Publications by authors named "Dermot Neely"

43 Publications

Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: An expert panel position statement from HEART UK.

Atherosclerosis 2020 11 15;313:126-136. Epub 2020 Sep 15.

Cardiovascular Trials Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom. Electronic address:

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19) has resulted in a pandemic. SARS-CoV-2 is highly contagious and its severity highly variable. The fatality rate is unpredictable but is amplified by several factors including advancing age, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension and obesity. A large proportion of patients with these conditions are treated with lipid lowering medication and questions regarding the safety of continuing lipid-lowering medication in patients infected with COVID-19 have arisen. Some have suggested they may exacerbate their condition. It is important to consider known interactions with lipid-lowering agents and with specific therapies for COVID-19. This statement aims to collate current evidence surrounding the safety of lipid-lowering medications in patients who have COVID-19. We offer a consensus view based on current knowledge and we rated the strength and level of evidence for these recommendations. Pubmed, Google scholar and Web of Science were searched extensively for articles using search terms: SARS-CoV-2, COVID-19, coronavirus, Lipids, Statin, Fibrates, Ezetimibe, PCSK9 monoclonal antibodies, nicotinic acid, bile acid sequestrants, nutraceuticals, red yeast rice, Omega-3-Fatty acids, Lomitapide, hypercholesterolaemia, dyslipidaemia and Volanesorsen. There is no evidence currently that lipid lowering therapy is unsafe in patients with COVID-19 infection. Lipid-lowering therapy should not be interrupted because of the pandemic or in patients at increased risk of COVID-19 infection. In patients with confirmed COVID-19, care should be taken to avoid drug interactions, between lipid-lowering medications and drugs that may be used to treat COVID-19, especially in patients with abnormalities in liver function tests.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490256PMC
November 2020

Lp(a): When and how to measure it.

Ann Clin Biochem 2021 01 28;58(1):16-21. Epub 2020 Oct 28.

Department of Blood Sciences and NIHR MedTech and IVD Centre, Newcastle Upon Tyne Hospitals, Newcastle Upon Tyne, UK.

Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement. This is becoming increasingly pertinent with the increasing recognition of lipoprotein(a) as an independent risk factor for cardiovascular disease in international guidelines and the emergence of novel antisense therapies to effectively reduce lipoprotein(a). This article raises awareness of the importance of measurement of lipoprotein(a) for the assessment of cardiovascular disease risk and gives guidance to clinical laboratories regarding choice of appropriate assays.
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http://dx.doi.org/10.1177/0004563220968473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791270PMC
January 2021

Is Alzheimer's Disease a Liver Disease of the Brain?

J Alzheimers Dis 2020 ;75(1):1-14

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Clinical specialization is not only a force for progress, but it has also led to the fragmentation of medical knowledge. The focus of research in the field of Alzheimer's disease (AD) is neurobiology, while hepatologists focus on liver diseases and lipid specialists on atherosclerosis. This article on AD focuses on the role of the liver and lipid homeostasis in the development of AD. Amyloid-β (Aβ) deposits accumulate as plaques in the brain of an AD patient long before cognitive decline is evident. Aβ generation is a normal physiological process; the steady-state level of Aβ in the brain is determined by balance between Aβ production and its clearance. We present evidence suggesting that the liver is the origin of brain Aβ deposits and that it is involved in peripheral clearance of circulating Aβ in the blood. Hence the liver could be targeted to decrease Aβ production or increase peripheral clearance.
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http://dx.doi.org/10.3233/JAD-190848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306895PMC
January 2020

The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome.

PLoS One 2020 10;15(1):e0227616. Epub 2020 Jan 10.

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.

Background: Non-ST elevation acute coronary syndrome (NSTEACS) occurs more frequently in older patients with an increased occurrence of recurrent cardiac events following the index presentation. Telomeres are structures consisting of repeated DNA sequences as associated shelterin proteins at the ends of chromosomes. We aim to determine whether telomere length (TL) and telomerase activity (TA) predicted poor outcomes in older patients presenting with NSTEACS undergoing invasive care.

Method: Older patients undergoing invasive management for NSTEACS were recruited to the ICON-1 biomarker study (NCT01933581). Peripheral blood mononuclear cells (PBMC) were recovered on 153 patients. DNA was isolated and mean TL was measured by quantitative PCR expressed as relative T (telomere repeat copy number) to S (single copy gene number) ratio (T/S ratio), and a telomere repeat amplification assay was used to assess TA during index presentation with NSTEACS. Primary clinical outcomes consisted of death, myocardial infarction (MI), unplanned revascularisation, stroke and significant bleeding recorded at 1 year. TL and TA were divided into tertile groups for analysis. Cox proportional hazards regression was performed. Ordinal regression was performed to evaluate the relationship between TL and TA and traditional cardiovascular risk factors at baseline.

Results: 298 patients were recruited in the ICON-1 study of which 153 had PBMC recovered. The mean age was 81.0 ± 4.0 years (64% male). Mean telomere length T/S ratio was 0.47 ± 0.25 and mean TA was 1.52 ± 0.61 units. The primary composite outcome occurred in 44 (28.8%) patients. There was no association between short TL or low TA and incidence of the primary composite outcome (Hazard Ratio [HR] 1.50, 95% Confidence Interval [CI] 0.68-3.34, p = 0.32 and HR 1.33, 95% CI 0.52-3.36, p = 0.51 respectively).

Conclusion: TL and TA are not found to be associated with the incidence of adverse outcomes in older patients presenting with NSTEACS undergoing invasive care.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT01933581.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227616PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953865PMC
April 2020

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action.

JAMA Cardiol 2020 02;5(2):217-229

Familial Hypercholesterolemia Foundation, Pasadena, California.

Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH.

Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created.

Conclusions And Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.
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http://dx.doi.org/10.1001/jamacardio.2019.5173DOI Listing
February 2020

HEART UK consensus statement on Lipoprotein(a): A call to action.

Atherosclerosis 2019 12 14;291:62-70. Epub 2019 Oct 14.

Department of Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk. Ten statements summarise the most salient points for practitioners and patients with high Lp(a). HEART UK recommends that Lp(a) is measured in adults as follows: 1) those with a personal or family history of premature atherosclerotic CVD; 2) those with first-degree relatives who have Lp(a) levels >200 nmol/l; 3) patients with familial hypercholesterolemia; 4) patients with calcific aortic valve stenosis and 5) those with borderline (but <15%) 10-year risk of a cardiovascular event. The management of patients with raised Lp(a) levels should include: 1) reducing overall atherosclerotic risk; 2) controlling dyslipidemia with a desirable non-HDL-cholesterol level of <100 mg/dl (2.5 mmol/l) and 3) consideration of lipoprotein apheresis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2019.10.011DOI Listing
December 2019

The association between vitamin D status and clinical events in high-risk older patients with non-ST elevation acute coronary syndrome undergoing invasive management.

PLoS One 2019 12;14(6):e0217476. Epub 2019 Jun 12.

Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.

There is a higher incidence of vitamin D deficiency in older adults. This may play a plausible mechanistic role in the occurrence of increased adverse events after non-ST elevation acute coronary syndrome (NSTEACS). This study investigated whether total vitamin D levels at the time of presentation predicted adverse outcomes in older adults undergoing invasive management of NSTEACS. Of the 629 patients screened, 300 high-risk older adults with NSTEACS managed by an invasive strategy were recruited. Serum total 25-hydroxyvitamin D was measured at index presentation. The primary outcome was defined as 1-year composite of all-cause mortality, acute coronary syndrome (ACS), unplanned repeat revascularisation, significant bleeding or stroke. Mean age was 80.5±4.8 years (61.9% male). Median vitamin D level was 29.5nmol/L [interquartile range IQR 16.0-53.0 nmol/L] and was split equally by the median for analysis forming two groups: high (median vitamin D 53.0 nmol/L [IQR 40.0-75.0]) and low (16.0 nmol/L [11.0-23.0]). The primary outcome occurred in 76 patients (25.9%); 32 (21.9%) in the low group and 44 (29.9%) in the high group, p = 0.12. Multivariable analyses showed no significant difference in the primary composite outcome at 1 year between the low and high group of baseline serum vitamin D (Hazard Ratio 1.20 [95% Confidence Interval 0.72-2.0], p = 0.48). Serum total vitamin D, measured at the time of angiography, was not associated with adverse outcomes at one year in this high-risk older cohort of patients with NSTEACS undergoing invasive management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217476PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561555PMC
March 2020

Coronary artery lesion phenotype in frail older patients with non-ST-elevation acute coronary syndrome undergoing invasive care.

EuroIntervention 2019 Jun 12;15(3):e261-e268. Epub 2019 Jun 12.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

Aims: The association of frailty with coronary plaque phenotype among older patients with non-ST-elevation acute coronary syndrome (NSTEACS) is not known. The aim of this study was to evaluate the association of frailty with coronary plaque phenotype among older patients with NSTEACS.

Methods And Results: Older patients with NSTEACS who underwent invasive angiography were recruited. Frailty was measured using the Fried frailty score. Following angiography, patients underwent greyscale and virtual histology intravascular ultrasound (VH-IVUS) imaging. Of the 90 patients, 26 (28.9%) were robust, 49 (54.4%) patients were pre-frail, and 15 (16.7%) were frail. Mean age was 80.9±3.8 years; 59 (65.6%) were male. Compared to robust patients, the pre-frail group had a significantly greater presence of high-risk lesions including VH thin-cap fibroatheroma (TCFA, p=0.011), minimum lumen area (MLA) ≤4 mm2 (p=0.016), TCFA+MLA ≤4 mm2 (p=0.005), TCFA+plaque burden (PB) ≥70% (p=0.005) and TCFA+PB ≥70%+MLA ≤4 mm2 (p=0.003). By age- and sex-adjusted logistic regression analysis, frailty was found to be strongly and independently associated with the presence of TCFA (odds ratio [OR] 2.81, 95% confidence interval [CI]:1.06-7.48, p=0.039).

Conclusions: This is the first study to report the relationship between frailty phenotype and coronary plaque morphology among frail older NSTEACS patients. ClinicalTrials.gov Identifier: NCT01933581.
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http://dx.doi.org/10.4244/EIJ-D-18-00848DOI Listing
June 2019

Cognitive Decline in Older Patients With Non- ST Elevation Acute Coronary Syndrome.

J Am Heart Assoc 2019 02;8(4):e011218

1 Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom.

Background Dementia is a growing health burden of an aging population. This study aims to evaluate the prevalence of cognitive impairment and the predictors of cognitive decline at 1 year in older patients with non-ST-elevation acute coronary syndrome undergoing invasive care. Methods and Results Older patients with non-ST-elevation acute coronary syndrome were recruited into the ICON1 study. Cognition was evaluated using Montreal Cognitive Assessment. The composite major adverse cardiovascular events comprised death, myocardial infarction, unplanned revascularization, stroke, and significant bleeding at 1 year. Of 298 patients, 271 had cognitive assessment at baseline, and 211 (78%) had follow-up Montreal Cognitive Assessment at 1 year. Mean age was 80.5±4.8 years. There was a high prevalence (n=130, 48.0%) of undiagnosed cognitive impairment (Montreal Cognitive Assessment score <26) at baseline. Cognitive impairment patients were more likely to reach major adverse cardiovascular events by Kaplan-Meier analysis ( P=0.047). Seventy-four patients (35.1%) experienced cognitive decline (Montreal Cognitive Assessment score drop by ≥2 points) at 1 year. Recurrent myocardial infarction was independently associated with cognitive decline at 1 year (odds ratio 3.19, 95% confidence interval 1.18-8.63, P=0.02) after adjustment for age and sex. Conclusions In older patients undergoing invasive management of non-ST-elevation acute coronary syndrome, there is a high prevalence of undiagnosed cognitive impairment at baseline. Recurrent myocardial infarction is independently associated with cognitive decline at 1 year. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01933581.
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http://dx.doi.org/10.1161/JAHA.118.011218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405683PMC
February 2019

One-year clinical outcomes in older patients with non-ST elevation acute coronary syndrome undergoing coronary angiography: An analysis of the ICON1 study.

Int J Cardiol 2019 Jan 28;274:45-51. Epub 2018 Sep 28.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK. Electronic address:

Aims: The aim of this prospective, observational study was to identify predictors of adverse outcome at one year, following invasive care of older patients with non-ST-elevation acute coronary syndrome (NSTEACS) according to frailty status.

Methods: Older patients (aged ≥ 75 years), presenting with NSTEACS, undergoing invasive coronary angiography with a view to revascularisation, underwent assessment of frailty, cognition, functional status and quality of life. Participants were categorised as robust, pre-frail or frail using the Fried criteria. The primary outcome comprised a composite of all-cause mortality, myocardial infarction, stroke, unplanned revascularisation and major bleeding, at one year. Cox proportional hazards regression was used to derive a multivariate risk score.

Results: Overall, the composite endpoint was observed in 81 participants (29%). There was a significant difference in the occurrence of the primary outcome in the 3 frailty groups (robust 18.0%, pre-frail 27.5% and frail 39%; p = 0.03; hazard ratio (HR) for frail vs. robust: 2.79, 95% Confidence Interval [CI] 1.28-6.08). Fried frailty classification, age (categorised as ≥85 years), raised Killip class, systolic blood pressure on admission, history of peripheral vascular disease (PVD), problems dressing self and implantation of a bare metal stent were identified as predictors of adverse events at one year, with a C-statistic of 0.77 (95% CI 0.71-0.83). A point-based clinical risk score (FRAIL-HEART) was defined, which had a C-statistic of 0.70 (95% CI 0.63-0.77) and significantly outperformed the GRACE 2 score.

Conclusion: Frailty is associated with adverse clinical outcomes, following invasive management of older patients with NSTEACS. The derived risk models may enable improved risk stratification in practice.
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http://dx.doi.org/10.1016/j.ijcard.2018.09.086DOI Listing
January 2019

Autoantibody to apolipoprotein A-1 in hepatitis C virus infection: a role in atherosclerosis?

Hepatol Int 2018 Jan 8;12(1):17-25. Epub 2018 Feb 8.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Background/purpose: One to three per cent of the world's population has hepatitis C virus (HCV) infection, which is not only a major cause of liver disease and cancer but also associated with an increased risk of atherosclerosis, despite an ostensibly favourable lipid profile. Autoantibodies are frequent in HCV infection and emerging evidence shows that autoantibodies could be valuable for cardiovascular disease (CVD) risk stratification. This study investigated a novel independent biomarker of CVD, autoantibodies to apolipoprotein A-1 (anti-apoA-1 IgG) and lipids in patients with chronic HCV before, during and after direct-acting anti-viral (DAA) therapy.

Methods: Eighty-nine blinded serum samples from 27 patients with advanced chronic HCV were assayed for lipids and anti-apoA-1 IgG by ELISA.

Results: Pre-treatment HCV viral load correlated with high-density lipoprotein cholesterol (HDL-C, r = 0.417; p = 0.042) and negatively with apolipoprotein (apo)B (r = - 0.497; p = 0.013) and markers of CVD risk, the apoB/apoA-1 ratio (r = - 0.490; p = 0.015) and triglyceride level (TG)/HDL-C ratio (r = - 0.450; p = 0.031). Fourteen (52%) of 27 patients had detectable anti-apoA-1 IgG autoantibodies pre-treatment; only two became undetectable with virological cure. Autoantibody-positive sera had lower apoA-1 (p = 0.012), HDL-C (p = 0.009) and total cholesterol (p = 0.006) levels.

Conclusions: This is the first report of the presence of an emerging biomarker for atherosclerosis, anti-apoA-1 IgG, in some patients with HCV infection. It may be induced by apoA-1 on the surface of HCV lipoviral particles. The autoantibodies inversely correlate with apoA-1 and HDL levels and may render HDL dysfunctional. Whether these hypothesis-generating findings have clinical implications in HCV patients requires further study.
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http://dx.doi.org/10.1007/s12072-018-9842-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814532PMC
January 2018

Genetic and Clinical Factors Are Associated With Statin-Related Myotoxicity of Moderate Severity: A Case-Control Study.

Clin Pharmacol Ther 2018 07 9;104(1):178-187. Epub 2017 Nov 9.

Institute of Cellular Medicine, Newcastle University, Newcastle, UK.

We evaluated the contribution of patient-specific clinical and genetic factors to statin-related muscle toxicity (SRM) without a significant creatine kinase elevation (125 cases related to simvastatin or atorvastatin and 481 controls). The association between 12 single nucleotide polymorphisms (SNPs) in nine candidate genes and clinical factors with SRM was evaluated. Of the 12 SNPs genotyped, only rs4149056 in SLCO1B1 was associated with SRM in univariate analysis (with any statin, odd ratio (OR) = 1.73, 95% confidence interval (CI) = 1.14-2.62, P = 0.010) and this association was influenced by sex (P = 0.006) and BMI (P = 0.02). In multivariate and binary logistic regression analyses, SLCO1B1 rs4149056 genotype (OR = 1.66, 95% CI: 1.08-2.54, P = 0.014) and sex (OR = 1.72, 95% CI = 1.15-2.59, P = 0.006) were independently associated with muscle toxicity related to statin treatment. Patient-specific genetic and clinical factors associated with increased systemic exposure to statins are implicated in the full spectrum of SRM, including myalgia in addition to severe myopathy.
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http://dx.doi.org/10.1002/cpt.887DOI Listing
July 2018

Hematopoiesis Shows Closer Correlation with Calculated Free Testosterone in Men than Total Testosterone.

J Appl Lab Med 2017 Jan;1(4):441-444

Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Trust, Newcastle-upon-Tyne, UK.

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http://dx.doi.org/10.1373/jalm.2016.022012DOI Listing
January 2017

HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom.

Atherosclerosis 2016 12 5;255:128-139. Epub 2016 Nov 5.

Department of Medicine and Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M139WL, UK; Cardiovascular Research Group, University of Manchester, Manchester, M139WL, UK.

This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.
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http://dx.doi.org/10.1016/j.atherosclerosis.2016.10.017DOI Listing
December 2016

Study to Improve Cardiovascular Outcomes in high-risk older patieNts (ICON1) with acute coronary syndrome: study design and protocol of a prospective observational study.

BMJ Open 2016 08 23;6(8):e012091. Epub 2016 Aug 23.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Introduction: The ICON1 study (a study to Improve Cardiovascular Outcomes in high-risk older patieNts with acute coronary syndrome) is a prospective observational study of older patients (≥75 years old) with non-ST-elevation acute coronary syndrome managed by contemporary treatment (pharmacological and invasive). The aim of the study was to determine the predictors of poor cardiovascular outcomes in this age group and to generate a risk prediction tool.

Methods And Analysis: Participants are recruited from 2 tertiary hospitals in the UK. Baseline evaluation includes frailty, comorbidity, cognition and quality-of-life measures, inflammatory status assessed by a biomarker panel, including microRNAs, senescence assessed by telomere length and telomerase activity, cardiovascular status assessed by arterial stiffness, endothelial function, carotid intima media thickness and left ventricular systolic and diastolic function, and coronary plaque assessed by virtual histology intravascular ultrasound and optical coherence tomography. The patients are followed-up at 30 days and at 1 year for primary outcome measures of death, myocardial infarction, stroke, unplanned revascularisation, bleeding and rehospitalisation.

Ethics And Dissemination: The study has been approved by the regional ethics committee (REC 12/NE/016). Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals.

Trial Registration Number: NCT01933581: Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2016-012091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013351PMC
August 2016

Maximum levels of hepatitis C virus lipoviral particles are associated with early and persistent infection.

Liver Int 2016 12 5;36(12):1774-1782. Epub 2016 Jul 5.

The Kirby Institute, UNSW Australia, Kensington, NSW, Australia.

Background & Aims: Hepatitis C virus (HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle (LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody-mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance.

Methods: LVP in non-fasting plasma was measured using the concentration of HCV RNA bound to large >100 nm sized lipoproteins after ex vivo addition of a lipid emulsion, that represented the maximum concentration of LVP (maxi-LVP). This method correlated with LVP in fasting plasma measured using iodixanol density gradient ultracentrifugation. Maxi-LVP was measured in a cohort of 180 HCV participants with recent HCV infection and detectable HCV RNA from the Australian Trial in Acute Hepatitis C (ATAHC) and Hepatitis C Incidence and Transmission Study in prison (HITS-p) cohorts.

Results: Spontaneous clearance occurred in 15% (27 of 180) of individuals. In adjusted analyses, low plasma maxi-LVP level was independently associated with spontaneous HCV clearance (≤827 IU/ml; adjusted odds ratio 3.98, 95% CI: 1.02, 15.51, P = 0.047), after adjusting for interferon lambda-3 rs8099917 genotype, estimated duration of HCV infection and total HCV RNA level.

Conclusions: Maxi-LVP is a biomarker for the maximum concentration of LVP in non-fasting samples. Low maxi-LVP level is an independent predictor of spontaneous clearance of acute HCV.
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http://dx.doi.org/10.1111/liv.13176DOI Listing
December 2016

Erratum to: PCSK9 inhibitors in the prevention of cardiovascular disease.

J Thromb Thrombolysis 2016 10;42(3):420

Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, M3.131, 3rd Floor William Leech Building, Newcastle upon Tyne, NE2 4HH, UK.

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http://dx.doi.org/10.1007/s11239-016-1373-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828237PMC
October 2016

Single-centre study of the diagnostic performance of plasma metanephrines with seated sampling for the diagnosis of phaeochromocytoma/paraganglioma.

Ann Clin Biochem 2017 Jan 28;54(1):143-148. Epub 2016 Sep 28.

1 Blood Sciences, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Background Measurement of plasma metanephrines is regarded as one of the best screening tests for phaeochromocytoma/paraganglioma. Current guidelines recommend that samples are ideally collected in the supine position after 30 min rest and interpreted using supine reference ranges, in order to optimize the diagnostic performance of the test. Current practice in our centre is to collect samples for plasma metanephrines from seated patients. The aim of the study was to determine, if seated sampling for plasma metanephrines provides acceptable diagnostic performance in our centre. Methods Clinical and laboratory data of 113 patients, gathered over a four-year period 2010-2014, were reviewed. All had undergone preoperative plasma metanephrines measurement and had postoperative histopathology confirmation or exclusion of phaeochromocytoma/paraganglioma. Results Of 113 patients included in the study, 40 had a histological diagnosis of phaeochromocytoma/paraganglioma. The remaining 73 patients had an alternative adrenal pathology. The diagnostic sensitivity of normetanephrine or metanephrine above the upper limit of our in-house seated reference range was 93%. However, excluding three cases of paraganglioma determined clinically and biochemically to be non-functional raised the sensitivity to 100%. Diagnostic specificity was 90%. Applying published supine reference ranges made no difference to diagnostic sensitivity in this group of patients but decreased diagnostic specificity to 75%. Conclusions While these data are derived from a relatively small study population, they demonstrate acceptable diagnostic performance for seated plasma metanephrines as a screening test for phaeochromocytoma/paraganglioma. These data highlight a high diagnostic sensitivity for plasma metanephrines with seated sampling in our centre.
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http://dx.doi.org/10.1177/0004563216650463DOI Listing
January 2017

PCSK9 inhibitors in the prevention of cardiovascular disease.

J Thromb Thrombolysis 2016 Oct;42(3):405-19

Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, M3.131, 3rd Floor William Leech Building, Newcastle upon Tyne, NE2 4HH, UK.

Reducing plasma levels of low-density lipoprotein cholesterol (LDL-C) remains the cornerstone in the primary and secondary prevention of cardiovascular disease. However, lack of efficacy and adverse effects mean that a substantial proportion of patients fail to achieve acceptable LDL-C levels with currently available lipid-lowering drugs. Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic strategy to reduce residual cardiovascular disease risk. Binding of PCSK9 to the LDL receptor targets the receptor for lysosomal degradation. The recognition that inhibition of PCSK9 increases LDL receptor activity has led to the development of a number of approaches to directly target PCSK9. Numerous monoclonal antibodies against PCSK9 are currently being evaluated in phase 3 trials, involving various patient categories on different background lipid-lowering therapies. Current evidence shows reductions in LDL-C levels of up to 70 % may be achieved with PCSK9 inhibition, independent of background statin therapy. This review examines the most recent evidence and future prospects for the use of PCSK9 inhibitors in the prevention of cardiovascular disease.
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http://dx.doi.org/10.1007/s11239-016-1364-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010583PMC
October 2016

Improving detection of familial hypercholesterolaemia in primary care using electronic audit and nurse-led clinics.

J Eval Clin Pract 2016 Jun 26;22(3):341-8. Epub 2015 Nov 26.

Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute of Cardiovascular Sciences, University College London, London, UK.

Rationale, Aims And Objectives: In the UK fewer than 15% of familial hypercholesterolemia (FH) cases are diagnosed, representing a major gap in coronary heart disease prevention. We wished to support primary care doctors within the Medway Clinical Commissioning Group (CCG) to implement NICE guidance (CG71) and consider the possibility of FH in adults who have raised total cholesterol concentrations, thereby improving the detection of people with FH.

Methods: Utilizing clinical decision support software (Audit+) we developed an FH Audit Tool and implemented a systematic audit of electronic medical records within GP practices, first identifying all patients diagnosed with FH or possible FH and next electronically flagging patients with a recorded total cholesterol of >7.5 mmol L(-1) or LDL-C > 4.9 mmol L(-1) (in adults), for further assessment. After a 2-year period, a nurse-led clinic was introduced to screen more intensely for new FH index cases. We evaluated if these interventions increased the prevalence of FH closer to the expected prevalence from epidemiological studies.

Results: The baseline prevalence of FH within Medway CCG was 0.13% (1 in 750 persons). After 2 years, the recorded prevalence of diagnosed FH increased by 0.09% to 0.22% (1 in 450 persons). The nurse advisor programme ran for 9 months (October 2013-July 2014) and during this time, the recorded prevalence of patients diagnosed with FH increased to 0.28% (1 in 357 persons) and the prevalence of patients 'at risk and unscreened' reduced from 0.58% to 0.14%.

Conclusions: Our study shows that two simple interventions increased the detection of FH. This systematic yet simple electronic case-finding programme with nurse-led review allowed the identification of new index cases, more than doubling the recorded prevalence of detected disease to 1 in 357 (0.28%). This study shows that primary care has an important role in identifying patients with this condition.
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http://dx.doi.org/10.1111/jep.12481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840360PMC
June 2016

Phaeochromocytoma and ACTH-dependent cushing's syndrome: tumour crf secretion can mimic pituitary cushing's disease.

Clin Endocrinol (Oxf) 2016 Feb 20;84(2):177-184. Epub 2015 Nov 20.

Department of Endocrinology, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK.

Introduction: 10% of corticotrophin (ACTH)-dependent Cushing's syndrome arises from secretion by extrapituitary tumours, with phaeochromocytoma implicated in a few cases. Ectopic secretion by phaeochromocytoma of corticotropin-releasing hormone (CRF), with secondary corticotroph hyperplasia, is even rarer, with only five cases in the literature hitherto. However, such cases may be classified as 'ectopic ACTH' due to incomplete verification.

Clinical Cases: We describe three patients with phaeochromocytoma and ACTH-dependent Cushing's syndrome in whom biochemical cure was achieved following unilateral adrenalectomy. Although unable to access a validated CRF assay within the timeframe for sample storage, we nevertheless inferred CRF secretion in 2 of 3 cases by tumour immunostaining (positive for CRF; negative for ACTH), supported in one case by pre-operative inferior petrosal sinus sampling (IPSS) indicative of pituitary ACTH source. Both cases were characterized by rapid postoperative wean off glucocorticoids, presumed to reflect the pituitary stimulatory-effect of CRF outweighing central negative feedback inhibition by hypercortisolaemia. By contrast, the tumour excised in a third case exhibited positive immunostaining for ACTH - negative for CRF - and postoperative recovery of hypothalamic-pituitary-adrenal axis took significantly longer.

Discussion: Ectopic CRF production is biochemically indistinguishable from ectopic ACTH secretion, except that IPSS mimics pituitary Cushing's disease and cortisol dynamics may normalize rapidly postadrenalectomy. CRF secretion can be inferred through tumour immunohistochemistry, even if no CRF assay is available. Unrecognized phaeochromocytoma ACTH secretion may underpin some cases of cardiovascular collapse postadrenalectomy through acute hypocortisolaemia. Despite advances in phaeochromocytoma genetics since previous reports, we were unable to identify somatic DNA defects associated with either ACTH or CRF secretion.
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http://dx.doi.org/10.1111/cen.12960DOI Listing
February 2016

Impact of using different guideline recommended serum natriuretic peptide thresholds on the diagnosis and referral rates of a diagnostic heart failure clinic.

Int J Clin Pract 2015 Nov 21;69(11):1349-56. Epub 2015 Jul 21.

Department of Cardiology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

Aims: The aims of this study were to determine the diagnostic yield of a dedicated heart failure diagnosis clinic and the impact of using different guideline recommended N-terminal pro B-type natriuretic peptide (NT-proBNP) referral thresholds on diagnosis and referral patterns.

Methods And Results: Patients referred by primary care between September 2011 and May 2013 were included in the analysis. Data collected included baseline characteristics, NT-proBNP levels, echocardiographic and clinical findings, final diagnosis and outcome. The impact of using Newcastle (locally modified age-adjusted NT-proBNP thresholds), National Institute for Health and Care Excellence (NICE) and European Society of Cardiology (ESC) NT-proBNP thresholds on diagnosis and referrals was determined by applying the different guidelines to this population. A total of 208 patients were referred; median age 77.5 years and 62.5% were women. Thirty-four patients (16.3%) had systolic heart failure, 50 patients (24.0%) had heart failure with preserved ejection fraction. One hundred and six patients (51.0%) did not have heart failure. Using NICE guidelines (NT-proBNP ≥ 400 ng/l) instead of the Newcastle age-adjusted NT-proBNP referral thresholds results in 59 fewer referrals, but eight heart failure diagnoses were missed. Using the ESC cut-off of NT-proBNP ≥ 125 ng/l would result in 88 additional referrals; one diagnosis of heart failure would be missed. Over a mean follow-up of 16.8 ± 6 months there were 21 deaths and 47 hospital admissions.

Conclusion: The Newcastle age-adjusted thresholds led to more referrals in comparison to NICE guidelines but are more sensitive in diagnosing heart failure. Using ESC recommended thresholds results in a similar diagnostic yield to our age-adjusted thresholds, but has the potential to significantly increase the referrals in patients ≥ 75 years, which may result in a lower diagnostic yield.
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http://dx.doi.org/10.1111/ijcp.12694DOI Listing
November 2015

Biochemistry laboratories should routinely report non-HDL-cholesterol.

Ann Clin Biochem 2015 Nov 17;52(Pt 6):629-31. Epub 2015 Jun 17.

Clinical Biochemistry Department, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

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http://dx.doi.org/10.1177/0004563215594818DOI Listing
November 2015

PCSK9, apolipoprotein E and lipoviral particles in chronic hepatitis C genotype 3: evidence for genotype-specific regulation of lipoprotein metabolism.

J Hepatol 2015 Apr 21;62(4):763-70. Epub 2014 Nov 21.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address:

Background & Aims: Hepatitis C virus (HCV) associates with lipoproteins to form "lipoviral particles" (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels. We measured LVP and PCSK9 in patients chronically infected with HCV genotype (G)3. PCSK9 concentrations were also measured in HCV-G1 to indirectly examine the role of LDLR in LVP clearance.

Methods: HCV RNA, LVP (d<1.07g/ml) and non-LVP (d>1.07g/ml) fractions, were quantified in patients with HCV-G3 (n=39) by real time RT-PCR and LVP ratios (LVPr; LVP/(LVP+non-LVP)) were calculated. Insulin resistance (IR) was assessed using the homeostasis model assessment of IR (HOMA-IR). Plasma PCSK9 concentrations were measured by ELISA in HCV-G3 and HCV-G1 (n=51).

Results: In HCV-G3 LVP load correlated inversely with HDL-C (r=-0.421; p=0.008), and apoE (r=-0.428; p=0.013). The LVPr varied more than 35-fold (median 0.286; range 0.027 to 0.969); PCSK9 was the strongest negative predictor of LVPr (R(2)=16.2%; p=0.012). HOMA-IR was not associated with LVP load or LVPr. PCSK9 concentrations were significantly lower in HCV-G3 compared to HCV-G1 (p<0.001). PCSK9 did not correlate with LDL-C in HCV-G3 or G1.

Conclusions: The inverse correlation of LVP with apoE in HCV-G3, compared to the reverse in HCV-G1 suggests HCV genotype-specific differences in apoE mediated viral entry. Lower PCSK9 and LDL concentrations imply upregulated LDLR activity in HCV-G3.
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http://dx.doi.org/10.1016/j.jhep.2014.11.016DOI Listing
April 2015

Endothelial dysfunction and coronary artery disease: a state of the art review.

Cardiol Rev 2015 May-Jun;23(3):119-29

From the *Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, United Kingdom; †Cardiothoracic Centre, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom; ‡Department of Biochemistry, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom; and §Regional Medical Physics Department, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.

Atherosclerotic coronary artery disease (CAD) is a major cause of morbidity and mortality in the developed world. Endothelial dysfunction plays an important role in the development of atherosclerosis and predicts cardiovascular (CV) outcomes independent of conventional CV risk factors. In recent years, there have been tremendous improvements in the pharmacological prevention and management of CAD. In this review, the pathophysiology of endothelial dysfunction in relation to CAD is discussed and various techniques of invasive and noninvasive assessments of peripheral and coronary endothelial function described. In addition, evidence for the association of endothelial dysfunction and CV outcomes has been examined and finally the role of therapeutic interventions in endothelial dysfunction has been discussed.
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http://dx.doi.org/10.1097/CRD.0000000000000047DOI Listing
January 2016

Utility of NT-proBNP as a rule-out test for left ventricular dysfunction in very old people with limiting dyspnoea: the Newcastle 85+ Study.

BMC Cardiovasc Disord 2014 Sep 26;14:128. Epub 2014 Sep 26.

Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.

Background: Guidelines advocate using B-type natriuretic peptides in the diagnostic work-up of suspected heart failure (HF). Their main role is to limit echocardiography rates by ruling out HF/LV dysfunction where peptide level is low. Recommended rule-out cut points vary between guidelines. The utility of B-type natriuretic peptides in the very old (85+) requires further investigation, with optimal cut points yet to be established. We examined NT-proBNP's utility, alone and in combination with history of myocardial infarction (MI), as a rule-out test for LV dysfunction in very old people with limiting dyspnoea.

Methods:

Design: Cross-sectional analysis.

Setting: Population-based sample; North-East England.

Participants: 155 people (aged 87-89) with limiting dyspnoea.

Measures: Dyspnoea assessed by questionnaire. Domiciliary echocardiography performed; LV systolic/diastolic function graded. NT-proBNP measured (Roche Diagnostics). Receiver operating characteristic analyses examined NT-proBNP's diagnostic accuracy for LV dysfunction.

Results: AUC for LVEF less than or equal to 50% was poor (0.58, 95% CI 0.49-0.65), but good for LVEF less than or equal to 40% (0.80, 95% CI 0.73-0.86). At ESC cut point (125 ng/l), few cases of systolic dysfunction were missed (NPV 94-100%, depending on severity), but echocardiography (88%) and false positive rates (56-81 per 100 screened) were high. At NICE cut point (400 ng/l), echocardiography (51%) and false positive rates (33-45) were lower; exclusionary performance was good for LVEF less than or equal to 40% (1 case missed per 100 screened, 15% of cases; NPV 97%), but poor for LVEF less than or equal to 50% (16 cases missed per 100 screened, 45% of cases; NPV 68%). Incorporating isolated moderate/severe diastolic dysfunction into target condition increased the proportion of cases missed (lower NPV), whilst improving case detection. Incorporating MI history as an additional referral prompt slightly reduced the number of cases missed at expense of higher echocardiography and false positive rates.

Conclusions: High echocardiography rates and poor exclusionary performance for mild degrees of systolic dysfunction and for diastolic dysfunction limit NT-proBNP's utility as a rule-out test for LV dysfunction in very old people with limiting dyspnoea. Incorporating MI history as an additional echocardiography prompt yields no overall benefit compared to using NT-proBNP level alone.
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http://dx.doi.org/10.1186/1471-2261-14-128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189162PMC
September 2014

Association of aging, arterial stiffness, and cardiovascular disease: a review.

Cardiol Rev 2014 Sep-Oct;22(5):223-32

From the *Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; †Institute of Ageing and Health, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; ‡Cardiothoracic Centre, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom; §Department of Biochemistry, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom.

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in the western world. Primary and secondary prevention strategies have improved tremendously. Conventional risk factors are identified and treated with intensive pharmacotherapy. Despite these measures, the incidence of CHD is on the rise in developed countries. Arterial stiffness has been identified as an independent risk factor for the development of CHD, both in the general population and in those with established CHD. This review examines the association of arterial stiffness with cardiovascular disease.
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http://dx.doi.org/10.1097/CRD.0000000000000009DOI Listing
April 2015

Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to combination antiviral therapy - a pilot randomised clinical trial.

Liver Int 2014 May 14;34(5):737-47. Epub 2013 Oct 14.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Background & Aims: Hepatitis C virus (HCV) utilises cholesterol and lipoprotein metabolism for replication and infectivity. Statins and omega-3 (n-3) polyunsaturated fatty acids (PUFA) have been shown to have antiviral properties in vitro. This open label pilot study evaluated the efficacy of fluvastatin (Lescol(®) 40-80 mg) and n-3 PUFA (Omacor(®) 1 g and 2-4 g) on HCV-RNA and lipoviral particles (LVP) in difficult to treat prior non-responders.

Methods: Patients (n = 60) were randomly allocated in a factorial design to: no active drug; low-dose n-3 PUFA; high-dose n-3 PUFA; fluvastatin; low-dose n-3 PUFA + fluvastatin; or high-dose n-3 PUFA + fluvastatin. 50/60 completed study drugs for 12 weeks and followed up to week 24. Comparison was made between fluvastatin (n = 24) vs no fluvastatin (n = 26) and n-3 PUFA high-dose (n = 17) vs low-dose (n = 17) vs none (n = 16). The primary outcomes were change in total HCV-RNA, LVP and ALT at week 12 compared with baseline. Secondary outcome was change in interferon-gamma-inducible protein-10 (IP10) as a measure of interferon activation.

Results: 35% had compensated cirrhosis and 45% were prior null responders. There was no significant change in total HCV RNA, LVP, non-LVP or LVP ratio in patients receiving fluvastatin or n-3 PUFAs. ALT was not significantly different in those treated with fluvastatin or n-3 PUFAs. 12 weeks of low-dose n-3 PUFA decreased median IP10 concentration by -39 pg/ml (-111, 7.0 pg/ml Q1-Q3).

Conclusions: Fluvastatin and n-3 PUFAs have no effect on plasma HCV-RNA or LVP. The effect of low-dose n-3 PUFA on IP10 warrants further prospective evaluation as a supplemental therapy to enhance interferon sensitivity.
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http://dx.doi.org/10.1111/liv.12316DOI Listing
May 2014

Hepatitis C virus and lipids in the era of direct acting antivirals (DAAs).

Clin Res Hepatol Gastroenterol 2013 Feb 5;37(1):10-6. Epub 2012 Sep 5.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

The six different HCV-genotypes have marked differences in response to therapy with pegylated interferon-α and ribavirin. The introduction of the direct acting antiviral (DAA) protease inhibitors, telaprevir and boceprevir in combination with pegylated interferon-α and ribavirin has become the new standard of care for genotype 1 infection. Several host factors associated with response to pegylated interferon-α and ribavirin are not as important in predicting response to triple therapy, and yet low-density lipoprotein cholesterol (LDLC) and statin use remain important associations of outcome with DAAs. This review focuses on the clinical associations between lipids and treatment response to interferon based antiviral treatments. We consider how understanding the interactions of HCV and host lipid metabolism remains relevant in the era of DAAs for genotype 1 infection and for treatment of non-genotype 1 chronic hepatitis C.
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http://dx.doi.org/10.1016/j.clinre.2012.07.002DOI Listing
February 2013