Remote Acute Assessment of Cardiac Patients Post-Acute Coronary Syndrome (TELE-ACS): A Randomized Controlled Trial.

BACKGROUND: Telemedicine programmes can provide remote diagnostic information to aid clinical decision that could optimize care and reduce unplanned re-admissions post ACS. OBJECTIVES: TELE-ACS is a randomized controlled trial which aims to compare a telemedicine-based approach versus standard care in patients following ACS. METHODS: Patients were suitable for inclusion with at least one cardiovascular risk factor and presenting with ACS and were randomized (1:1) prior to discharge. The primary outcome was time to first readmission at 6-months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events and patient reported symptoms. The primary analysis was performed according to intention to treat. The trial was registered on ClinicalTrial.gov (NCT05015634). RESULTS: 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6-months (hazard ratio [HR] 0.24; 95% confidence interval [CI] 0.13 to 0.44; p < 0.001) and ED attendance (HR 0.59; 95% CI 0.59; 95% CI 0.40 to 0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm versus 9% in standard therapy arm). The occurrence of chest pain (9% versus 24%), breathlessness (21% versus 39%) and dizziness (6% versus 18%) at 6-months was lower in the telemedicine group. CONCLUSIONS: The TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization and patient reported symptoms.

The cardiovascular effects of GLP-1 receptor agonists beyond obesity and type 2 diabetes: An anti-atherosclerotic action.

Obesity and overweight affect almost one third of the European population. Obesity and its associated conditions, including type 2 diabetes, significantly impact healthcare systems, life expectancy and quality of life. The emergence of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of obesity, with or without diabetes, has provided an effective alternative to metabolic surgery and dietary interventions. We are now beginning to understand their pleiotropic effects beyond weight loss, such as their favourable impact on cardiovascular profiles. The aim of this review is to summarize available preclinical and clinical data on the beneficial effects of GLP-1 receptor agonists on atherosclerosis and cardiovascular disease which has the potential to substantially broaden the scope of their clinical applications.

Transcatheter Aortic Valve Implantation to Treat Degenerated Aortic, Mitral and Tricuspid Bioprosthesis.

Transcatheter aortic valve implantation (TAVI) is now well established as the treatment of choice for patients with native aortic valve stenosis who are high or intermediate risk for surgical aortic valve replacement. Recent data has also supported the use of TAVI in patients at low surgical risk and also in anatomical subsets that were previously felt to be contra-indicated including bicuspid aortic valves and aortic regurgitation. With advancements and refinements in procedural techniques, the application of this technology has now been further expanded to include the management of degenerated bioprosthesis. After the demonstration of feasibility and safety in the management of degenerated aortic bioprosthetic valves, mitral and tricuspid bioprosthetic valve treatment is now also well-established and provides an attractive alternative to performing redo surgery. In this review, we appraise the latest clinical evidence and highlight procedural considerations when utilising TAVI technology in the management of degenerated aortic, mitral or tricuspid prosthesis.

Pulmonary hypertension associated mortality in the United States from 2003 to 2020: an observational analysis of time trends and disparities.

Background: Pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality. In the last two decades, significant advances have been made in management of World Health Organization (WHO) group 1 PH. However, there are no approved targeted pharmacotherapies for PH secondary to left-sided heart diseases or chronic hypoxic lung diseases which are thought to account for more than 70-80% of the disease burden. No recent investigation has analyzed and compared the mortality burden related to WHO group 1 PH with the mortality burden with WHO groups 2-5 PH at the national level in the United States (US). We hypothesize that WHO group 1 PH-related mortality has improved over the last two decades in comparison to WHO groups 2-5 PH. Methods: In this study, we used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) the underlying cause of death database to study age-standardized mortality rates related to PH in the US from 2003 to 2020. Results: A total of 126,526 deaths were recorded from PH in the US between 2003 and 2020. Across the study period, PH-related ASMR increased from 17.81 per million population in 2003 to 23.89 in 2020 with a percentage change (PC) of +34%. However, there are contrasting mortality trends in WHO group 1 PH when compared to WHO groups 2-5 PH. Data demonstrated a decline in mortality from group 1 PH regardless of gender. In contrast, an increase in mortality from WHO groups 2-5 PH was observed, accounting for the major proportion of the overall PH mortality burden in recent years. Conclusions: PH-related mortality continues to an increase primarily due to increase in mortality attributed to WHO groups 2-5 PH. These findings have notable public health implications. Screening and risk assessment tools for secondary PH, risk factor modification, and novel management strategies are vital to improve outcomes.

Atrial fibrillation/atrial flutter related mortality trends in the US population 2010-2020: Regional, racial, sex variations.

BACKGROUND: There is an evolving need to evaluate atrial fibrillation/atrial flutter (AF/AFL) mortality trends across races, sexes, geographic regions and urbanization statuses to better understand management inequalities. METHODS: This observational study utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Mortality rates due to AF/AFL as underlying and contributing causes of death between 2010 and 2020 were investigated. Mortality trends due to AF/AFL as contributing causes of death for different races, sexes, census regions and urbanization statuses were analyzed using annual percentage change (APC), and Joinpoint regression analysis. RESULTS: Mortality from AF/AFL as the underlying cause was increasing across the US until 2016 (APC 4.8%), followed by a plateau 2016-2020 (APC 0.0 %). Conversely, the mortality rate due to AF/AFL as a contributing cause increases 2010-2020 (APC 3.3%). The mortality rate in both sexes significantly increased in almost all groups, with the largest increase seen in Non-Hispanic Black males. Rural areas had a higher mortality rate (36.9 and 22.9 per 100,000 for males and females in 2020, respectively) and higher slope of increase than urban areas in total US population. Non-Hispanic White people had greater mortality than Non-Hispanic Black people; however, Non-Hispanic Black mortality rates are increasing at a faster rate in urban areas. CONCLUSION: AF/AFL as the underlying cause of death has plateaued from 2016 across the US 2010-2020; whilst AF/AFL as contributing cause of death is increasing. Significant discrepancies in mortality rates are identified between races and urbanization status.

Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.

BACKGROUND: Infective endocarditis (IE) remains a life-threatening disease with high morbidity and mortality. OBJECTIVES: To describe temporal trends in IE incidence, mortality and survival over the last 30 years. METHODS: Nineteen high-income countries (the 'EU 15+') were included. Age-standardised and sex-stratified incidence rates (ASIRs) and mortality rates (ASMRs) for IE were extracted from the Global Burden of Disease (GBD) database between 1990 and 2019, and mortality to incidence ratios (ASMIRs) were calculated. Trends were analysed using Joinpoint regression analysis. RESULTS: ASIRs were higher in males than females and increased in both sexes in all countries between 1990 and 2019. A recent steep rise in ASIRs was noted in several countries including the UK, the USA and Germany. ASMRs increased for both sexes in all countries except Finland and Austria. The largest increase in ASMR was observed in females in Italy (+246%). ASMIRs were generally higher in females compared to males, with large increases in ASMIRs (indicating worsening survival) at the end of the 20th century, but more recent stabilisation or decline across the study cohort. CONCLUSIONS: While the incidence and mortality of IE have increased over the last 30 years, recent data suggest that these trends have plateaued or reversed in most countries studied. However, a recent surge in incidence in several countries (including the USA and UK) is of concern, while unfavourable outcomes in females also merit attention. More encouragingly, this analysis provides the first indication of improving IE survival at population level, supporting recent advances in diagnosis and treatment.

Temporal trend analysis of rheumatic heart disease burden in high-income countries between 1990 and 2019.

AIMS: To assesses trends in rheumatic heart disease (RHD) burden in high-income, European Union 15+ (EU15+) countries between 1990 and 2019. METHODS AND RESULTS: Cross-sectional analysis of the incidence and mortality of RHD was conducted using data from the Global Burden of Disease Study (GBD) database. Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were extracted for EU15 + countries per sex for each of the years from 1990-2019, inclusive, and mortality-to-incidence indices (MII) were computed. Joinpoint regression analysis was used for the description of trends. Over 29 years, an overall declining trend in RHD incidence and mortality across EU 15 + nations were observed. There was significant variability in RHD incidence and mortality rates across high-income countries. However, both RHD incidence and mortality were higher among females compared to males across EU15 + countries over the observed period. The most recent incidence trend, starting predominantly after 2014, demonstrated a rise in RHD incidence in most countries for both sexes. The timing of this RHD resurgence corresponds temporally with an influx of migrants and refugees into Europe. The recent increasing RHD incidence rates ranged from + 0.4% to + 24.7% for males, and + 0.6% to + 11.4% for females. CONCLUSIONS: More than half of EU15 + nations display a recent increase in RHD incidence rate across both sexes. Possible factors associated with this rise are discussed and include increase in global migration from nations with higher RHD prevalence, host nation factors such as migrants' housing conditions, healthcare access and migrant health status on arrival.

Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis.

BACKGROUND: Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis. OBJECTIVES: The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants. METHODS: The authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr-/-) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization. RESULTS: LO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr-/- mice, in the vicinity of macrophages. CONCLUSIONS: The authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.

Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study.

BACKGROUND: There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. METHODS AND FINDINGS: We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor. CONCLUSIONS: These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. TRIAL REGISTRATION: ClinicalTrials.gov - NCT03507309.

Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery.

We aimed to investigate if major vascular surgery induces LDL oxidation, and whether circulating antibodies against malondialdehyde-modified LDL (MDA-LDL) alter dynamically in this setting. We also questioned relationships between these biomarkers and post-operative cardiovascular events. Major surgery can induce an oxidative stress response. However, the role of the humoral immune system in clearance of oxidized LDL following such an insult is unknown. Plasma samples were obtained from a prospective cohort of 131 patients undergoing major non-cardiac vascular surgery, with samples obtained preoperatively and at 24- and 72 h postoperatively. Enzyme-linked immunoassays were developed to assess MDA-LDL-related antibodies and complexes. Adverse events were myocardial infarction (primary outcome), and a composite of unstable angina, stroke and all-cause mortality (secondary outcome). MDA-LDL significantly increased at 24 h post-operatively (p < 0.0001). Conversely, levels of IgG and IgM anti-MDA-LDL, as well as IgG/IgM-MDA-LDL complexes and total IgG/IgM, were significantly lower at 24 h (each p < 0.0001). A smaller decrease in IgG anti-MDA-LDL related to combined clinical adverse events in a post hoc analysis, withstanding adjustment for age, sex, and total IgG (OR 0.13, 95% CI [0.03-0.5], p < 0.001; p value for trend <0.001). Major vascular surgery resulted in an increase in plasma MDA-LDL, in parallel with a decrease in antibody/complex levels, likely due to antibody binding and subsequent removal from the circulation. Our study provides novel insight into the role of the immune system during the oxidative stress of major surgery, and suggests a homeostatic clearance role for IgG antibodies, with greater reduction relating to downstream adverse events.

An observational epidemiological study to analyze intracerebral hemorrhage across the United States: Incidence and mortality trends from 1990 to 2017.

OBJECTIVES: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US. MATERIALS AND METHODS: Observational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs). RESULTS: Overall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%). CONCLUSION: Decreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately.

Trends in Mortality From Aortic Stenosis in Europe: 2000-2017.

Background: Trends in mortality from aortic stenosis across European countries are not well-understood, especially given the significant growth in transcatheter aortic valve implantation (TAVI) in the last 10 years. Methods: Age-standardised death rates were extracted from the World Health Organisation Mortality Database, using the International Classification of Diseases 10th edition code for non-rheumatic aortic stenosis for those aged > 45 years between 2000 and 2017. The UK and countries from the European Union with at least 1,000,000 inhabitants and at least 50% available datapoints over the study period were included: a total of 23 countries. Trends were described using Joinpoint regression analysis. Results: No reductions in mortality were demonstrated across all countries 2000-2017. Large increases in mortality were found for Croatia, Poland and Slovakia for both sexes (>300% change). Mortality plateaued in Germany from 2008 in females and 2012 in males, whilst mortality in the Netherlands declined for both sexes from 2007. Mortality differences between the sexes were observed, with greater mortality for males than females across most countries. Conclusions: Mortality from aortic stenosis has increased across Europe from 2000 to 2017. There are, however, sizable differences in mortality trends between Eastern and Western European countries. The need for health resource planning strategies to specifically target AS, particularly given the expected increase with ageing populations, is highlighted.

The Placebo-Controlled Effect of Percutaneous Coronary Intervention on Exercise Induced Changes in Anti-Malondialdehyde-LDL Antibody Levels in Stable Coronary Artery Disease: A Substudy of the ORBITA Trial.

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significant component of oxidised LDL. The effects of exercise on levels of MDA-LDL and anti-MDA-LDL antibodies are not well-understood. Furthermore, it is not known whether these can be modified in patients with coronary artery disease by percutaneous coronary intervention (PCI). Methods: The Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multi-centre randomised trial of PCI vs. placebo procedure for angina relief. Serum samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2) exercise and post-randomisation (6-weeks following the PCI or placebo procedure), pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developed assays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies. Results: One hundred ninety-six of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severe single vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial had blood available for analysis. With exercise at pre-randomisation (P2-P1) there was no significant change in adjusted MDA-LDL (-0.001, 95% CI -0.004 to 0.001; p = 0.287); however, IgG and IgM anti-MDA-LDL significantly declined (-0.022, 95% CI -0.029 to -0.014, p < 0.0001; -0.016, 95% CI -0.024 to -0.008, p = 0.0002, respectively). PCI did not have a significant impact on either the pre-exercise values (P3 controlling for P1) of MDA-LDL (p = 0.102), IgG (p = 0.444) or IgM anti-MDA-LDL (p = 0.909). Nor did PCI impact the exercise induced changes in these markers (P4 controlling for P1, P2, and P3) for MDA-LDL (p = 0.605), IgG (p = 0.725) or IgM anti-MDA-LDL (p = 0.171). Pre-randomisation ischaemia on stress echo did not impact these interactions. Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies in patients with severe single vessel coronary disease, possibly indicating an induction in homoeostatic clearance via the innate immune system. However, PCI did not ameliorate this effect.

Restricted Use of Echocardiography in Suspected Endocarditis during COVID-19 Lockdown: A Multidisciplinary Team Approach.

BACKGROUND: Infective endocarditis (IE) is challenging to manage in the COVID-19 lockdown period, in part given its reliance on echocardiography for diagnosis and management and the associated virus transmission risks to patients and healthcare workers. This study assesses utilisation of the endocarditis team (ET) in limiting routine echocardiography, especially transoesophageal echocardiography (TOE), in patients with suspected IE, and explores the effect on clinical outcomes. METHODS: All patients discussed at the ET meeting at Imperial College Healthcare NHS Trust during the first lockdown in the UK (23 March to 8 July 2020) were prospectively included and analysed in this observational study. RESULTS: In total, 38 patients were referred for ET review (71% male, median age 54 [interquartile range 48, 65.5] years). At the time of ET discussion, 21% had no echo imaging, 16% had point-of-care ultrasound only, and 63% had formal TTE. In total, only 16% underwent TOE. The ability of echocardiography, in those where it was performed, to affect IE diagnosis according to the Modified Duke Criteria was significant (p=0.0099); however, sensitivity was not affected. All-cause mortality was 17% at 30 days and 25% at 12 months from ET discussion in those with confirmed IE. CONCLUSION: Limiting echocardiography in patients with a low pretest probability (not probable or definite IE according to the Modified Duke Criteria) did not affect the diagnostic ability of the Modified Duke Criteria to rule out IE in this small study. Moreover, restricting nonessential echocardiography, and importantly TOE, in patients with suspected IE through use of the ET did not impact all-cause mortality.

A Novel Immunoassay for Malondialdehyde-Conjugated Low-Density Lipoprotein Measures Dynamic Changes in the Blood of Patients Undergoing Coronary Artery Bypass Graft Surgery.

Oxidized low-density lipoproteins play an important role in tissue pathology. In this study, we report a sensitive novel enzyme-linked immunosorbent assay for the detection of malondialdehyde-modified low-density lipoprotein (MDA-LDL), a key component of oxidized LDL. The assay is capable of measuring a variable presence of MDA-LDL within human plasma and serum. We demonstrate the robust nature of the assay on samples stored for over 20 months, as well as high inter-operator reproducibility (r = 0.74, p < 0.0001). The assay was capable of detecting dynamic changes in patient blood samples after coronary artery bypass graft surgery, indicating synthesis or release of MDA-LDL with the oxidative stress of surgery, followed by homeostatic clearance. This robust, sensitive and specific assay for circulating MDA-LDL will serve as a valuable translational tool for the improved detection of oxidative forms of LDL in response to a range of physiological or pathological stimuli, with potential clinical applicability.

Size matters in atrial fibrillation: the underestimated importance of reduction of contiguous electrical mass underlying the effectiveness of catheter ablation.

Evidence has accumulated over the last century of the importance of a critical electrical mass in sustaining atrial fibrillation (AF). AF ablation certainly reduces electrically contiguous atrial mass, but this is not widely accepted to be an important part of its mechanism of action. In this article, we review data showing that atrial size is correlated in many settings with AF propensity. Larger mammals are more likely to exhibit AF. This is seen both in the natural world and in animal models, where it is much easier to create a goat model than a mouse model of AF, for example. This also extends to humans-athletes, taller people, and obese individuals all have large atria and are more likely to exhibit AF. Within an individual, risk factors such as hypertension, valvular disease and ischaemia can enlarge the atrium and increase the risk of AF. With respect to AF ablation, we explore how variations in ablation strategy and the relative effectiveness of these strategies may suggest that a reduction in electrical atrial mass is an important mechanism of action. We counter this with examples in which there is no doubt that mass reduction is less important than competing theories such as ganglionated plexus ablation. We conclude that, when considering future strategies for the ablative therapy of AF, it is important not to discount the possibility that contiguous electrical mass reduction is the most important mechanism despite the disappointing consequence being that enhancing success rates in AF ablation may involve greater tissue destruction.

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.