82 results found
Ono M, Tomaniak M, Koenig W, et al., 2022, Impact of white blood cell count on clinical outcomes in patients treated with aspirin-free ticagrelor monotherapy after percutaneous coronary intervention: insights from the GLOBAL LEADERS trial., Eur Heart J Cardiovasc Pharmacother, Vol: 8, Pages: 39-47
AIMS: The aim of this study was to investigate the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) stratified according to the baseline white blood cell (WBC) count. METHODS AND RESULTS: This is a post hoc analysis of the GLOBAL LEADERS trial, a multi-centre, open-label, randomized all-comer trial in patients undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual anti-platelet therapy [DAPT]) with the reference strategy (12-month aspirin monotherapy following 12-month DAPT). Patients were stratified into two WBC groups, either < or ≥median WBC count of 7.8 × 109 cells/L (lower or higher WBC group, respectively). The primary endpoint was a composite of all-cause mortality or new Q-wave myocardial infarction at 2 years. Of 14 576 patients included in the present study, 7212 patients (49.5%) were classified as the lower WBC group, who had a significantly lower risk of both ischaemic and bleeding outcomes at 2 years. At 2 years, the experimental strategy was associated with a significant lower incidence of the primary endpoint compared with the reference strategy in the lower WBC group [2.8% vs. 4.2%; hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.52-0.86] but not in the higher WBC group (4.8% vs. 4.7%; HR: 1.01; 95% CI: 0.82-1.25; Pinteraction=0.013). There were no significant differences in the risks of Bleeding Academic Research Consortium type 3 or 5 bleeding between two anti-platelet strategies regardless of the WBC groups. CONCLUSION: Increased WBC counts, which may reflect degree of inflammation, at the time of index procedure may attenuate the anti-ischaemic benefits of ticagrelor monotherapy observed in patients with lower WBC counts.
Mohan P, Hartley A, Khaldi H, et al., 2021, Use of Intravascular Lithotripsy in a Population With a High Prevalence of Renal Disease and Diabetes: Insights From Real-World Data, Publisher: ELSEVIER SCIENCE INC, Pages: B169-B169, ISSN: 0735-1097
Hartley A, Khamis R, Al-Lamee R, et al., 2021, 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, Frontiers in Cardiovascular Medicine, Vol: 8, ISSN: 2297-055X
Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significantcomponent of oxidized LDL. The effects of exercise on levels of MDA-LDL and antiMDA-LDL antibodies are not well understood. Furthermore, it is not known whetherthese can be modified in patients with coronary artery disease by percutaneouscoronary intervention (PCI).Methods: The Objective Randomised Blinded Investigation with optimal medicalTherapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multicentre randomised trial of PCI versus placebo procedure for angina relief. Serumsamples were available at four time-points: pre-randomisation pre- (P1) and post- (P2)exercise and post-randomisation (six-weeks following the PCI or placebo procedure),pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developedassays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.Results: 196 of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severesingle vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial hadblood available for analysis. With exercise at pre-randomisation (P2 - P1) there wasno 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 didnot 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 PCIimpact the exercise induced changes in these markers (P4 controlling for P1, P2, andP3) for MDA-LDL (p=0.605), IgG (p=0.725) or IgM anti-MDA-LDL (p=0.171). Prerandomisation ischaemia on stress echo did not impact these interactions.Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies inpatients with severe single vessel coronary disease, possibly indicating an inductionin homoeostatic
Hartley A, Shalhoub J, Khamis R, 2021, Trends in mortality from aortic stenosis in Europe: 2000-2017, Frontiers in Cardiovascular Medicine, Vol: 8, Pages: 1-9, ISSN: 2297-055X
BackgroundTrends in mortality from aortic stenosis across European countries are not wellunderstood, especially given the significant growth in transcatheter aortic valveimplantation (TAVI) in the last 10 years.MethodsAge-standardised death rates were extracted from the World Health OrganisationMortality Database, using the International Classification of Diseases 10th editioncode for non-rheumatic aortic stenosis for those aged >45 years between 2000 and2017. The UK and countries from the European Union with at least 1,000,000inhabitants and at least 50% available datapoints over the study period were included:a total of 23 countries. Trends were described using Joinpoint regression analysis.ResultsNo reductions in mortality were demonstrated across all countries 2000-2017. Largeincreases in mortality were found for Croatia, Poland and Slovakia for both sexes(>300% change). Mortality plateaued in Germany from 2008 in females and 2012 inmales, whilst mortality in the Netherlands declined for both sexes from 2007. Mortalitydifferences between the sexes were observed, with greater mortality for males thanfemales across most countries.ConclusionsMortality from aortic stenosis has increased across Europe from 2000 to 2017. Thereare, however, sizable differences in mortality trends between Eastern and WesternEuropean countries. The need for health resource planning strategies to specificallytarget AS, particularly given the expected increase with aging populations, ishighlighted.
Nurek M, Rayner C, Freyer A, et al., 2021, Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study, BRITISH JOURNAL OF GENERAL PRACTICE, Vol: 71, Pages: E815-E825, ISSN: 0960-1643
Hajhosseiny R, Munoz C, Cruz G, et al., 2021, Coronary magnetic resonance angiography in chronic coronary syndromes, Front Cardiovasc Med, Vol: 8, ISSN: 2297-055X
Cardiovascular disease is the leading cause of mortality worldwide, with atherosclerotic coronary artery disease (CAD) accounting for the majority of cases. X-ray coronary angiography and computed tomography coronary angiography (CCTA) are the imaging modalities of choice for the assessment of CAD. However, the use of ionising radiation and iodinated contrast agents remain drawbacks. There is therefore a clinical need for an alternative modality for the early identification and longitudinal monitoring of CAD without these associated drawbacks. Coronary magnetic resonance angiography (CMRA) could be a potential alternative for the detection and monitoring of coronary arterial stenosis, without exposing patients to ionising radiation or iodinated contrast agents. Further advantages include its versatility, excellent soft tissue characterisation and suitability for repeat imaging. Despite the early promise of CMRA, widespread clinical utilisation remains limited due to long and unpredictable scan times, onerous scan planning, lower spatial resolution, as well as motion related image quality degradation. The past decade has brought about a resurgence in CMRA technology, with significant leaps in image acceleration, respiratory and cardiac motion estimation and advanced motion corrected or motion-resolved image reconstruction. With the advent of artificial intelligence, great advances are also seen in deep learning-based motion estimation, undersampled and super-resolution reconstruction promising further improvements of CMRA. This has enabled high spatial resolution (1 mm isotropic), 3D whole heart CMRA in a clinically feasible and reliable acquisition time of under 10 min. Furthermore, latest super-resolution image reconstruction approaches which are currently under evaluation promise acquisitions as short as 1 min. In this review, we will explore the recent technological advances that are designed to bring CMRA closer to clinical reality.
Hartley A, Khamis R, 2021, A novel immunoassay for malondialdehyde-conjugated low-density lipoprotein measures dynamic changes in the blood of patients undergoing coronary artery bypass graft surgery, Antioxidants, Vol: 10, Pages: 1-14, ISSN: 2076-3921
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 malondial-dehyde-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 trans-lational tool for the improved detection of oxidative forms of LDL in response to a range of physiological or pathological stimuli, with potential clinical applicability.
Rajkumar C, Shun-Shin M, Seligman H, et al., 2021, Placebo-controlled efficacy of percutaneous coronary intervention for focal and diffuse patterns of stable coronary artery disease, Circulation: Cardiovascular Interventions, Vol: 14, Pages: 809-818, ISSN: 1941-7640
Background Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from ORBITA to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom endpoints.Methods164 patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment prior to randomization. Focal disease was defined as 0.03 iFR unit drop within 15mm, rather than over a longer distance. Analyses were performed using regression modelling. ResultsIn the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (focal mean FFR and iFR 0.600.15 and 0.650.24, diffuse 0.780.10 and 0.880.08 respectively, p<0.0001). With adjustment for this difference, PCI for focal stenoses resulted in significantly greater reduction in stress echo ischemia than PCI for diffuse disease (p<0.05). The effect of PCI on between-arm pre-randomization-adjusted exercise time was 9.32 seconds (95% CI, -17.1 to 35.7s; p=0.487). When stratified for pattern of disease, there was no detectable difference between focal and diffuse CAD (Pinteraction=0.700). PCI improved Seattle Angina Questionnaire angina frequency score and freedom from angina more than placebo (p=0.034; p=0.0035). However, there was no evidence of interaction between the physiological pattern of CAD and these effects (Pinteraction=0.436; Pinteraction=0.908).ConclusionPCI achieved significantly greater reduction of stress echocardiography ischemia in focal compared to diffuse CAD. However, for symptom endpoints, no such difference was observed.
Albaghdadi MS, Ikegami R, Kassab MB, et al., 2021, Near-Infrared Autofluorescence in Atherosclerosis Associates With Ceroid and Is Generated by Oxidized Lipid-Induced Oxidative Stress, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 41, Pages: E385-E398, ISSN: 1079-5642
Marceddu C, Hartley A, Caga-Anan M, et al., 2021, FIRST IN VIVO PRETARGETED PET IMAGING OF ATHEROSCLEROSIS WITH ANTIBODIES AGAINST FORMS OF MODIFIED LIPOPROTEINS, Publisher: BMJ PUBLISHING GROUP, Pages: A126-A128, ISSN: 1355-6037
Hartley A, Williams M, Kaura A, et al., 2021, IGM AND IGG ANTI-OXIDISED LOW-DENSITY LIPOPROTEIN ANTIBODIES PREDICT PROTECTIVE ATHEROSCLEROTIC CHARACTERSTICS ON CARDIAC CT: A SUBSTUDY OF THE SCOTTISH COMPUTED TOMOGRAPHY OF THE HEART (SCOT-HEART) TRIAL, Publisher: BMJ PUBLISHING GROUP, Pages: A162-A162, ISSN: 1355-6037
Mikhail G, Khawaja SA, Mohan P, et al., 2021, COVID-19 and its impact on the cardiovascular system, Open Heart, Vol: 8, Pages: 1-9, ISSN: 2053-3624
Objectives: The clinical impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare NHS Trust, United Kingdom.Methods: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7th March to 7th April 2020. Patient data was collected for baseline demographics, co-morbidities and in-hospital outcomes, especially relating to cardiovascular intervention.Results:Mean age was 67.4±16.1 years and 62.2%(n=310) were male. 64.1%(n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4%(n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%,p<0.001). Only 4 COVID-19 patients had invasive coronary angiography,2 underwent percutaneous coronary intervention and 1 required a permanent pacemaker implantation. 7.0%(n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39,1.31-4.40,p=0.005) and history of hypertension (OR 1.88 ,1.01-3.55,p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for.Conclusion:Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.
Thompson D, Al-Lamee R, Foley M, et al., 2021, Achieving optimal adherence to medical therapy by telehealth: Findings from the ORBITA medication adherence sub-study, Pharmacology Research and Perspectives, Vol: 9, Pages: e00710-e00710, ISSN: 2052-1707
INTRODUCTION: The ORBITA trial of percutaneous coronary intervention (PCI) versus a placebo procedure for patients with stable angina was conducted across six sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimization protocol and interpretation of the main trial endpoints. METHODS: Prescribing data were collected throughout the trial. Self-reported adherence was assessed, and urine samples collected at pre-randomization and at follow-up for direct assessment of adherence using high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS). RESULTS: Self-reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre-randomization and at follow-up in the PCI versus placebo groups respectively was: clopidogrel, 96% versus 90% and 98% versus 94%; atorvastatin, 95% versus 92% and 92% versus 91%; perindopril, 95% versus 97% and 85% versus 100%; bisoprolol, 98% versus 99% and 96% versus 97%; amlodipine, 99% versus 99% and 94% versus 96%; nicorandil, 98% versus 96% and 94% versus 92%; ivabradine, 100% versus 100% and 100% versus 100%; and ranolazine, 100% versus 100% and 100% versus 100%. CONCLUSIONS: Adherence levels were high throughout the study when quantified by self-reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimization protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online.
Khan TZ, Haskard D, Hartley A, et al., 2021, 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), Antioxidants, Vol: 10, ISSN: 2076-3921
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
Naderi H, Robinson S, Swaans MJ, et al., 2021, Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide, PERFUSION-UK, Vol: 36, Pages: 547-558, ISSN: 0267-6591
Seligman H, Sen S, Nijjer S, et al., 2020, Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers, Interventional Cardiology Review, Vol: 15, Pages: e16-e16, ISSN: 1756-1477
Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff.
Little C, Jabbour R, Kotecha T, et al., 2020, Primary PCI for STEMI During the COVID-19 Pandemic in London: A Systematic Analysis of Pathway Activation and Outcomes, 32nd Annual Transcatheter Cardiovascular Therapeutics Symposium (TCT CONNECT), Publisher: ELSEVIER SCIENCE INC, Pages: B96-B96, ISSN: 0735-1097
Rajkumar C, Shun-Shin M, Seligman H, et al., 2020, Placebo-Controlled Efficacy of Percutaneous Coronary Intervention for Focal and Diffuse Patterns of Stable Coronary Artery Disease: A Secondary Analysis From ORBITA, 32nd Annual Transcatheter Cardiovascular Therapeutics Symposium (TCT CONNECT), Publisher: ELSEVIER SCIENCE INC, Pages: B165-B165, ISSN: 0735-1097
Abdelrahman KM, Chen MY, Dey AK, et al., 2020, Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies JACC State-of-the-Art Review, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 76, Pages: 1226-1243, ISSN: 0735-1097
Despite advanced understanding of the biology of atherosclerosis, coronary heart disease remains the leading cause of death worldwide. Progress has been challenging as half of the individuals who suffer sudden cardiac death do not experience premonitory symptoms. Furthermore, it is well-recognized that also a plaque that does not cause a haemodynamically significant stenosis can trigger a sudden cardiac event, yet the majority of ruptured or eroded plaques remain clinically silent. In the past 30 years since the term 'vulnerable plaque' was introduced, there have been major advances in the understanding of plaque pathogenesis and pathophysiology, shifting from pursuing features of 'vulnerability' of a specific lesion to the more comprehensive goal of identifying patient 'cardiovascular vulnerability'. It has been also recognized that aside a thin-capped, lipid-rich plaque associated with plaque rupture, acute coronary syndromes (ACS) are also caused by plaque erosion underlying between 25% and 60% of ACS nowadays, by calcified nodule or by functional coronary alterations. While there have been advances in preventive strategies and in pharmacotherapy, with improved agents to reduce cholesterol, thrombosis, and inflammation, events continue to occur in patients receiving optimal medical treatment. Although at present the positive predictive value of imaging precursors of the culprit plaques remains too low for clinical relevance, improving coronary plaque imaging may be instrumental in guiding pharmacotherapy intensity and could facilitate optimal allocation of novel, more aggressive, and costly treatment strategies. Recent technical and diagnostic advances justify continuation of interdisciplinary research efforts to improve cardiovascular prognosis by both systemic and 'local' diagnostics and therapies. The present state-of-the-art document aims to present and critically appraise the latest evidence, developments, and future perspectives in detection, prevent
van den Berg VJ, Vroegindewey MM, Kardys I, et al., 2019, Anti-oxidized LDL antibodies and coronary artery disease: a systematic review, Antioxidants (Basel), Vol: 8, ISSN: 2076-3921
Antibodies to oxidized LDL (oxLDL) may be associated with improved outcomes in cardiovascular disease. However, analysis is restricted by heterogenous study design and endpoints. Our objective was to conduct a comprehensive systematic review assessing anti-oxLDL antibodies in relation to coronary artery disease (CAD). Through a systematic literature search, we identified all studies assessing the relationship of either, IgG or IgM ox-LDL/ copper-oxLDL/ malondialdehyde-LDL, with coronary atherosclerosis or cardiovascular events in populations with, and without, established CAD. Systematic review best practices were adhered to and study quality was assessed. An initial electronic database search identified 2059 records, which was subsequently followed by abstract and full-text review. Finally, we included 18 studies with over 1811 patients with CAD. The studies varied according to populations studied, conventional cardiovascular risk factors and interventional modalities used to assess CAD. IgM anti-oxLDL antibodies were found to indicate protection from more severe CAD and possibly cardiovascular events, whilst the relationship with IgG is more complex and difficult to elucidate, with studies reporting divergent results. In this systematic review, there is evidence that suggests a relationship between anti-oxLDL antibodies and CAD, especially for the IgM subclass. However, further studies, with well-characterized prospective cohorts, will be important to clarify these associations.
Kaura A, Hartley A, Panoulas V, et al., 2019, HsCRP predicts mortality beyond troponin in 102,337 patients with suspected acute coronary syndrome (CRP-RISK study), Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 1302-1302, ISSN: 0195-668X
Kaura A, Hartley A, Panoulas V, et al., 2019, THE ROLE OF HIGH-SENSITIVITY C-REACTIVE PROTEIN IN PREDICTING MORTALITY BEYOND TROPONIN IN OVER 100,000 PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME (NIHR HEALTH INFORMATICS COLLABORATIVE CRP-RISK STUDY), Annual Conference of the British-Cardiovascular-Society (BCS) - Digital Health Revolution, Publisher: BMJ PUBLISHING GROUP, Pages: A120-A121, ISSN: 1355-6037
Kaura A, Hartley A, Panoulas V, et al., 2019, HSCRP PREDICTS MORTALITY BEYOND TROPONIN IN 102,337 PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME IN THE UK NATIONAL INSTITUTE FOR HEALTH RESEARCH CRP-RISK STUDY, 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 10-10, ISSN: 0735-1097
Hartley A, Haskard D, Khamis R, 2019, Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy, Trends in Cardiovascular Medicine, Vol: 29, Pages: 22-26, ISSN: 1050-1738
van den Berg VJ, Haskard DO, Fedorowski A, et al., 2018, IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)., EBioMedicine, Vol: 36, Pages: 63-72, ISSN: 2352-3964
BACKGROUND: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis. OBJECTIVES: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics. METHODS: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386 days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively. FINDINGS: From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p = 0.012; p = 0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p = 0.027) and percentage of plaque occupied by necrotic core (p = 0.011), as well as lipid core burden index (p = 0.024) in the worst 4 mm segment. INTERPRETATION: Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.
Khan TZ, Haskard D, Caga-Anan M, et al., 2018, 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), 86th Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: E31-E32, ISSN: 0021-9150
Al-Lamee R, Thompson D, Dehbi H-M, et al., 2018, Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial., Lancet, Vol: 391, Pages: 31-40, ISSN: 0140-6736
BACKGROUND: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. METHODS: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. FINDINGS: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding
Hartley A, Haskard D, Khamis R, 2018, Markers of Apoptosis predict cardiovascular outcomes and point to 'response to injury' as a common pathway leading to diabetes and cardiovascular events, EBioMedicine, Vol: 28, Pages: 19-20, ISSN: 2352-3964
Metabolic stress, chronic vascular injury and cellular apoptosis are considered as instrumentally connected in the pathogenesis of atherosclerosis and diabetes (Gistera and Hansson, 2017). The work from Mattisson et al. (Mattisson et al., 2017) sheds light on this potentially important pathway linking cell-mediated death and cardiovascular outcomes. The study spans translational science, from describing an elegant laboratory technique using Fas ligand to induce apoptosis in peripheral blood mononuclear cells and demonstrating release of TNF receptor 1 (TNFR-1), TNF-related apoptosis-inducing ligand receptor 2 (TRAILR-2) and Fas, to studying the cell death receptor plasma levels in a large well-characterized prospective population.
Pandey S, Haskard DO, Khamis R, 2017, Developing a strategy for interventional molecular imaging of oxidized low density lipoprotein in atherosclerosis. An auto-commentary., Molecular Imaging, Vol: 16, ISSN: 1536-0121
The identification of vulnerable coronary artery atherosclerotic plaques offers the prospect of either localized or systematic therapeutic targeting in order to prevent myocardial infarction. Molecular imaging of atherosclerosis adds to morphological imaging by focusing on the immunobiology hidden in and behind the endothelium and therefore may be able to improve the identification of prospective culprit lesions. Our focus has been on identifying arterial accumulation of oxidized low density lipoprotein (oxLDL) by exploiting advances in knowledge of vascular pathobiology. Here, we reflect on our work developing Near Infra-Red Fluorescence (NIRF) imaging of oxLDL using LO1, a monoclonal autoantibody generated in our laboratory. We detail progress to date and discuss our vision on taking the work through the early translational pipeline towards a multi-targeted approach in imaging rupture prone atherosclerotic plaques. Ultimately, molecular imaging of coronary arteries should be able to assess the regional risk that is specific to a lesion, which can then be used in concert with global risk factors to personalize the therapeutic strategy for patients in a way that goes beyond generalized population-based therapies.
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