Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies.

Background: The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention.

Methods And Findings: To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

Low eosinophil and low lymphocyte counts and the incidence of 12 cardiovascular diseases: a CALIBER cohort study.

Background: Eosinophil and lymphocyte counts are commonly performed in clinical practice. Previous studies provide conflicting evidence of association with cardiovascular diseases.

Methods: We used linked primary care, hospitalisation, disease registry and mortality data in England (the CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records) programme).

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues.

Comparison of variance estimators for meta-analysis of instrumental variable estimates.

Background: Mendelian randomization studies perform instrumental variable (IV) analysis using genetic IVs. Results of individual Mendelian randomization studies can be pooled through meta-analysis. We explored how different variance estimators influence the meta-analysed IV estimate.

HAPRAP: a haplotype-based iterative method for statistical fine mapping using GWAS summary statistics.

Motivation: Fine mapping is a widely used approach for identifying the causal variant(s) at disease-associated loci. Standard methods (e.g.

Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study.

Background: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation.

Objectives: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population.

Addressing ethical challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT).

Background: The conduct of international collaborative genomics research raises distinct ethical challenges that require special consideration, especially if conducted in settings that are research-naïve or resource-limited. Although there is considerable literature on these issues, there is a dearth of literature chronicling approaches taken to address these issues in the field. Additionally no previous ethical guidelines have been developed to support similar research in Trinidad and Tobago.

Clinical Role of the "Venous" Ultrasound to Identify Lower Extremity Pathology.

Background: Accreditation in peripheral venous testing can be obtained based on femoropopliteal (FP) duplex ultrasound evaluation, and many laboratories limit their examination to this segment only. This simplified protocol detects acute FP deep venous thrombosis (DVT) but misses calf vein DVT, superficial venous thrombosis, chronic DVT, venous reflux, and other nonvenous findings potentially responsible for the patients' presenting conditions. A protocol limited to the FP segment results in additional unnecessary testing and can create patient dissatisfaction.

Association of Lipid Fractions With Risks for Coronary Artery Disease and Diabetes.

Importance: Low-density lipoprotein cholesterol (LDL-C) is causally related to coronary artery disease (CAD), but the relevance of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) is uncertain. Lowering of LDL-C levels by statin therapy modestly increases the risk of type 2 diabetes, but it is unknown whether this effect is specific to statins.

Objective: To investigate the associations of 3 routinely measured lipid fractions with CAD and diabetes through mendelian randomization (MR) using conventional MR and making use of newer approaches, such as multivariate MR and MR-Egger, that address the pleiotropy of genetic instruments where relevant.

Marginal role for 53 common genetic variants in cardiovascular disease prediction.

Objective: We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed.

Methods: Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up.

Selecting instruments for Mendelian randomization in the wake of genome-wide association studies.

Mendelian randomization (MR) studies typically assess the pathogenic relevance of environmental exposures or disease biomarkers, using genetic variants that instrument these exposures. The approach is gaining popularity-our systematic review reveals a greater than 10-fold increase in MR studies published between 2004 and 2015. When the MR paradigm was first proposed, few biomarker- or exposure-related genetic variants were known, most having been identified by candidate gene studies.

Mendelian Randomisation study of the influence of eGFR on coronary heart disease.

Impaired kidney function, as measured by reduced estimated glomerular filtration rate (eGFR), has been associated with increased risk of coronary heart disease (CHD) in observational studies, but it is unclear whether this association is causal or the result of confounding or reverse causation. In this study we applied Mendelian randomisation analysis using 17 genetic variants previously associated with eGFR to investigate the causal role of kidney function on CHD. We used 13,145 participants from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium and 194,427 participants from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus Coronary Artery Disease (CARDIoGRAMplusC4D) consortium.

The next frontier of office-based inferior vena cava filter placement.

Objective: There is an increasing number of procedures that traditionally were performed in the inpatient setting that are now becoming office-based procedures. These include peripheral endovascular procedures such as angiograms, angioplasties, dialysis access interventions, and treatment for venous insufficiency. We chose to evaluate the feasibility, safety of inferior vena cava (IVC) filter placement in the office-based setting.

In-patient adult and pediatric vascular ultrasound: Distribution and rate of positive findings.

Introduction We examined the rate of positive findings and the distribution of vascular ultrasounds in the pediatric and adult population. Prior literature has noted a low rate of positive findings in adult vascular ultrasounds but there is little literature on pediatric vascular ultrasound. Methods We reviewed our vascular duplex database on inpatients less than 18 years old and compared it to the adult inpatient vascular duplex exams from 2005 to 2010.

Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans.

Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms.

A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering.

Aim: To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome.

Patients & Methods: In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p < 1 × 10(-4) (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE.

Complications with office-based venoplasties and stenting and their clinical correlation.

Background: Endovenous therapy by venoplasty and stenting is rapidly gaining momentum and popularity in treatment of chronic venous insufficiency (nonthrombotic iliac vein lesions, in particular). The purpose of this study was to examine the results of office-based venoplasty and stenting procedures that were performed at our office-based facility from July 28, 2012, until April 28, 2013. The study focused on any complications during and after the procedure.

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase.

Background: Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized.

Objectives: This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways.

Methods: Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.

A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers.

Background: Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers. The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy (HBOT), arterial pump devices, and pharmacologic agents (pentoxifylline, cilostazol, and iloprost) in this setting.

Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011.

The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine.

Background: Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

Background: Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis.

Methods: We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease.