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Research ArticleAccepted Article

Cardiovascular Event Risk in Rheumatoid Arthritis is Higher than in Type 2 Diabetes: a 15 Year Longitudinal Study

R. Agca, L.H.G.A. Hopman, K.C.J. Laan, V.P. van Halm, M.J.L. Peters, Y.M. Smulders, J.M. Dekker, G. Nijpels, C.D.A. Stehouwer, A.E. Voskuyl, M. Boers, W.F. Lems and M.T. Nurmohamed
The Journal of Rheumatology May 2019, jrheum.180726; DOI: https://doi.org/10.3899/jrheum.180726
R. Agca
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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L.H.G.A. Hopman
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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K.C.J. Laan
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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V.P. van Halm
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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M.J.L. Peters
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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Y.M. Smulders
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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J.M. Dekker
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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G. Nijpels
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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C.D.A. Stehouwer
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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A.E. Voskuyl
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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M. Boers
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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W.F. Lems
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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M.T. Nurmohamed
From Amsterdam Rheumatology and immunology Center, Department of Rheumatology, Reade, Amsterdam, The Netherlands; Amsterdam Rheumatology and immunology Center, Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, Academic Medical Center, Department of Cardiology, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of General Practice, Amsterdam, The Netherlands; Amsterdam UMC, VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands; Maastricht University Medical Center, Department of Internal Medicine, Maastricht, The Netherlands; Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands; Amsterdam UMC, VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands. Address correspondence to R. Agca, MD Amsterdam Rheumatology and immunology Center, location VU University Medical Center & Reade P.O. Box 7057, 1007 MB Amsterdam. E-mail: r_agca@hotmail.com
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Abstract

Objective Cardiovascular (CV) disease risk is increased in rheumatoid arthritis (RA). However, longterm follow-up studies investigating this risk are scarce.

Methods CARRÉ is a prospective cohort study investigating CV disease and its risk factors in 353 patients with longstanding RA. CV endpoints were assessed at baseline, 3, 10 and 15 years after the start of the study and are compared to a reference cohort(n=2540) including a large number of patients with type 2 diabetes(DM).

Results 95 RA patients developed a CV event during 2973 person-years, resulting in an incidence rate of 3.20 per 100 person-years. 257 CV events were reported in the reference cohort during 18874 person-years, resulting in an incidence rate of 1.36 per 100 person-years. Age and sex adjusted hazard rates(HR) for CV events were increased for RA(HR 2.07, 95%CI 1.57–2.72, P<0.01) and DM (HR 1.51, 95%CI 1.02–2.22, P=0.04) compared to the non-diabetic participants. HR was still increased in RA (HR 1.82, 95%CI 1.32–2.50, P<0.01) after additional adjustment for CV risk factors. Patients with both RA and DM or insulin resistance had the highest HR for developing CV disease (2.21, 95%CI 1.01–4.80, P=0.046 and 2.67, 95%CI 1.30–5.46, P<0.01, respectively).

Conclusion The incidence rate of CV events in established RA was more than double that of the general population. RA patients have an even higher risk of CV disease than patients with DM. This risk remained after adjustment for traditional CV risk factors suggesting that systemic inflammation is an independent contributor to CV risk.

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Accepted manuscript
Cardiovascular Event Risk in Rheumatoid Arthritis is Higher than in Type 2 Diabetes: a 15 Year Longitudinal Study
R. Agca, L.H.G.A. Hopman, K.C.J. Laan, V.P. van Halm, M.J.L. Peters, Y.M. Smulders, J.M. Dekker, G. Nijpels, C.D.A. Stehouwer, A.E. Voskuyl, M. Boers, W.F. Lems, M.T. Nurmohamed
The Journal of Rheumatology May 2019, jrheum.180726; DOI: 10.3899/jrheum.180726

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Accepted manuscript
Cardiovascular Event Risk in Rheumatoid Arthritis is Higher than in Type 2 Diabetes: a 15 Year Longitudinal Study
R. Agca, L.H.G.A. Hopman, K.C.J. Laan, V.P. van Halm, M.J.L. Peters, Y.M. Smulders, J.M. Dekker, G. Nijpels, C.D.A. Stehouwer, A.E. Voskuyl, M. Boers, W.F. Lems, M.T. Nurmohamed
The Journal of Rheumatology May 2019, jrheum.180726; DOI: 10.3899/jrheum.180726
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