Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci.

Gender-specific diagnostic performance of a new high-sensitivity cardiac troponin I assay for detection of acute myocardial infarction.

Background: The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date.

Methods: The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction.

Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene study.

Context: Leptin is produced in white adipose tissue, but also in human coronary atherosclerotic lesions.

Objective: The aim of this study is to assess the prognostic value of leptin in patients with proven coronary artery disease (CAD) (N = 1907).

Methods: AtheroGene is a contemporary CAD cohort study (N = 3229).

The Predictive Value of Depressive Symptoms for All-Cause Mortality: Findings From the PRIME Belfast Study Examining the Role of Inflammation and Cardiovascular Risk Markers.

Objectives: To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality.

Methods: Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory.

Diagnostic and prognostic value of circulating microRNAs in heart failure with preserved and reduced ejection fraction.

microRNAs (miRNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating miRNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease miRNAs have been proven to be reliable diagnostic biomarkers for different disease entities.

miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease.

Background: Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD.

Sex Differences in Correlates of Intermediate Phenotypes and Prevalent Cardiovascular Disease in the General Population.

Background: There are marked sex differences in cardiovascular disease (CVD) manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences.

Methods And Results: In 5000 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic, and electrocardiographic variables.

Prognostic use of soluble fms-like tyrosine kinase-1 and placental growth factor in patients with coronary artery disease.

Background: Intention of the study is to assess the cardiovascular mortality of patients with coronary artery disease (CAD) with the biomarkers of angiogenesis PlGF and its endogenous inhibitor sFlt-1.

Methods: The cohort included n = 1848 patients with CAD and 282 subjects without CAD. In 85 patients cardiovascular mortality, as combination of fatal myocardial infarction or any cardiac death, during a median follow-up duration of 3.

ADMA and arginine derivatives in relation to non-invasive vascular function in the general population.

Objective: Nitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population.

Approach And Results: In 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT).

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.

History of transient ischaemic attack, myocardial infarction and hyperlipidaemia affects outcome following carotid artery stenting.

Aims: This prospective registry study was intended to evaluate outcomes and predictors of adverse events following carotid artery stenting (CAS).

Methods And Results: Patients received neurological and duplex exams before CAS, prior to discharge and at 30- and 180-day follow-up. Multiple regression analysis included patient- and procedure-related characteristics.

ADMA, subclinical changes and atrial fibrillation in the general population.

Background: Pathways of oxidative stress, nitric oxide bioavailability and L-arginine derivatives are hypothesized to be related to atrial fibrillation (AF). Circulating methylated L-arginine metabolites can be assessed in the general population and may show an association with AF.

Methods: We determined L-arginine and its metabolites asymmetric dimethylarginine (ADMA), L-N(ω)-monomethylarginine (NMMA) and symmetric dimethylarginine (SDMA) in the population-based Gutenberg Health Study (n=5000), mean age 55 ± 11 years, 51% men, in association with clinical variables of AF such as electrocardiographic and echocardiographic measures and manifest AF.

Reference intervals of plasma homoarginine from the German Gutenberg Health Study.

Background: Low circulating homoarginine has been associated with adverse cardiovascular (CV) outcome and mortality in patients at risk and in the general population. The present study aimed to define plasma homoarginine reference intervals from a representative population sample to improve risk stratification between healthy individuals and individuals at risk.

Methods: We determined age- and sex-specific reference intervals for circulating plasma homoarginine in a subgroup of 786 healthy participants (no CV disease or risk factors) of the Gutenberg Health Study.

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels.

Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study.

Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study.

Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans.

Aims: Heme oxygenase-1 (HO-1) confers protection to the vasculature and suppresses inflammatory properties of monocytes and macrophages. It is unclear how HO-1 determines the extent of vascular dysfunction in mice and humans.

Methods And Results: Decreased HO-1 activity and expression was paralleled by increased aortic expression and activity of the nicotinamide dinucleotide phosphate oxidase Nox2 in HO-1 deficient Hmox1⁻/⁻ and Hmox1(⁺/⁻) compared with Hmox1⁺/⁺ mice.

Paclitaxel-Coated Balloon in Infrapopliteal Arteries: 12-Month Results From the BIOLUX P-II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries).

Objectives: The aim of BIOLUX P-II (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries) trial was to compare the safety and efficacy of a novel paclitaxel-coated drug-eluting balloon (DEB) versus an uncoated balloon (percutaneous transluminal angioplasty [PTA]) in de novo or native restenotic lesions of the infrapopliteal arteries in patients with claudication and critical limb ischemia.

Background: DEB have shown promising results in femoropopliteal lesions, but data for infrapopliteal lesions are scarce.

Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Lesions: 24-Month Results of IN.PACT SFA.

Background: Evidence from large, randomized, controlled peripheral artery disease trials reporting long-term outcomes using drug-coated balloons (DCBs) is limited. Previously, the DCB showed favorable 1-year outcomes compared with conventional percutaneous transluminal angioplasty (PTA), yet durability of the treatment effect with DCBs remains unknown.

Objectives: This study sought to investigate the longer-term outcomes of a paclitaxel-eluting DCB compared to PTA for femoropopliteal lesions.

Extensive alterations of the whole-blood transcriptome are associated with body mass index: results of an mRNA profiling study involving two large population-based cohorts.

Background: Obesity, defined as pathologically increased body mass index (BMI), is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood.

High-sensitivity troponin and novel biomarkers for the early diagnosis of non-ST-segment elevation myocardial infarction in patients with atrial fibrillation.

Aims: To evaluate the diagnostic performance of high-sensitivity troponin I (hsTnI) and other novel biomarkers for diagnosing non-ST-segment elevation myocardial infarction (NSTEMI) in patients with atrial fibrillation.

Methods: In an acute chest pain cohort (N=1673), mean age 61.4±13.

Drug-Coated Balloon Versus Standard Balloon for Superficial Femoral Artery In-Stent Restenosis: The Randomized Femoral Artery In-Stent Restenosis (FAIR) Trial.

Background: Drug-coated balloon angioplasty (DCBA) was shown to be superior to standard balloon angioplasty (POBA) in terms of restenosis prevention for de novo superficial femoral artery disease. For in-stent restenosis, the benefit of DCBA over POBA remains uncertain.

Methods And Results: One hundred nineteen patients with superficial femoral artery in-stent restenosis and chronic limb ischemia were recruited over 34 months at 5 German clinical sites and prospectively randomized to either DCBA (n=62) or POBA (n=57).

One-Year Outcomes Following Directional Atherectomy of Infrapopliteal Artery Lesions: Subgroup Results of the Prospective, Multicenter DEFINITIVE LE Trial.

Purpose: To report a subgroup analysis of the prospective, multicenter, single-arm DEFINITIVE LE trial to assess the effectiveness of directional atherectomy for the treatment of infrapopliteal artery lesions at 1 year.

Methods: In the DEFINITIVE LE trial, follow-up assessments occurred up to 1 year postprocedure. Of the 800 patients enrolled, 145 subjects with 189 infrapopliteal lesions met the criteria for this analysis.

Impact of number of prescribed medications on visit-to-visit variability of blood pressure: implications for design of future trials of renal denervation.

Background: Visit-to-visit blood pressure (BP) variability limits the ability to detect therapeutic effects in hypertension trials.

Methods: To enable future renal denervation trials to detect smaller effect sizes and reliably identify technical improvements, we examined within-patient visit-to-visit BP variability, quantified as SD of change from baseline to final BP (SDΔ), in renal denervation (RDN) trials, trials of BP-lowering tablets, and the VOLTAGE study including 4151 patients.

Results: The control arms of RDN trials had more visit-to-visit BP variability than tablet trials (SDΔ 23.