P. Fesler

Retinal vascular caliber is associated with cardiovascular biomarkers of oxidative stress and inflammation: the POLA study.

Purpose Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology. Patients and Methods Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3) activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP) and orosomucoid. Results In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (pu200a=u200a0.003) whereas larger venular caliber was associated with higher levels of hsCRP (pu200a=u200a0.0001) and orosomucoid (pu200a=u200a0.01). Conclusion In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.

Validation of a new standardized cystatin C turbidimetric assay: Evaluation of the three novel CKD-EPI equations in hypertensive patients

OBJECTIVESnAnalytical and clinical performances of the new standardized cystatin C particle-enhanced turbidimetric immunoassay (PETIA) using DiaSys reagents on Olympus AU2700® analyzer were evaluated.nnnDESIGN AND METHODSnWe have studied imprecision, linearity, limit of detection and limit of quantification of this new immunoassay. Method comparison was assessed in relation to results generated by the standardized Siemens-particle-enhanced nephelometric immunoassay (PENIA). In order to evaluate the clinical relevance of this assay, estimated glomerular filtration rate (GFR) was calculated using MDRD, CKD-EPI creatinine, CKD-EPI cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012 equations and compared to GFR measured using urinary clearance of (99m)Tc-DTPA in 100 hypertensive patients.nnnRESULTSnCystatin C measurements using DiaSys reagents have reliable analytical performances and are comparable to the standardized Siemens-PENIA method (bias of 0.01 mg/L). The mean measured GFR was 90.0±29.7 mL/min/1.73 m². Bias and accuracy of the three CKD-EPI equations were better than the MDRD. Both CKD-EPI creatinine-based and cystatin C-based formulae had similar bias, precision and accuracy. The combined creatinine-cystatin C equation was significantly more accurate and precise than the CKD-EPI creatinine equation in patients with GFR above 60 mL/min/1.73 m².nnnCONCLUSIONSnThe use of cystatin C in a combined equation with creatinine could improve the accuracy of eGFR in the reference interval.

Retinal vascular caliber is associated with renal function in apparently healthy subjects

Purpose:u2002 To assess the relation between retinal vascular caliber and renal function.

Arterial stiffness: an independent determinant of adaptive glomerular hyperfiltration after kidney donation

After kidney donation, the remaining kidney tends to hyperfiltrate, thus limiting the initial loss of renal function. The potential determinants of this adaptive glomerular hyperfiltration (GHF) and specifically the influence of arterial function are poorly known. In 45 normotensive healthy kidney donors [51 ± 10 yr (mean ± SD), 39 females], glomerular filtration rate (GFR) was measured as the clearance of continuously infused (99m)Tc-DTPA and timed urine collections at baseline, i.e., before donation, and 1 yr after donation. GHF was computed as postdonation GFR minus half of baseline GFR. Arterial function was assessed as baseline carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AIx). After kidney donation, no significant change in blood pressure (BP) was observed, but two subjects developed hypertension. GFR decreased from 107 ± 19 to 73 ± 15 ml·min(-1)·1.73 m(-2), and mean GHF was 20 ± 10 ml·min(-1)·1.73 m(-2). In univariate analysis, GHF was inversely correlated to age (r(2) = 0.24, P = 0.01), baseline PWV (r(2) = 0.23, P = 0.001), and Aix (r(2) = 0.11, P = 0.031). Nevertheless, GHF was not correlated to baseline peripheral or central BP. In multivariate analysis, baseline PWV, but not AIx, remained inversely correlated to GHF, independently of age, baseline mean BP, and GFR (model r(2) = 0.34, P < 0.001). In healthy subjects selected for renal donation, increased arterial stiffness is associated with decreased postdonation compensatory hyperfiltration.

Retinal vascular caliber associated with cardiac and renal target organ damage in never-treated hypertensive patients

The aim of this study was to assess the relationship between retinal vascular caliber and target organ damage in HT patients.

In-depth haemodynamic phenotyping of pulmonary hypertension due to left heart disease

The commonest cause of pulmonary hypertension (PH) is left heart disease (LHD). The current classification system for definitions of PH-LHD is under review. We therefore performed prospective in-depth invasive haemodynamic phenotyping in order to assess the site of increased pulmonary vascular resistance (PVR) in PH-LHD subsets. Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned PVR in larger arterial (Rup, upstream resistance) and small arterial plus venous components (Rds, downstream resistance). In the case of small vessel disease, Rup decreases and Rds increases. Inhaled nitric oxide (NO) testing was used to assess acute vasoreactivity. Right ventricular afterload (PVR, pulmonary arterial compliance and effective arterial elastance) was significantly higher in combined post- and pre-capillary PH (Cpc-PH, n=35) than in isolated post-capillary PH (Ipc-PH, n=20). Right ventricular afterload decreased during inhalation of NO in Cpc-PH and idiopathic pulmonary arterial hypertension (n=31), but remained unchanged in Ipc-PH. Rup was similar in Cpc-PH (66.8±10.8%) and idiopathic pulmonary arterial hypertension (65.0±12.2%; p=0.530) suggesting small vessel disease, but significantly higher in Ipc-PH (96.5±4.5%; p<0.001) suggesting upstream transmission of elevated left atrial pressure. Right ventricular afterload is driven by elevated left atrial pressure in Ipc-PH and is further increased by elevated small vessel resistance in Cpc-PH. Cpc-PH is responsive to inhaled NO. Our data support current definitions of PH-LHD subsets. Combined post- and pre-capillary PH is characterised by pre-capillary pulmonary vascular disease and a positive response to inhaled NO http://ow.ly/G2nF30iYTeJ

Application of the 2015/2016 EULAR recommendations for cardiovascular risk in daily practice: data from an observational study

The European League Against Rheumatism (EULAR) recently updated the recommendations for cardiovascular disease (CVD) risk management in patients with rheumatoid arthritis (RA).1 In contrast to the 2009 recommendations which advised to multiply by 1.5 the global CVD risk in the presence of certain RA-specific criteria,2 the 2015/2016 update recommends to multiply by 1.5 the global CVD risk for all patients with RA. It also considers the use of carotid ultrasound to screen asymptomatic atherosclerotic plaques. Indeed, the majority of the CVD events occur in the ‘low’ and ‘intermediate’ risk groups and carotid plaque detection to classify patients improves cardiovascular risk prediction.3 The European Society of Cardiology guidelines classify patients with carotid plaque at very high CVD risk.4 Immediate statin use is indicated in those patients if low-density lipoprotein cholesterol is ≥0.7u2009g/L.4 In a post hoc analysis, we evaluated the impact of the updated 2015/2016 EULAR CVD recommendations …

Malnutrition and retinal vascular caliber in the elderly: the POLA study.

PURPOSEnThe pathway linking late-life malnutrition to greater risk of cardiovascular disease is unclear. Microcirulatory changes assessed by retinal vascular caliber have been linked with increased risk of stroke and coronary heart disease. The purpose of this study was to examine whether retinal vascular calibers are associated with malnutrition in elderly subjects free of cardiovascular diseases.nnnMETHODSnThis was a cross-sectional analysis of a community-dwelling cohort comprising 1145 individuals aged 60 years and older. Retinal vascular caliber was measured from fundus photographs using a semiautomated, standardized imaging software. Malnutrition was assessed using body mass index (BMI) < 18.5 kg/m(2) and biomarkers of protein malnutrition: plasma albumin and transthyretin.nnnRESULTSnIn a multivariate model controlling for cardiovascular risk factors, retinal venular caliber was related to BMI (P = 0.0002) with an increased mean caliber for individuals with obesity and for those with low BMI. After multivariate adjustment for age, sex, hypertension, smoking, high-density lipoprotein (HDL) cholesterol, glomerular filtration rate and BMI, lower levels of albumin or transthyretin were associated with larger retinal venular caliber (P = 0.026 and P = 0.0018, respectively), that remain significant when adjusting for CRP (P = 0.040 and P = 0.0060, respectively) or orosomucoid (P = 0.034 and P = 0.0020, respectively). The relationships between retinal arteriolar caliber and BMI, albumin and transthyretin did not reach significance (P = 0.14, P = 0.12, and P = 0.15, respectively).nnnCONCLUSIONSnProtein malnutrition was identified as an additional factor associated with retinal venular dilatation beyond inflammation. This suggests that early microvascular changes may be one of the underlying mechanisms of increased risk of cardiovascular disease observed in elderly subjects suffering from malnutrition.

Evaluation of five immunoturbidimetric assays for urinary albumin quantification and their impact on albuminuria categorization

OBJECTIVESnThe study was designed to evaluate the performance of five automated immunoturbidimetric assays to quantify urinary albumin, each corresponding to a combination of a reagent and an analyzer (Olympus on AU640, Roche on Cobas Integra, Abbott on Architect, Ortho-Clinical Diagnostics Vitros on Fusion and Siemens on Dimension).nnnDESIGN AND METHODSnTo assess imprecision, albumin was measured in three urinary pools with a mean value of 25, 66 and 131 mg/L. One hundred and eight patient urine samples were then used to compare each turbidimetric method using the Passing-Bablok regression and Bland-Altman analyses. Concordance of the albumin/creatinine ratio (ACR), according to the albuminuria classifications proposed by the KDIGO, was calculated to test the agreement between the different assays.nnnRESULTSnAll immunoturbidimetric methods evaluated in this study exhibited acceptable imprecision (CV<6%). Mean values for 108 urine samples varied from 0.5 to 762.2 mg/L. Significant differences were found (p<0.05) between all methods except between Olympus and Ortho (p=1.0) and between Abbott and Roche (p=0.12). Regarding the albuminuria categories based on the ACR proposed by the KDIGO, only the classification obtained with the Roche method was significantly different from the four other methods (p<0.001).nnnCONCLUSIONSnWe demonstrated that all assays were not strictly equivalent which could affect ACR categories in clinical practice, suggesting the need for harmonization of commercial methods.

sST2 as a New Biomarker of Chronic Kidney Disease-Induced Cardiac Remodeling: Impact on Risk Prediction

Heart failure is the most frequent cardiac complication of chronic kidney disease (CKD). Biomarkers help identify high-risk patients. Natriuretic peptides (BNP and NT-proBNP) are largely used for monitoring patients with cardiac failure but are highly dependent on glomerular filtration rate (GFR). Soluble suppression of tumorigenicity 2 (sST2) biomarker is well identified in risk stratification of cardiovascular (CV) events in heart failure. Furthermore, sST2 is included in a bioclinical score to stratify mortality risk. The aims of this study were to evaluate (i) the interest of circulating sST2 level in heart dysfunction and (ii) the bioclinical score (Barcelona Bio-Heart Failure risk calculator) to predict the risk of composite outcome (major adverse coronary events) and mortality in the CKD population. A retrospective study was carried out on 218 CKD patients enrolled from 2004 to 2015 at Montpellier University Hospital. sST2 was measured by ELISA (Presage ST2® kit). GFR was estimated by the CKD-EPI equation (eGFR). Indices of cardiac parameters were performed by cardiac echography. No patient had reduced ejection fraction. 112 patients had left ventricular hypertrophy, and 184 presented cardiac dysfunction, with structural, functional abnormalities or both. sST2 was independent of age and eGFR (ρ = 0.05, p = 0.44, and ρ = −0.07, p = 0.3, respectively). Regarding echocardiogram data, sST2 was correlated with left ventricular mass index (ρ = 0.16, p = 0.02), left atrial diameter (ρ = 0.14, p = 0.04), and volume index (ρ = 0.13, p = 0.05). sST2 alone did not change risk prediction of death and/or CV events compared to natriuretic peptides. Included in the Barcelona Bio-Heart Failure (BCN Bio-HF) score, sST2 added value and better stratified the risk of CV events and/or death in CKD patients (p < 0.0001). To conclude, sST2 was associated with cardiac remodeling independently of eGFR, unlike other cardiac biomarkers. Added to the BCN Bio-HF score, the risk stratification of death and/or CV events in nondialyzed CKD patients was highly improved.