Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.

In the aftermath of the COVID-19 pandemic, we are witnessing an unprecedented wave of post-infectious complications. Most prominently, millions of patients with Long-Covid complain about chronic fatigue and severe post-exertional malaise. Therapeutic apheresis has been suggested as an efficient treatment option for alleviating and mitigating symptoms in this desperate group of patients. However, little is known about the mechanisms and biomarkers correlating with treatment outcomes. Here, we have analyzed in different cohorts of Long-Covid patients specific biomarkers before and after therapeutic apheresis. In patients that reported a significant improvement following two cycles of therapeutic apheresis, there was a significant reduction in neurotransmitter autoantibodies, lipids, and inflammatory markers. Furthermore, we observed a 70% reduction in fibrinogen, and following apheresis, erythrocyte rouleaux formation and fibrin fibers largely disappeared as demonstrated by dark field microscopy. This is the first study demonstrating a pattern of specific biomarkers with clinical symptoms in this patient group. It may therefore form the basis for a more objective monitoring and a clinical score for the treatment of Long-Covid and other postinfectious syndromes.

Post COVID and Apheresis - Where are we Standing?

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

Obesity and COVID-19: What are the Consequences?

Obesity is an increasing health problem all over the world. In combination with the current COVID-19 pandemic, this has turned into a massive challenge as individuals with overweight and obesity at all ages show a significant increase in their risk of getting severe COVID-19. Around 20% of all patients that were hospitalized for COVID-19 suffered from obesity alone, whereas obesity in combination with other metabolic comorbidities, such as type 2 diabetes and hypertension, account for up to 60% of all hospitalizations in relation to COVID-19. Therefore, it is of immense importance to put the spotlight on the high incidence of obesity present already in childhood both by changing the individual minds and by encouraging politicians and the whole society to commence preventive interventions for achieving a better nutrition for all social classes all over the world. In the current review, we aim to explain the different pathways and mechanisms that are responsible for the increased risk of severe COVID-19 in people with overweight and obesity. Furthermore, we discuss how the pandemic has led to weight gains in many people during lockdown. At the end, we discuss the importance of preventing such an interface between a non-communicable disease like obesity and a communicable disease like COVID-19 in the future.

Diabetes and COVID-19: Short- and Long-Term Consequences.

When the corona pandemic commenced more than two years ago, it was quickly recognized that people with metabolic diseases show an augmented risk of severe COVID-19 and an increased mortality compared to people without these comorbidities. Furthermore, an infection with SARS-CoV-2 has been shown to lead to an aggravation of metabolic diseases and in single cases to new-onset metabolic disorders. In addition to the increased risk for people with diabetes in the acute phase of COVID-19, this patient group also seems to be more often affected by long-COVID and to experience more long-term consequences than people without diabetes. The mechanisms behind these discrepancies between people with and without diabetes in relation to COVID-19 are not completely understood yet and will require further research and follow-up studies during the following years. In the current review, we discuss why patients with diabetes have this higher risk of developing severe COVID-19 symptoms not only in the acute phase of the disease but also in relation to long-COVID, vaccine breakthrough infections and re-infections. Furthermore, we discuss the effects of lockdown on glycemic control.

Hypertriglyceridaemia: contemporary management of a neglected cardiovascular risk factor.

Hypertriglyceridaemia represents one of the most prevalent lipid abnormalities, however it is often eclipsed by focus on LDL cholesterol and is frequently overlooked by clinicians, despite it being an important cardiovascular risk factor. For most patients, hypertriglyceridaemia arises from a combination of environmental factors and multiple genetic variations with small effects. Even in cases with apparent familial clustering of hypertriglyceridaemia, a monogenetic cause is rarely identified. Common secondary causes include obesity, uncontrolled diabetes, alcohol, and various commonly used drugs. Correction of these factors, along with lifestyle optimisation, should be prioritised prior to commencing medication. The goal of drug treatment is to reduce the risk of cardiovascular disease in those with moderate hypertriglyceridaemia and the risk of pancreatitis in those with severe hypertriglyceridaemia. Recent and ongoing trials demonstrate the important role of triglycerides (TG) in determining residual risk in patients with cardiovascular disease (CVD) already established on statin therapy. Novel and emerging data on omega-3 fatty acids (high-dose icosapent ethyl) and the selective PPAR modulator pemafibrate are eagerly awaited and may provide further clarity for clinicians in determining which patients will benefit from TG lowering and help inform clinical guidelines. There are numerous novel therapies on the horizon that reduce TG by decreasing the activity of proteins that inhibit lipoprotein lipase such as apolipoprotein C-III (including Volanesorsen which was recently approved in Germany) and ANGPTL 3/4 which may offer promise for the future.

Oxidised LDL and Anti-Oxidised LDL Antibodies Are Reduced by Lipoprotein Apheresis in a Randomised Controlled Trial on Patients with Refractory Angina and Elevated Lipoprotein(a).

Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation between oxidised LDL (oxLDL) levels and atherosclerotic burden as well as rates of cardiovascular events. Antibodies against oxLDL (anti-oxLDL) are involved in the removal of oxLDL. Lipoprotein apheresis (LA), which removes lipoproteins using extra-corporeal processes, is an established means of reducing Lp(a), and thereby reduces cardiovascular events. The aim of this study was to investigate the effect of LA on oxLDL and anti-oxLDL levels amongst those with refractory angina in the context of raised Lp(a). Methods: We performed a sub-study within a randomised controlled crossover trial involving 20 patients with refractory angina and raised Lp(a) > 500 mg/L, comparing the effect of three months of blinded weekly LA or sham, followed by crossover to the opposite study arm. We utilized enzyme-linked immunosorbent assays (ELISA) to quantify oxLDL and IgG/ IgM anti-oxLDL antibody levels at baseline and following three months of active LA or sham sessions. Results: Following three months of LA, there was a 30% reduction in oxLDL from 0.37 ± 0.06 to 0.26 ± 0.04 with a mean drop of -0.11 units (U) (95% CI -0.13, -0.09) compared to no significant change with sham therapy (p < 0.0001 between treatment arms). LA also led to a 22% reduction in levels of IgG and IgM anti-oxLDL, again with no significant change demonstrated during sham (p = 0.0036 and p = 0.012, respectively, between treatment arms). Conclusion: Amongst patients with refractory angina in the context of elevated Lp(a), LA significantly lowers levels of oxLDL and anti-oxLDL antibodies, representing potential mechanisms by which LA yields symptomatic and prognostic benefits in this patient cohort.

Evaluation of a novel rapid genomic test including polygenic risk scores for the diagnosis and management of familial hypercholesterolaemia.

Introduction: Familial hypercholesterolaemia (FH) is a common autosomal dominant genetic condition, characterised by elevated LDL cholesterol (LDL-C), leading to premature cardiovascular disease (CVD). Early and accurate diagnosis, with implementation of preventative therapies, has a major impact on reducing premature CVD, morbidity and mortality. Genetic testing is recommended to confirm clinical diagnosis in the proband and enable cascade testing in relatives. There is growing evidence that the risk of CVD conferred by hypercholesterolaemia depends not only on monogenic causes but also on polygenic factors. GENinCode has developed a novel genomic testing system (Lipid inCode®) which we have assessed against an accredited National Health Service (NHS UK) genetic screening service in order to validate its diagnostic and clinical utility. Methods: DNA samples from 40 index cases who had been referred for FH testing in an ISO15189-accredited NHS genetic screening service, were retrospectively tested using the Lipid inCode® assay. The results were compared with those from NHS testing. Results: There was absolute concordance in variant detection between both diagnostic tests for monogenic and polygenic FH, the only difference being in the interpretation and classification of DNA variants based on ACMG guidelines, which did not differ by more than one classification class.  The Lipid inCode® test was equivalent to the NHS test in providing comprehensive genetic analysis that included the assessment of both monogenic (FH) and polygenic determinants of blood cholesterol and including a pharmacogenomic assessment of predisposition to statin-related myopathy. Conclusion: The Lipid inCode® diagnostic test can be undertaken with rapid turnaround and gave the same results as those reported by standard NHS genetic laboratory testing. In addition to assessment of monogenic FH, the Lipid inCode® assay provides additional genetic data, such as polygenic factors contributing to hypercholesterolaemia, a polygenic risk score (PRS) for coronary artery disease (CAD), pharmacogenomic testing for statin myopathy, and genetic predisposition to raised Lp(a).

Prevalence of cardiovascular events in genetically confirmed versus unconfirmed familial hypercholesterolaemia.

Introduction: Genetic testing for familial hypercholesterolaemia (FH) is not yet established for widespread use internationally to provide diagnostic confirmation, in part due to high cost and resource requirement. We need to establish whether genetic testing is clinically justified in terms of risk stratification and prediction of cardiovascular events. Methods:We performed a single tertiary cardiac centre retrospective evaluation of patients with FH managed within our genetic screening service. We evaluated the prevalence of cardiovascular events in genetically confirmed cases of FH compared to those unconfirmed upon genetic testing, to assess whether gene positivity confers a higher risk phenotype. We also compared the clinical characteristics of the genetically confirmed and unconfirmed group. Results:Amongst adult patients (≥18 years) with genetically confirmed heterozygous FH (n=87), 34% (30/87) had one or more documented CV events. In comparison a lower event rate was observed in adult patients with genetically unconfirmed FH (n=170) with 25% (42/170) experiencing one or more documented CV events. Additional cardiovascular risk factors were more prevalent in the unconfirmed group including hypertension, co-morbidities, higher age and body mass index which may have modified the difference in cardiovascular risk. Conclusion:Genetic testing in FH may be clinically justified and appears to identify a subset of patients with higher risk of cardiovascular events. However, the risk difference is modified by alternative cardiovascular risk factors and co-morbidities which may be more prevalent in genetically unconfirmed FH.

Lipoprotein apheresis efficacy, challenges and outcomes: A descriptive analysis from the UK Lipoprotein Apheresis Registry, 1989-2017.

BACKGROUND AND AIMS: In 2008, the National Institute of Health and Care Excellence in the UK recommended that patients undergoing lipoprotein apheresis (LA) should be included in an anonymised registry. The UK Lipoprotein Apheresis Registry was subsequently established in 2011. METHODS: Between 2011 and 2017, data was entered retrospectively and prospectively by seven LA centres in the UK for 151 patients. Twenty-two patients were involved in a research study and were therefore excluded from the analysis. Observational data was analysed for the remaining 129 patients. RESULTS: Most patients had heterozygous familial hypercholesterolaemia (HeFH) (45.0%); 23.3% had homozygous FH (HoFH); 7.8% had hyper-lipoproteinaemia (a) (Lp(a)) and 24.0% had other forms of dyslipidaemia. Detailed treatment data is available for 63 patients relating to 348 years of LA treatment. The number of years of treatment per patient ranged from 1 to 15. The mean reduction in interval mean LDL-C from the pre-procedure baseline was 43.14%. The mean reduction in interval mean Lp(a) from baseline was 37.95%. The registry data also shows a 62.5% reduction in major adverse cardiovascular events (MACE) between the 2 years prior to, and the first 2 years following introduction of LA. CONCLUSIONS: The data generated by the UK Lipoprotein Apheresis Registry demonstrates that LA is a very efficient method of reducing LDL-C and Lp(a) and lowers the incidence rate of MACE. LA is an important tool in the management of selected patients with HoFH and drug-resistant dyslipidaemias.

Impact of lipoprotein apheresis on thrombotic parameters in patients with refractory angina and raised lipoprotein(a): Findings from a randomized controlled cross-over trial.

BACKGROUND: Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis. OBJECTIVES: The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a). METHODS: In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays. RESULTS: Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham. CONCLUSION: Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina.

Lipid Profiles in Lyme Borreliosis: A Potential Role for Apheresis?

Dyslipidemia and dyslipoproteinemia are common causes of metabolic and cardiovascular diseases. On the other hand, intracellular bacteria, such as Borrelia burgdorferi, utilize host lipids to survive and disseminate within the host. Recent data suggest that elevated lipids are a contributing factor to the maintenance and severity of Lyme disease and its complications. Here we review and discuss the role of lipids in Borreliosis and report on a pilot trial to examine the potential roles of circulating lipids and lipoproteins in patients with Borrelia infection. In this analysis we assessed the clinical and lipid profiles of 519 patients (319 women, 200 men) with a proven history of Lyme disease, before and after an extracorporeal double membrane filtration. Lipid profiles pre- and post-apheresis were analyzed in conjunction with clinical symptoms and parameters of inflammation. Circulating cholesterol, triglycerides, LDL, LP(a), and other inflammatory lipids were significantly reduced after the apheresis, while symptoms of the disorder and bioindexes of inflammation such as CRP improved. Further studies should be initiated to investigate the possibly causal relation between Lyme disease and circulating lipids and to design appropriate therapeutic strategies.

Vascular access in lipoprotein apheresis: a retrospective analysis from the UK's largest lipoprotein apheresis centre.

INTRODUCTION: Lipoprotein apheresis (LA) has proven to be an effective, safe and life-saving therapy. Vascular access is needed to facilitate this treatment but has recognised complications. Despite consistency in treatment indication and duration there are no guidelines in place. The aim of this study is to characterise vascular access practice at the UK's largest LA centre and forward suggestions for future approaches. METHODS: A retrospective analysis of vascular access strategies was undertaken in all patients who received LA treatment in the low-density lipoprotein (LDL) Apheresis Unit at Harefield Hospital (Middlesex, UK) from November 2000 to March 2016. RESULTS: Fifty-three former and current patients underwent 4260 LA treatments. Peripheral vein cannulation represented 79% of initial vascular access strategies with arteriovenous (AV) fistula use accounting for 15%. Last used method of vascular access was peripheral vein cannulation in 57% versus AV fistula in 32%. Total AV fistula failure rate was 37%. CONCLUSIONS: Peripheral vein cannulation remains the most common method to facilitate LA. Practice trends indicate a move towards AV fistula creation; the favoured approach receiving support from the expert body in this area. AV fistula failure rate is high and of great concern, therefore we suggest the implementation of upper limb ultrasound vascular mapping in all patients who meet treatment eligibility criteria. We encourage close ties between apheresis units and specialist surgical centres to facilitate patient counselling and monitoring. Further prospective data regarding fistula failure is needed in this expanding treatment field.

Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial.

AIMS: To determine the clinical impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point of quantitative myocardial perfusion, as well as secondary end points including atheroma burden, exercise capacity, symptoms, and quality of life. METHODS: We conducted a single-blinded randomized controlled trial in 20 patients with refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint was change in quantitative myocardial perfusion reserve (MPR) assessed by cardiovascular magnetic resonance. Secondary endpoints included measures of atheroma burden, exercise capacity, symptoms and quality of life. RESULTS: The primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31-0.63) compared with sham (-0.16; 95% CI - 0.33-0.02) yielding a net treatment increase of 0.63 (95% CI 0.37-0.89; P < 0.001 between groups). Improvements with apheresis compared with sham also occurred in atherosclerotic burden as assessed by total carotid wall volume (P < 0.001), exercise capacity by the 6 min walk test (P = 0.001), 4 of 5 domains of the Seattle angina questionnaire (all P < 0.02) and quality of life physical component summary by the short form 36 survey (P = 0.001). CONCLUSION: Lipoprotein apheresis may represent an effective novel treatment for patients with refractory angina and raised lipoprotein(a) improving myocardial perfusion, atheroma burden, exercise capacity and symptoms.

Prevalence of obstructive coronary artery disease and prognosis in patients with stable symptoms and a zero-coronary calcium score.

AIMS: CT calcium scoring (CTCS) and CT cardiac angiography (CTCA) are widely used in patients with stable chest pain to exclude significant coronary artery disease (CAD). We aimed to resolve uncertainty about the prevalence of obstructive coronary artery disease and long-term outcomes in patients with a zero-calcium score (ZCS). METHODS AND RESULTS: Consecutive patients with stable cardiac symptoms referred for CTCS or CTCS and CTCA from chest pain clinics to a tertiary cardiothoracic centre were prospectively enrolled. In those with a ZCS, the prevalence of obstructive CAD on CTCA was determined. A follow-up for all-cause mortality was obtained from the NHS tracer service. A total of 3914 patients underwent CTCS of whom 2730 (69.7%) also had a CTCA. Half of the patients were men (50.3%) with a mean age of 56.9 years. Among patients who had both procedures, a ZCS was present in 52.2%, with a negative predictive value of 99.5% for excluding ≥70% stenosis on CTCA. During a mean follow-up of 5.2 years, the annual event rate was 0.3% for those with ZCS compared with 1.2% for CS ≥1. The presence of non-calcified atheroma on CTCA in patients with ZCS did not affect the prognostic value (P = 0.98). CONCLUSION: In patients with stable symptoms and a ZCS, obstructive CAD is rare, and prognosis over the long-term is excellent, regardless of whether non-calcified atheroma is identified. A ZCS could reliably be used as a 'gatekeeper' in this patient cohort, obviating the need for further more expensive tests.

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

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.

The impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a): Objectives and methods of a randomised controlled trial.

It is well established that Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor and predictor of major adverse cardiovascular events. Lipoprotein apheresis is currently the most effective approved treatment available, with minimal effect conferred by conventional lipid lowering agents. A growing body of evidence suggests that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although more prospective research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation is extremely challenging to manage. There is a significant unmet need to establish therapeutic options. Our goal is to determine the impact of lipoprotein apheresis on clinical parameters and symptoms of patients with refractory angina secondary to advanced coronary disease and raised Lp(a). Determining whether we should aggressively lower Lp(a) in such patients remains a very important question, which could potentially impact on the management of a large population. We will also gain insight into how this treatment works and the mechanisms via which Lp(a) increases cardiovascular risk. We are currently conducting a prospective, randomised controlled crossover study of patients with refractory angina and raised Lp(a), randomised to undergoing three months of weekly lipoprotein apheresis or sham apheresis. Patients will then crossover to the opposite study arm after a 1 month wash-out phase. We will assess myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised LDL and their antibodies, exercise capacity, angina and quality of life at the beginning and end of treatment, to determine the net true treatment effect on the above parameters. This is a novel area of research, as previous studies have not assessed the role of lipoprotein apheresis in patients with refractory angina and raised Lp(a) in a prospective randomised controlled manner.

High prevalence of raised lipoprotein(a) in patients with refractory angina.

BACKGROUND: Angina that is refractory to conventional medical therapy and revascularisation, remains challenging to manage and poses significant burden to patients. Elevated lipoprotein(a) [Lp(a)] has emerged as an important independent cardiovascular risk factor and predictor of adverse outcomes in atherosclerotic disease. The prevalence of raised Lp(a) amongst patients with refractory angina has not yet been defined. OBJECTIVE: To establish the prevalence of raised [Lp(a)] >500 mg/L in patients with refractory angina. METHODS: We conducted an epidemiological screening pilot study in 75 patients with refractory angina from a UK tertiary cardiac centre. We determined the proportion of the cohort with raised Lp(a) >500 mg/L using an isoform-insensitive method. In addition, a full fasting lipid profile (including: LDL cholesterol, HDL cholesterol, total cholesterol to HDL ratio and triglycerides) was obtained. Patients were also asked about the presence of conventional cardiovascular risk factors. RESULTS: Our study demonstrated that 60% of the 75 patients with refractory angina had raised Lp(a) levels of >500 mg/L. The median and inter-quartile range of Lp(a) values were 771 mg/L (162 mg/L,1260 mg/L) respectively. CONCLUSIONS: This high prevalence of raised Lp(a) detected in our cohort with refractory angina may suggest a causal role. Further research is necessary to confirm this association and prospective studies are needed to explore the potential therapeutic benefit of Lp(a) reduction in patients with refractory angina.

The expanding role of lipoprotein apheresis in the treatment of raised lipoprotein(a) in ischaemic heart disease and refractory angina.

It is increasingly recognised that lipoprotein(a) [Lp(a)], an inherited, genetically-determined form of LDL-cholesterol, is an independent cardiovascular risk factor and predictor of adverse cardiovascular outcomes. Lp(a) is felt to increase cardiovascular risk via its pro-thrombotic effect and by enhancing intimal lipoprotein deposition. Lipoprotein apheresis is currently the most effective treatment for raised Lp(a). There is a growing body of evidence suggesting that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although much more research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation, is extremely challenging to manage. Treatment options for such patients remain very limited. We describe the case of a patient with refractory angina and raised lipoprotein(a) in whom aggressive reduction of Lp(a) with lipoprotein apheresis successfully ameliorated the progression of coronary stenosis and provided effective and durable relief of angina symptoms. In our centre, we are currently conducting a prospective, randomised controlled cross-over study of patients with refractory angina and raised Lp(a), randomised to undergoing lipoprotein apheresis or 'sham' apheresis with assessment of myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised phospholipids and their antibodies, exercise capacity, angina symptoms and quality of life at the beginning and end of treatment.