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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Targets for cholesterol reduction are part of the Quality Outcomes Framework and general practitioners have to meet these targets to fulfil their remuneration package. By contrast, there are no targets for the accuracy of cholesterol or other lipid measurements and no recent surveys on performance of these assays. We have assessed the performance of lipid measurement of the available methods in the UK. Methods: Serum samples collected from individual donors attending the national blood service were distributed after values were obtained from a secondary reference laboratory. Samples were sent to participant laboratories to assess different methods' analytical performance on single donation specimens, on routine external quality assessment pooled specimens, on specimens subjected to a range of freeze-thaw cycles and on frozen-stored specimens. Results: Differences in measured cholesterol were found that were method-dependent and related to triglyceride content. HDL-cholesterol (HDL-C) showed significant positive bias in all assays. Individual donor specimens showed no significant changes with differing numbers of freeze-thaw cycles. Pooled serum was stable for up to six months. Conclusions: Most cholesterol measurements are accurate but some methods are affected by triglyceride interference. HDL-C methods show significant positive bias. Although there are potential matrix effects introduced as a result of specimen preparation, additional work is needed to show if these effects are present in fresh patient samples. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)