Chronic inflammatory diseases and all-cause, cardiovascular and mortality related to other causes: association with risk factors, subclinical Atherosclerosis and fatal and non-fatal events in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

• Grant number: 19/23734-6
• Support type: Research Projects - Thematic Grants
• Duration: December 01, 2020 - November 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Isabela Judith Martins Bensenor
• Grantee: Isabela Judith Martins Bensenor
• Home Institution: Hospital Universitário (HU). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Co-Principal Investigators: Paulo Andrade Lotufo
• Assoc. researchers: Airlane Pereira Alencar ; Alessandra Carvalho Goulart ; Alexandre da Costa Pereira ; Ana Cristina de Medeiros Ribeiro ; Andre Russowsky Brunoni ; Aytan Miranda Sipahi ; Bianca de Almeida Pititto ; Carolina Castro Porto Silva Janovsky ; Eloisa Silva Dutra de Oliveira Bonfá ; Fernando Barbosa Júnior ; Itamar de Souza Santos ; José Augusto Sgarbi ; Luciana Andrade Carneiro Machado ; Márcio Sommer Bittencourt ; Raul Dias dos Santos Filho ; Rosa Maria Rodrigues Pereira ; Rosa Weiss Telles ; Sandhi Maria Barreto ; Sandra Gofinet Pasoto

Abstract

Chronic inflammatory diseases and mortality: association with risk factors, subclinical Atherosclerosis and fatal and non-fatal cardiovascular events in the ELSA-Brasil Some studies suggest that inflammatory diseases such as Rheumatoid Arthritis, systemic erythematosus lupus, celiac disease, psoriasis and other rheumatologic diseases - Sjögren Syndrome and Vasculitis - would be associated with subclinical Atherosclerosis and cardiovascular outcomes. ELSA-Brasil is a prospective cohort study focused in the evaluation of classical and non-classical cardiovascular risk factors associated to cardiovascular disease and their relationship with the incidence of cardiovascular disease and Diabetes. The objective of this study is to evaluate the incidence of subclinical Atherosclerosis measured by the Coronary Artery Calcium (CAC) and the Carotid Intima-Media Thickness (CIMT) as well as the incidence of fatal and non-fatal cardiovascular outcomes and of causes of death (all-cause mortality, cardiovascular mortality and other causes of death) in participants that refer previous medical diagnosis of inflammatory diseases at baseline or in the follow-up of the study. The identification of inflammatory diseases were done by questions about previous medical diagnosis of inflammatory diseases, use of specific medication to treat inflammatory diseases and the presence of biomarkers to be tested as part of this study using stored biological samples in nitrogen collected in 2008-2010 with a 9-years follow-up: rheumatoid factor, anti-CCP antibodies (Rheumatoid Arthritis), FAN, anti-DNA antibodies, Anti-SM antibodies (systemic erythematous lupus), anti-transglutaminase IgA antibodies (celiac disease) , anti-RO and anti-LA antibodies (Sjögren Syndrome) and ANCA antibodies (Vasculitis). We are also going to study the association of thyroid function, anti-TPO antibodies (auto-immune) and psychiatric disorders (also with a possible inflammatory action). Lipid paradox paradox - subgroup of patients with Rheumatoid Arthritis with low levels of cholesterol but higher incidence of cardiovascular outcomes - with conventional and non-conventional techniques such as vertical ultra-centrifugation and by nuclear magnetic resonance (metabolomics) as well as to detect the presence of lipid paradox in other inflammatory diseases. As part of the approach to be used to face the scientific and technological challenges of the project and how to overcome these challenges, the study includes an aleatory subsample of 1500 subjects that are representative of the 15105 participants of the study and that can be the group of comparison without disease in all analyses. This fact permits the test of biomarkers in a smaller sample of 3000 participants including cases and controls. The study also has biological samples stored since 2008-2010, therefore the analyses can be done immediately without the necessity of a new blood drawn and with a long follow-up. The study has lipid particle tests using new non-conventional methods that can help to understand lipid paradox. Results will be analyzed using Poisson regression or Cox proportional hazards with the calculation of relative risk and presented crude, adjusted by sociodemographic risk factors e with multivariate adjustment by probable confounding factors. We will use survival analyses with Kaplan-Meier curves compared using log-rank test. The expected results include the association of inflammatory diseases with an earlier and more severe subclinical Atherosclerosis and a higher incidence of cardiovascular outcomes and all-cause, cardiovascular, and mortality related to other causes in participants with disease compared to others with no disease; and the investigation of lipid paradox of Rheumatoid Arthritis and its identification in other inflammatory diseases. The results will be presented in national and international meetings, articles published in open journals divulged in the lay population. (AU)