Raffaele De Caterina

Long-term Use of Anti-inflammatory Drugs and Risk of Atrial Fibrillation

BACKGROUND Previous reports have described an association between the use of corticosteroids (steroidal anti-inflammatory drugs [SAIDs]) and the risk of atrial fibrillation (AF). We sought to determine the existence of a similar association for non-SAIDs (NSAIDs). METHODS We identified patients aged 40 to 89 years with a first-ever diagnosis of AF in 1996 in a United Kingdom primary care database and classified them as having paroxysmal or chronic AF. After validation with their primary care physicians, 1035 patients were confirmed as having incident chronic AF and 525 as having paroxysmal AF. Two separate nested case-control analyses estimated the risk of first-time chronic and paroxysmal AF among users of SAIDs and NSAIDs. RESULTS We confirmed the previously reported association between current use of SAIDs and chronic AF (rate ratio [RR], 2.49; 95% confidence interval [CI], 1.56-3.97). However, we also found that the current use of NSAIDs was associated with an increased risk of chronic AF (RR, 1.44; 95% CI, 1.08-1.91). Such risk was further increased among long-term users with a treatment duration of longer than 1 year (RR, 1.80; 95% CI, 1.20-2.72). The increased risk of chronic AF was not explained by the occurrence of heart failure. The use of NSAIDs was not associated with paroxysmal AF. CONCLUSIONS The use of NSAIDs, as for SAIDs, is associated with an increased risk of chronic AF. Because the use of anti-inflammatory drugs in general is a marker for underlying inflammatory disorders, inflammation may be the common cause for the use of anti-inflammatory drugs and chronic AF.

Documento de Consenso de Expertos sobre el uso de agentes antiplaquetarios

Carlo Patrono (Chairperson)* (Italy), Fedor Bachmann (Switzerland), Colin Baigent (UK), Christopher Bode (Germany), Raffaele De Caterina (Italy), Bernard Charbonnier (France), Desmond Fitzgerald (Ireland), Jack Hirsh (Canada), Steen Husted (Denmark), Jan Kvasnicka (Czech Republic), Gilles Montalescot (France), Luis Alberto Garcia Rodriguez (Spain), Freek Verheugt (The Netherlands), Jozef Vermylen (Belgium), Lars Wallentin (Sweden)

Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalized Nutrition: Part 2 - Ethics, Challenges and Endeavors of Precision Nutrition

Nutrigenetics considers the influence of individual genetic variation on differences in response to dietary components, nutrient requirements and predisposition to disease. Nutrigenomics involves the study of interactions between the genome and diet, including how nutrients affect the transcription and translation process plus subsequent proteomic and metabolomic changes, and also differences in response to dietary factors based on the individual genetic makeup. Personalized characteristics such as age, gender, physical activity, physiological state and social status, and special conditions such as pregnancy and risk of disease can inform dietary advice that more closely meets individual needs. Precision nutrition has a promising future in treating the individual according to their phenotype and genetic characteristics, aimed at both the treatment and prevention of disease. However, many aspects are still in progress and remain as challenges for the future of nutrition. The integration of the human genotype and microbiome needs to be better understood. Further advances in data interpretation tools are also necessary, so that information obtained through newer tests and technologies can be properly transferred to consumers. Indeed, precision nutrition will integrate genetic data with phenotypical, social, cultural and personal preferences and lifestyles matters to provide a more individual nutrition, but considering public health perspectives, where ethical, legal and policy aspects need to be defined and implemented.

Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity

Chronic diseases, including obesity, are major causes of morbidity and mortality in most countries. The adverse impacts of obesity and associated comorbidities on health remain a major concern due to the lack of effective interventions for prevention and management. Precision nutrition is an emerging therapeutic approach that takes into account an individuals genetic and epigenetic information, as well as age, gender, or particular physiopathological status. Advances in genomic sciences are contributing to a better understanding of the role of genetic variants and epigenetic signatures as well as gene expression patterns in the development of diverse chronic conditions, and how they may modify therapeutic responses. This knowledge has led to the search for genetic and epigenetic biomarkers to predict the risk of developing chronic diseases and personalizing their prevention and treatment. Additionally, original nutritional interventions based on nutrients and bioactive dietary compounds that can modify epigenetic marks and gene expression have been implemented. Although caution must be exercised, these scientific insights are paving the way for the design of innovative strategies for the control of chronic diseases accompanying obesity. This document provides a number of examples of the huge potential of understanding nutrigenetic, nutrigenomic, and nutriepigenetic roles in precision nutrition.

Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation

Objectives Our objective was to examine gender differences in clinical presentation, management and prognosis of atrial fibrillation (AF) in a contemporary cohort. Methods In 6412 patients, 39.7% women, of the PREvention oF thromboembolic events – European Registry in Atrial Fibrillation, we examined gender differences in symptoms, risk factors, therapies and 1-year incidence of adverse outcomes. Results Men with AF were on average younger than women (mean±SD: 70.1±10.7 vs 74.1±9.7 years, p<0.0001). Women more frequently had at least one AF-related symptom at least occasionally compared with men (95.4% in women, 89.8% in men, p<0.0001). Prescription of oral anticoagulation was similar, with an increase of non-vitamin K antagonist oral anticoagulants from 5.9% to 12.6% in women and from 6.2% to 12.6% in men, p<0.0001 for both. Men were more frequently treated with electrical cardioversion and ablation (20.6% and 6.3%, respectively) than women (14.9% and 3.3%, respectively), p<0.0001. Women had 65% (OR: 0.35; 95% CI (0.22 to 0.56)) lower age-adjusted and country-adjusted odds of coronary revascularisation, 40% (OR: 0.60; (0.38 to 0.93)) lower odds of acute coronary syndrome and 20% (OR: 0.80; (0.68 to 0.96)) lower odds of heart failure at 1 year. There were no statistically significant gender differences in 1-year stroke/transient ischaemic attack/arterial thromboembolism and major bleeding events. Conclusion In a ‘real-world’ European AF registry, women were more symptomatic but less likely to receive invasive rhythm control therapy such as electrical cardioversion or ablation. Further study is needed to confirm that these differences do not disadvantage women with AF.

Low-Dose Aspirin and Upper Gastrointestinal Bleeding in Primary Versus Secondary Cardiovascular Prevention A Population-Based, Nested Case–Control Study

Background—The benefit–risk profile of low-dose aspirin in primary prevention of cardiovascular disease is unclear. We sought to quantify upper gastrointestinal bleeding (UGIB) risk associated with low-dose aspirin in secondary versus primary prevention patients. Methods and Results—We performed a population-based nested case–control study using The Health Improvement Network (THIN) Database between 2000 and 2007. We identified 2049 cases of UGIB and 20 000 controls, frequency-matched to the cases on age, sex, and calendar year, who were subdivided into primary (without previous cardiovascular disease) and secondary (with previous cardiovascular disease) prevention populations. We estimated the relative risk of UGIB associated with the use of low-dose aspirin by multivariate logistic regression. The UGIB risk in patients taking low-dose aspirin relative to nonusers was significantly higher in the primary (adjusted relative risk, 1.90; 95% confidence interval, 1.59–2.26) than in the secondary (relative risk, 1.40; 95% confidence interval, 1.14–1.72; P value for the difference=0.0014) prevention cohort. However, as the baseline risk of UGIB was lower in the primary than in the secondary prevention cohort, numbers needed to harm per 1 year of low-dose aspirin use were 601 and 391 for primary and secondary prevention, respectively. Conclusions—The relative risk of UGIB in patients taking low-dose aspirin is higher when used for primary than for secondary cardiovascular disease prevention, but this difference is more than compensated by the lower baseline risk in the primary prevention population. Such estimates are important for an assessment of the net clinical benefit in primary prevention.

OUTCOMES IN 2824 PATIENTS WITH VALVULAR HEART DISEASE TREATED WITH EDOXABAN OR WARFARIN IN THE ENGAGE AF-TIMI 48 TRIAL

Use of NOACs in patients (pts) with atrial fibrillation (AF) and valvular heart disease (VHD) is under scrutiny. We explored outcomes in pts with AF +/- VHD in ENGAGE AF-TIMI 48 comparing edoxaban with warfarin. We defined VHD as mitral/aortic valve surgery (bioprosthetic valve, repair,

EFFICACY AND SAFETY OF APIXABAN COMPARED WITH WARFARIN ACCORDING TO AGE FOR STROKE PREVENTION IN ATRIAL FIBRILLATION

The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban as compared with warfarin reduced the rate of stroke, death and bleeding. We evaluated these and other pre-specified outcomes in relation to age. 18201 patients with AF and a raised

Revascularization Strategies in Multivessel Coronary Artery Disease

Multivessel coronary artery disease (MVCAD) is traditionally defined as the presence of a ≥50% diameter stenosis in more than one epicardial vessel. It is documented in 40–60% of patients undergoing coronary angiography and, depending on the clinical presentation, is associated with adverse outcomes compared with single-vessel disease. The management of patients with MVCAD is influenced not only by the extent and severity of disease, but also by the clinical presentation, left ventricular systolic function, and the presence of comorbidities such as diabetes and chronic kidney disease.

Proceedings of the 11th Congress of the International Society of Nutrigenetics and Nutrigenomics (ISNN 2017)

The International Society of Nutrigenetics and Nutrigenomics (ISNN) held its 11th annual Congress in Los Angeles, California, between September 16 and 19, 2017. In addition to 2 keynote lectures, 4 plenary sessions included presentations by internationally renowned speakers on cutting-edge areas of research and new discoveries in genetics/genomics, the microbiome, and nutrition. Scientific topics included multi-omics approaches; diet and the microbiome; cancer, longevity, and metabolism; moving the field forward; and translational/educational aspects and the future of medicine. There was also an accepted oral abstracts session designed specifically to provide young investigators and trainees with the opportunity to present their work, as well as a session focused on industry-academic partnerships, which included a roundtable discussion afterwards. Overall, the 11th ISNN Congress was an exciting and intellectually stimulating meeting focused on understanding the impact of biological interactions between genes and nutrients on health and disease. These efforts continued the decade-long tradition of the annual ISNN Congress to provide an interdisciplinary platform for scientists from various disciplines to discuss research ideas and advance the fields of nutrigenetics and nutrigenomics.