Patterns of Multimorbidity and Their Effects on Adverse Outcomes in Rheumatoid Arthritis: a Study of 5658 UK Biobank Participants

Overview

Journal BMJ Open

Specialty General Medicine

Date 2020 Nov 25

PMID 33234629

Citations 16

Authors

Ross McQueenie

Barbara I Nicholl

Bhautesh D Jani

Jordan Canning

Sara Macdonald

Colin McCowan

Joanne Neary

Susan Browne

Frances S Mair

Stefan Siebert

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA).

Design: Population-based longitudinal cohort study.

Setting: UK Biobank.

Participants: UK Biobank participants (n=502 533) aged between 37 and 73 years old.

Primary Outcome Measures: Primary outcome measures were risk of all-cause mortality and MACE.

Methods: We examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox's proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor.

Results: 75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and 4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports.

Conclusion: Those with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity.

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References

Wolfe F . Pain extent and diagnosis: development and validation of the regional pain scale in 12,799 patients with rheumatic disease. J Rheumatol. 2003; 30(2):369-78. View

Safiri S, Kolahi A, Hoy D, Smith E, Bettampadi D, Mansournia M . Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis. 2019; 78(11):1463-1471. DOI: 10.1136/annrheumdis-2019-215920. View

Gron K, Ornbjerg L, Hetland M, Aslam F, Khan N, Jacobs J . The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program. Clin Exp Rheumatol. 2014; 32(6):869-77. View

Jani B, Nicholl B, McQueenie R, Connelly D, Hanlon P, Gallacher K . Multimorbidity and co-morbidity in atrial fibrillation and effects on survival: findings from UK Biobank cohort. Europace. 2017; 20(FI_3):f329-f336. PMC: 6277149. DOI: 10.1093/europace/eux322. View

Andrews J, Trupin L, Yelin E, Hough C, Covinsky K, Katz P . Frailty and reduced physical function go hand in hand in adults with rheumatoid arthritis: a US observational cohort study. Clin Rheumatol. 2017; 36(5):1031-1039. PMC: 5930487. DOI: 10.1007/s10067-017-3541-9. View

Craig C, Marshall A, Sjostrom M, Bauman A, Booth M, Ainsworth B . International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003; 35(8):1381-95. DOI: 10.1249/01.MSS.0000078924.61453.FB. View

Cooksey R, Brophy S, Kennedy J, Gutierrez F, Pickles T, Davies R . Cardiovascular risk factors predicting cardiac events are different in patients with rheumatoid arthritis, psoriatic arthritis, and psoriasis. Semin Arthritis Rheum. 2018; 48(3):367-373. DOI: 10.1016/j.semarthrit.2018.03.005. View

del Rincon I, Battafarano D, Restrepo J, Erikson J, Escalante A . Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheumatol. 2014; 66(2):264-72. DOI: 10.1002/art.38210. View

Gabriel S, Crowson C, Kremers H, Doran M, Turesson C, OFallon W . Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. Arthritis Rheum. 2003; 48(1):54-8. DOI: 10.1002/art.10705. View

10.

Logstrup B, Olesen K, Masic D, Gyldenkerne C, Thrane P, Ellingsen T . Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease. Ann Rheum Dis. 2020; 79(9):1182-1188. DOI: 10.1136/annrheumdis-2020-217154. View

11.

Ferguson L, Siebert S, McInnes I, Sattar N . Cardiometabolic comorbidities in RA and PsA: lessons learned and future directions. Nat Rev Rheumatol. 2019; 15(8):461-474. DOI: 10.1038/s41584-019-0256-0. View

12.

Luque Ramos A, Redeker I, Hoffmann F, Callhoff J, Zink A, Albrecht K . Comorbidities in Patients with Rheumatoid Arthritis and Their Association with Patient-reported Outcomes: Results of Claims Data Linked to Questionnaire Survey. J Rheumatol. 2019; 46(6):564-571. DOI: 10.3899/jrheum.180668. View

13.

Lauper K, Courvoisier D, Chevallier P, Finckh A, Gabay C . Incidence and Prevalence of Major Adverse Cardiovascular Events in Rheumatoid Arthritis, Psoriatic Arthritis, and Axial Spondyloarthritis. Arthritis Care Res (Hoboken). 2018; 70(12):1756-1763. DOI: 10.1002/acr.23567. View

14.

Humphreys J, Warner A, Chipping J, Marshall T, Lunt M, Symmons D . Mortality trends in patients with early rheumatoid arthritis over 20 years: results from the Norfolk Arthritis Register. Arthritis Care Res (Hoboken). 2014; 66(9):1296-301. PMC: 4226330. DOI: 10.1002/acr.22296. View

15.

Sokka T, Abelson B, Pincus T . Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol. 2008; 26(5 Suppl 51):S35-61. View

16.

Solomon D, Goodson N, Katz J, Weinblatt M, Avorn J, Setoguchi S . Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis. 2006; 65(12):1608-12. PMC: 1798453. DOI: 10.1136/ard.2005.050377. View

17.

Dalbeni A, Giollo A, Bevilacqua M, Cioffi G, Tagetti A, Cattazzo F . Traditional cardiovascular risk factors and residual disease activity are associated with atherosclerosis progression in rheumatoid arthritis patients. Hypertens Res. 2020; 43(9):922-928. DOI: 10.1038/s41440-020-0441-1. View

18.

Listing J, Kekow J, Manger B, Burmester G, Pattloch D, Zink A . Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab. Ann Rheum Dis. 2013; 74(2):415-21. PMC: 4316844. DOI: 10.1136/annrheumdis-2013-204021. View

19.

Peeters G, Alshurafa M, Schaap L, de Vet H . Diagnostic accuracy of self-reported arthritis in the general adult population is acceptable. J Clin Epidemiol. 2014; 68(4):452-9. DOI: 10.1016/j.jclinepi.2014.09.019. View

20.

Nicola P, Maradit-Kremers H, Roger V, Jacobsen S, Crowson C, Ballman K . The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years. Arthritis Rheum. 2005; 52(2):412-20. DOI: 10.1002/art.20855. View