Publications
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Watts GF, Gidding SS, Hegele RA, et al., 2023, International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia, Nature Reviews Cardiology, Vol: 20, Pages: 845-869, ISSN: 1759-5010
This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. FH, a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.
Thompson GR, 2023, RESOLVING THE CHOLESTEROL CONTROVERSY: The Scientists Who Proved the Lipid Hypothesis of Causation of Atherosclerosis and Coronary Heart Disease, ISBN: 9781800613973
Resolving the Cholesterol Controversy recounts the science and scientific personalities behind the chain of discoveries upon which the lipid hypothesis of atherosclerosis was built. The narrative covers a period of just under 100 years, starting with Anitschkow’s experiments with cholesterol-fed rabbits in 1913, and recounts the endeavours and achievements of the leading actors in this protracted scientific drama. The cast is drawn from an extraordinary variety of scientific disciplines: pathology, biophysics, epidemiology, nutrition, cardiology, lipidology, genetics, microbiology, pharmacology, and clinical trial design. Most of the scientists believed that cholesterol played a causal role in atherosclerosis and cardiovascular disease, but there were some who dissented strongly from this conclusion. The breadth of scientific disciplines involved in proving the lipid hypothesis is matched by the geographical spread of the participants. Anitschkow worked in Russia, Endo discovered the first statin in Japan, their commercial development by Merck took place in the USA and evidence of benefit from lowering cholesterol came from trials conducted in Scandinavia and the UK. The subsequent meta-analysis of these statin trials in 2005 proved the validity of the lipid hypothesis beyond any doubt. The history of how this all came about and its impact upon health policy and medical practice is recalled here in Resolving the Cholesterol Controversy.
Thompson GR, 2022, The scientific basis and future of lipoprotein apheresis, Therapeutic Apheresis and Dialysis, Vol: 26, Pages: 32-36, ISSN: 1744-9979
Lipoprotein apheresis plays a vital role in the management of the severe hyperlipidemias that predispose to atherosclerosis. Determinants of efficacy are the acute reduction in lipoproteins achieved by each apheresis procedure, their frequency, and the fractional catabolic rates and hence pool sizes of low-density lipoprotein (LDL) or lipoprotein (a) (Lp(a)) of the patient being treated. A useful criterion of the efficacy of apheresis plus lipid-lowering drug therapy is the decrease in the interval (time-averaged) mean of serum total or LDL cholesterol or Lp(a) between procedures, expressed as the percent decrease in the interval means below the maximal levels of these lipoproteins when off all treatment. Recent advances in lipid-lowering drug therapy may diminish the use of lipoprotein apheresis but will not abolish its unique role as a therapeutic "last chance saloon," especially for children and pregnant women with homozygous familial hypercholesterolemia.
Thompson GR, 2021, Use of apheresis in the age of new therapies for familial hypercholesterolaemia, CURRENT OPINION IN LIPIDOLOGY, Vol: 32, Pages: 363-369, ISSN: 0957-9672
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- Citations: 2
Thompson G, 2021, Use of apheresis in the age of new therapies for FH, Current Opinion in Lipidology, ISSN: 0957-9672
Thompson GR, 2021, FH through the retrospectoscope, Journal of Lipid Research, Vol: 62, Pages: 1-9, ISSN: 0022-2275
After training as a gastroenterologist in the UK, the author became interested in lipidology while he was a research fellow in the USA and switched careers after returning home. Together with Nick Myant, he introduced the use of plasma exchange to treat familial hypercholesterolemia (FH) homozygotes and undertook non-steady state studies of LDL kinetics, which showed that the fractional catabolic rate of LDL remained constant irrespective of pool size. Subsequent steady-state turnover studies showed that FH homozygotes had an almost complete lack of receptor-mediated LDL catabolism, providing in vivo confirmation of the Nobel Prize-winning discovery by Goldstein and Brown that LDL receptor dysfunction was the cause of FH. Further investigation of metabolic defects in FH revealed that a significant proportion of LDL in homozygotes and heterozygotes was produced directly via a VLDL-independent pathway. Management of heterozygous FH has been greatly facilitated by statins and proprotein convertase subtilisin/kexin type 9 inhibitors but remains dependent upon lipoprotein apheresis in homozygotes. In a recent analysis of a large cohort treated with a combination of lipid-lowering measures, survival was markedly enhanced in homozygotes in the lowest quartile of on-treatment serum cholesterol. Emerging therapies could further improve the prognosis of homozygous FH; whereas in heterozygotes, the current need is better detection.
Thompson GR, 2020, PCSK9 inhibitors for homozygous familial hypercholesterolemia useful but seldom sufficient, Journal of the American College of Cardiology, Vol: 76, Pages: 143-145, ISSN: 0735-1097
Thompson GR, 2020, Medicine My Vocation, Fishing My Recreation: Memoirs Of A Physician And Flyfisherman, Publisher: World Scientific, ISBN: 9781786348135
This book is about the author's life motivated by two pursuits: medicine, his profession and flyfishing, his favourite recreation.
Pottle A, Thompson G, Barbir M, et al., 2020, Lipoprotein apheresis efficacy, challenges and outcomes: A descriptive analysis from the UK Lipoprotein Apheresis Registry, 1989-2017 (vol 290, pg 44, 2019), ATHEROSCLEROSIS, Vol: 294, Pages: 16-16, ISSN: 0021-9150
Pottle A, Thompson G, Barbir M, et al., 2019, Lipoprotein apheresis efficacy, challenges and outcomes: A descriptive analysis from the UK Lipoprotein Apheresis Registry, 1989-2017, ATHEROSCLEROSIS, Vol: 290, Pages: 44-51, ISSN: 0021-9150
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- Citations: 22
Thompson GR, Parhofer K, 2019, Current role of lipoprotein apheresis, Current Atherosclerosis Reports, Vol: 21, ISSN: 1523-3804
Purpose of ReviewLipoprotein apheresis is a very efficient but time-consuming and expensive method of lowering levels of low-density lipoprotein cholesterol, lipoprotein(a)) and other apoB containing lipoproteins, including triglyceride-rich lipoproteins. First introduced almost 45 years ago, it has long been a therapy of “last resort” for dyslipidaemias that cannot otherwise be managed. In recent years new, very potent lipid-lowering drugs have been developed and the purpose of this review is to define the role of lipoprotein apheresis in the current setting.Recent FindingsLipoprotein apheresis still plays an important role in managing patients with homozygous FH and some patients with other forms of hypercholesterolaemia and cardiovascular disease. In particular, patients not achieving treatment goals despite modern lipid-lowering drugs, either because these are not tolerated or the response is insufficient. Recently, lipoprotein(a) has emerged as an important cardiovascular risk factor and lipoprotein apheresis has been used to decrease lipoprotein(a) concentrations in patients with marked elevations and cardiovascular disease. However, there is considerable heterogeneity concerning the recommendations by scientific bodies as to which patient groups should be treated with lipoprotein apheresis.SummaryLipoprotein apheresis remains an important tool for the management of patients with severe drug-resistant dyslipidaemias, especially those with homozygous FH.
David A, Cegla J, Walji S, et al., 2018, Hypercholesterolemia with low versus high likelihood of polygenic origin: a single centre experience, HEART UK 32nd Annual Medical and Scientific Conference on Hot Topics in Atheroscloerosis and Cardiovascular Disease, Publisher: Elsevier, Pages: E7-E7, ISSN: 1567-5688
Introduction: A large proportion of patients that meet Simon Broome diagnostic criteria for Familial Hypercholesterolemia (FH) have no single-gene mutations (FH-negative patients) and an LDL-C SNP score suggestive of a low likelihood of hypercholesterolemia (HC) of polygenic origin. In these patients, unknown genetic causes of FH may be present. Aims: to compare the clinical characteristics of: 1) FH-negative versus FH-positive patients and 2) FH-negative patients with high versus low likelihood of polygenic (LPg) HC.Methods: Genetic data, lipid profile, history of cardiovascular events (CVE) and family history of CVE were obtained in 109 index cases (age range 17-81years) with a clinical diagnosis of possible or definite FH.Results: FH-negative patients (n=78) were older when diagnosed with HC compared to FH-positive patients (n=31): age at diagnosis 50±11 vs 31±12, p<0.001. Moreover, they had lower LDL cholesterol (C) levels pre-treatment (5.8±0. 9 vs 6.8±1.5mmol/L, p<0.001), but higher HDL-C levels (1.6±0.5 vs 1.3±0.3mmol/L, p<0.03) compared to FH-positive patients. No difference in age at diagnosis (p=0.92), LDL-C (p=0.63) and HDL-C (p=0.25) levels pre-treatment was present between FH-negative with high-LPg (n=50) versus low-LPg (n=28). Physical stigmata of HC were commoner in FH-negative low-LPg (8/21, 38.1%) versus high-LPg (3/40, 7.5%) patients (p<0.001). Moreover, 22% low-LPg patients had suffered a CVE versus 8% high-LPg patients, although this was not statistically significant (p=0.15). No difference was found in the prevalence of physical stigmata of HC (p=0.93) or history of CVE (p=0.64) in FH-negative versus FH-positive patients. There was no significant difference in total cholesterol, triglycerides, Lp(a) levels as well as the prevalence of hypertension, smoking, diabetes/IGT or family history of premature CVE between FH-negative versus FH-positive or FH-negative with high-LPg versus low-LPg patien
Thompson GR, Blom DJ, Marais AD, et al., 2018, Survival in homozygous familial hypercholesterolaemia is determined by the on-treatment level of serum cholesterol, European Heart Journal, Vol: 39, Pages: 1162-1168, ISSN: 1522-9645
AimsHomozygous familial hypercholesterolaemia (FH) is a rare inherited disorder characterized by extreme hypercholesterolaemia from birth, accelerated atherosclerosis, and premature death. Many forms of lipid-lowering therapies have been used in the past, but definitive evidence of benefit has been lacking. We therefore undertook a retrospective survey of lipid levels and clinical outcomes of FH homozygotes treated with a combination of lipid-lowering measures between 1990 and 2014 in South Africa and the UK.Methods and resultsWe divided 133 previously statin-naive homozygotes into quartiles according to their on-treatment levels of serum cholesterol and compared the occurrence of any death, cardiovascular death, and major adverse cardiovascular events (MACE) between the quartiles during 25 years of follow-up, using Cox and competing risks regression analysis. Patients in Quartile 4, with an on-treatment serum cholesterol >15.1 mmol/L, had a hazard ratio of 11.5 for any death compared with those in Quartile 1, with an on-treatment cholesterol of < 8.1 mmol/L. Those in Quartiles 2 and 3 combined, with on-treatment cholesterol of 8.1–15.1 mmol/L had a hazard ratio of 3.6 compared with Quartile 1. These differences were statistically significant (P < 0.001) and remained so after adjustments for confounding factors (P = 0.04). Significant differences between quartiles were also evident for cardiovascular deaths and MACE.ConclusionThese findings provide unequivocal evidence that the extent of reduction of serum cholesterol achieved by a combination of therapeutic measures, including statins, ezetimibe, lipoprotein apheresis, and evolocumab, is a major determinant of survival in homozygous FH.
Thompson GR, 2018, Survival in homozygous familialhypercholesterolaemia is determined by theon-treatment level of serumcholesterol, European Heart Journal, Vol: 39, Pages: 1162-1168, ISSN: 1522-9645
AimsHomozygous familial hypercholesterolaemia (FH) is a rare inherited disorder characterized by extreme hypercholesterolaemia from birth, accelerated atherosclerosis, and premature death. Many forms of lipid-lowering therapies have been used in the past, but definitive evidence of benefit has been lacking. We therefore undertook a retrospective survey of lipid levels and clinical outcomes of FH homozygotes treated with a combination of lipid-lowering measures between 1990 and 2014 in South Africa and the UK.Methods and resultsWe divided 133 previously statin-naive homozygotes into quartiles according to their on-treatment levels of serum cholesterol and compared the occurrence of any death, cardiovascular death, and major adverse cardiovascular events (MACE) between the quartiles during 25 years of follow-up, using Cox and competing risks regression analysis. Patients in Quartile 4, with an on-treatment serum cholesterol >15.1 mmol/L, had a hazard ratio of 11.5 for any death compared with those in Quartile 1, with an on-treatment cholesterol of < 8.1 mmol/L. Those in Quartiles 2 and 3 combined, with on-treatment cholesterol of 8.1–15.1 mmol/L had a hazard ratio of 3.6 compared with Quartile 1. These differences were statistically significant (P < 0.001) and remained so after adjustments for confounding factors (P = 0.04). Significant differences between quartiles were also evident for cardiovascular deaths and MACE.ConclusionThese findings provide unequivocal evidence that the extent of reduction of serum cholesterol achieved by a combination of therapeutic measures, including statins, ezetimibe, lipoprotein apheresis, and evolocumab, is a major determinant of survival in homozygous FH.
France M, Rees A, Datta D, et al., 2016, HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom, Atherosclerosis, Vol: 255, Pages: 128-139, ISSN: 0021-9150
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.
Thompson GR, 2016, The Nobel dilemma: to reward scientific discovery or benefit to mankind?, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, Vol: 109, Pages: 513-514, ISSN: 1460-2725
Thompson GR, Seed M, Naoumova RP, et al., 2015, Improved cardiovascular outcomes following temporal advances in lipid-lowering therapy in a genetically-characterised cohort of familial hypercholesterolaemia homozygotes, Atherosclerosis, Vol: 243, Pages: 328-333, ISSN: 0021-9150
Background and aimsThere is a paucity of data concerning the influence of lipid-lowering therapy on cardiovascular (CV) outcomes in patients with homozygous familial hypercholesterolaemia (FH). To redress this a retrospective analysis was undertaken of the demographic features, lipid levels, low density lipoprotein receptor and Autosomal Recessive Hypercholesterolaemia gene mutations, CV outcomes and vital status of 44 FH homozygotes referred to a single centre in the UK between 1964 and 2014.MethodsData were obtained from past publications, case records and death certificates. Differences in categorical and continuous variables between living and dead patients were analysed using Fisher's exact test and an independent t-test respectively.ResultsDuring the 50 years covered by this survey 13 patients have died, 30 are still alive and 1 was lost to follow up. The mean age of Alive patients was 32.6 ± 11.5 versus 28.3 ± 14.9 years in Dead ones (P = 0.31) and they were born 18 years later (P = 0.0001). Pre-treatment serum total cholesterol (TC) was similar in Alive and Dead (20.2 ± 5.1 v 21.3 ± 4.4 mmol/l, P = 0.52) but on-treatment TC was lower in Alive than Dead (8.1 ± 2.8 v 14.5 ± 6.0 mmol/l, P = 0.0001) and CV adverse events were far less frequent (eg aortic stenosis, 33% v 77%, P = 0.02).ConclusionsThe lower on-treatment TC and fewer CV adverse events in FH homozygotes still living reflect advances in apheresis and drug therapy since the 1990s. Further improvements in prognosis can be expected with the impending introduction of novel lipid-lowering agents.
Carter NJ, Hill NE, Nicol ED, et al., 2015, Dyslipidaemia and the military patient, JOURNAL OF THE ROYAL ARMY MEDICAL CORPS, Vol: 161, Pages: 206-210, ISSN: 0035-8665
Thompson GR, 2015, Obituary of Dr NB Myant, ATHEROSCLEROSIS, Vol: 240, Pages: 437-438, ISSN: 0021-9150
Thompson GR, 2015, Managing homozygous familial hypercholesterolaemia from cradle to grave, ATHEROSCLEROSIS SUPPLEMENTS, Vol: 18, Pages: 16-20, ISSN: 1567-5688
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- Citations: 15
Gibbons G, Soutar A, Thompson GR, 2015, In Memoriam: Nick Myant (1917 - 2015)., J Lipid Res
Stefanutti C, Thompson GR, 2015, Lipoprotein Apheresis in the Management of Familial Hypercholesterolaemia: Historical Perspective and Recent Advances, CURRENT ATHEROSCLEROSIS REPORTS, Vol: 17, ISSN: 1523-3804
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- Citations: 47
Thompson GR, Seed M, 2014, Lipoprotein( a): the underestimated cardiovascular risk factor, HEART, Vol: 100, Pages: 534-535, ISSN: 1355-6037
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- Citations: 10
Thompson GR, Griffin M, Bond D, et al., 2014, OF CHOLESTEROL-FED RABBITS AND LDL RECEPTOR-DEFICIENT MEN, Autumn Meeting of the British-Atherosclerosis-Society (BAS), Publisher: ELSEVIER IRELAND LTD, Pages: E8-E8, ISSN: 0021-9150
Thompson G, Mabuchi H, 2014, Akira Endo: The discovery of statins, Pioneers of Medicine Without a Nobel Prize, Pages: 251-270, ISBN: 9781783263837
Thompson G, 2014, Preface, Pioneers of Medicine Without a Nobel Prize, Pages: ix-x
Thompson GR, Seed M, 2014, The management of familial hypercholesterolaemia, Primary Care Cardiovascular Journal, Vol: 7, Pages: 89-91, ISSN: 1756-5138
Homozygous familial hypercholesterolaemia (FH) is a rare disorder with a very high risk of premature cardiac death that must be diagnosed and treated from childhood onwards, usually with lifelong lipoprotein apheresis. Heterozygous FH is much commoner, with a high risk of cardiovascular disease in adults that can be prevented by early diagnosis and statin therapy.
Walji S, Neuwirth C, Thompson GR, 2013, Lipoprotein apheresis for the treatment of familial hypercholesterolemia, CLINICAL LIPIDOLOGY, Vol: 8, Pages: 573-586, ISSN: 1758-4299
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- Citations: 7
Thompson GR, 2013, The evidence-base for the efficacy of lipoprotein apheresis in combating cardiovascular disease, ATHEROSCLEROSIS SUPPLEMENTS, Vol: 14, Pages: 67-70, ISSN: 1567-5688
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- Citations: 52
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