Patients with rheumatoid arthritis (RA) continue to experience a 30-40% excess mortality risk despite advances in disease management in the past two decades. During prior grant years, we established that cardiovascular (CV) disease is the leading cause of death in RA, and CV disease is increased 1.5-2 fold in patients with RA compared to the general population. We and others have shown that the excess CV mortality in RA has declined recently, but overall excess mortality in RA has not improved. We hypothesize that efforts to improve overall survival in RA by reducing CV death have failed because the systemic inflammation in RA affects multiple body systems, and the majority of patients exhibit complex health problems involving multiple, interrelated chronic health conditions (multimorbidity). In recent years the proportion of RA patients with multimorbidity and the mean number of morbidities per patient have increased. The goal of this application is to determine the complex interrelation between multimorbidity, RA disease activity, RA therapies, lifestyle, and other risk factors, and their impact on outcomes in patients with RA.
The aims of this project are to: (1) determine multimorbidity clusters among persons with RA compared to similar persons without RA; (2) determine the impact of multimorbidity on long-term outcomes; and (3) develop and validate risk scores for common morbidities in RA.
These aims will be accomplished utilizing the Rochester Epidemiology Project to expand (to n=2,295) and extend the existing population-based cohort of persons with RA, and utilizing a cohort of persons with RA (n>50,000) in the OptumLabs Data Warehouse. Multimorbidity clusters will be determined for persons with RA of different ages, sexes, races/ethnicities and geographic regions of the US. Longitudinal multimorbidity trajectories will be identified and their impact on outcomes among persons with RA will be compared to similar persons without RA. The impact of multimorbidity on mortality, physical functioning (determined by yearly assessments gathered over 20 years), healthcare utilization (outpatient visits, hospitalizations, emergency room visits and preventive services), and achievement of remission in RA will also be determined. New morbidity risk scores will be developed for cardiovascular disease, interstitial lung disease, and gastrointestinal bleeds/perforations. These and the existing scores for osteoporotic fractures and serious infections will be externally validated using the OptumLabs Data Warehouse. This information will determine how to identify persons with RA at the greatest risk for accumulating multimorbidity and how multimorbidity contributes to poor outcomes among persons with RA. Our findings will also stimulate the development of preventive strategies to delay the onset of multimorbidity (e.g., prevention of serious infections), which would slow the progression of multimorbidity and age-related declines in physical functioning and ultimately extend the lifespans of persons with RA.

Public Health Relevance

/ PUBLIC HEALTH RELEVANCE Persons with rheumatoid arthritis continue to experience a 30-40% excess mortality risk despite advances in disease management and reductions in excess cardiovascular disease deaths in the past two decades. In recent years the proportion of people with rheumatoid arthritis who have multiple, interrelated chronic health conditions (multimorbidity) and the mean number of morbidities per person have increased. Understanding the complex epidemiology of longitudinal multimorbidity trajectories and their influence on outcomes in persons with rheumatoid arthritis will help us to identify individuals at risk earlier in life and to develop interventions to prevent multimorbidity and its adverse health outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR046849-16A1
Application #
9590445
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Witter, James
Project Start
2000-09-01
Project End
2023-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
16
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Wilton, Katelynn M; Matteson, Eric L; Crowson, Cynthia S (2018) Risk of Obstructive Sleep Apnea and Its Association with Cardiovascular and Noncardiac Vascular Risk in Patients with Rheumatoid Arthritis: A Population-based Study. J Rheumatol 45:45-52
Crowson, Cynthia S; Rollefstad, Silvia; Ikdahl, Eirik et al. (2018) Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis 77:48-54
Sheen, Youn Ho; Rolfes, Mary C; Wi, Chung-Il et al. (2018) Association of Asthma with Rheumatoid Arthritis: A Population-Based Case-Control Study. J Allergy Clin Immunol Pract 6:219-226
Richter, Michael D; Crowson, Cynthia S; Matteson, Eric L et al. (2018) Orthopedic Surgery Among Patients With Rheumatoid Arthritis: A Population-Based Study to Identify Risk Factors, Sex Differences, and Time Trends. Arthritis Care Res (Hoboken) 70:1546-1550
Scanlon, Erin M; Mankad, Rekha; Crowson, Cynthia S et al. (2017) Cardiovascular risk assessment in patients with rheumatoid arthritis: a correlative study of noninvasive arterial health testing. Clin Rheumatol 36:763-771
Ni Mhuircheartaigh, Orla; Crowson, Cynthia S; Gabriel, Sherine E et al. (2017) Fragility Fractures Are Associated with an Increased Risk for Cardiovascular Events in Women and Men with Rheumatoid Arthritis: A Population-based Study. J Rheumatol 44:558-564
Crowson, Cynthia S; Rollefstad, Silvia; Kitas, George D et al. (2017) Correction: Challenges of developing a cardiovascular risk calculator for patients with rheumatoid arthritis. PLoS One 12:e0175605
Davis 3rd, John M; Lin, Grace; Oh, Jae K et al. (2017) Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population. Int J Cardiol 240:379-385
Myasoedova, Elena; Gabriel, Sherine E; Matteson, Eric L et al. (2017) Decreased Cardiovascular Mortality in Patients with Incident Rheumatoid Arthritis (RA) in Recent Years: Dawn of a New Era in Cardiovascular Disease in RA? J Rheumatol 44:732-739
Crowson, Cynthia S; Gabriel, Sherine E; Semb, Anne Grete et al. (2017) Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk scores: a validation analysis of patients from seven countries. Rheumatology (Oxford) 56:1102-1110

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