Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study.

Objective: To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death. Design: Prospective cohort study. Setting: UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years). Participants: 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study. Main outcome measures: Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Results: Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99). Conclusions: Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

Polypharmacy in Older People With Heart Failure: Roles of the Geriatrician and Pharmacist.

Heart failure (HF) is a common health condition that typically affects older adults. Many people with HF are cared for on an inpatient basis, by noncardiologists, such as acute medical physicians, geriatricians and other physicians. Treatment options for HF are ever increasing, and adherence to guidelines for prognostic therapy contributes to polypharmacy, which is very familiar to clinicians who care for older people. This article explores the recent trials in both HF with reduced ejection fraction and HF with preserved ejection fraction and the limitations of international guidance in their management with respect to older people. In addition, this article discusses the challenge of managing polypharmacy in those with advanced age, and the importance of involving a geriatrician and pharmacist in the HF multidisciplinary team to provide a holistic and person-centred approach to optimisation of HF therapies.

Palpitations in the Cancer Patient.

Cancer and cardiovascular diseases (CVD) are among the leading causes of death worldwide. In response to the growing population of cancer patients and survivors with CVD, the sub-specialty of cardio-oncology has been developed to better optimise their care. Palpitations are one of the most common presenting complaints seen in the emergency room or by the primary care provider or cardiologist. Palpitations are defined as a rapid pulsation or abnormally rapid or irregular beating of the heart and present a complex diagnostic entity with no evidence-based guidelines currently available. Palpitations are a frequent occurrence in people with cancer, and investigations and treatment are comparable to that in the general population although there are some nuances. Cancer patients are at a higher risk of arrhythmogenic causes of palpitations and non-arrhythmogenic causes of palpitations. This review will appraise the literature with regards to the development and management of palpitations in the cancer patient.

Prevención del stroke en fibrilación auricular. Hallazgos del registro GLORIA-AF / Stroke Prevention In Atrial Fibrillation. Findings From The Gloria-Af Registry

RESUMEN Introducción: El GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) es un registro internacional, prospectivo, en tres fases, para determinar la seguridad y eficacia del dabigatrán en pacientes con fibrilación auricular no valvular recientemente diagnosticada, en riesgo de stroke. La fase II empezó cuando el dabigatrán, el primer anticoagulante oral no antagonista de la vitamina K (NOAC) estuvo disponible. Objetivos: Describir los datos clínicos basales de la fase II en la población general y el seguimiento a 2 años de aquellos que recibieron dabigatrán. Material y Métodos: Se reclutaron un total de 15 644 pacientes, de los cuales 15 308 fueron elegibles y 4873 recibieron dabigatrán. Se analizaron las características de la fibrilación auricular, los hallazgos en el seguimiento y las enfermedades concomitantes. Los datos fueron analizados usando estadísticas descriptivas. Resultados: Del total de pacientes elegibles, el 45,5% eran mujeres, con una edad promedio de 71 (rango intercuartilo: 64-78) años. Los pacientes eran de Europa (47,9%), América del Norte (22,2%), Asia (20,1%), América Latina (6,0%) y Medio Oriente/ África (3,9%). La mayoría se encontraba en alto riesgo de stroke (CHA2DS2-VASc score >2; 86,1%); un 13,9% tuvieron riesgo moderado (CHA2DS2-VASc score >1). El 80,3% recibieron anticoagulantes orales; de ellos, el 47,9% recibieron NOAC y el 32,4%, antagonistas de la vitamina K (VKA); 12,0% recibieron agentes antiagregantes plaquetarios y el 7,6% no recibieron tratamiento antitrombótico. A 2 años de seguimiento, el 70,5% permanecieron en dabigatrán. Conclusiones: Los datos de la fase II del registro GLORIA-AF demostraron que, en FA no valvular, los NOAC han sido ampliamente adoptados en la práctica clínica y fueron más frecuentemente prescriptos que los VKA. No obstante, una gran proporción de pacientes en todo el mundo permanecieron sin tratamiento.

ABSTRACT Background: GLORIA-AF is a prospective, global, 3-phase registry program to determine the safety and effectiveness of dabigatran in patients with newly diagnosed non-valvular atrial fibrillation at risk of stroke. Phase II began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives: To describe phase II baseline clinical data in the general population and 2-year follow-up of those patients treated with dabigatran. Methods: A total of 15,644 patients were enrolled, 15,308 of whom were eligible and 4,873 received dabigatran. Atrial fibrillation disease characteristics, follow-up findings and concomitant diseases were collected. Data were analyzed using descriptive statistics. Results: Of the total eligible patients, 45.5% were female; median age was 71.0 (interquartile range: 64, 78) years. Patients were from Europe (47.9%), North America (22.2%), Asia (20.1%), Latin America (6.0%), and the Middle East/Africa (3.9%). Most had high stroke risk (CHA2DS2-VASc score ≥2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc =1). Overall, 80.3% received oral anticoagulants, of whom 47.9% received NOACs and 32.4% vitamin K antagonists (VKA); 12.0% received anti-platelet agents; and 7.6% received no antithrombotic treatment. At 2-year follow-up, 70.5% remained on dabigatran. Conclusions: Data from GLORIA-AF phase II showed that in non-valvular AF, NOACs have been highly adopted in clinical practice, becoming more frequently prescribed than VKAs. Worldwide, however, a large proportion of patients remain undertreated.

Cost-effectiveness and screening performance of ECG handheld machine in a population screening programme: The Belgian Heart Rhythm Week screening programme.

AIMS: Overall, 40% of patients with atrial fibrillation are asymptomatic. The usefulness and cost-effectiveness of atrial fibrillation screening programmes are debated. We evaluated whether an atrial fibrillation screening programme with a handheld electrocardiogram (ECG) machine in a population-wide cohort has a high screening yield and is cost-effective. METHODS: We used a Markov-model based modelling analysis on 1000 hypothetical individuals who matched the Belgian Heart Rhythm Week screening programme. Subgroup analyses of subjects ≥65 and ≥75 years old were performed. Screening was performed with one-lead ECG handheld machine Omron® HeartScan HCG-801. RESULTS: In both overall population and subgroups, the use of the screening procedure diagnosed a consistently higher number of diagnosed atrial fibrillation than not screening. In the base-case scenario, the screening procedure resulted in 106.6 more atrial fibrillation patient-years, resulting in three fewer strokes, 10 more life years and five more quality-adjusted life years (QALYs). The number needed-to-screen (NNS) to avoid one stroke was 361. In subjects ≥65 years old, we found 80.8 more atrial fibrillation patient-years, resulting in three fewer strokes, four more life-years and five more QALYs. The NNS to avoid one stroke was 354. Similar results were obtained in subjects ≥75 years old, with a NNS to avoid one stroke of 371. In the overall population, the incremental cost-effectiveness ratio for any gained QALY showed that the screening procedure was cost-effective in all groups. CONCLUSIONS: In a population-wide screening cohort, the use of a handheld ECG machine to identify subjects with newly diagnosed atrial fibrillation was cost-effective in the general population, as well as in subjects ≥65 and subjects ≥75 years old.

Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists-naive patients with atrial fibrillation.

BACKGROUND: Vitamin K antagonists (VKAs) reduce cardiovascular events (CVEs) in atrial fibrillation (AF) when a time in therapeutic range (TiTR) >70% is achieved. Factors affecting the time to achieve the TR (TtTR) are unknown. METHODS: Prospective observational study including 1,406 nonvalvular AF patients starting VKAs followed for a mean of 31.3months (3,690 patient/year); TiTR, TtTR, and SAMe-TT2R2 score were calculated, and CVEs were recorded. RESULTS: Median TtTR was 8.0days (interquartile range 5.0-18.0). Patients with high TtTR (ie, >75th percentile) were more likely to be in AF than in sinus rhythm at entry (odds ratio [OR]: 1.423, P=.011). Median TiTR was 60.0%; low TiTR (below median) was associated with SAMe-TT2R2 score (OR: 1.175, P=.001), high TtTR (>75th percentile, OR: 1.357, P=.017), and number of international normalized ratio checks (OR: 0.998, P=.049). We recorded 113 CVEs (3.1%/y), with a higher rate seen in patients with TtTR >75th percentile compared to those below (log-rank test, P=.006). A multivariable Cox regression analysis showed that SAMe-TT2R2 score (hazard ratio [HR]: 1.331, P<.001), TtTR >75th percentile (HR: 1.505, P=.047), TiTR <70% (HR: 1.931, P=.004), number of international normalized ratio checks (HR: 0.988, P<.001), digoxin (HR: 1.855, P=.008), and proton-pump inhibitors (HR: 0.452, P<.001) were independently associated with CVEs. CONCLUSIONS: High TtTR is associated with poorer long-term quality of VKAs therapy. Patients with TtTR >18days or with high SAMe-TT2R2 score should be considered for treatment with non-vitamin K oral anticoagulants.

Cerebrovascular disease, associated risk factors and antithrombotic therapy in a population screening cohort: Insights from the Belgian Heart Rhythm Week programme.

Background Cerebrovascular disease confers a major healthcare burden worldwide and is a major cause of death and disability. Several well-established risk factors, such as atrial fibrillation (AF), are associated with cerebrovascular disease and antithrombotic therapy reduces risk. Design This study was a subgroup analysis from the Belgian Heart Rhythm Week, a nationwide AF awareness programme. Methods We studied subjects screened between 2012 and 2014 with available data on clinical risk factors and antithrombotic treatment. Results Of the 38,034 subjects eligible for this analysis, 1513 (4.0%) reported a positive clinical history for cerebrovascular disease. Logistic regression analysis found that age, hypertension, diabetes mellitus, history of vascular disease, history of heart failure and history of AF (all p < 0.001) were independently associated with cerebrovascular disease. Among subjects with history of cerebrovascular disease and AF, 1.7% were taking oral anticoagulant drugs only, while both oral anticoagulant drugs and aspirin were used in 61.5% of subjects, aspirin in 4.3% of patients and no antithrombotic therapy in 32.5% of subjects. Among those subjects without AF, the corresponding figures were 0.8, 9.5, 2.0 and 87.6%, respectively. Conclusions The prevalence of cerebrovascular disease in this contemporary population screening project was higher than that reported in the general population and was associated with the major known stroke risk factors. Sub-optimal antithrombotic therapy management was evident, with a low use of oral anticoagulant drugs among patients with AF and a low use of aspirin among subjects without AF.

Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: The PCSK9-REACT study.

BACKGROUND: Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme might be associated with increased activation of platelets. We aimed to assess the relationship between PCSK9 levels, platelet reactivity and ischemic outcomes. METHODS: Consecutive ACS patients receiving prasugrel or ticagrelor and undergoing percutaneous coronary intervention (PCI) were enrolled in a prospective, observational study. Adenosine diphosphate (ADP)-induced platelet aggregation was determined by Multiplate Analyzer in the maintenance phase of treatment with prasugrel or ticagrelor. Major adverse cardiovascular events (MACEs) defined as composite of cardiovascular death, myocardial infarction, unstable angina, stent thrombosis, repeat revascularization, ischemic stroke were evaluated at 12months. RESULTS: A direct association was found between increased PCSK9 serum levels and platelet reactivity (r=0.30; p=0.004). When assessed according to tertile values of PCSK9, there was a significant increase in platelet reactivity in the upper vs lower tertile (p=0.02). Clinical outcome was available at follow-up in 178 subjects. In the upper PCSK9 tertile 13/59 (22.03%) patients experienced a clinical MACE at one year, vs 2/59 (3.39%) patients in the lower PCSK9 tertile. At one-year follow-up, PCSK9 was independently associated with increased ischemic MACEs: hazard ratio for upper vs lower PCSK9-level tertile was 2.62 (95% confidence interval 1.24-5.52; p=0.01). CONCLUSIONS: These findings suggest that increased PCSK9 levels are associated with higher platelet reactivity and are a possible predictor of ischemic events in ACS patients undergoing PCI.

Prevalencia de la fibrilación auricular en la población general y en grupos de alto riesgo: estudio ECHOES

Resumen Objetivos: establecer la prevalencia de la fibrilación auricular (FA) en la población general en el Reino Unido y en los individuos con factores de riesgo. Método y resultados: se estableció la prevalencia de la FA electrocardiográfica en grupos seleccionados de forma prospectiva; se seleccionaron aleatoriamente 3.960 individuos de la población, mayores de 45 años; 782 tenían diagnóstico previo de insuficiencia cardíaca y 1.062 con antecedente de infarto de miocardio, hipertensión, angina de pecho o diabetes. Los pacientes también fueron evaluados clínicamente y mediante ecocardiografía. Se hizo un seguimiento de la mortalidad durante ocho años. Se encontró FA en 78 de la muestra aleatoria de la población (2,0%). La prevalencia fue de 1,6% en las mujeres y de 2,4% en los hombres, aumentando con la edad, yendo desde 0,2% en los sujetos de entre 45 y 54 años, hasta 8,0% en los de 75 años o mayores. La mitad de todos los casos eran en pacientes de 75 años o mayores. Solo 23 de los 78 (29,5%) con diagnóstico de FA estaban recibiendo warfarina. De los 782 pacientes, 175 (22,4%) con diagnóstico de insuficiencia cardíaca presentaban FA, y 95 (54,3%) de ellos tenían una función ventricular izquierda normal. Se constató FA en 14 de los 244 (5,7%) pacientes con antecedentes de infarto de miocardio; en 15 de los 388 (3,9%) pacientes con hipertensión; en 15 de los 321 (4,7%) pacientes con angina, y en 11 de los 208 (5,3%) pacientes diabéticos. Ajustando por edad y sexo, la mortalidad fue 1,57 veces mayor en quienes presentaban FA. Conclusión: la FA es frecuente en ancianos y en personas con factores de riesgo clínico. Un tamizaje de estos grupos permitiría identificar a muchos individuos con FA. El uso de anticoagulación era bajo en la época en que se hizo la evaluación inicial, a fines de los años 90, pero la práctica puede haber cambiado en los últimos tiempos.

Summary Aim: To establish the prevalence of atrial fibrillation (AF) in the general population in the UK, and in those with risk factors. Methods and results: The prevalence of AF on electrocardiography was established in prospectively selected groups: 3960 randomly selected from the population, aged 45+; 782 with a previous diagnosis of heart failure; and 1062 with a record of myocardial infarction, hypertension, angina, or diabetes. Patients were also assessed clinically and with echocardiography. Mortality was tracked for 8 years. Atrial fibrillation was found in 78 of the random population sample (2.0%). Prevalence was 1.6% in women and 2.4% in men, rising with age from 0.2% in those aged 45-54 to 8.0% in those aged 75 and older. Half of all cases were in patients aged 75 and older. Only 23 of the 78 (29.5%) of those in AF took warfarin. Of the 782 patients, 175 (22.4%) with a diagnosis of heart failure were in AF, with normal left ventricular function in 95 (54.3%) of these. Atrial fibrillation was found in 14 of the 244 (5.7%) of those with a history of myocardial infarction, 15 of the 388 (3.9%) of those with hypertension, 15 of the 321 (4.7%) of those with angina, and 11 of the 208 (5.3%) of diabetics. Adjusting for age and sex, mortality was 1.57 times higher for those in AF. Conclusion: Atrial fibrillation is common in the elderly and those with clinical risk factors. Screening these groups would identify many with AF. Use of anticoagulation was low at the time of the initial assessments in the late 1990s; practice may have changed recently

Does obesity influence target organ damage and outcomes in patients with malignant phase hypertension? The West Birmingham Malignant Hypertension Project.

Several studies have suggested that hypertension has a stronger detrimental impact on cardiovascular outcome in lean than in obese persons, but neutral or opposite results have also been reported. We investigated the impact of baseline body mass index (BMI) at presentation with the most severe form of hypertension, that is, malignant phase hypertension (MPH) on the primary outcome of 'death or dialysis' in these patients. A total of 184 patients (overall mean (s.d.) age 48 (13) years; 61% male; 62% White-European; 20% African-Caribbean, 18% South-Asian) from the West Birmingham MPH Register were included. The patients were grouped according to their BMI (underweight, normal weight, overweight and obese groups). Ninety-three primary outcomes occurred during a median (interquartile range) follow-up of 10.7 (5.8-18.6) years. No significant baseline differences in age or ethnicity were seen between the study groups. Overweight and obese patients included a larger proportion of females, but less smokers than those underweight or of normal weight. There was no inter-group difference in retinopathy (P=0.25), proteinuria (P=0.08), haematuria (P=0.56) and left ventricular hypertrophy (P=0.14). In univariate analyses, BMI was predictive of death or dialysis (0.95 (0.90-1.00), P=0.046) but multivariate analyses showed that only baseline age (odds ratio (95% confidence intervals) 1.06 (1.03-1.09), P<0.001), smoking (2.89 (1.40-5.92), P=0.004), creatinine level (1.01 (1.01-1.02), P=0.001) and estimated glomerular filtration rates (0.99 (0.93-1.00), P=0.047) were independently associated with death or dialysis. BMI was not an independent predictor of adverse outcomes in MPH patients. Age, smoking status, creatinine levels and estimated glomerular filtration rates at diagnosis of MPH were independent predictors for death or dialysis in this high-risk population of hypertensive patients.

Rationale and study design of a cross sectional study documenting the prevalence of Heart Failure amongst the minority ethnic communities in the UK: the E-ECHOES Study (Ethnic--Echocardiographic Heart of England Screening Study).

BACKGROUND: Heart failure is an important cause of cardiovascular morbidity and mortality. Studies to date have not established the prevalence heart failure amongst the minority ethnic community in the UK. T'he aim of the E-ECHOES (Ethnic--Echocardiographic Heart of England Screening Study)is to establish, for the first time, the community prevalence and severity of left ventricular systolic dysfunction (LVSD) and heart failure amongst the South Asian and Black African-Caribbean ethnic groups in the UK. METHODS/DESIGN: This is a community based cross-sectional population survey of a sample of South Asian (i.e. those originating from India, Pakistan, Bangladesh) and Black African-Caribbean male and female subjects aged 45 years and over. Data collection undertaken using a standardised protocol comprising a questionnaire incorporating targeted clinical history taking, physical examination, and investigations with resting electrocardiography and echocardiography; and blood sampling with consent. This is the largest study on heart failure amongst these ethnic groups. Full data collection started in September 2006 and will be completed by August 2009. DISCUSSION: The E-ECHOES study will enable the planning and delivery of clinically and cost-effective treatment of this common and debilitating condition within these communities. In addition it will increase knowledge of the aetiology and management of heart failure within minority ethnic communities.

Abnormal soluble CD40 ligand and C-reactive protein concentrations in hypertension: relationship to indices of angiogenesis.

BACKGROUND: Abnormal inflammation, platelets and angiogenesis are involved in the pathophysiology of cardiovascular disease (CVD). OBJECTIVE: To test the hypothesis that concentrations of high sensitive C-reactive protein (CRP, an index of inflammation) and soluble CD40 ligand (sCD40L, an index of platelet activation) would be abnormal in hypertension, and in turn, be related to plasma indices of angiogenesis, the angiopoietins-1 and -2, and vascular endothelial growth factor (VEGF), in addition to the presence or absence of CVD. METHODS: Using a cross-sectional approach, we measured plasma concentrations of CRP, sCD40L, VEGF, and angiopoietins-1 and -2 in 147 patients with hypertension (85 with a history of CVD event/s, 62 CVD event-free) and 68 age- and sex-matched healthy controls. RESULTS: Concentrations of sCD40L (P = 0.039), CRP (P < 0.001), angiopoietin-1 (P < 0.001), angiopoietin-2 (P = 0.003) and VEGF (P < 0.001) were all greater amongst hypertensive patients than in controls. There were no significant differences in sCD40L and VEGF concentrations between hypertensive individuals with and without CVD events, but CRP and angiopoietin-1 concentrations were significantly greater amongst those with CVD events. On multiple regression analysis, sCD40L was associated with angiopoietin-2 (P = 0.01) and VEGF (P = 0.007) in hypertensive individuals, but no such associations were found within the healthy control group. CONCLUSION: In patients with hypertension, sCD40L was associated with increased circulating markers of abnormal angiogenesis (angiopoietin-2, VEGF). The interaction between sCD40L and angiogenesis may contribute to the pathophysiology of CVD in hypertension.

Plasma levels of tissue factor and soluble E-selectin in sickle cell disease: relationship to genotype and to inflammation.

BACKGROUND: Microvascular occlusion, the pathophysiological hallmark of sickle cell disease (SCD), is a complex multifactorial process with alterations in coagulation, endothelial function and inflammation. However, relationships between these process in the two most common genotypes, HbSS and HbSC, are unknown. We hypothesized differences in the hypercoagulable state [as assessed by tissue factor (TF), fibrinogen and D-dimer], endothelial function [markers soluble E-selectin (sE-sel) and von Willebrand factor (vWf)], and inflammation [markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] in these two SCD genotypes. Citrated plasma TF, sE-sel, vWf, fibrinogen and fibrin D-dimer, and serum IL-6 and hsCRP (enzyme-linked immunosorbent assay/Clauss) were measured in 64 patients with SCD (27 with HbSS disease) and 42 AA subjects matched for age and ethnic origin. TF (P = 0.0014), sE-sel (P = 0.001) and, as expected, vWf, D-dimer, and hsCRP (all P < or = 0.01), but not fibrinogen or IL-6, were raised in the SCD patients compared with the AA subjects. However, only vWf and, as expected, D-dimer (all P < or = 0.01) were higher in HbSS disease than in HbSC disease. Raised plasma TF and sE-sel in SCD compared with HbAA subjects may contribute to the increased risk of thrombotic disease in this group. Raised vWf in HbSS compared with HbSC may be important in determining pathophysiology in these two genotypes. Positive correlations between IL-6 and TF in both HbSC and HbSS disease leads us to speculate that inflammation may be important in coagulation activation in these patients, or vice versa. However, lack of correlation of sE-sel with inflammatory markers implies that other mechanisms are responsible for increased levels of this marker of endothelial activation.