Chinese dietary intake of sodium (estimated by 24-hour urinary excretion) is higher than in Mexico,22 as well as in many Western populations,24 and because dietary sodium predicts SBP independently of BMI,26 variation in sodium intake may partly account for these between-population differences.Our findings in this adipose Mexican metropolitan population differ to some extent from those previously seen in other populations. For example, in a previous meta-analysis of 900 000 individuals from mostly Western populations recruited during the second half of the 20th century , a 5 kg/m13 blood pressure at entry into our study (as for most other cohort studies) relied on the use of manual sphygmomanometers, which are subject to observer-dependent random error, as well as digit preference.26 In addition, although we excluded from our analyses very extreme values, more modest measurement errors in our anthropometric measurements would tend to lead to some underestimation of the associations seen with blood pressure, with the magnitude of bias higher for those markers that are more difficult to measure precisely . Our estimates from this Hispanic population are, however, broadly comparable with estimates obtained by Mendelian-randomization studies of the relevance of adiposity to blood pressure that have been conducted in other populations. For example, a Mendelian randomization study of 14 BMI-associated single-nucleotide polymorphisms measured in 34 500 adults from 8 European population-based cohorts found that a 1 kg/m2 genetically elevated BMI increased SBP by 0.7 mm Hg .9 Similarly, an FTO polymorphism study in >145 000 participants from 30 mostly white cohorts found 1-kg/m2 genetically elevated BMI to be associated with a 0.9 mm Hg  increase in SBP and 0.5 mm Hg  increase in DBP.10Alternatively, differences may reflect the way in which blood pressure or central anthropometry was measured. By contrast with the use of automated blood pressure machines in the China Kadoorie study,28 This is again consistent with analyses of 500 000 Chinese adults, in which there was little association between central markers of adiposity and blood pressure after adjustment for BMI and no suggestion of any threshold levels.13 However, some studies in other populations have indicated that although general and central anthropometrically defined adiposity both predict the development of hypertension,16 markers of central adiposity may be more discriminatory for predicting cardiovascular risk factors than markers of general adiposity.15Our results are consistent with the hypothesis generated by other studies that, in Mexican adults, adipose tissue in general may be more relevant to blood pressure than the site of the adipose tissue per se.28 We studied 6 commonly used anthropometric markers of adiposity, but others , together with body imaging  could further disentangle the relevance to blood pressure of visceral versus other fat depots, as well as of muscle or lean mass. Such measures are, however, difficult to collect in large prospective studies in low- or middle-income countries where resources for research may be more limited. In the current study, a resurvey of 10 000 surviving participants involving additional bioimpedance measures is currently underway. Future work will therefore allow some exploration of how blood pressure in Hispanics varies with, for instance, measures of total fat mass. Elsewhere, the more advanced imaging methods of phenotyping adiposity are being used in populations with moderate levels of adiposity , allowing for an even more detailed investigation of the role of adiposity on blood pressure in that mostly white population.Proposed mechanisms behind the association of adiposity with blood pressure are complex and include dysfunctional adipose tissue–promoting activation of the sympathetic nervous system and the renin–angiotensin–aldosterone pathway, and adiponectin deficiency reducing nitric oxide production and increasing systemic inflammation and oxidative stress.2, but in other populations, the relationship between BMI and blood pressure has been shown to continue down to at least 18 kg/m2.1 Despite this, however, those same studies have shown that the risk of death from cardiovascular disease is, if anything, higher at BMI <22.5 kg/m2 than at 22.5 kg/m2.1,29 Suggesting that low BMI may be correlated with other factors that have strong adverse effects on health. Adiposity influences blood lipids and glucose as well as blood pressure, and together these 3 risk factors have been estimated to explain 46% of the excess ischemic heart disease risk and 76% of the excess stroke risk associated with higher BMI .30 Cardiovascular risk reduction through weight reduction is likely to act largely through these causal pathways. Indeed, risk scores for the prediction of cardiovascular events have only tended to include markers of adiposity when information on these other risk factors is not available.31In our study, just 7671/111 911 participants (7%) had a BMI of <22.5 kg/m32 In 2013, Mexico’s National Strategy for Prevention and Control of Overweight, Obesity and Diabetes, included a range of programs related to health education, improved exercise opportunities, and taxation .33 Our results indicate that, should this strategy be successful, it may lead to considerable population-wide benefits through blood pressure reduction as well as the benefits to be gained by reducing the incidence of diabetes mellitus.In Mexico, adiposity is extremely common, and its consequences through blood pressure and diabetes mellitus are a major public health concern.The chief acknowledgment is to the study participants.This work was supported by the Wellcome Trust , the Mexican Health Ministry (SSA), the National Council of Science and Technology, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council.None.


Pulmonary hypertension is associated with increased morbidity and mortality in chronic obstructive pulmonary disease (COPD). Since pulmonary artery (PA) size increases in pulmonary hypertension, we measured PA cross-sectional area using magnetic resonance imaging (MRI) to test the hypothesis that pulmonary hyperinflation due to gas trapping is associated with PA cross-sectional area in COPD.The MESA COPD Study recruited participants with COPD and controls from two population-based cohort studies ages 50–79 years with 10 or more pack-years and free of clinical cardiovascular disease. Body plethysmography was performed according to standard criteria. Cardiac MRI was performed at functional residual capacity to measure the cross-sectional area of the main PA. Percent emphysema was defined as the percentage of lung voxels less than -950 Hounsfield units as assessed via x-ray computed tomography. Analyses were adjusted for age, gender, height, weight, race-ethnicity, the forced expiratory volume in one second, smoking status, pack-years, lung function, oxygen saturation, blood pressure, left ventricular ejection fraction and percent emphysema.2. A one standard deviation increase in residual volume was independently associated with an increase in main PA cross-sectional area of 0.55 cm2 . In contrast, there was no evidence for an association with percent emphysema or total lung capacity.Among 106 participants, mean residual volume was 1.98±0.71 L and the mean PA cross-sectional area was 7.23±1.72 cmIncreased residual volume was associated with a larger PA in COPD, suggesting that gas trapping may contribute to pulmonary hypertension in COPD. Chronic obstructive pulmonary disease (COPD) is characterized by accelerated age-related loss in lung function and progressive airflow obstruction that is only partially reversible . COPD isThe gold standard to diagnose and characterize the degree of PH is right heart catheterization, a relatively safe but still invasive procedure. Echocardiographic estimates of pulmonary artery (PA) pressures are subject to significant error in patients with COPD, given the technical challenges that arise from pulmonary hyperinflation with hyperexpansion of the chest , 9. PA dPH in COPD is caused by a combination of factors, including alveolar hypoxia acutely causing hypoxic pulmonary vasoconstriction , chronicWe hypothesized that greater residual volume, a standard clinical measure of pulmonary hyperinflation and alveolar gas trapping on body plethysmography , would bThe MESA COPD Study is a cross-sectional study of smokers nested among the Multi-Ethnic Study of Atherosclerosis (MESA) and the A V6200 Series Autobox  and an OMI rolling barrel spirometer were used to perform body plethysmography and post-bronchodilator spirometry, respectively, following American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations , 32 and Gas trapping was defined as residual volume or residual volume/TLC above the upper limit of normal; hyperexpansion was defined as FRC or TLC above the upper limit of normal.Cardiac MRI was performed at 1.5 Tesla  using the MESA protocol as previously described . An obliTo measure left ventricular function, the entire heart was imaged in short-axis orientation with 12 or more slices. All cine images had temporal resolution of 48 msec and were retrospectively reconstructed at overlapping 20–35 msec intervals over the cardiac cycle with 40 phases. Semi-automated contouring was used to determine left ventricular volumes and ejection fraction  . CardiacTo measure the volume of the left atrium (LA), an experienced operator defined the LA endocardial and epicardial borders at the frame of the largest LA volume using the Multimodality Tissue tracking software  on long-axis 2-chamber and 4-chamber cine MR images. The volume was calculated using the biplane method as follows: LA volume = (0.848 * area4chamber * area2chamber)/(length2chamber + length4chamber)/2 .A GE 64-slice helical scanner  with 0.75 mm slice thickness was used to perform full-lung thoracic CT on the participants. Images were obtained at suspended full inspiration. Percent emphysema was assessed via the Apollo software  at a single, independent reading center blinded to other participant The percentage of total voxels within the lung field with values below -950 Hounsfield units (HU) was designated as percent emphysema  .Anthropometry, blood pressure and other co-variates: Age, gender and race or ethnic group were self-reported. Height, weight, seated blood pressure were measured according to the MESA protocol [protocol . SmokingThe institutional review boards of the participating institutions, which include Columbia University, UCLA, Johns Hopkins, University of Iowa, Northwestern University, University of Washington, and the National Heart, Lung, and Blood Institute, approved the study procedures. Written informed consent was obtained from all participants in the MESA COPD Study.The cohort was stratified by quartiles of percent predicted residual volume for descriptive purposes. The initial analysis of the relationship between systolic and diastolic PA cross-sectional area and residual volume was performed using multiple linear regression with adjustment for the following potential confounders and precision variables: age, gender, height, weight, race-ethnicity, FEV1, resting oxygen saturation, cohort and percent emphysema. The full model additionally included smoking history and status, blood pressure and left ventricular ejection fraction. To minimize the possibility of confounding by body size, the analyses were repeated for another measure of hyperinflation, residual volume to TLC ratio (RV/TLC). Analyses for PA cross-sectional area and percent emphysema proceeded in a similar fashion. Analyses were weighted according to the inverse ratio of sample prevalence to source study prevalence, as previously described , to avoiOf the 106 participants, the mean age was 69.5±5 years and 57% were male. 2 increase in the main PA systolic cross-sectional area . Results were very similar and equally significant for the main PA diastolic cross-sectional area  were associated with PA dimensions. These findings suggest that gas trapping, but not emphysema, are associated with pulmonary vascular remodeling in current and former smokers.The present report is the first, to the best of our knowledge, to consider the relationship between pulmonary hyperinflation, gas trapping and PA size. A few prior studies have shown a relationship between pulmonary hyperinflation and increased PA pressure. The classic experiments by West elucidated the relationship between alveolar pressure and regional pulmonary blood flow, demonstrating that increasing alveolar pressure in the presence of constant pulmonary arterial pressure results in decreasing regional pulmonary blood flow. These experiments helped define the concept of the “West lung zones” . Hakim aThe effect of gas trapping and hyperinflation on PA pressure and pulmonary vascular resistance in patients with COPD has been previously studied in small but interventional studies. Harris and colleagues reported that voluntary hyperventilation to achieve high minute ventilation in patients with chronic bronchitis resulted in increased PA pressures and increased pulmonary vascular resistance but that it had no such effect in normal patients . SimilarIt has been postulated that emphysematous destruction of the pulmonary vasculature contributes to elevated pulmonary vascular pressures in COPD . HoweverThe present findings and above studies suggest that impaired left ventricular filling and concomitant reductions in stroke volume related to percent emphysema, which have been previously observed in a large, population-based cohort free of clinical cardiovascular disease  and in tThe present study has several limitations. First, because pulmonary cross-sectional area was measured rather than PA pressure, the proposed mechanism of increased PA pressure from downstream alveolar vessel compression leading to PA dilatation remains speculative. Conceivably, hyperinflation could cause architectural changes of the pulmonary vasculature leading to an increase in PA cross-sectional area without necessarily an increase in PA pressure. The testing necessary to demonstrate whether the increased PA cross-sectional area is from increased PA pressure or another cause are too invasive to be applied to a population-based study of participants free of clinical cardiovascular disease with predominantly mild to moderate COPD. Further work is needed to elucidate the direct relationship between hyperinflation and PA pressure by directly measuring or estimating PA pressures in patients with mild to moderate COPD. Second, residual confounding by left ventricular diastolic dysfunction may have contributed to the observed association. Smith and colleagues, in the same cohort as this study, observed that greater residual volume and RV/TLC ratio is associated with greater left ventricular mass . HoweverIn conclusion, increased residual volume, a measure of pulmonary hyperinflation and gas trapping, was independently associated with increased PA cross-sectional area. In contrast, there was no evidence of a relationship of emphysema severity to PA dimensions. These results suggest that gas trapping may be a cause of increased PA pressure in COPD, possibly from alveolar vessel compression by distended alveoli.S1 Table-950 HU, forced expired volume in the first second and oxygen saturation. Model 2 was additionally adjusted for smoking status, pack-years of smoking history, systolic blood pressure, diastolic blood pressure and left ventricular ejection fraction. Abbreviations: CI denotes confidence interval, HU Hounsfield units, RV residual volume, TLC total lung capacity and FEV1 forced expired volume in the first second.Mean differences in model 1 were adjusted for age, gender, race or ethnic group, height, weight, cohort, percent emphysema(DOCX)Click here for additional data file.S2 Table-950 HU, forced expired volume in the first second, oxygen saturation, smoking status, pack-years of smoking history, systolic blood pressure, and diastolic blood pressure. Abbreviations: CI denotes confidence interval, HU Hounsfield units, RV right ventricle.Models were adjusted for age, gender, race or ethnic group, height, weight, cohort, percent emphysema(DOCX)Click here for additional data file.S3 Table-950 HU, forced expired volume in the first second, oxygen saturation, smoking status, pack-years of smoking history, systolic blood pressure, and diastolic blood pressure. Abbreviations: CI denotes confidence interval, HU Hounsfield units, RV right ventricle.Models were adjusted for age, gender, race or ethnic group, height, weight, cohort, percent emphysema(DOCX)Click here for additional data file.


Our results suggest that an easy prognostic approach based on the combination of three biomarkers, although with partially-overlapping pathophysiological mechanisms, is able to identify patients with the highest risk of heart failure progression.Galectin-3 and ST2 are emerging biomarkers involved in myocardial fibrosis. We evaluate the relevance of a multiparametric biomarker approach based on increased serum levels of NT-proBNP, galectin-3, and ST2 in stratifying the prognosis of chronic heart failure (CHF) outpatients. In 315 CHF outpatients in stable clinical condition clinical and echocardiographic evaluations were performed. Routine chemistry and serum levels of NT-proBNP, galectin-3, and ST2 were also assessed. During a 12 month follow-up, cardiovascular death, and/or heart failure (HF) occurred in 64 patients. The presence of NT-proBNP, galectin-3, and ST2 were higher than the recommended cutoffs and were all associated with events at univariate Cox regression analysis, as well as in a multivariate analysis including the three biomarkers. When a score based on the number of biomarkers above the recommended cut-offs was used (in a range of 0–3), it was associated with events both with respect to the univariate (HR 2.96, 95% CI 2.21–3.95,  Over the last few decades there has been a growing interest in the use of biomarkers for diagnosis, prognostic stratification, and guiding therapy in heart failure (HF) patients . NatriurConsidering the distinct information carried by these three biomarkers, they could be used in order to achieve an improvement in the predictive accuracy of events. However, there are conflicting results regarding this issue. Several studies, including a recent meta-analysis , investiFinally, few studies were aimed at prospectively evaluating the possible usefulness of a multi-biomarker approach in order to stratify short- and mid-term prognosis and support their possible usefulness for differentiating patients’ risk and better planning follow-ups.The aim of our study was to investigate the possible integration of information carried by increased serum levels of NT-proBNP, Gal-3, and ST2 in order to better stratify the risk for heart failure progression in a group of chronic heart failure outpatients.A population of consecutive outpatients affected by CHF of any origin was referred to the Heart Failure Unit of the Cardiology Unit of Policlinic Hospital of Bari and was enrolled between May 2013 and May 2016. At the time of enrollment, they had been clinically stable for at least 30 days  and had received conventional medical and electrical therapy for at least three months previously, if not contraindicated. Patients with acute decompensated heart failure (ADHF) and renal failure requiring dialysis were excluded from the study. The study was approved by the local ethics committee and all patients gave their written informed consent for the study.Baseline evaluations. At the time of enrolment all patients underwent a medical visit, an ECG, an echocardiographic examination, and gave a blood sample for chemical evaluations.Medical examination and electrocardiogram. A documented record was made for each patient, including ischemic heart disease, arterial hypertension and diabetes mellitus diagnosis, as well as a history of ventricular arrhythmic events. During medical examination, New York Heart Association (NYHA) class and arterial pressure were evaluated. Heart rhythm and heart rate were assessed by a12-lead ECG.Echocardiographic evaluation. All patients underwent an echocardiographic evaluation using an echocardiograph . Left Ventricular end-diastolic (LVEDV) and end-systolic (LVESV) were recorded as absolute values and adjusted for body surface area, and left ventricular ejection fraction (LVEF) was calculated using Simpson’s rule. Mitral (MR) and tricuspid regurgitation (TR) were semi-quantitatively evaluated with arbitrary units ranging from 0 to 4. Tricuspid annular plane excursion (TAPSE) was used to assess the right ventricular systolic function [function . Dilatatfunction . PulmonaChemical evaluations. Blood samples were taken, after subjects remained in supine position for at least 10 minutes, in order to evaluate serum creatinine, urea, hemoglobin, NT-proBNP. The GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (GFRCKD-EPI). Galectin-3 levels were evaluated in the plasma with an enzyme-linked immunosorbent assay , while ST2 was assessed by a kit . In order to assess the presence of abnormal values of NT-proBNP, ST2, and Galectin-3, the current recommended cut-offs were considered .Follow-up. The patients received follow-up as outpatients according to the protocol of our Heart Failure Unit. The occurrence of death and hospitalizations within the first 12 months were recorded reflecting the underlying cause. Deaths were classified as being due to cardiovascular or non-cardiovascular causes. In cases of death outside the hospital, or in other centers, relatives were interviewed and related medical documentation was acquired. The primary end-point was a composite of cardiovascular death and HF related hospitalization.Statistical analysis. Continuous variables are expressed as mean values ± SD. Categorical variables are expressed as the absolute frequency or percentage. Pearson's linear correlations were used to assess the relationship among biomarkers and the other studied variable.Comparisons among groups were performed by ANOVA analysis and post-hoc comparisons by Newman-Keuls test comparisons among groups of the categorical variables that were performed with the chi-square test or Fisher test.p < 0.05 to retain covariates in the model. To avoid multicollinearity, redundant variables were dropped from the multivariable regression models in the case of pairwise correlations between continuous variables exceeding 0.50 as Pearson’s coefficient, including the variable with the strongest individual effect size [The event-free survival curves were based on Kaplan–Meier analyses. Univariate Cox’s proportional hazards model was used to assess the association of variables with the endpoints. For all variables, hazard ratios (HRs) with their 95% confidence intervals (CIs) are given. The final reference model for the primary endpoint was developed with a Cox multivariate regression analysis including all of the univariate predictors by using a forward stepwise selection approach with ect size . To testModel discrimination was examined with the c-statistic. To quantify the clinical impact of RRI on the models, integrated discrimination improvement (IDI), and category-free net reclassification improvement (NRI) were calculated. IDI considers the change in the estimated prediction probabilities as a continuous variable. NRI were calculated as the observed event rate increase among the individuals for whom the predicted risk goes up and the observed event rate decrease among those for whom the predicted risk declines .2, Urea > 50 mg/dL, hemoglobin < 12 g/dL, natremia < 135 mEq/L), the BIOSTAT-CHF [Finally, the independent association of biomarker score with primary end-point was tested by a multivariate regression models separately, including the presence of traditional biomarkers according to the recommended cut-offs  and STATA software, Version 12 . A total of 315 patients were enrolled, 230 (73%) affected by heart failure with reduced ejection fraction, 69 (22%) by heart failure with mid-range ejection fraction and 16 (5%) by heart failure with preserved ejection fraction. Baseline clinical characteristics of study population are shown in As shown in p < 0.001; free NRI 0.338; p < 0.001).As shown in In Biomarker scores also remained significantly associated with events with respect to the multivariate regression analysis in a model including the traditional biomarkers, i.e., the presence of low sodium levels, of low hemoglobin, high urea, and of a GFR below 60 mL/min with a significant IDI and free NRI .Finally, with respect to the univariate analysis, the biomarker scores showed a C-index greater than that of the BIOSTAT-CHF model (C-index 0.70) and similar to that of the MAGIC score (C-index 0.80). Moreover, an independent and significant association with events was found with respect to the multivariate analysis after correction for BIOSTAT-CHF, as well as after correction with MAGIC score . When thThe main findings of this study are that a score based on the integration of three biomarkers, i.e., NT-proBNP, Gal-3, and ST2, provides better prognostic stratification for predicting short and mid-term occurrence of heart failure progression, thus suggesting the possible usefulness of this simple approach in clinical practice.Risk stratification of patients affected by heart failure is based on a number of clinical and laboratory evaluations. Among these parameters, blood levels of cardiac biomarkers give the possibility of predicting outcomes, in terms of recurrent heart failure-related readmissions and death. Although biomarkers cannot replace the clinical assessment based on history, or physical and laboratory examination, in any case, they can offer an objective and reproducible parameter for risk estimation. This could be useful in those clinical settings, such as primary care and community care medicine, in which cardiological examinations like echocardiograms are not easy to perform.Up to now the only biomarkers strongly recommended in risk stratification have been natriuretic peptides. They have an established role in the prognostic evaluation of heart failure patients, with the highest grade of recommendation in the last ACCF/AHA HF guidelines for estimating prognosis or disease severity both in the acute and chronic patients . HoweverOn the basis of these limitations, there has been growing interest in combining different biomarker measurements, reflecting multiple biological processes of HF progression, in order to improve risk stratification and overcome some of the limits of natriuretic peptides ,30. In tOur results confirm that Gal-3 and ST2 carry different information from NT-proBNP. This is particularly evident when the correlation with the other clinical variables evaluated in our study is considered. In fact, ST2 appears less influenced by age or renal function. Gal-3 seems to be a biomarker strongly influenced by renal function, weakly correlated with left ventricular diastolic and systolic functions.Moreover, our study demonstrates that the integration of the information carried by altered Gal-3 and ST2 to that of NT-proBNP improves the risk stratification of CHF patients by adding an incremental prognostic value. In particular, it is possible to divide the population into four groups of risk according to the number of altered biomarkers, i.e., a group at low risk with no biomarker elevated, a group at low–intermediate risk with only one biomarker elevated (NT-proBNP or one of the fibrosis biomarkers), a group at intermediate–high risk with two biomarkers elevated, and a high risk group with all the biomarkers altered.From a methodological point of view we demonstrated this hypothesis by prospectively studying a homogenous group of outpatients in stable clinical conditions, following-up on them for one year. We censored the follow-up at this time considering that any prognostic parameter evaluated at the time of a visit should provide information about short- and mid-term follow-up in order to better assess whether an intensive follow-up was needed or not. Moreover, we used the cut-offs of biomarkers currently recommended in order to better reflect the use of biomarkers in routine practice.Finally, to better define the prognostic usefulness of the biomarker prognostic model proposed, we compared it with the BIOSTAT-CHF, a recently-validated model for predicting mortality and hospitalization of CHF patients. The biomarker score showed a similar C-index and proved to be significantly and independently associated with events, adding incremental prognostic information to the BIOSTAT-CHF model.The main limitation of our study is that the real impact of a biomarker strategy should be demonstrated by studies evaluating if the management of patients based on the biomarkers-strategy is able to reduce heart failure hospitalization thus supporting their use by a cost-effectiveness analysis. Moreover, the biomarker strategy should be compared with that based on echocardiography in order to better understand if it can be alternative or not. Finally, the clinical characteristics of our population do not reflect those of the general population affected by heart failure. They were younger and mainly affected by heart failure with reduced ejection fraction. This is due to the fact that our heart failure unit is a regional tertiary center with a program for heart transplantation and/or left ventricular assist device implantation. This is a further limitation of our study.Our results support the possible usefulness of the combination of NT-proBNP, ST2, and Galectin-3 in order to identify the patients with the highest risk of heart failure progression in the short and mid-term follow-up. This can be due to the fact that these biomarkers can integrate with each other, reflecting different pathophysiological substrates leading to worsening heart failure.


Noise, as the most common pollutant in the industrial environment, can lead to hearing loss and negatively affect other organs such as the cardiovascular system. Cigarette smoking is a popular habit among some workers, and can also have a negative effect on the cardiovascular system. This study was aimed to investigate the effect of simultaneous exposure to noise and cigarette smoke on the blood pressure of workers at a manufacturing factory.This cross-sectional study enrolled 604 workers at a steel factory. Information relating to workers’ demography, employment, and risk factors were recorded. Based on the level of smoking per day, workers exposed to noise fell into one of the four following groups: 1) Non-smokers exposed to noise <85 DB; 2) Smokers exposed to noise <85 DB; 3) Non-smokers exposed to noise ≥85 DB; 4) Smokers exposed to noise ≥85 DB. A t-test, analysis of variance (ANOVA), and logistic regression were applied for analysis using SPSS v11.5.The prevalence of hypertension, cigarette smoking, and exposure to noise ≥85 DB was 11.6%, 15.3%, and 56.4%, respectively, among the workers. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 112.3 and 73.9 mmHg, respectively. A significant difference was observed between systolic and diastolic blood pressures in four groups (P=0.001). Posthoc test showed a significant difference between groups 1 and 3 (P=0.001). Regression analysis indicated no significant difference in workers who were simultaneously exposed to noise and cigarette smoke.This study demonstrates that noise is an important factor in terms of hypertension, with no significant differences observed in the prevalence of hypertension between workers who were simultaneously exposed to noise and cigarette smoke. It is suggested that workers’ blood pressure should be regularly monitored in noisy environments. As the most common pollutant in industrial environments, noise can lead to hearing loss and many other negative effects on functions such as the cardiovascular system. Various studies have shown that environments with a noise level above 85 DB could negatively increase blood pressure among workers –6. It seOn the other hand, noise changes the heart beat, decreases heart output, and increases respiratory rate –9. Because the presence of high blood pressure in a noisy environment could in the long term cause chronic hypertension, investigating the relationship between high blood pressure and exposure to noise is of considerable importance .Up to 2009, the prevalence of tobacco smoking was approximately 26% in Western countries . There aThe association between high blood pressure and smoking is still under investigation. Some studies have demonstrated that blood pressure increases in smokers ,17, espe Cotinine, the main metabolite of nicotine, is a vasodilator and could, therefore, decrease blood pressure . For theThis study was a cross-sectional survey carried out in a steel factory in Khorassan Province over a period from 2014 to 2015. All 604 participants were male and had more than 1 year of work experience, and all knowingly contributed to the research. Exclusion criteria in this study were a diagnosis of hypertension, diabetes, chronic cardiovascular, or kidney diseases, and use of drugs such as corticosteroids which affect blood pressure before beginning employment at the factory. After exclusion of 17 workers diagnosed with diabetes, three with chronic kidney disease, one taking corticosteroids, and three presenting with high blood pressure, 580 workers were included in the final analysis. This study was approved by the Ethics Committee of Mashhad University of Medical Sciences (code: 930365).Required demographic, medical, and employment data were assembled through interviews. Demographic data consisted of age, gender, body mass index (BMI), marital status, educational degree, medical history , and lifestyle . As the workers included made no regular use of hearing protection devices, this factor was not assessed. In this study, the term exercise refers to regular 30-minute sessions of exercise, 3 days per week ; smokersThe heights and weights of the workers were measured, and their BMI was calculated by dividing their weight by the square of their height. Blood pressure was measured using 10–1240cm cuffs from ALPK2. SBP and DBP were measured twice, at least 30 minutes after eating, exercising, or smoking  twice a Finally, participants were classified into four groups on the basis of data collected with respect to their level of exposure to noise and cigarette smoke, as follows: 1) Non-smokers exposed to noise <85 DB; 2) Smokers exposed to noise <85 DB; 3) Non-smokers exposed to noise ≥85 DB; 4) Smokers exposed to noise ≥85 DB.Mean values, standard deviation (SD), and range are presented for quantitative variables. A t-test and analysis of variance (ANOVA) were used for comparison of the variables in each group. A Chi-square test was utilized for comparing qualitative variables. Logistic regression analysis was used to eliminate confounding variables and assess the relationship between exposure to noise and smoke and hypertension. All tests showing a confidence level equal to 95% and a significance level less than 0.05 were considered significant. All statistical calculations were conducted using SPSS version 16.2, the average work experience was 12.4 (2–24) years, and the average SBP and DBP were 112.3 (70–180) and 73.9 (40–105) mmHg, respectively. The research sample in this study consisted of 580 workers at a steel factory. The average age was 39.1 (21–64) years, the average BMI was 24.9 (16.4–36.6) kg/mAn ANOVA test was applied to examine the average SBP and DBPs . A signiA chi-square test was utilized to assess the prevalence of systolic and diastolic hypertension in the four groups . AlthougThis study examined the effect of simultaneous exposure to noise and cigarette smoke on workers’ blood pressure. The observed difference in systolic and diastolic hypertension was statistically significant, but not clinically significant. This observation is consistent with the findings of Chang et al. who conducted a prospective cohort study in Taiwan over a 10-year period .In the current study, a significant difference was observed between mean systolic and diastolic hypertension in Groups 1 and 3 comparing those exposed and not exposed to noise. This shows that prohibited noise levels could negatively increase the prevalence of systolic and diastolic hypertension, although no synergic effect was observed in the concurrency of noise and cigarette smoke. In another study reported by Sancini et al., a significant increase was seen in average SBP and DPB in the group exposed to noise ; consistThe greatest prevalence of high blood pressure and systolic and diastolic hypertension was observed among non-smokers who were exposed to the prohibited level of noise (Group 3). Logistic regression analysis was applied to assess the relationship between prevalence of hypertension in the presence of the confounding variables of age and regular exercise in the four groups. This analysis did not indicate any significant differences between systolic and diastolic hypertension among the groups. Previous research in 1,205 workers in the textile industry revealed a prevalence of hypertension that was 1.34 times greater than that in the control group . This diAziz et al. examined the relationship between smoking and high blood pressure in 712 males and females and found no significant relationship between the prevalence of hypertension and smoking, which was consistent with the results of the present study , AlthougIn the current study, no significant relationship was observed between simultaneous exposure to noise and high blood pressure, and no significant association was seen between being exposed to the prohibited level of noise and smoking and high blood pressure after controlling for confounding variables. This may be due to the insufficient number of smokers in the population in this study. One of the limitations of this study is its subjective nature, since workers may not be totally honest due to the culture dominant in the society which discourages smoking, alcohol intake, and using other forms of smoking such as opium. Another limitation was the cross-sectional design, which did not allow investigation of the association between smoking and being exposed to noise. Innovation could be considered one of the strengths of this study, since the effect of simultaneous exposure to noise and cigarette smoke on blood pressure has not been examined so far. It is suggested that a longitudinal study is carried out on larger sample sizes.Although no association was found between smoking and being exposed to noise, this may be due to the insufficient number of smokers in the study population. However, a relationship between noise and hypertension was observed, and it is therefore suggested that a longitudinal study is carried out on larger sample sizes.


Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD.p < 0.01 considered significant).Eighty ADPKD patients  and 50 healthy subjects  were enrolled in the study. Serum levels of 384 miRs were determined by Biomark Real Time PCR. Groups were compared using the limma method with multiple-testing correction as proposed by Smyth (corrected p < 0.001]). Adjusting for age and starting CKD stage using multiple binary logistic regression analysis did not abrogate the predictive value.Comparing ADPKD to HS, we found significant differences in blood levels of 18 miRs (3 more and 15 less abundant). Of these, miR-3907, miR-92a-3p, miR-25-3p and miR-21-5p all rose while miR-1587 and miR-3911 decreased as renal function declined in both cross-sectional and longitudinal analysis. Using ROC analysis, an increased baseline miR-3907 in the circulation predicted a > 10% loss of GFR over the following 12 months  contains supplementary material, which is available to authorized users. Autosomal dominant polycystic kidney disease (ADPKD) is a congenital progressive disease resulting in chronic kidney disease (CKD) that often progresses to end-stage renal disease (ESRD). In most patients, renal function is sufficient to live a normal life until the fourth to sixth decades of life but thereafter declines . The maiMicroRNAs (miRs) are small, non-coding RNA molecules that modulate many different intracellular pathways negatively regulating gene expression at the post-transcriptional level. As each miR has multiple putative targets, and as the distribution of miRs vary between cell types and over time, they are likely to play a physiological role . In renaIn the present pilot study, we asked if circulating miRs would differentiate ADPKD patients from healthy subjects under clinically relevant conditions, and if levels of any circulating miR would predict the furure clinical course of ADPKD during one year of follow-up.Among the patients with ADPKD included in the Turkish Society of Nephrology’s Polycystic Kidney Disease Working Group Registry, we screened those scheduled to receive followed-up by the Medical Faculty of Erciyes University between June 2013 and January 2015. The study was approved by the Erciyes University Ethical Review Board  prior to start, and all participants signed written informed consent forms after being informed about the study and given time to consider their participation.2 and those with diagnosed cardiovascular disorders, diabetes mellitus or an active infection were all excluded. The patients were invited to enroll by post, and those that accepted all signed written informed consent forms. Demographic characteristics , renal manifestations  and cardiovascular manifestations  were hen recorded using a web-based data collection form. Using the above criteria, 80 ADPKD patients were included in the study. A total of 50 healthy subjects were also recruited by advertisement and gave written, informed consent to participate. Both patients and controls were asked to undergo ambulatory blood pressure monitoring to diagnose the presence or absence of hypertension. Data of 24 h urine samples was collected at inclusion and in the patients again after exactly 12 months of follow-up (n = 80) to determine eGFR (mean of urinary creatinine and urea clearances) and proteinuria levels.Eligible patients were those aged 18–70 years under regular follow-up and meeting the above diagnostic criteria for ADPKD. Patients with a known glomerular filtration rate (eGFR) <15 ml/min/1.73 mn = 10).Twenty-four-hour blood pressure monitoring was performed using a Del Mar Medical Ressurometer Model P6 , and the results were assessed using the companion software. Ambulatory measurements were conducted once every 15 min from 7 a.m. until 11 p.m., and once every 30 min from 11 p.m. until 7 a.m. Evaluation was performed taking the mean values of day and night blood pressures into account. Hypertension was considered to be present if the average systolic pressure was ≥130 mmHg and/or the average diastolic pressure was ≥80 mmHg over the 24-h, or if the individual was taking antihypertensive medication  with the resulting serum aliquoted into 200 μl and stored at −80 °C until RNA isolation. Total RNA was isolated using Trizol (500 μL)  according to the manufacturer’s instructions and stored at -80 °C.Isolated RNA samples were reverse-transcribed into complementary DNA (cDNA) in 5 μl final reaction volumes using MicroRNA Reverse Transcription Kit . cDNA samples were kept at -80 °C until PCR analysis. Next, we performed pre-amplification using the PreAmp Master Mix  together with the miScript miRNA PCR Array Human Serum & Plasma 384HC  . Preamplified cDNA samples were diluted with low EDTA (0.1 mM) TE Buffer (1:5). A BioMark IFC controller HX  was used to mix a total of 3.15 μl diluted preAmplified cDNA with appropriate amounts of Universal PCR Master Mix,  and 20X GE Sample Loading Reagent  in a Dynamic 96.96 array plate microfluidic system . Real-Time PCR was performed automatically using a thermal mixing protocol followed by 50 °C for 120 s, 70 °C for 1800 s, 25 °C for 600 s, then followed 95 °C for 600 s. Finally, 23 cycles with 94 °C for 15 s, 55 °C for 30 s, 70 °C for 30 s followed by 60 °C for 60 s. All of the genetic studies were performed by experienced operators in the Genome and Stem Cell Center at Erciyes University (GENKOK).-ΔΔCT method. To detect the differentially expressed miRs, the linear models for microarray and RNA-Seq data (limma) procedure was used along with false discovery rate correction of p values according to Smyth ) or non-hypertensive (HT-). Comparing miRNAs copy numbers between these groups, patients with hypertension had signficantly different levels of 21 miRs when compared to non-hypertensives . However, these differences were not obvious when HT+ and HT- patients were compared with controls  during follow-up. Using data of baseline and follow-up eGFR, we estimated each patients’ decline during the year (median − 5 [range + 2 to −29] mL/min/1.73m2/ year). Patients were then grouped into two groups according to if their loss over the period was ≤10% or >10% of their baseline value. 30 patients had progression rate above 10%.As expected, there was a small but statistically significant decrease in eGFR (74 ± 35 to 69 ± 32 mL/min/1.73mp < .0001).Next, we assessed the relative predictive value of the miRs that differed significantly between hypertensive and non-hypertensive ADPKD to predict the future loss of eGFR >10%. Of these, only miR-3907 was significantly predictive in ROC analysis Fig. . The senAdditionally, we performed univariate and multiple binary logistic regression analysis comparing the realtionship between selected variables and progression outcomes in all patients. A loss of eGFR >10% during follow-up was independently associated with age, CKD stage and miR-3907  is the most common genetic cause of chronic kidney disease , 13. WhiWe found significant differing levels of multiple miRs both between ADPKD patients and healthy controls, as well as between ADPKD hypertensives (HT+) and non-hypertensives (HT-). In each case the differences were at most 3-fold, while the overlap between HT+ and HT- groups was significant and apparently not associated with blood pressure Fig. . Differe2+-channel in the endoplasmic reticulum reported to be a main effector of PKD 1 and 2-induced calcium signaling [2+-amplified Ca2+ release. Similarly, IP(3)RIP has been demonstrated to robustly enhance Ca2+-mediated inhibition of IP(3)R Ca(2+) release [2+-release, triggering a compensatory downregulation of IP(3)RIP through miR-targeting of its’ mRNA.While miR-3907 is not predicted to target mRNA derived from PKD1 or 2, the canonical ADPKD-associated genes, it is highly likely to bind to mRNA of the inositol 1,4,5-trisphosphate receptor (IP3R) interacting protein (IP(3)RIP) . This isignaling . Indeed, release . SpeculaThe source cells and targets of the miRs identified in the present study may also the molecular pathogenesis of ADPKD. miR silencing of target mRNAs is mediated by complementary sequences (miR recognition element) located in the 3′ untranslated region (UTR) of the mRNA matching approximately 2–8 nucleotides (the seed region) at the 5′ end of the miR. Thus, any given miR is likely to have more than one target mRNA. Despite this complexity, recent research has elucidated specific roles for individual miRs in kidney development and physiology , 10, 17.Cpk mouse model [As shown in Fig. se model . Finallyse model .Other signalling pathways regulated by the miRs significantly different between the groups in our data include apoptosis, where miR-92a-3p and miR-202-5p have both been reported to display phenotype-relavant protective roles in models of IgA . FinallyA number of weaknesses in the present study must be acknowledged. The absence of a non-ADPKD CKD control group is a weakness, especially as our data suggests that eGFR is a significant determinant of several miRs. Also, the limited number of patients combined with the lack of ultrasonographically measured renal volumes also limits the interpretation of the data. Nonetheless our data are among the first measuring miRs in ADPKD and may serve as a foundation for future candidate-based studies.The present study suggests (a) that random blood-sampling in a clinical setting can yield meaningful patterns of miRs, (b) that these patterns vary between healthy subjects and those with kidney disease, and, finally, (c) that increased copy numbers of miR-3907 in the circulation predicts the future decline in eGFR among ADPKD patients followed for 12 months.


Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT).Cross-sectional study including 65 individuals: controls (n = 20) and Fabry patients . Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia. CD80 mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes.Controls and Fabry patients did not differ in age, eGFR and gender. However, UPCR, uCD80 and podocyturia were significantly higher in Fabry patients than in controls. As expected, Fabry patients not on ERT were younger and a higher percentage were females. Non-ERT Fabry patients had less advanced kidney disease than ERT Fabry patients: UPCR was lower and eGFR higher, but uCD80 and podocyturia did not differ between non-ERT or ERT Fabry patients. There was a significant correlation between uCD80 and UPCR in the whole population  and in Fabry patients . Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uCD80 expression in cultured podocytes.Fabry disease is characterized by early occurrence of increased uCD80 excretion that appears to be a consequence of glycolipid accumulation. The potential for uCD80 excretion to reflect early, subclinical renal Fabry involvement should be further studied. Fabry disease is an X-linked storage disease due to mutations in the GLA gene encoding α-galactosidase A, leading to the lysosomal accumulation of enzyme substrates, namely globotriaosylceramide (Gb3), lyso-globotriaosylceramide (lyso-Gb3) and galabiosylceramide . The intIn this study, we explored the urinary excretion of CD80 in patients with Fabry disease and the potential drivers of CD80 expression.This is cross-sectional, observational study included 65 individuals. A group of 20 healthy subjects without known clinical morbidities or pharmacological treatment was recruited among potential kidney donors and subjects with normal laboratory results and clinical history. In addition, 45 Fabry patients were studied. Of them 23 were not treated with enzyme replacement therapy (ERT) while 22 had received ERT for at least 12 months with agalsidase beta 1 mg/kg administered every fortnight . Fabry disease was diagnosed in all cases by low enzymatic alpha galactosidase A activity in dried blood spots and peripheral blood leukocytes, and confirmed by the identification of a GLA gene mutation. Patient characteristics are outlined in Table g for 5 min in a cytospin. The supernatant was discarded and the sediment was stored in 100 µl aliquots at room temperature mixed with a 1.5 ml solution of 40 % formaldehyde diluted in phosphate-buffered saline (PBS) (pH 7.2–7.4) to reach a final 10 % concentration. Podocyte nuclei were stained with 40,6-diamidino-2-phenylindole (DAPI). Podocytes were identified by immunofluorescence using anti-synaptopodin as the primary antibody  and IgG anti-rabbit Alexa Fluor® 488  as the secondary antibody. Samples were analyzed employing an epifluorescent microscope. Following our standardized technique, podocytes were counted in 10 randomly chosen 20× fields and the average of the counted podocytes in the microscopy fields was considered as the final count for each subject. Results were corrected based on the urinary creatinine concentration of the initial urinary volume of 20 ml employed for podocyte counting [We have previously described the method to study podocyturia in detail . Brieflycounting , 25.®, affymetrix eBioscience, San Diego, CA USA).Serum creatinine was assessed the same week that urine was collected for podocyte counting. UPCR was measured from the specimen employed for podocyte assessment. The urinary concentration of CD80 was determined employing a Human CD80 Instant ELISA . One microgram RNA was reverse transcribed with High Capacity cDNA Archive Kit . Real-time PCR reactions were performed on the ABI Prism 7500 sequence detection PCR system (Applied Biosystems) according to the manufacturer’s protocol using the DeltaDelta Ct method , 17. ExpKidney samples were obtained from excess tissue corresponding to kidney nephrectomy specimens donated to the biobank of the IIS-Fundacion Jimenez Diaz Biobank after diagnostic evaluation was performed. The local Ethics Committee approved the study protocol and informed consent was obtained. Control human kidney specimens were taken from normal portions of renal tissue from patients who underwent surgery because of localized renal tumors. One renal biopsy from a male Fabry patient was studied, a 69 year old with serum creatinine 4.2 mg/dl, proteinuria 0.7 g/24 h. Immunohistochemistry was carried out in paraffin-embedded tissue section 5 μm thick. The primary antibody was mouse monoclonal anti-CD80 . Sections were counterstained with Carazzi’s hematoxylin. Negative controls included incubation with a non-specific immunoglobulin of the same isotype as the primary antibody.Results are expressed as median and ranges. Variables were analyzed using the Wilcoxon Mann–Whitney test. Correlations between variables were obtained with the Spearman correlation coefficient. Results were considered significant when p < 0.05. The statistical program employed was InfoStat 2016, Córdoba Argentina.Controls and Fabry patients did not diff in age, eGFR or gender. However, UPCR, uCD80 and podocyturia were significantly higher in Fabry patients Table . Fabry pSince uCD80 was increased in the urine of Fabry patients, we next explored the expression of CD80 in human Fabry disease tissue. No expression of CD80 was observed in control kidneys. However, immunohistochemistry confirmed CD80 expression in podocytes in a kidney biopsy from a Fabry patient Fig. .Fig. 1ExSince uCD80 was increased early in Fabry nephropathy, even in the group of patients with better preserved eGFR and lower albuminuria, we explored whether glycolipids accumulated in Fabry disease may increase CD80 expression in kidney cells. We had previously shown that lyso-Gb3, at concentrations found in the circulation of Fabry disease patients, increases the expression of diverse mediators of kidney injury in a time- and dose-dependent fashion, with peak response observed at 100 nM and 24 h , 17. LysIn the present study, we have confirmed that in Fabry disease podocytes are lost in urine in higher amounts than in controls and that this is an early feature, present already in patients with subclinical kidney disease. If maintained over time, this may lead to podocyte loss and to the classical glomerular lesion of Fabry nephropathy: focal and segmental glomerulosclerosis. A novel finding is that uCD80 excretion is also increased early in Fabry nephropathy. While there was a correlation between uCD80 and proteinuria, the lack of correlation between uCD80 and podocyturia suggests that podocyturia appears not to be linked to the activation of CD80 signaling pathways and that uCD80 and podocyturia reflect different aspects of kidney injury in Fabry nephropathy. Moreover, we have identified lyso-Gb3 as a potential driver of CD80 expression in podocytes. Lyso-Gb3 had been previously shown to increase the expression or secretion of TGFβ1, CD74, Notch1 and MCP-1 in podocytes , 17. ThuIn Fabry disease, silent and heavier podocyturia occurred in younger individuals when median eGFR and proteinuria were still normal. Furthermore, uCD80 was already elevated in younger patients and females that were not yet on ERT, suggesting that it may be an early marker of kidney injury. In addition, uCD80 remained increased in patients on ERT. Since this was a cross-sectional study, it is unknown whether uCD80 had been higher at the start of ERT and had decreased but not normalized with ERT. Whether earlier therapeutic interventions could normalize uCD80 levels requires further investigations. The current literature remarks that in Fabry disease, early ERT initiation is associated to better long-term results , 30. HowFabry nephropathy is a glomerulopathy. Thus, it is not surprising that the metabolic defect triggers the expression of inflammatory and fibrotic molecules, growth factors, cytokines and chemokines, as is the case for other glomerulopathies , 32. In It is currently unknown whether podocyte CD80 expression contributes to the pathogenesis of Fabry nephropathy by altering the shape, rearranging actin and altering glomerular permeability thus promoting proteinuria , 34. IndSince upregulated podocyte CD80 expression has been observed in several glomerulopathies, increased uCD80 levels are not expected to be diagnostic of Fabry nephropathy. Thus, they cannot presently replace renal biopsy. At present, assessment of podocyturia should be considered an experimental procedure. While it is a promising technique, since podocyte turnover is very limited and loss of podocytes results in irreversible glomerular injury, methods are not standardized for routine clinical assessment. It is likely that podocyturia is influenced by different factors, including availability of podocytes (it may decrease with advanced kidney disease due to loss of glomeruli) and rate of injury or death of remaining podocytes. In this regard, molecules expressed in stressed podocytes are likely shed and be present in urine as a result, without necessarily implying the urinary excretion of the podocyte of origin.There are several limitations in our study: In absolute terms, the number of patients is small and the study is cross-sectional. However, few studies in rare renal diseases are able to recruit higher number of patients, and a prospective study will require several years of follow-up, given the 40 year natural history of Fabry nephropathy. We have not directly addressed the cellular source of CD80 in vivo in the studied patients. Whether the uCD80 originates from lymphocytes, neutrophils and/or dendritic cells, or from abnormal CD80 expression in podocytes, tubular or endothelial cells is unknown. Our findings are based on a highly sensitive and specific human ELISA, but are limited to urine, and we cannot discern whether there are differences in the behavior of circulating and urinary CD80 levels. However, an unrelated Fabry kidney biopsy and cell culture data suggest that podocytes could be one of the sources of uCD80. While some patients were off ERT and others on ERT, the cross sectional nature of the study does not allow to draw definitive conclusions on the role of podocyturia and excretion of CD80 as treatment monitoring biomarkers. The off ERT and on ERT groups are not comparable. Patients not yet on ERT were significantly younger and we have only one assessment for patients on ERT: in the absence of baseline values, it is unknown how these parameters might have changed upon initiation of ERT.In summary, we confirmed the early development of podocyturia in Fabry patients. Moreover, we observed an early increase in uCD80. The fact that CD80 expression is increased by lyso-Gb3 in podocytes suggests that uCD80 may be an early marker of kidney injury in Fabry disease and also a marker of continued renal injury by glycolipids and future studies exploring the potential of uCD80 to reflect early, subclinical renal Fabry involvement are warranted.In Fabry disease podocyturia and urinary excretion of CD80 rise early in the disease process, even in patients with normal renal function. CD80 expression appears to be driven by exposure to glycolipids such as lyso-Gb3. This suggests that podocyturia and urinary CD80 expression may provide information into early and continuing kidney injury in Fabry disease. This hypothesis should be confirmed in larger longitudinal studies.


Central hemodynamic indices have been demonstrated to correlate with coronary artery disease (CAD). However, in the context of type 2 diabetes mellitus (DM), this correlation has not been fully illustrated. Therefore, this study was employed to investigate the impact of DM on the correlation between aortic augmentation index and the severity of coronary artery disease.In this study, we analyzed 197 patients who underwent coronary angiography at Anzhen Hospital from September 2015 to January 2016. Central hemodynamics were non-invasively measured with BPro® device . The severity of CAD was defined according to SYNTAX scores. Type 2 diabetes was defined according to ADA guidelines. AIx@75 was defined as AIx normalized to a heart rate of 75 bpm. Receiver operating characteristics (ROC) determined the optimal cut-off value of AIx@75 to predict moderate to severe CAD. Multivariate logistic regression analysis evaluated the correlation between central hemodynamic parameters and CAD severity.p < 0.05). The cut-off value of AIx@75 to predict moderate-to-severe CAD as SYNTAX score more than 22 was 71.45. (2) In non-diabetic patients, correlation analysis revealed that AIx@75, augmentation pressure and peak relative time were significantly correlated with CAD severity (p < 0.05). After adjustment, AIx@75 remained as the only independent predictor of moderate-to-severe CAD . (3) In diabetic patients, the correlation between central hemodynamic parameters and the severity of CAD did not exist.Eighty-four (42.6 %) of the studied subjects were diabetic patients. Our findings were that (1) AIx@75 was significantly correlated with SYNTAX. (ROC analyzed AUC: 0.638, 95 % CI 0.555–0.721, Aortic augmentation index was significantly related to the severity of CAD and was an independent predictor of severe CAD. However, clinical practitioners should note that its value in DM populations was compromised. Central pressures are revealed to be better related to cardiovascular events than are peripheral pressures . FurtherType 2 diabetes mellitus (DM) is a common comorbidity for CAD. Diabetic patients with CAD demonstrate accelerated progression of coronary atherosclerosis, leading to worse clinical outcome . ArteriaPrevious studies have failed to elucidate the effect of comorbidities like type 2 diabetes mellitus on the correlation between central hemodynamic indices and CAD. In view of these considerations, we initiated the present study to investigate the correlation between non-invasively measured central hemodynamic parameters and the severity of CAD. Meanwhile, we explored in detail the influence of type 2 diabetes on the correlation.The cross-sectional study was performed at Anzhen Hospital in Beijing. We consecutively included patients who underwent coronary angiography at our center from September 2015 to January 2016. Exclusion criteria: 1. Patients without complete baseline data; 2. Patients whose central pressure measurement was not readable; 3. Patients who had previous coronary intervention or coronary artery bypass grafting, atrial fibrillation, or hemodynamically significant valvular heart disease were excluded. This study was approved by the Institutional Ethics Committee of Anzhen Hospital and all subjects gave written informed consent.Noninvasive blood pressure and pulse wave analysis were performed prior to coronary angiography with the commercially available BPro® device with A-Pulse CASP software . The BPro® device captured the radial waveform, which was subsequently used to generate central systolic pressure by N-point moving average method as described before . Periphewww.syntaxscore.com. The following is 12categorization of CAD severity assessed by SYNTAX score according to guidelines: low as ≤22, moderate as 23–32 and severe as ≥33 [Coronary angiography (CAG) was primarily performed through the trans-radial approach with standardized technique. To reach consensus, all coronary angiograms were visually assessed by at least two experienced interventional cardiologists. The extent and severity of coronary artery disease were determined by SYNTAX scores. The anatomical SYNTAX score was calculated with online calculator version 2.1 at e as ≥33 , 11.t test (two-tailed) or Mann-Whitney U-test for continuous data and the Pearson’s χ2- or Fisher’s exact test. Spearman’s correlation coefficient (two-tailed) was used for the analysis of the correlation between AIx and SYNTAX scores. The receiver-operating characteristic curve was used to evaluate the predictive accuracy of AIx@75 for moderate to severe CAD; the highest Youden index (J statistic) representing the maximum potential effectiveness was used to determine the optimal cut-off AIx@75 value. Logistic regression analysis was employed for multivariate and univariate analysis. A p value of <0.05 was considered statistically significant.The data were analyzed with the SPSS 15.0 software . Continuous variables were presented as mean ± standard deviation (SD) and categorical variables as percentages. Comparisons between groups were made by using the unpaired student p > 0.05), nor were laboratory findings and medications.Our study consecutively enrolled 318 patients. A total of 85, 20 and 16 patients were excluded due to a history of percutaneous coronary intervention, coronary bypass grafting and atrial fibrillation, respectively. The analysis of 197 participants compared 113 non-diabetic with 84 diabetic patients. Baseline characteristics are summarized in Table p < 0.05).Table p = 0.4).In the total patient group, univariate analysis revealed that AIx@75 was significantly correlated with SYNTAX score. AIx@75 value to predict the presence of moderate-to-severe CAD was 71.45  and diabetic groups .In addition, the correlation between central hemodynamic indices and SYNTAX score differed between groups: univariate logistic analysis showed that higher AIx@75, AP and lower PRT were significantly correlated with SYNTAX score in the non-diabetic group, but not correlated in the diabetic group. Similarly, multivariate logistic analysis showed that higher AIx@75 was significantly correlated with SYNTAX score in the non-diabetic group only Table . Figure To the best of our knowledge, this is the first study investigating the impact of type 2 diabetes on the relationship between non-invasively measured central hemodynamic parameters and CAD.Cho SW et al. found that AIx was significantly associated with the extent of CAD in the younger group . TanindiWe categorized our patients into diabetic versus non-diabetic groups and found that the predictive value of AIx was profound in non-diabetic patients only. Our findings are in line with Agnoletti D et al.  who founAIx is defined as a ratio of augmentation pressure and pulse pressure. Therefore, it is necessary to consider both elements when analyzing its changes. It has been proposed that global stiffening of arteries augments systolic pressure mainly through the increase of wave reflections, whereas local stiffening of proximal aorta amplifies forward pressure wave , 17. StuType 2 diabetes has been proven to be associated with increased central artery stiffness , 16, 18.First, the present study was limited by its relatively small sample size; thus, future research evaluating a larger number of patients is necessary. Second, the study’s observational design, permitted potential confounders to affect the result even after adjustment. Third, long-term follow up studies should be implemented to explore the possible predictive value of AIx for cardiovascular outcomes in non-diabetic patients. Forth, the current study didn’t record patient-reported duration of DM and DM-related organ damage. It will be valuable to investigate the impact of the duration or status of the disease on the correlation in future research.Aortic augmentation index is significantly related to the severity of CAD and is an independent predictor of more severe CAD. However, its value in DM population was compromised, which might be related to DM-specific arterial changes and clinical practitioners should be aware of the fact.


Background. To analyze the effects of factors other than the ocular trauma score parameters on visual outcomes in open globe injuries. Methods. Open globe injuries primarily repaired in our hospital were reviewed. The number of surgeries, performance of pars plana vitrectomy (PPV), lens status, affected tissues , intravitreal hemorrhage, intraocular foreign body, glaucoma, anterior segment inflammation, loss of iris tissue, cutting of any prolapsed vitreous in the primary surgery, penetrating injury, and the time interval between the trauma and repair were the thirteen variables evaluated using linear regression analysis. Results. In total, 131 eyes with a mean follow-up of 16.1 ± 4.7 (12–36) months and a mean age of 33.8 ± 22.2 (4–88) years were included. The regression coefficients were 0.502, 0.960, 0.831, −0.385, and −0.506 for the performance of PPV, aphakia after the initial trauma, loss of iris tissue, penetrating injury, and cutting of any prolapsed vitreous in the primary surgery, respectively (P < 0.05 for these variables). Conclusions. The performance of PPV, aphakia after the initial trauma, and loss of iris tissue were associated with poor visual outcomes, whereas cutting any prolapsed vitreous in the primary repair and penetrating-type injury were associated with better visual outcomes. Open globe injuries are some of the most common causes of irreversible vision impairment worldwide . All theKuhn et al. evaluated greater than 2,500 injuries and defined an ocular trauma score (OTS) . The OTSThe aim of our study was to analyze the effects of factors other than the OTS parameters on final visual outcomes in open globe injuries.In this study, we reviewed the medical records of patients at the Eskisehir Osmangazi University Hospital of Faculty of Medicine to whom emergent eye surgery was suggested for initial treatment from January 2012 to April 2015. The study was approved by the Institutional Review Board (2016-25). The data collection conformed to all the local laws and was compliant with the principles of the Declaration of Helsinki. The inclusion criteria for this study were as follows: (1) the patient was capable of describing his/her vision at the initial and final examinations; (2) a primary repair of an open globe injury was performed at our hospital; (3) complete charts were accessible, including the OTS parameters and details of the surgeries performed; and (4) follow-up of at least 12 months occurred.Informed consent was obtained from all the subjects or their parents before we performed each treatment. All primary surgeries were performed by experienced ophthalmologists  under general anesthesia. The other surgeries, specifically pars plana vitrectomy (PPV) procedures, cataract surgeries, and evisceration of the globe, were performed by the vitreoretinal, cataract, and oculoplastic services of our department, respectively.Computed tomography of the head and orbit was performed for all patients over 17 years of age to exclude foreign bodies and orbital-wall fractures. Postoperative care was applied based on previous studies , 13. Syst-test was used to compare the initial BCVAs with the final visual outcomes. The final visual outcomes were compared among cases over 17 years old, between 7 and 17 years old, and under 7 years old using one-way ANOVA. The relationship between the OTS and the visual outcomes was determined using univariate linear regression analysis. A multiple linear regression analysis was performed to demonstrate the effects of the thirteen independent variables on the final visual outcome. The multicollinearity among the independent variables was measured using the VIF (variance inflation factor) scores. All the VIF scores were <5, which indicated that these variables were uncorrelated. A model was constructed using the final visual outcome as a dependent variable and our thirteen factors as independent variables. The backward stepwise elimination method was used to identify the influences of potential confounders and their statistical significance on the visual outcome, and this was followed by the formation of a regression equation. The influence of the significant variables according to the multiple linear regression model was analyzed with an independent sample t-test. Statistical analyses were performed using IBM SPSS Statistics version 21.0. P values < 0.05 were required for statistical significance.The paired sample P = 0.201). The mean follow-up time was 16.1 ± 4.7 (12–36) months. Patching was prescribed in eight patients under 9 years old. The OTS for each case was calculated according to the findings in The record review identified one hundred fifty-two patients. One hundred thirty-one open globe injuries (sixty-three right and sixty-eight left eyes) satisfied the inclusion criteria. Ninety-six patients (73%) were male. Ninety-nine (75.6%) patients were over 17 years old, nineteen patients (14.5%) were between 7 and 17 years old, and thirteen patients (9.9%) were under 7 years old. The mean final BCVA in logMAR units was 1.53 ± 1.13, 1.14 ± 1.12, and 1.11 ± 0.65 in cases >17 years old, between 7 and 17 years old, and <7 years old, respectively (P < 0.001). The regression coefficient for the OTS was −0.039, which indicated that a one-unit increase in the OTS resulted in a 0.039-unit decrease in the visual acuity in logMAR.The mean OTS was 53.8 ± 14.3 (26–90). The effect of the OTS on the visual outcome was significant based on univariate linear regression, and the coefficient of variation was 0.281 (P < 0.001). The final BCVA was NLP in fourteen (10.7%), LP in seven (5.3%), HM in twenty-five (19.1%), 19/200–1/100 Snellen in twenty-two (16.8%), 4/10–1/10 Snellen in thirty-two (24.4%), and ≥5/10 Snellen in thirty-one (23.7%) eyes. Evisceration was performed in six cases.The mean initial BCVA in logMAR units was 2.47 ± 0.61 (0.15–2.90), whereas the mean final BCVA was 1.43 ± 1.10 (0–2.90) .The results of the multiple linear regression analysis and the backward stepwise elimination methods are presented in Tables The performance of a PPV, aphakia after the initial trauma, the loss of iris tissue, a penetrating injury, and the cutting of any prolapsed vitreous in the primary surgery are the independent variables with significant effects on the final visual outcome.The comparisons of the initial BCVAs between the cases with and without these five significant independent variables are presented in The initial BCVAs were significantly reduced in cases with aphakia after the initial trauma, a loss of iris tissue, or an injury caused by blunt trauma.The comparisons of the final BCVAs between the cases with or without these five significant independent variables are presented in The final BCVAs were significantly reduced in the patients who underwent PPV and in cases with aphakia after an initial trauma, the loss of iris tissue, or an injury caused by blunt trauma.A regression equation obtained from the backward stepwise elimination was as follows:Final BCVA = 0.914 + 0.502 × performance of PPV + 0.960 × aphakia after initial trauma + 0.831 × loss of iris tissue − 0.385 × penetrating injury − 0.506 × cutting any prolapsed vitreous in the primary surgery. The independent variables in the equation are Boolean indicator variables .In this study, a significant correlation was identified between the OTS and visual outcomes in one hundred thirty-one open globe injuries. Serious visual impairment was developed in approximately one-half of the cases with a BCVA below 0.1 Snellen. Independent variables other than the OTS parameters were analyzed. The eyes were evaluated in regard to our management  and the findings at the initial surgery and during the follow-up visits. We demonstrated that the performance of PPVs, aphakia after the initial trauma, and the loss of iris tissue significantly inhibited the final visual outcomes, whereas the cutting of any prolapsed vitreous in the primary repair and penetrating-type injuries had positive effects on the final visual outcomes.In this study, we reported that the age, number of surgeries performed, the eye tissue affected , the development of IVH, glaucoma or anterior segment inflammation, the presence of an intraocular foreign body, and the time interval between the trauma and repair did not have significant effects on the final BCVAs. Although the performance of PPVs decreased the final visual outcomes significantly, the total number of procedures did not significantly influence the final BCVAs. Procedures other than PPVs, specifically cataract surgeries and anterior segment revisions, could have improved the outcomes, which might have offset the poor prognosis in the patients who underwent a PPV. Although it is not always reliable, in many studies, the zone of injury is defined according to the location of the most posterior aspect of the injury . Zone 1 Retinal detachment is one of the parameters included in the OTS . It was Aphakia after the initial trauma and the loss of iris tissue were associated with a poor final outcome. The presence of these two variables might reflect the severity of the injury. Lens extrusion and iris damage are associated with poor functional outcomes , 16, 19.Globe rupture is one of the OTS parameters associated with poor visual outcomes . A penetThe strengths of this study include the long follow-up time, the evaluation of thirteen factors and their associations with visual outcomes using regression analyses, and the relatively large number of eyes included. There are some limitations associated with the evaluated factors. The aim of this study was to analyze variables other than the OTS parameters. Thus, we interpreted thirteen variables and obtained a regression equation that included the significant variables. The equation might be useful for estimating the final BCVAs; however, other possible predictors, such as the OTS parameters, hyphema, choroidal hemorrhage, and causes of the injuries, were not included in the model for the regression analyses. If these variables were evaluated, several of them could have been included in the equation. Another limitation associated with the possible predictors included was the consideration of these factors as independent variables for statistical purposes. The multicollinearity that was calculated supported the independence of the variables; however, some of these factors obviously affect each other, including the number of surgeries and the performance of PPVs. The majority of our cases were adult patients, and the age did not significantly affect our outcomes. If the percent of young cases was increased, age could have been one of the significant variables affecting outcomes. On the other hand, we could have analyzed children separately because of the unique problems in children's eyes after ocular trauma, mainly the risk of amblyopia .According to the regression equation, the performance of PPV, aphakia after the initial trauma, and loss of iris tissue were associated with poor visual outcomes, whereas cutting any prolapsed vitreous in the primary repair and penetrating-type injury were associated with better visual outcomes. Further studies are required that should include additional possible predictors to obtain a more reliable equation for estimating the visual outcome.