Clinical management of the lipoprotein abnormalities associated with diabetes mellitus requires e... more Clinical management of the lipoprotein abnormalities associated with diabetes mellitus requires effective laboratory assessment. Lipoprotein abnormalities vary according to the aetiology of the diabetes, but both type 1 and type 2 diabetes may result in quantitative and/or qualitative changes in lipoproteins. Routine assessment is based on assays that are readily available thanks to high-throughput automated analytical techniques. Preanalytical considerations, such as the need to fast and analytical performance of individual assays, should be considered in the context of the requirements for clinical decision-making. In particular, the risk of macrovascular complications of diabetes can be anticipated by consideration of major cardiovascular risk factors including total cholesterol (TC), fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), from which additional indicators such as low-density lipoprotein cholesterol (LDL-C) and non-HDL cholesterol (NHDL-C) may be derived.
Refsum's Disease is an inherited metabolic disorder in which a metabolite of branched chain f... more Refsum's Disease is an inherited metabolic disorder in which a metabolite of branched chain fatty acids accumulates due to lack of appropriate oxidative enzymes. Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. Besides retinal degeneration or retinal dystrophy associated with adult onset retinitis pigmentosa, additional symptoms include chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, as well as skeletal, cardiac, hepatic, and renal abnormalities. Current management includes avoidance of dietary sources of branched chain fatty acids and regular plasmapheresis to prevent accumulation of these compounds to ameliorate progressive neurological deficits. Two brothers with Refsum's disease who experienced progressive symptoms despite optimal diet and plasmapheresis were commenced on a novel therapy. We report the effect of the intestin...
Low plasma levels of high-density-lipoprotein cholesterol (HDL-C) and high triglyceride (TG) are ... more Low plasma levels of high-density-lipoprotein cholesterol (HDL-C) and high triglyceride (TG) are strongly associated with cardiovascular disease (CVD). Clinical recognition of this high-risk population demands accurate measurement of HDL-C, whereas cost and clinical demand dictate that optimal HDL-C measurement requires fully automated methods that avoid manual precipitation. Commercial techniques use specific reagents to selectively expose and "directly" measure cholesterol in HDL. However, these "direct" methods may experience interference from the cholesterol content of triglyceride-rich-lipoproteins (TRL), leading to analytical overestimation of HDL-C, with subsequent underestimation of low-density-lipoprotein cholesterol (LDL-C) and of CVD risk. The aim of this study was…
Background: Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based pheno... more Background: Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based phenotyping are standard methods for identifying patients who experience post-succinylcholine (SC) apnea attributable to inherited variants of the BChE enzyme. Our aim was to develop PCR-based assays for BCHE mutation detection and implement them for routine diagnostic use at a university teaching hospital. Methods: Between 1999 and 2002, we genotyped 65 patients referred after prolonged post-SC apnea. Five BCHE gene mutations were analyzed. Competitive oligo-priming (COP)-PCR was used for flu-1, flu-2, and K-variant and direct DNA sequencing analysis for dibucaine and sil-1 mutations. Additional DNA sequencing of BCHE coding regions was provided when the five-mutation screen was negative or mutation findings were inconsistent with enzyme activity. Results: Genotyping identified 52 patients with primary hypocholinesterasemia attributable to BCHE mutations, and in 44 individuals the abnormalit...
There is now significant evidence to support an independent causal role for lipoprotein(a) (Lp(a)... more There is now significant evidence to support an independent causal role for lipoprotein(a) (Lp(a)) as a risk factor for atherosclerotic cardiovascular disease. Plasma Lp(a) concentrations are predominantly determined by genetic factors. However, research into Lp(a) has been hampered by incomplete understanding of its metabolism and proatherogeneic properties and by a lack of suitable animal models. Furthermore, a lack of standardized assays to measure Lp(a) and no universal consensus on optimal plasma levels remain significant obstacles. In addition, there are currently no approved specific therapies that target and lower elevated plasma Lp(a), although there are recent but limited clinical outcome data suggesting benefits of such reduction. Despite this, international guidelines now recognize elevated Lp(a) as a risk enhancing factor for risk reclassification. This review summarises the current literature on Lp(a), including its discovery and recognition as an atherosclerotic cardi...
Plasma lipidomic measures may enable improved prediction of cardiovascular outcomes in secondary ... more Plasma lipidomic measures may enable improved prediction of cardiovascular outcomes in secondary prevention. The aim of this study is to determine the association of plasma lipidomic measurements with cardiovascular events and assess their potential to predict such events. Plasma lipids (n = 342) were measured in a retrospective subcohort (n = 5,991) of the LIPID study. Proportional hazards regression was used to identify lipids associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and cardiovascular death. Multivariable models adding lipid species to traditional risk factors were created using lipid ranking established from the Akaike information criterion within a 5-fold cross-validation framework. The results were tested on a diabetic case cohort from the ADVANCE study (n = 3,779). Specific ceramide species, sphingolipids, phospholipids, and neutral lipids containing omega-6 fatty acids or odd-chain fatty acids wer...
The authors sought to evaluate the plaque-modifying effects of low-dose colchicine therapy plus o... more The authors sought to evaluate the plaque-modifying effects of low-dose colchicine therapy plus optimal medical therapy (OMT) in patients post-acute coronary syndrome (ACS), as assessed by coronary computed tomography angiography (coronary CTA). Colchicine therapy has been postulated to have beneficial anti-inflammatory effects in patients with ACS, translating into reduction in future adverse cardiovascular events. However, whether favorable plaque modification underpins this is yet unproven. In this prospective nonrandomized observational study of 80 patients with recent ACS (<1 month), patients received either 0.5 mg/day colchicine plus OMT or OMT alone and were followed for 1 year. Our primary outcome was change in low attenuation plaque volume (LAPV), a marker of plaque instability on coronary CTA and robust predictor of adverse cardiovascular events. Secondary outcomes were changes in other coronary CTA measures and in high-sensitivity C-reactive protein (hsCRP). Mean durat...
It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associ... more It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma...
Journal of atherosclerosis and thrombosis, Jan 24, 2017
Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprote... more Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often under-treated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, web-based Rare Disease Registry Fram...
Background: Clinical lipid measurements do not show the full complexity of the altered lipid meta... more Background: 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. Methods: 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). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year fo...
The Journal of clinical endocrinology and metabolism, Jan 4, 2016
Impaired postprandial chylomicron metabolism induces hypertriglyceridemia and may increase risk o... more Impaired postprandial chylomicron metabolism induces hypertriglyceridemia and may increase risk of atherosclerotic cardiovascular disease (ASCVD). Omega-3 fatty acid ethyl ester (ω-3 FAEE) supplementation decreases plasma triglycerides. However, its effect on postprandial chylomicron metabolism in familial hypercholesterolemia (FH) has not yet been investigated. We aimed to examine the effect of ω-3 FAEE supplementation on postprandial responses in plasma triglycerides, very-low-density lipoprotein (VLDL)-apoB-100 and apoB-48 in FH patients receiving standard cholesterol-lowering treatment. We carried out an 8-week open-label, randomized, cross-over intervention trial to test the effect of oral supplementation with 4 g/day ω-3 FAEE (46% eicosapentaenoic acid and 38% docosahexaenoic acid) on postprandial triglyceride, VLDL-apoB-100 and apoB-48 responses in FH patients following ingestion of an oral fat load. Plasma total and incremental triglyceride, VLDL-apoB-100 and apoB-48 0-10 h ...
The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists, 2004
Impaired lipoprotein metabolism is one of the major aetiological factors for the pathogenesis of ... more Impaired lipoprotein metabolism is one of the major aetiological factors for the pathogenesis of atherosclerosis and cardiovascular disease (CVD). Assessment is usually made in the fasting state, and particular attention is directed towards the measurement of the cholesterol content of both the low and high-density lipoprotein fractions. By comparison, a massive amount of lipid fluxes through the intra-vascular compartment during the post-prandial period. This has led to the hypothesis that atherosclerosis could be partially, or even predominantly, due to the pathological effects of this flux of post-prandial lipoproteins on the vessel wall. This justifies efforts to systematically study the relationship between the lipoprotein responses to food (particularly fat) ingestion and cardiovascular disease or its surrogate markers. This review will consider the mechanisms by which post-prandial metabolism might affect the risk of CVD. It will examine the evidence for and against such an a...
This study compared the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, f... more This study compared the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, fish oil, and placebo on plasma lipids and lipoproteins in patients with mixed hyperlipidemia. After an initial run-in phase, 32 patients were randomized for 6 weeks to either (1) pravastatin 40 nig/d, n=10; (2) fish 011 (himega 6 g/d, equivalent to 3 g to-3 fatty acids/d), n=10; or (3)
Clinical management of the lipoprotein abnormalities associated with diabetes mellitus requires e... more Clinical management of the lipoprotein abnormalities associated with diabetes mellitus requires effective laboratory assessment. Lipoprotein abnormalities vary according to the aetiology of the diabetes, but both type 1 and type 2 diabetes may result in quantitative and/or qualitative changes in lipoproteins. Routine assessment is based on assays that are readily available thanks to high-throughput automated analytical techniques. Preanalytical considerations, such as the need to fast and analytical performance of individual assays, should be considered in the context of the requirements for clinical decision-making. In particular, the risk of macrovascular complications of diabetes can be anticipated by consideration of major cardiovascular risk factors including total cholesterol (TC), fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), from which additional indicators such as low-density lipoprotein cholesterol (LDL-C) and non-HDL cholesterol (NHDL-C) may be derived.
Refsum's Disease is an inherited metabolic disorder in which a metabolite of branched chain f... more Refsum's Disease is an inherited metabolic disorder in which a metabolite of branched chain fatty acids accumulates due to lack of appropriate oxidative enzymes. Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. Besides retinal degeneration or retinal dystrophy associated with adult onset retinitis pigmentosa, additional symptoms include chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, as well as skeletal, cardiac, hepatic, and renal abnormalities. Current management includes avoidance of dietary sources of branched chain fatty acids and regular plasmapheresis to prevent accumulation of these compounds to ameliorate progressive neurological deficits. Two brothers with Refsum's disease who experienced progressive symptoms despite optimal diet and plasmapheresis were commenced on a novel therapy. We report the effect of the intestin...
Low plasma levels of high-density-lipoprotein cholesterol (HDL-C) and high triglyceride (TG) are ... more Low plasma levels of high-density-lipoprotein cholesterol (HDL-C) and high triglyceride (TG) are strongly associated with cardiovascular disease (CVD). Clinical recognition of this high-risk population demands accurate measurement of HDL-C, whereas cost and clinical demand dictate that optimal HDL-C measurement requires fully automated methods that avoid manual precipitation. Commercial techniques use specific reagents to selectively expose and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;directly&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; measure cholesterol in HDL. However, these &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;direct&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; methods may experience interference from the cholesterol content of triglyceride-rich-lipoproteins (TRL), leading to analytical overestimation of HDL-C, with subsequent underestimation of low-density-lipoprotein cholesterol (LDL-C) and of CVD risk. The aim of this study was…
Background: Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based pheno... more Background: Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based phenotyping are standard methods for identifying patients who experience post-succinylcholine (SC) apnea attributable to inherited variants of the BChE enzyme. Our aim was to develop PCR-based assays for BCHE mutation detection and implement them for routine diagnostic use at a university teaching hospital. Methods: Between 1999 and 2002, we genotyped 65 patients referred after prolonged post-SC apnea. Five BCHE gene mutations were analyzed. Competitive oligo-priming (COP)-PCR was used for flu-1, flu-2, and K-variant and direct DNA sequencing analysis for dibucaine and sil-1 mutations. Additional DNA sequencing of BCHE coding regions was provided when the five-mutation screen was negative or mutation findings were inconsistent with enzyme activity. Results: Genotyping identified 52 patients with primary hypocholinesterasemia attributable to BCHE mutations, and in 44 individuals the abnormalit...
There is now significant evidence to support an independent causal role for lipoprotein(a) (Lp(a)... more There is now significant evidence to support an independent causal role for lipoprotein(a) (Lp(a)) as a risk factor for atherosclerotic cardiovascular disease. Plasma Lp(a) concentrations are predominantly determined by genetic factors. However, research into Lp(a) has been hampered by incomplete understanding of its metabolism and proatherogeneic properties and by a lack of suitable animal models. Furthermore, a lack of standardized assays to measure Lp(a) and no universal consensus on optimal plasma levels remain significant obstacles. In addition, there are currently no approved specific therapies that target and lower elevated plasma Lp(a), although there are recent but limited clinical outcome data suggesting benefits of such reduction. Despite this, international guidelines now recognize elevated Lp(a) as a risk enhancing factor for risk reclassification. This review summarises the current literature on Lp(a), including its discovery and recognition as an atherosclerotic cardi...
Plasma lipidomic measures may enable improved prediction of cardiovascular outcomes in secondary ... more Plasma lipidomic measures may enable improved prediction of cardiovascular outcomes in secondary prevention. The aim of this study is to determine the association of plasma lipidomic measurements with cardiovascular events and assess their potential to predict such events. Plasma lipids (n = 342) were measured in a retrospective subcohort (n = 5,991) of the LIPID study. Proportional hazards regression was used to identify lipids associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and cardiovascular death. Multivariable models adding lipid species to traditional risk factors were created using lipid ranking established from the Akaike information criterion within a 5-fold cross-validation framework. The results were tested on a diabetic case cohort from the ADVANCE study (n = 3,779). Specific ceramide species, sphingolipids, phospholipids, and neutral lipids containing omega-6 fatty acids or odd-chain fatty acids wer...
The authors sought to evaluate the plaque-modifying effects of low-dose colchicine therapy plus o... more The authors sought to evaluate the plaque-modifying effects of low-dose colchicine therapy plus optimal medical therapy (OMT) in patients post-acute coronary syndrome (ACS), as assessed by coronary computed tomography angiography (coronary CTA). Colchicine therapy has been postulated to have beneficial anti-inflammatory effects in patients with ACS, translating into reduction in future adverse cardiovascular events. However, whether favorable plaque modification underpins this is yet unproven. In this prospective nonrandomized observational study of 80 patients with recent ACS (<1 month), patients received either 0.5 mg/day colchicine plus OMT or OMT alone and were followed for 1 year. Our primary outcome was change in low attenuation plaque volume (LAPV), a marker of plaque instability on coronary CTA and robust predictor of adverse cardiovascular events. Secondary outcomes were changes in other coronary CTA measures and in high-sensitivity C-reactive protein (hsCRP). Mean durat...
It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associ... more It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma...
Journal of atherosclerosis and thrombosis, Jan 24, 2017
Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprote... more Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often under-treated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, web-based Rare Disease Registry Fram...
Background: Clinical lipid measurements do not show the full complexity of the altered lipid meta... more Background: 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. Methods: 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). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year fo...
The Journal of clinical endocrinology and metabolism, Jan 4, 2016
Impaired postprandial chylomicron metabolism induces hypertriglyceridemia and may increase risk o... more Impaired postprandial chylomicron metabolism induces hypertriglyceridemia and may increase risk of atherosclerotic cardiovascular disease (ASCVD). Omega-3 fatty acid ethyl ester (ω-3 FAEE) supplementation decreases plasma triglycerides. However, its effect on postprandial chylomicron metabolism in familial hypercholesterolemia (FH) has not yet been investigated. We aimed to examine the effect of ω-3 FAEE supplementation on postprandial responses in plasma triglycerides, very-low-density lipoprotein (VLDL)-apoB-100 and apoB-48 in FH patients receiving standard cholesterol-lowering treatment. We carried out an 8-week open-label, randomized, cross-over intervention trial to test the effect of oral supplementation with 4 g/day ω-3 FAEE (46% eicosapentaenoic acid and 38% docosahexaenoic acid) on postprandial triglyceride, VLDL-apoB-100 and apoB-48 responses in FH patients following ingestion of an oral fat load. Plasma total and incremental triglyceride, VLDL-apoB-100 and apoB-48 0-10 h ...
The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists, 2004
Impaired lipoprotein metabolism is one of the major aetiological factors for the pathogenesis of ... more Impaired lipoprotein metabolism is one of the major aetiological factors for the pathogenesis of atherosclerosis and cardiovascular disease (CVD). Assessment is usually made in the fasting state, and particular attention is directed towards the measurement of the cholesterol content of both the low and high-density lipoprotein fractions. By comparison, a massive amount of lipid fluxes through the intra-vascular compartment during the post-prandial period. This has led to the hypothesis that atherosclerosis could be partially, or even predominantly, due to the pathological effects of this flux of post-prandial lipoproteins on the vessel wall. This justifies efforts to systematically study the relationship between the lipoprotein responses to food (particularly fat) ingestion and cardiovascular disease or its surrogate markers. This review will consider the mechanisms by which post-prandial metabolism might affect the risk of CVD. It will examine the evidence for and against such an a...
This study compared the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, f... more This study compared the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, fish oil, and placebo on plasma lipids and lipoproteins in patients with mixed hyperlipidemia. After an initial run-in phase, 32 patients were randomized for 6 weeks to either (1) pravastatin 40 nig/d, n=10; (2) fish 011 (himega 6 g/d, equivalent to 3 g to-3 fatty acids/d), n=10; or (3)
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