PubTransformer

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Neil R Poulter - Top 30 Publications

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.

Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.

Day-to-day fasting glycaemic variability in DEVOTE: associations with severe hypoglycaemia and cardiovascular outcomes (DEVOTE 2).

The Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) was a double-blind, randomised, event-driven, treat-to-target prospective trial comparing the cardiovascular safety of insulin degludec with that of insulin glargine U100 (100 units/ml) in patients with type 2 diabetes at high risk of cardiovascular events. This paper reports a secondary analysis investigating associations of day-to-day fasting glycaemic variability (pre-breakfast self-measured blood glucose [SMBG]) with severe hypoglycaemia and cardiovascular outcomes.

DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality.

The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality.

Liraglutide and Renal Outcomes in Type 2 Diabetes.

In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown.

Cancer risks of anti-hyperglycemic drugs for type 2 diabetes treatment - a clinical appraisal.

A clinical appraisal of existing scientific literature sought to assess the need for long-term prospective epidemiological studies to investigate an increased cancer risk of anti-hyperglycemic medication in type 2 diabetes.

Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes.

Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec.

May Measurement Month: a global blood pressure screening campaign.

May Measurement Month: a new joint global initiative by the International Society of Hypertension and the World Hypertension League to raise awareness of raised blood pressure.

Raised blood pressure is the biggest single contributing risk factor to death and the burden of disease worldwide. However, international data suggest that fewer than half of those with hypertension are aware of their condition. In May 2017, the International Society of Hypertension and the World Hypertension League are leading a global initiative - May Measurement Month (MMM) - to raise awareness of the importance of screening. MMM will be a cross-sectional survey of men and women aged ≥18 who have not had their BP measured since 30 April 2016.

2016 Dietary Salt Fact Sheet and Call to Action: The World Hypertension League, International Society of Hypertension, and the International Council of Cardiovascular Prevention and Rehabilitation.

Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus.

Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes mellitus or cardiovascular disease. Lipidomics enables the assessment of hundreds of lipid species as potential markers for disease risk.

Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events) - DEVOTE 1.

DEVOTE was designed to evaluate the cardiovascular safety of insulin degludec (IDeg) vs insulin glargine U100 (IGlar) in patients with T2D at high risk of cardiovascular events. DEVOTE is a phase 3b, multicenter, international, randomized, double-blind, active comparator-controlled trial, designed as an event-driven trial that would continue until 633 positively adjudicated primary events were accrued. The primary end point was the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Patients with T2D at high risk of cardiovascular complications were randomized 1:1 to receive either IDeg or IGlar, each added to background therapies. This trial was designed to demonstrate statistical noninferiority of IDeg vs IGlar for the primary end point. DEVOTE enrolled 7,637 patients between October 2013 and November 2014 at 436 sites in 20 countries. Of these, 6,506 patients had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. DEVOTE was designed to provide conclusive evidence regarding the cardiovascular safety of IDeg relative to IGlar in a high-risk population of patients with T2D.

Personalized absolute benefit of statin treatment for primary or secondary prevention of vascular disease in individual elderly patients.

To estimate the absolute treatment effect of statin therapy on major adverse cardiovascular events (MACE; myocardial infarction, stroke and vascular death) for the individual patient aged ≥70 years.

An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK).

The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial investigated whether ACE-inhibition reduces small abdominal aortic aneurysms (AAA) growth rate, independent of blood pressure (BP) lowering.

Is It Time to Reappraise Blood Pressure Thresholds and Targets? A Statement From the International Society of Hypertension-A Global Perspective.

High Blood Pressure 2016: Why Prevention and Control Are Urgent and Important. The World Hypertension League, International Society of Hypertension, World Stroke Organization, International Diabetes Foundation, International Council of Cardiovascular Prevention and Rehabilitation, International Society of Nephrology.

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.

The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.

Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study.

In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events.

LEADER-4: blood pressure control in patients with type 2 diabetes and high cardiovascular risk: baseline data from the LEADER randomized trial.

As glucagon-like peptide-1 receptor agonists lower blood pressure (BP) in type 2 diabetes mellitus (T2DM), we examined BP control in relation to targets set by international bodies prior to randomization in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial.

A Call to Regulate Manufacture and Marketing of Blood Pressure Devices and Cuffs: A Position Statement From the World Hypertension League, International Society of Hypertension and Supporting Hypertension Organizations.

Hypertension.

Raised blood pressure is the biggest single contributor to the global burden of disease and to global mortality. The numbers of people affected and the prevalence of high blood pressure worldwide are expected to increase over the next decade. Preventive strategies are therefore urgently needed, especially in less developed countries, and management of hypertension must be optimised. Genetic advances in some rare causes of hypertension have been made lately, but the aggregate effect on blood pressure of all the genetic loci identified to date is small. Hence, intervention on key environmental determinants and effective implementation of trial-based therapies are needed. Three-drug combinations can control hypertension in about 90% of patients but only if resources allow identification of patients and drug delivery is affordable. Furthermore, assessment of optimal drug therapy for each ethnic group is needed.

The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials.

The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.

Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.

The value of N-terminal pro-B-type natriuretic peptide in determining antihypertensive benefit: observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

We investigated 3 hypotheses: (1) N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts cardiovascular disease events in patients with hypertension, (2) NT-proBNP is associated with blood pressure variability, and (3) NT-proBNP predicts benefit from antihypertensive regimens. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized a subset of 6549 patients at risk with no history of coronary heart disease to either atenolol-based or amlodipine-based blood pressure-lowering treatment. During 5.5 years of follow-up, 485 cardiovascular disease cases accrued and were matched with 1367 controls. Baseline and 6-month in-trial NT-proBNP were measured. The results show that NT-proBNP improves cardiovascular disease risk prediction beyond established predictors, continuous net reclassification improvement of 22.3% (P<0.0001). Furthermore, a 1-mm Hg increase in the SD of systolic blood pressure was associated with 2% higher baseline NT-proBNP in a multivariable regression analysis (P<0.0001). However, NT-proBNP predicted cardiovascular disease risk independently of blood pressure variation (odds ratio per SD increase in log NT-proBNP 1.24; 95% confidence interval, 1.06-1.45; P=0.007). Atenolol-based treatment led to a 69.6% increase in NT-proBNP at 6 months (P<0.0001). In contrast, amlodipine-based treatment reduced NT-proBNP by 36.5% (P<0.0001). Amlodipine recipients who achieved a 6-month NT-proBNP below the median (61 pg/mL) were at lower risk of cardiovascular disease when compared with those who did not (odds ratio, 0.58; 95% confidence interval, 0.37-0.91) after adjustment for confounders inclusive of baseline NT-proBNP and achieved blood pressure. If confirmed, these novel results suggest that NT-proBNP, as well as aiding cardiovascular disease risk assessment, may also help assess the efficacy of specific antihypertensive regimens. Further relevant studies seem warranted.

Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.

Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM).

Evaluation of C-reactive protein before and on-treatment as a predictor of benefit of atorvastatin: a cohort analysis from the Anglo-Scandinavian Cardiac Outcomes Trial lipid-lowering arm.

The aim of this study was to determine whether baseline and on-statin C-reactive protein (CRP) are independent predictors of cardiovascular (CV) outcome beyond low-density lipoprotein cholesterol (LDL-C).

The association of high-density lipoprotein cholesterol with cancer incidence in type II diabetes: a case of reverse causality?

Low high-density lipoprotein cholesterol (HDL-C) and type II diabetes are associated with an increased risk for cancer. Patients with type II diabetes typically have low HDL-C; however, the association between HDL-C and cancer has not been examined in this population.

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Resting heart rate and the risk of microvascular complications in patients with type 2 diabetes mellitus.

A higher resting heart rate is associated with an increased probability of cardiovascular complications and premature death in patients with type 2 diabetes mellitus. The impact of heart rate on the risk of developing microvascular complications, such as diabetic retinopathy and nephropathy, is, however, unknown. The present study tests the hypothesis that a higher resting heart rate is associated with an increased incidence and a greater progression of microvascular complications in patients with type 2 diabetes mellitus.

Commentary: Shaper and Jones, 'serum-cholesterol, diet and coronary heart-disease in Africans and Asians in Uganda': 50-year-old findings only need interpretational fine tuning to come up to speed!

Is plasma renin activity a biomarker for the prediction of renal and cardiovascular outcomes in treated hypertensive patients? Observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

Plasma renin activity (PRA) has been shown to predict future cardiovascular (CV) events in observational studies and in clinical trials and to be associated with the prevalence of chronic renal disease in hypertensive subjects. In a nested case-control study, we explored the relationship between CV and renal outcomes and all-cause mortality with baseline measurements of PRA among hypertensive adults randomized in the ASCOT trial.