A genome-wide association study of circulating galectin-3.

Galectin-3 is a lectin involved in fibrosis, inflammation and proliferation. Increased circulating levels of galectin-3 have been associated with various diseases, including cancer, immunological disorders, and cardiovascular disease. To enhance our knowledge on galectin-3 biology we performed the first genome-wide association study (GWAS) using the Illumina HumanCytoSNP-12 array imputed with the HapMap 2 CEU panel on plasma galectin-3 levels in 3,776 subjects and follow-up genotyping in an additional 3,516 subjects.

C-reactive protein, fibrinogen, and cardiovascular disease prediction.

Background: There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events.

Methods: We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen.

Prediction models for risk of developing type 2 diabetes: systematic literature search and independent external validation study.

Objective: To identify existing prediction models for the risk of development of type 2 diabetes and to externally validate them in a large independent cohort.

Data Sources: Systematic search of English, German, and Dutch literature in PubMed until February 2011 to identify prediction models for diabetes.

Design: Performance of the models was assessed in terms of discrimination (C statistic) and calibration (calibration plots and Hosmer-Lemeshow test).

UMOD as a susceptibility gene for end-stage renal disease.

Background: In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant.

Methods: To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls.

Dietary acid load and metabolic acidosis in renal transplant recipients.

Background And Objectives: Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs.

Dietary protein, blood pressure and renal function in renal transplant recipients.

Hypertension is highly prevalent among renal transplant recipients (RTR) and a risk factor for graft failure and cardiovascular events. Protein intake has been claimed to affect blood pressure (BP) in the general population and may affect renal function. We examined the association of dietary protein with BP and renal function in RTR.

Plasma COOH-terminal proendothelin-1: a marker of fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in type 2 diabetes? (ZODIAC-29).

Objective: The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes.

Research Design And Methods: A total of 1,225 patients with type 2 diabetes participated in this prospective observational study of two combined cohorts. Three clinical end points were studied: fatal cardiovascular events, all-cause mortality, and new-onset albuminuria.

Albuminuria, estimated GFR, traditional risk factors, and incident cardiovascular disease: the PREVEND (Prevention of Renal and Vascular Endstage Disease) study.

Background: Abnormal levels of both albuminuria and estimated glomerular filtration rate (eGFR) have been reported separately to be associated with cardiovascular risk. This study assessed the contribution of each separately in correctly identifying individuals at cardiovascular risk in the general population beyond traditional risk markers.

Study Design: Prospective community-based cohort study.

Influence of age on the prognostic value of mid-regional pro-adrenomedullin in the general population.

Objective: Experimental studies have shown that adrenomedullin (ADM) has an important role in circulatory homeostasis. Mid-regional pro-ADM (MR-proADM) is a stable form of ADM. Observational studies found an important association with age, body mass index and kidney function.

Growth-differentiation factor 15 predicts worsening of albuminuria in patients with type 2 diabetes.

Objective: Development of micro- or macroalbuminuria is associated with increased risk of cardiorenal complications, particularly in diabetes. For prevention of transition to micro- or macroalbuminuria, more accurate prediction markers on top of classical risk markers are needed. We studied a promising new marker, growth-differentiation factor (GDF)-15, to predict transition to increasing stage of albuminuria in type 2 diabetes mellitus (T2DM).

Plasma renin and outcome in the community: data from PREVEND.

Aims: The renin-angiotensin system plays a central role in patients with established cardiovascular (CV) disease, but the prognostic effect of plasma renin in the community is unclear.

Methods And Results: The relationship between plasma renin concentration and CV events was studied in 6228 subjects who were enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, and who were not using antihypertensive medication. Plasma renin concentration was measured using a direct automated immunochemiluminescent assay.

Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy.

Background: Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy.

Methods: Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15-300 mg/24h) were randomized to receive benfotiamine (n = 39) or placebo (n = 43).

High-sensitive troponin T and N-terminal pro-B type natriuretic peptide are associated with cardiovascular events despite the cross-sectional association with albuminuria and glomerular filtration rate.

Aims: It has been suggested that troponins and natriuretic peptides can be falsely elevated in subjects with impaired kidney function because of decreased renal clearance. The value of these biomarkers in subjects with impaired kidney function has therefore been debated. We tested in a population-based cohort study, first, whether high-sensitive troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels are cross-sectionally associated with the estimated glomerular filtration rate (eGFR) and albuminuria, and secondly, whether these markers are associated with cardiovascular outcome, independent of eGFR, albuminuria and conventional cardiovascular risk factors.

Apolipoprotein A-II influences apolipoprotein E-linked cardiovascular disease risk in women with high levels of HDL cholesterol and C-reactive protein.

Background: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups.

Methodology/principal: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II).

Plasma bilirubin and late graft failure in renal transplant recipients.

Exogenous bilirubin has been shown to protect against oxidative stress in ischemia-reperfusion injury. Oxidative stress has been implicated in the pathophysiology of chronic transplant dysfunction leading to late graft failure after renal transplantation. We prospectively investigated whether high endogenous bilirubin is protective against development of late graft failure in renal transplant recipients (RTR).

Association between sodium intake and change in uric acid, urine albumin excretion, and the risk of developing hypertension.

Background: A high-sodium diet has little short-term effect on blood pressure in nonhypertensive individuals but, for unclear reasons, is associated with hypertension if consumed long term. We hypothesized that a chronically high sodium intake would be associated with increases in biomarkers of endothelial dysfunction, specifically serum uric acid (SUA) and urine albumin excretion (UAE), and that high sodium intake would be associated with incident hypertension among those with higher SUA and UAE.

Methods And Results: We prospectively analyzed the associations between sodium intake and the change in SUA (n=4062) and UAE (n=4146) among participants of the Prevention of Renal and Vascular End Stage Disease (PREVEND) study who were not taking antihypertensive medications.

CUBN as a novel locus for end-stage renal disease: insights from renal transplantation.

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study).

Parental history of type 2 diabetes and cardiometabolic biomarkers in offspring.

Background: Parental history of type 2 diabetes (T2D) is associated with cardiometabolic risk. We aimed to investigate the associations of parental history of T2D with cardiometabolic biomarkers and to subsequently investigate to what extent these putative associations were explained by modifiable factors.

Materials And Methods: Cross-sectionally, we analysed a random sample of 2001 participants without T2D (20-70 years) from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL).

Dietary acid load and risk of hypertension: the Rotterdam Study.

Background: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP).

Design: The analyses included 2241 participants aged ≥55 y who were free of hypertension at baseline (1990-1993) and who had complete dietary and BP data. Dietary data were obtained from a 170-item food-frequency questionnaire.

Sodium intake and blood pressure in renal transplant recipients.

Background: Hypertension is common among renal transplant recipients (RTR) and a risk factor for graft failure and mortality. Sodium intake is a well-established determinant of blood pressure (BP) in the general population. However, data in RTR are limited.

The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.

Background: A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown.

Protein supplementation lowers blood pressure in overweight adults: effect of dietary proteins on blood pressure (PROPRES), a randomized trial.

Background: Dietary protein intake may help to manage blood pressure (BP) and prevent complications associated with elevated BP.

Objective: The objective of this study was to determine whether 4 wk of increased protein intake (∼25% compared with ∼15% of energy intake that isoenergetically replaces carbohydrate intake) lowers office and daytime BP compared with increased carbohydrate intake.

Design: A randomized, double-blind, parallel study compared consumption of 3 × 20 g protein/d (20% pea, 20% soy, 30% egg, and 30% milk-protein isolate) with 3 × 20 g maltodextrin/d.