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Author: Paul Nestel (86)


Dec
2017

Coronary heart disease is a major cause of heart failure. Availability of risk-prediction models that include both clinical parameters and biomarkers is limited. We aimed to develop such a model for prediction of incident heart failure.

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Dec
2017

A single assessment of psychological distress, which includes depression and anxiety, has been associated with increased mortality in patients with coronary heart disease, but the prognostic importance of persistence of distress symptoms is less certain.
To determine whether intermittent and/or persistent psychological distress is associated with long-term cardiovascular (CV) and total mortality in patients with stable coronary artery disease.
950 participants in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial completed at least four General Health Questionnaires (GHQ-30) at baseline and after ½, 1, 2 and 4 years.

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Dec
1969

Background: Neck circumference (NC) is a predictor of cardiometabolic risk. The objective of this study was to explore the relationship of NC to muscle sympathetic nerve activity (MSNA) within an overweight and obese population. Methods: The study design was a retrospective cross-sectional analysis.

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Jan
2017

Plasma sphingolipids including ceramides, and gangliosides are associated with insulin resistance (IR) through effects on insulin signalling and glucose metabolism. Our studies of subjects with metabolic syndrome (MetS) showed close relationships between IR and sympathetic nervous system (SNS) activity including arterial norepinephrine (NE). We have therefore investigated possible associations of IR and SNS activity with complex lipids that are involved in both insulin sensitivity and neurotransmission.

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Nov
2016

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.
Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionization-tandem mass spectrometry on a case-cohort (n=3779) subset from the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation).

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May
2016

We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, cause-specific mortality, and cancer incidence from extended follow-up of the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial.
LIPID initially compared pravastatin and placebo over 6 years in 9014 patients with previous coronary heart disease. After the double-blind period, all patients were offered open-label statin therapy.

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Dec
2015

In patients with stable coronary heart disease (CHD), we aimed to assess 1. the prognostic power of biomarkers reflecting haemodynamics, micronecrosis, inflammation, coagulation, lipids, neurohumoral activity, and renal function; 2. whether changes in concentrations of these biomarkers over 12 months affected subsequent CHD risk; and 3.

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Aug
2015

The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms. This study was conducted to examine the inter-relationships between changes in sympathetic nervous system (SNS) activity, vascular function and insulin clearance during a weight loss program.

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Sep
2015

Postprandial lipemia represents a risk factor for chronic diseases, including type 2 diabetes. Little is known about the effect of dietary fat on the plasma lipidome in the postprandial period.
The objective of this study was to assess the effect of dairy fat and soy oil on circulating postprandial lipids in men.

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Aug
2015

The National Heart Foundation of Australia (NHFA) 2008 review on omega-3 long-chain polyunsaturated fatty acids (LCPUFA) made recommendations with respect to supplementation for primary and secondary prevention of cardiovascular disease. Since then, new findings have been published regarding the relationship between omega-3 polyunsaturated fatty acids, including supplementation, and cardiovascular health.
A literature search was undertaken in PubMed and Medline, for literature published between January 1, 2007 and August 31, 2013.

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Jul
2015

Insulin resistance is associated with blunted sympathetic nervous system (SNS) response to carbohydrate ingestion which may contribute to postprandial hypotension and impaired body weight homeostasis.
This study was conducted to examine the effects of pharmacological insulin sensitization on whole-body norepinephrine kinetics during a standard 75-g oral glucose tolerance test (OGTT) in obese, insulin resistant subjects with metabolic syndrome.
Un-medicated individuals (n=42, mean age 56±0.

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Apr
2015

Impaired insulin clearance contributes to the hyperinsulinemia of obesity, yet relatively little is known concerning the pathophysiological determinants of insulin clearance in obese populations.
To examine the cross-sectional relationship between insulin clearance and resting sympathetic nervous system activity in a cohort of obese subjects with metabolic syndrome.
Unmedicated, nonsmoking subjects (31 male, 27 female; aged 56 ± 1 year; body mass index 33.

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Sep
2014

Insulin resistance and sympathetic nervous system overactivity are closely associated and contribute to cardiovascular risk.
The objective of the study was to test the hypotheses that pharmacological improvement in insulin sensitivity would (1) attenuate sympathetic neural drive and (2) enhance neuronal norepinephrine uptake.
A randomized, double-blind trial was conducted in 42 obese, unmedicated individuals with metabolic syndrome (mean age 56 ± 1 y, body mass index 34 ± 0.

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Mar
2014

The goal of this article was to review the causal link between trans fatty acids (TFA) produced from partially hydrogenated vegetable oil (PHVO) and cardiovascular disease (CVD) risk and its likely mechanisms. The potential risk of TFA from ruminant dairy and meats, which are currently the major sources of dietary TFA, is also discussed.
Evidence was derived from observational studies of large cohorts followed up prospectively; from randomized controlled trials of clinical interventions; and from specific case-control studies that investigated biomarkers in tissues.

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Jan
2014

Reports have suggested that the consumption of dairy foods may reduce risk of type 2 diabetes on the basis of evidence of raised circulating ruminant fatty acids.
We determined whether certain phospholipid species and fatty acids that are associated with full-fat dairy consumption may also be linked to diminished insulin resistance.
Four variables of insulin resistance and sensitivity were defined from oral-glucose-tolerance tests in 86 overweight and obese subjects with metabolic syndrome.

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Oct
2013

Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events.
The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.

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Feb
2014

This study sought to assess whether baseline and change in contemporary sensitive troponin I (TnI) levels predicts coronary heart disease (CHD) death and myocardial infarction (MI), and to determine the effects of pravastatin on TnI levels.
The role of troponins in predicting long-term outcomes in patients with stable CHD is not clearly defined.
The LIPID (Long-Term Intervention With Pravastatin in Ischaemic Disease) study randomized patients with cholesterol levels of 155 to 271 mg/dl 3 to 36 months after MI or unstable angina to placebo or pravastatin 40 mg per day.

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Dec
2013

Association between lipoprotein(a) (Lp(a)) level and a first-ever coronary (CHD) event is recognized. Less is evident in patients with overt CHD and stable symptoms in whom we investigated associations between Lp(a) and future events.
Relationships between Lp(a) concentration and CHD and cardiovascular disease outcomes during 6 years' median follow-up were evaluated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study.

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Mar
2014

This study was conducted to examine (1) the effects of dietary weight loss on indices of norepinephrine (NE) turnover and (2) whether baseline hyperinsulinemia modulates sympathetic neural adaptations.
Obese individuals aged 56 ± 1 year, BMI 32.5 ± 0.

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Dec
2013

The association between consumption of full-fat dairy foods and CVD may depend partly on the nature of products and may not apply to low-fat dairy foods. Increased circulating levels of inflammatory biomarkers after consumption of dairy product-rich meals suggest an association with CVD. In the present study, we tested the effects of low-fat and full-fat dairy diets on biomarkers associated with inflammation, oxidative stress or atherogenesis and on plasma lipid classes.

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Feb
2013

Nonalcoholic fatty liver disease (NAFLD) has emerged as a clear risk factor for cardiovascular risk. Through its association with metabolic syndrome including insulin resistance and type 2 diabetes, NAFLD certainly has strong indirect associations with cardiovascular risk. Recent population studies have strengthened the association with prevalent coronary heart disease.

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Feb
2013

Altered cardiac structure and function have been reported in prediabetic and diabetic populations; however, the contribution of the sympathetic nervous system (SNS) to these changes has yet to be delineated.
Our objective was to examine interrelationships between glucose metabolism, left ventricular mass and function, and SNS activity in obese metabolic syndrome subjects.
Unmedicated impaired glucose tolerant (IGT) (n = 31) or treatment-naive type 2 diabetic (T2D) (n = 25) subjects, matched for age (mean 58 ± 1 years), gender, body mass index (32.

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Feb
2013

Plant sterols as ingredients to functional foods are recommended for lowering LDL cholesterol. However, there is an ongoing discussion whether the use of plant sterols is safe.
Genetic analyses showed that common variants of the ATP binding cassette transporter G8 (ABCG8) and ABO genes are associated with elevated circulating plant sterols and higher risk for cardiovascular disease.

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Sep
2012

Cellular cholesterol efflux is a key step in reverse cholesterol transport and may depend on the metabolism of apolipoprotein (apo) B-100, apoA-I, and apoA-II.
We examined the associations between cholesterol efflux and plasma concentrations and kinetics of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL)-apoB-100, high-density lipoprotein (HDL)-apoA-I, and HDL-apoA-II in men. DESIGN, SUBJECTS, AND METHODS: Thirty men were recruited from the community with a wide range of body mass index.

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Oct
2012

Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.

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Mar
2012

The associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented.
To evaluate the relative strength of the associations of LDL-C, non-HDL-C, and apoB with cardiovascular risk among patients treated with statin therapy.
Meta-analysis of individual patient data from randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.

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Feb
2012

High-density lipoprotein (HDL) encompasses a heterogeneous population of lipoproteins with differences in functionality. The impact of HDL heterogeneity on its ability to support HDL-mediated cholesterol efflux has not been previously studied in patients with type 2 diabetes mellitus (T2DM).
To examine the relationships between various HDL subtypes and cholesterol efflux from macrophages in patients with T2DM.

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Feb
2012

The sympathetic nervous system is an important physiological modulator of basal and postprandial energy expenditure.
Our objective was to investigate whether the variability of weight loss attained during hypocaloric dietary intervention is related to individual differences in baseline sympathetic drive and nutritional sympathetic nervous system responsiveness.
Untreated obese subjects (n = 42; body mass index = 32.

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Mar
2012

Infusion of reconstituted HDL (rHDL) leads to changes in HDL metabolism as well as to an increased capacity of plasma to support cholesterol efflux providing an opportunity to investigate mechanisms linking cholesterol efflux to changes in plasma HDL.
Patient plasmas after infusion of rHDL were tested ex vivo for their capacity to stimulate cholesterol efflux. Reconstituted HDL enhanced mobilization of cholesterol from tissues in vivo as shown by rising HDL cholesterol concentrations over the infusion period.

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Apr
2011

Current dietary recommendations advise reducing the intake of saturated fatty acids (SFAs) to reduce coronary heart disease (CHD) risk, but recent findings question the role of SFAs. This expert panel reviewed the evidence and reached the following conclusions: the evidence from epidemiologic, clinical, and mechanistic studies is consistent in finding that the risk of CHD is reduced when SFAs are replaced with polyunsaturated fatty acids (PUFAs). In populations who consume a Western diet, the replacement of 1% of energy from SFAs with PUFAs lowers LDL cholesterol and is likely to produce a reduction in CHD incidence of ≥2-3%.

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Mar
2011

Sympathetic nervous system (SNS) overactivity participates in both the pathogenesis and adverse clinical complications of metabolic syndrome (MetS) obesity.
We conducted a prospective lifestyle intervention trial to compare the effects of active weight loss and extended weight loss maintenance on SNS function and MetS components.
Untreated subjects (14 males, four females; mean age, 53 ± 1 yr; body mass index, 30.

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Mar
2011

Metabolic syndrome (MetS) obesity is an independent risk factor for chronic kidney disease. This study was conducted to examine the effects of lifestyle interventions on renal parameters and putative metabolic, neuroadrenergic and hemodynamic mediators of renal injury.
Untreated men and women (mean age 55 ± 1 years; BMI 32.

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Jun
2010

Linoleic acid reassessed.

Curr Opin Lipidol 2010 Jun;21(3):253-5
Paul Nestel

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Jan
2010

Prospective evidence on the extent to which serum lipid concentrations in older persons respond to dietary modification is scarce. It is not clear whether such behavioral changes are relevant in the context of more commonly initiated treatments with lipid-lowering drugs. We therefore examined whether individual changes in the consumption of dietary fatty acids or main food sources were associated with changes in the serum lipid profile of older Australians.

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Jan
2010

Sympathetic nervous system (SNS) overactivity contributes to the pathogenesis and target organ complications of obesity. This study was conducted to examine the effects of lifestyle interventions (weight loss alone or together with exercise) on SNS function.
Untreated men and women (mean age 55 +/- 1 year; BMI 32.

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Jun
2009

This review provides a reappraisal of the potential effects of dairy foods, including dairy fats, on cardiovascular disease (CVD)/coronary heart disease (CHD) risk. Commodities and foods containing saturated fats are of particular focus as current public dietary recommendations are directed toward reducing the intake of saturated fats as a means to improve the overall health of the population. A conference of scientists from different perspectives of dietary fat and health was convened in order to consider the scientific basis for these recommendations.

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May
2009

The purpose of this study was to examine the effects of weight loss on sympathetic nervous system responsiveness to glucose ingestion in obese subjects with metabolic syndrome, in whom such responses are reportedly blunted.
Thirty four subjects, 19 insulin resistant and 15 insulin sensitive and aged 55 +/- 1 years (mean +/- SE) with BMI 31.6 +/- 0.

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Dec
2008

This review considers within the epidemiology of dairy fats and cardiovascular risk including the effects of 1. Fats within different dairy foods, 2. Specific dairy fatty acids including ruminant trans fats (TFA), conjugated linoleic acid (CLA), myristic acid and 3.

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Jan
2009

Glucose ingestion stimulates sympathetic nervous system (SNS) activity in lean subjects, whereas blunted responses have been reported in the obese.
The objective was to investigate the impact of insulin resistance on the SNS response to oral glucose.
Nineteen insulin-resistant (IR) and 12 insulin-sensitive (IS) obese subjects with the metabolic syndrome and matched for age, sex, and blood pressure participated.

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May
2009

Reactive oxygen species (ROS) contribute to neointimal smooth muscle proliferation by yet to be defined mechanisms. We examined the effects of a novel isoflavone 3,7-dihydroxy-isoflav-3-ene (DHIF) on development of neointimal lesions in relation to ROS elevations and cell signaling in injured arteries. Carotid arteries of rabbits treated with vehicle or DHIF were injured with a balloon catheter and effects on proliferation, apoptosis, vessel structure, ROS, NF-kappaB activation, cyclooxygenase and gene expression examined.

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Jul
2008

Dyslipidaemia is a common condition managed in general practice.
This article reviews the evidence and gives practical advice for the management of dyslipidaemia in general practice.
It is essential to identify people at risk of cardiovascular disease (CVD) and to instigate appropriate treatment strategies.

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Aug
2008

Dysregulated apolipoprotein (apo)C-III metabolism may account for hypertriglyceridemia and increased cardiovascular risk in the metabolic syndrome. This study investigated the dose-dependent effect of rosuvastatin on VLDL apoC-III transport in men with the metabolic syndrome.
Twelve men with the metabolic syndrome were studied in a randomized double-blind crossover trial of 5-week intervention periods with placebo, 10 mg rosuvastatin, or 40 mg rosuvastatin, with 2-week placebo washouts between each period.

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Apr
2008

Plasma concentration of high density lipoprotein (HDL) is one of the most reliable negative risk factors for CVD. There is however convincing experimental and clinical evidence that plasma concentration of HDL does not convey the full picture of atheroprotective properties of HDL. HDL functionality, i.

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Apr
2008

We sought to determine the association between two major biomarkers, the inactive N-terminal fragment of brain natriuretic peptide (NT-proBNP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and long-term cardiovascular outcomes in a cohort of subjects who had a myocardial infarction or unstable angina 3-36 months previously.
Plasma NT-proBNP and TIMP-1 were measured in a nested case control study of 250 randomly matched subject pairs enrolled in the long-term intervention with pravastatin in ischaemic disease (LIPID) and LIPID extended follow-up studies. Cases (n = 250) were defined as those who had a cardiovascular death, non-fatal myocardial infarction or stroke during the studies.

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Dec
1969

Dietary plant sterols supplementation has been demonstrated in some studies to lower plasma total and LDL cholesterol in hypercholesterolemic subjects. The cholesterol lowering action of plant sterols remains to be investigated in subjects with the metabolic syndrome. In a randomized, crossover study of 2 x 4 week therapeutic periods with oral supplementation of plant sterols (2 g/day) or placebo, and two weeks placebo wash-out between therapeutic periods, we investigated the effects of dietary plant sterols on lipoprotein metabolism in nine men with the metabolic syndrome.

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Feb
2008

Low plasma concentration of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular disease and a feature of the metabolic syndrome. Rosuvastatin has been shown to increase HDL cholesterol concentration, but the mechanisms remain unclear.
Twelve men with the metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-wk therapeutic periods with placebo, 10 mg/d rosuvastatin, or 40 mg/d rosuvastatin, with 2-wk placebo washout between each period.

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Apr
2008

The effects of the statin, rosuvastatin on indices of reverse cholesterol transport were studied in a randomized, placebo-controlled, cross-over trial in 25 overweight subjects with defined metabolic syndrome.
Four weeks' treatment with 40 mg/day rosuvastatin significantly reduced levels of plasma cholesterol (44%), LDL cholesterol (60%) and triglyceride (38%). HDL cholesterol (mean [S.

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