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Pérez N, Gargiulo MDLÁ, Khoury M, Suárez L, Correa MDLÁ, Pera M, Saravia N, Gómez G. Elderly-onset rheumatoid arthritis receives less aggressive therapies than young-onset rheumatoid arthritis in an Argentinian cohort. REUMATOLOGIA CLINICA 2024; 20:136-141. [PMID: 38443231 DOI: 10.1016/j.reumae.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 10/26/2023] [Indexed: 03/07/2024]
Abstract
OBJECTIVES When rheumatoid arthritis (RA) starts after the age of 60 it is called elderly-onset rheumatoid arthritis (EORA) and when it starts earlier, young-onset rheumatoid arthritis. (YORA). There are few Latin American studies that compared both groups. The objective of the study was to evaluate differences in the clinical characteristics, evolution and treatment among patients with RA with onset before or after 60 years of age. MATERIALS AND METHODS Observational study of patients with RA attended consecutively in four centers in Argentina. Sociodemographic data, comorbidities, clinical manifestations at diagnosis, presence of rheumatoid factor and/or anti-CCP (cyclic citrullinated peptide) and treatments received were collected. At the last visit, swollen and tender joints, assessment of disease activity by the patient and physician, the presence of radiographic erosions, and functional status using the HAQ-DI were recorded. RESULTS 51 patients from each group were analyzed. The EORA group had a significantly higher proportion of smokers (58.8% vs. 35.3%, p = 0.029), cardiovascular history (54.9% vs. 21.6%, p = 0.001), abrupt onset (49% vs. 29.4%, p = 0.034) or with symptoms similar to PMR (19.6% vs. 0%, p = 0.001). Lower methotrexate doses were used in the EORA group: 19 mg (15-25) vs. 21.9 mg (20-25) (p = 0.0036) and more frequently did not receive bDMARDs or tsDMARDs. DISCUSSION AND CONCLUSIONS The benefits of intensive treatment in patients with RA have been described. In this study, the use of DMARDs in the EORA group was less intensive, suggesting that advanced age constitutes a barrier in the therapeutic choice.
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Affiliation(s)
- Nicolás Pérez
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", Ciudad Autónoma de Buenos Aires, Argentina.
| | - María de Los Ángeles Gargiulo
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", Ciudad Autónoma de Buenos Aires, Argentina.
| | - Marina Khoury
- Docencia e Investigación, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", Ciudad Autónoma de Buenos Aires, Argentina.
| | - Lorena Suárez
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", Ciudad Autónoma de Buenos Aires, Argentina.
| | | | - Mariana Pera
- Servicio de Reumatología, Hospital Ángel Cruz Padilla, San Miguel de Tucumán, Tucumán, Argentina.
| | - Natali Saravia
- Servicio de Reumatología, Hospital Tornú, Ciudad Autónoma de Buenos Aires, Argentina.
| | - Graciela Gómez
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", Ciudad Autónoma de Buenos Aires, Argentina.
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Madenidou AV, Mavrogeni S, Nikiphorou E. Cardiovascular Disease and Cardiac Imaging in Inflammatory Arthritis. Life (Basel) 2023; 13:life13040909. [PMID: 37109438 PMCID: PMC10143346 DOI: 10.3390/life13040909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 04/01/2023] Open
Abstract
Cardiovascular morbidity and mortality are more prevalent in inflammatory arthritis (IA) compared to the general population. Recognizing the importance of addressing this issue, the European League Against Rheumatism (EULAR) published guidelines on cardiovascular disease (CVD) risk management in IA in 2016, with plans to update going forward based on the latest emerging evidence. Herein we review the latest evidence on cardiovascular disease in IA, taking a focus on rheumatoid arthritis, psoriatic arthritis, and axial spondylarthritis, reflecting on the scale of the problem and imaging modalities to identify disease. Evidence demonstrates that both traditional CVD factors and inflammation contribute to the higher CVD burden. Whereas CVD has decreased with the newer anti-rheumatic treatments currently available, CVD continues to remain an important comorbidity in IA patients calling for prompt screening and management of CVD and related risk factors. Non-invasive cardiovascular imaging has been attracting much attention in view of the possibility of detecting cardiovascular lesions in IA accurately and promptly, even at the pre-clinical stage. We reflect on imaging modalities to screen for CVD in IA and on the important role of rheumatologists and cardiologists working closely together.
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Atzeni F, Maiani S, Corda M, Rodríguez-Carrio J. Diagnosis and management of cardiovascular risk in rheumatoid arthritis: main challenges and research agenda. Expert Rev Clin Immunol 2023; 19:279-292. [PMID: 36651086 DOI: 10.1080/1744666x.2023.2170351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) exhibit a cardiovascular (CV) risk that is 1.5-2.0 times higher compared to the general population. This CV risk excess is likely caused by the involvement of chronic inflammation and immune dysregulation. Therefore, conventional algorithms and imaging techniques fail to fully account for this risk excess and provide a suboptimal risk stratification, hence limiting clinical management in this setting. AREAS COVERED Compelling evidence has suggested a role for adaptations of conventional algorithms (Framingham, SCORE, AHA, etc) or the development of RA-specific algorithms, as well as the use of a number of several, noninvasive imaging techniques to improve CV risk assessment in RA populations. Similarly, in-depth analyses of atherosclerosis pathogenesis in RA patients have shed new light into a plethora of soluble biomarkers (such as inflammatory cytokines, vascular remodeling mediators or autoantibodies) that may provide incremental value for CV risk stratification. EXPERT OPINION Extensive research has demonstrated a lack of performance of chart adaptations in capturing real CV risk in RA population, as well as for RA-specific algorithms. Similarly, limitations have been detected in the use of soluble mediators. The development of a novel, RA-specific algorithm including classical and non-traditional risk factors may be advisable.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Silvia Maiani
- Clinical Cardiology, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Marco Corda
- S.C. Cardiologia UTIC, ARNAS, G.Brotzu, Cagliari, Italy
| | - Javier Rodríguez-Carrio
- Area of Immunology, Department of Functional Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.,Area of Metabolism, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
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Liu S, Song LP, Li RB, Feng LH, Zhu H. Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by nuclear factor-κB pathway. World J Clin Cases 2021; 9:2181-2191. [PMID: 33869594 PMCID: PMC8026846 DOI: 10.12998/wjcc.v9.i10.2181] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/13/2021] [Accepted: 02/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The role of macrophages in rheumatoid arthritis (RA) and its mechanism have attracted much attention in RA pathogenesis. Macrophages accumulate in the synoviums of RA, and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages, leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction, which has made macrophages a potential target of RA drugs. Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity. It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio.
AIM To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA.
METHODS Elderly patients with RA and joint effusion were selected, including 10 men and 25 women, with an average age of 66.37 ± 4.42 years. Patients were treated with oral administration of 25 mg Iguratimod (Iremod, State Food and Drug Administration Approval No. H20110084) twice daily for 12 wk. Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment. Venous blood and joint effusion fluid were collected, mononuclear macrophages were extracted and expression of cell surface markers CD86, CD64, CD163, and CD206 was analyzed by flow cytometry. The concentration of inflammatory factors interleukin (IL)-6, IL-1β, transforming growth factor-β, and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay. Expression of mononuclear cells inhibitor of nuclear factor-κB (IκB) and phosphorylated IκB in peripheral blood was analyzed by western blotting.
RESULTS Disease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly. The percentage of cell surface markers CD86 and CD64 decreased significantly, and the percentage of CD163 and CD206 increased significantly (P < 0.05). The inflammatory factors IL-6 and IL-1β decreased significantly, and transforming growth factor-β and IL-4 increased significantly. Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment, and its phosphorylation level was significantly decreased (P < 0.05).
CONCLUSION Iguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway, thus improving symptoms of RA.
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Affiliation(s)
- Sha Liu
- Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar 161005, Heilongjiang Province, China
| | - Li-Ping Song
- Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar 161005, Heilongjiang Province, China
| | - Rong-Bin Li
- Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar 161005, Heilongjiang Province, China
| | - Le-Heng Feng
- Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar 161005, Heilongjiang Province, China
| | - Hui Zhu
- Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar 161005, Heilongjiang Province, China
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Yazdani K, Xie H, Avina-Zubieta JA, Zheng Y, Abrahamowicz M, Lacaille D. Has the excess risk of acute myocardial infarction in rheumatoid arthritis relative to the general population declined? A population study of trends over time. Semin Arthritis Rheum 2021; 51:442-449. [PMID: 33735663 DOI: 10.1016/j.semarthrit.2021.03.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 02/03/2021] [Accepted: 03/01/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To evaluate secular trend in ten-year risk of incident acute myocardial infarction (AMI) in incident rheumatoid arthritis (RA) relative to the general population. METHODS We conducted a retrospective study of population-based incident RA cohorts with RA incidence from 1997 to 2004 in British Columbia, Canada, with matched general population comparators, using administrative health data. RA and their matched cohorts were divided according to the year of RA incidence, defined according to the first RA visit of the case definition. Incident AMI was defined as the first event occurring within 10 years from RA incidence. Secular trend was assessed using delayed-entry Cox models with an interaction term between the year of RA onset and indicator of RA vs. general population. Linear, quadratic and spline functions of year of RA onset were compared to assess possibility of nonlinear trends. The model with the lowest AIC was selected to interpret the results. Sensitivity analyses were conducted to account for potential effect of unmeasured (e.g. smoking) or partially measured (e.g. obesity) confounders in administrative data, on the interaction term. RESULTS Overall, 23,237 RA and 46,474 general population controls experienced 1,133 and 1,606 incident AMIs, respectively. A linear Cox model was selected as the model best fitting the AMI events. Overall, RA patients were found to have a 21% higher risk of AMI than the matched general population controls [1.21 (1.10, 1.32); p < 0.001]. A significant linear decline in risk of AMI was observed in RA patients [0.94 (95% CI 0.91, 0.97) p = <0.0001], and in the general population [0.93 (0.91, 0.95); p = <0.0001]. The change in AMI risk over time did not differ in RA compared to the general population [p-value of interaction term=0.49]. Our results remained similar after adjusting for the potential effect of confounders on the interaction term, and no difference in the change in risk of AMI over time was observed between RA and the general population. CONCLUSION Our findings suggest a decline in 10-year risk of AMI in RA, and in the general population. The decline in the risk of AMI over time did not differ between RA and the general population, such that the excess risk of AMI in RA relative to the general population, has remained the same.
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Affiliation(s)
- Kiana Yazdani
- Arthritis Research Canada, 5591 Number 3 Rd, Richmond V6X 2C7, British Columbia, Canada; Experimental Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Hui Xie
- Arthritis Research Canada, 5591 Number 3 Rd, Richmond V6X 2C7, British Columbia, Canada; Faculty of Health Science, Simon Fraser University, Vancouver, Canada
| | - J Antonio Avina-Zubieta
- Arthritis Research Canada, 5591 Number 3 Rd, Richmond V6X 2C7, British Columbia, Canada; Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of British Columbia, Canada; Experimental Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Yufei Zheng
- Arthritis Research Canada, 5591 Number 3 Rd, Richmond V6X 2C7, British Columbia, Canada
| | - Michal Abrahamowicz
- Arthritis Research Canada, 5591 Number 3 Rd, Richmond V6X 2C7, British Columbia, Canada; Department of Epidemiology, Biostatistics and Occupational Health McGill University, Montreal, Quebec, Canada
| | - Diane Lacaille
- Arthritis Research Canada, 5591 Number 3 Rd, Richmond V6X 2C7, British Columbia, Canada; Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of British Columbia, Canada; Experimental Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
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Chiu YM, Lu YP, Lan JL, Chen DY, Wang JD. Lifetime Risks, Life Expectancy, and Health Care Expenditures for Rheumatoid Arthritis: A Nationwide Cohort Followed Up From 2003 to 2016. Arthritis Rheumatol 2020; 73:750-758. [PMID: 33295139 PMCID: PMC8247851 DOI: 10.1002/art.41597] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 11/17/2020] [Indexed: 11/10/2022]
Abstract
Objective This study was undertaken to estimate the cumulative incidence rate of rheumatoid arthritis (RA) in the Taiwanese population ages 16–84 years, and life expectancy, loss of life expectancy, and lifetime health care expenditures for incident RA in Taiwan after 2003, when biologics began to be prescribed. Methods We obtained all claims data for the period 1999 to 2016 from the National Health Insurance program of Taiwan, and validated the data against the Catastrophic Illness Registry to establish the study cohort. We estimated the survival function for RA and extrapolated to lifetime using a rolling‐over algorithm. For every RA case, we simulated sex‐, age‐, and calendar year–matched referents from vital statistics and estimated their life expectancy. The difference between the life expectancy of the referent and the life expectancy of the RA patient was the loss of life expectancy for the RA patient. Average monthly health care expenditures were multiplied by the corresponding survival rates and summed up throughout the lifetime to calculate the lifetime health care expenditures. Results A total of 29,352 new RA cases were identified during 2003–2016. There was a decreasing trend in cumulative incidence rate in those ages 16–84 for both sexes. Mean life expectancy after diagnosis of RA was 26.3 years, and mean lifetime cost was $72,953. RA patients had a mean loss of life expectancy of 4.97 years. Women with RA survived 1–2 years longer than men with RA of the same age, which resulted in higher lifetime expenditures for the former. Since the life expectancy for women in Taiwan was 6–7 years higher than that for men, the loss of life expectancy for women with RA was higher than that for men with RA. Annual health care expenditures were similar for both sexes. Conclusion Our findings indicate that since biologics became available, RA patients have lived longer and had higher lifetime expenditures, which should be monitored and evaluated for cost‐effectiveness.
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Affiliation(s)
- Ying-Ming Chiu
- China Medical University and China Medical University Hospital, Taichung, Taiwan
| | - Yi-Peng Lu
- National Cheng Kung University, Tainan, Taiwan
| | - Joung-Liang Lan
- China Medical University and China Medical University Hospital, Taichung, Taiwan
| | - Der-Yuan Chen
- China Medical University and China Medical University Hospital, Taichung, Taiwan
| | - Jung-Der Wang
- National Cheng Kung University and National Cheng Kung University Hospital, Tainan, Taiwan
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Poolman TM, Gibbs J, Walker AL, Dickson S, Farrell L, Hensman J, Kendall AC, Maidstone R, Warwood S, Loudon A, Rattray M, Bruce IN, Nicolaou A, Ray DW. Rheumatoid arthritis reprograms circadian output pathways. Arthritis Res Ther 2019; 21:47. [PMID: 30728072 PMCID: PMC6366099 DOI: 10.1186/s13075-019-1825-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 01/15/2019] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE We applied systems biology approaches to investigate circadian rhythmicity in rheumatoid arthritis (RA). METHODS We recruited adults (age 16-80 years old) with a clinical diagnosis of RA (active disease [DAS28 > 3.2]). Sleep profiles were determined before inpatient measurements of saliva, serum, and peripheral blood mononuclear leukocytes (PBML). Transcriptome and proteome analyses were carried out by RNA-SEQ and LC-MS/MS. Serum samples were analysed by targeted lipidomics, along with serum from mouse collagen induced-arthritis (CIA). Bioinformatic analysis identified RA-specific gene networks and rhythmic processes differing between healthy and RA. RESULTS RA caused greater time-of-day variation in PBML gene expression, and ex vivo stimulation identified a time-of-day-specific RA transcriptome. We found increased phospho-STAT3 in RA patients, and some targets, including phospho-ATF2, acquired time-of-day variation in RA. Serum ceramides also gained circadian rhythmicity in RA, which was also seen in mouse experimental arthritis, resulting from gain in circadian rhythmicity of hepatic ceramide synthases. CONCLUSION RA drives a gain in circadian rhythmicity, both in immune cells, and systemically. The coupling of distant timing information to ceramide synthesis and joint inflammation points to a systemic re-wiring of the circadian repertoire. Circadian reprogramming in response to chronic inflammation has implications for inflammatory co-morbidities and time-of-day therapeutics.
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Affiliation(s)
- Toryn M Poolman
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK.,NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK and Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX37LE, UK
| | - Julie Gibbs
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK
| | - Amy L Walker
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK
| | - Suzanna Dickson
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK
| | - Laura Farrell
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK
| | | | - Alexandra C Kendall
- Laboratory for Lipidomics and Lipid Biology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9PT, UK.,Specialist Medicine, Central Manchester Foundation Trust, Manchester, M13 9PL, UK
| | - Robert Maidstone
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK
| | - Stacey Warwood
- Biological Mass Spectrometry Core Research Facility, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK
| | - Andrew Loudon
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK
| | - Magnus Rattray
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK
| | - Ian N Bruce
- Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.,NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Anna Nicolaou
- Laboratory for Lipidomics and Lipid Biology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9PT, UK. .,Specialist Medicine, Central Manchester Foundation Trust, Manchester, M13 9PL, UK.
| | - David W Ray
- Division of Digestion, Endocrinology and Metabolism, The University of Manchester, Manchester, M13 9PT, UK. .,NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK and Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX37LE, UK.
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Calcification of coronary arteries in early rheumatoid arthritis prior to anti-rheumatic therapy. Rheumatol Int 2017; 38:211-217. [DOI: 10.1007/s00296-017-3860-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 10/19/2017] [Indexed: 02/04/2023]
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Development and validation of a multivariate predictive model for rheumatoid arthritis mortality using a machine learning approach. Sci Rep 2017; 7:10189. [PMID: 28860558 PMCID: PMC5579234 DOI: 10.1038/s41598-017-10558-w] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 08/11/2017] [Indexed: 12/15/2022] Open
Abstract
We developed and independently validated a rheumatoid arthritis (RA) mortality prediction model using the machine learning method Random Survival Forests (RSF). Two independent cohorts from Madrid (Spain) were used: the Hospital Clínico San Carlos RA Cohort (HCSC-RAC; training; 1,461 patients), and the Hospital Universitario de La Princesa Early Arthritis Register Longitudinal study (PEARL; validation; 280 patients). Demographic and clinical-related variables collected during the first two years after disease diagnosis were used. 148 and 21 patients from HCSC-RAC and PEARL died during a median follow-up time of 4.3 and 5.0 years, respectively. Age at diagnosis, median erythrocyte sedimentation rate, and number of hospital admissions showed the higher predictive capacity. Prediction errors in the training and validation cohorts were 0.187 and 0.233, respectively. A survival tree identified five mortality risk groups using the predicted ensemble mortality. After 1 and 7 years of follow-up, time-dependent specificity and sensitivity in the validation cohort were 0.79–0.80 and 0.43–0.48, respectively, using the cut-off value dividing the two lower risk categories. Calibration curves showed overestimation of the mortality risk in the validation cohort. In conclusion, we were able to develop a clinical prediction model for RA mortality using RSF, providing evidence for further work on external validation.
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Myasoedova E, Gabriel SE, Matteson EL, Davis JM, Therneau TM, Crowson CS. 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 2017; 44:732-739. [PMID: 28365576 PMCID: PMC5457313 DOI: 10.3899/jrheum.161154] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2017] [Indexed: 12/25/2022]
Abstract
OBJECTIVE To assess trends in cardiovascular (CV) mortality in patients with incident rheumatoid arthritis (RA) in 2000-07 versus the previous decades, compared with non-RA subjects. METHODS The study population consisted of Olmsted County, Minnesota, USA residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria was met in 1980-2007) and non-RA subjects from the same underlying population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2014. Followup was truncated for comparability. Aalen-Johansen methods were used to estimate CV mortality rates, adjusting for competing risk of other causes. Cox proportional hazards models were used to compare CV mortality by decade. RESULTS The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 yrs; 68% women for both groups). Patients with incident RA in 2000-07 had markedly lower 10-year overall CV mortality (2.7%, 95% CI 0.6-4.9%) and coronary heart disease (CHD) mortality (1.1%, 95% CI 0.0-2.7%) than patients diagnosed in 1990-99 (7.1%, 95% CI 3.9-10.1% and 4.5%, 95% CI 1.9-7.1%, respectively; HR for overall CV death: 0.43, 95% CI 0.19-0.94; CHD death: HR 0.21, 95% CI 0.05-0.95). This improvement in CV mortality persisted after accounting for CV risk factors. Ten-year overall CV mortality and CHD mortality in 2000-07 RA incidence cohort was similar to non-RA subjects (p = 0.95 and p = 0.79, respectively). CONCLUSION Our findings suggest significantly improved overall CV mortality, particularly CHD mortality, in patients with RA in recent years. Further studies are needed to examine the reasons for this improvement.
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Affiliation(s)
- Elena Myasoedova
- From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, Minnesota; Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
- E. Myasoedova, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; C.S. Crowson, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; E.L. Matteson, MD MPH, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; J.M. Davis III, MD, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; T.M. Therneau, PhD, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; S.E. Gabriel, MD, MSc, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, and Rutgers Robert Wood Johnson Medical School.
| | - Sherine E Gabriel
- From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, Minnesota; Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- E. Myasoedova, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; C.S. Crowson, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; E.L. Matteson, MD MPH, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; J.M. Davis III, MD, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; T.M. Therneau, PhD, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; S.E. Gabriel, MD, MSc, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, and Rutgers Robert Wood Johnson Medical School
| | - Eric L Matteson
- From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, Minnesota; Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- E. Myasoedova, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; C.S. Crowson, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; E.L. Matteson, MD MPH, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; J.M. Davis III, MD, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; T.M. Therneau, PhD, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; S.E. Gabriel, MD, MSc, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, and Rutgers Robert Wood Johnson Medical School
| | - John M Davis
- From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, Minnesota; Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- E. Myasoedova, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; C.S. Crowson, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; E.L. Matteson, MD MPH, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; J.M. Davis III, MD, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; T.M. Therneau, PhD, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; S.E. Gabriel, MD, MSc, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, and Rutgers Robert Wood Johnson Medical School
| | - Terry M Therneau
- From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, Minnesota; Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- E. Myasoedova, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; C.S. Crowson, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; E.L. Matteson, MD MPH, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; J.M. Davis III, MD, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; T.M. Therneau, PhD, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; S.E. Gabriel, MD, MSc, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, and Rutgers Robert Wood Johnson Medical School
| | - Cynthia S Crowson
- From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, Minnesota; Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- E. Myasoedova, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; C.S. Crowson, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; E.L. Matteson, MD MPH, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; J.M. Davis III, MD, MS, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science; T.M. Therneau, PhD, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science; S.E. Gabriel, MD, MSc, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, and Rutgers Robert Wood Johnson Medical School
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11
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Tournadre A, Mathieu S, Soubrier M. Managing cardiovascular risk in patients with inflammatory arthritis: practical considerations. Ther Adv Musculoskelet Dis 2016; 8:180-191. [PMID: 27721904 DOI: 10.1177/1759720x16664306] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Patients with inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, have higher rates of cardiovascular mortality. While the increased cardiovascular risk is only explained to some extent, a lot of research is currently conducted to improve our understanding of its pathogenesis, risk stratification, and optimal cardiovascular risk management. This review sought to report epidemiological data pertaining to the cardiovascular disease burden in patients with inflammatory arthritis, underlying mechanisms accounting for excessive cardiovascular risk, along with recommendations regarding risk assessment and management in this patient population.
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Affiliation(s)
- Anne Tournadre
- Rheumatology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Sylvain Mathieu
- Rheumatology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Martin Soubrier
- Rheumatology Department, CHU Gabriel Montpied, 58 Rue Montalembert, F-63000 Clermont-Ferrand, France
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12
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Effect of age at rheumatoid arthritis onset on clinical, radiographic, and functional outcomes: The ESPOIR cohort. Joint Bone Spine 2016; 83:511-5. [PMID: 26992954 DOI: 10.1016/j.jbspin.2015.09.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2015] [Accepted: 09/09/2015] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To investigate whether age at disease onset determines clinical, radiographic or functional outcomes in a cohort of early RA. METHODS The ESPOIR cohort is a multicenter cohort of patients with early arthritis. We selected patients fulfilling the 2010 ACR/EULAR criteria for RA during the first 3years of follow-up. Patients were pooled into 3 groups by age at RA onset: <45years (young-onset RA [YORA]), 45 to 60years (intermediate-onset RA [IORA]) and>60years (late-onset RA [LORA]). The following outcomes were compared at baseline and during the first 3years of follow-up: Simple Disease Activity Index (SDAI) remission rate, one additional erosion, Health Assessment Questionnaire Disability Index (HAQ-DI)<0.5 and first disease-modifying anti-rheumatic drug (DMARD) continuation rate. RESULTS We included 698 patients (median [interquartile range] age 50.3 [39.8-57.2]years), 266 YORA, 314 IORA, and 118 LORA. At 1year, SDAI remission was greater for YORA than IORA and LORA (P<0.0001). Having at least one additional erosion was greater for LORA and IORA than YORA after 1year (P=0.009) and 3years (P=0.017). The proportion of patients with HAQ score<0.5 was greater for YORA than IORA and LORA at 1 (P=0.007), 2 and 3years. First DMARD continuation rate was lower for YORA than other groups during the 3years (P=0.005). CONCLUSIONS In a cohort of early RA, young age at disease onset is associated with high rate of remission at 1year, no radiographic progression at 3years and low functional score during 3-year follow-up.
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Navarro-Millán I, Yang S, DuVall SL, Chen L, Baddley J, Cannon GW, Delzell ES, Zhang J, Safford MM, Patkar NM, Mikuls TR, Singh JA, Curtis JR. Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration. Ann Rheum Dis 2016; 75:341-7. [PMID: 25609412 PMCID: PMC4752663 DOI: 10.1136/annrheumdis-2013-204987] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2013] [Revised: 11/04/2014] [Accepted: 11/07/2014] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA). METHODS The incidence of hospitalised myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles. RESULTS There were 37,568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48). CONCLUSIONS In this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.
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Affiliation(s)
- Iris Navarro-Millán
- Birmingham VA Medical Center, Birmingham, Alabama, USA
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Shuo Yang
- Birmingham VA Medical Center, Birmingham, Alabama, USA
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Scott L DuVall
- VA Salt Lake City Health Care System and University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Lang Chen
- Birmingham VA Medical Center, Birmingham, Alabama, USA
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - John Baddley
- Birmingham VA Medical Center, Birmingham, Alabama, USA
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Grant W Cannon
- VA Salt Lake City Health Care System and University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - Elizabeth S Delzell
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Jie Zhang
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Monika M Safford
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Nivedita M Patkar
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Ted R Mikuls
- Omaha VA and University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Jasvinder A Singh
- Birmingham VA Medical Center, Birmingham, Alabama, USA
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
| | - Jeffrey R Curtis
- Birmingham VA Medical Center, Birmingham, Alabama, USA
- University of Alabama at Birmingham Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA
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14
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Horiuchi AC, Pereira LHC, Kahlow BS, Silva MB, Skare TL. Rheumatoid arthritis in elderly and young patients. REVISTA BRASILEIRA DE REUMATOLOGIA 2015; 57:491-494. [PMID: 29037323 DOI: 10.1016/j.rbre.2015.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 06/24/2015] [Indexed: 01/21/2023] Open
Affiliation(s)
- Ariane Carla Horiuchi
- Hospital Universitário Evangélico de Curitiba, Serviço de Reumatologia, Curitiba, PR, Brazil
| | | | - Bárbara Stadler Kahlow
- Hospital Universitário Evangélico de Curitiba, Serviço de Reumatologia, Curitiba, PR, Brazil
| | - Marilia Barreto Silva
- Hospital Universitário Evangélico de Curitiba, Serviço de Reumatologia, Curitiba, PR, Brazil
| | - Thelma L Skare
- Hospital Universitário Evangélico de Curitiba, Serviço de Reumatologia, Curitiba, PR, Brazil.
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15
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Horiuchi AC, Pereira LHC, Kahlow BS, Silva MB, Skare TL. Rheumatoid arthritis in elderly and young patients. REVISTA BRASILEIRA DE REUMATOLOGIA 2015; 57:S0482-5004(15)00125-4. [PMID: 26421887 DOI: 10.1016/j.rbr.2015.06.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 05/07/2015] [Accepted: 06/24/2015] [Indexed: 11/20/2022] Open
Affiliation(s)
- Ariane Carla Horiuchi
- Serviço de Reumatologia, Hospital Universitário Evangélico de Curitiba, Curitiba, PR, Brasil
| | | | - Bárbara Stadler Kahlow
- Serviço de Reumatologia, Hospital Universitário Evangélico de Curitiba, Curitiba, PR, Brasil
| | - Marilia Barreto Silva
- Serviço de Reumatologia, Hospital Universitário Evangélico de Curitiba, Curitiba, PR, Brasil
| | - Thelma L Skare
- Serviço de Reumatologia, Hospital Universitário Evangélico de Curitiba, Curitiba, PR, Brasil.
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16
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Arts EEA, Fransen J, den Broeder AA, Popa CD, van Riel PLCM. The effect of disease duration and disease activity on the risk of cardiovascular disease in rheumatoid arthritis patients. Ann Rheum Dis 2015; 74:998-1003. [PMID: 24458537 DOI: 10.1136/annrheumdis-2013-204531] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 01/03/2014] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Disease duration and disease activity may be associated with an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objectives of this study were to investigate (1) the relationship between duration of inflammation and the development of CVD in RA patients and (2) the relationship between RA disease activity over time and CVD in patients with RA. METHODS RA patients with a follow-up of ≥6 months in the Nijmegen early RA cohort without prior CVD were included. Disease activity over time was calculated using the time-averaged 28 joint disease activity score (DAS28) for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were used for the analyses. RESULTS During follow-up of the 855 patients that were included, 154 CV events occurred. The course of hazards over time did not indicate a change in the risk of CVD over the course of RA (disease duration), which is also reflected by the absence of a deflection in the survival curves. The survival distributions did not differ between patients with a disease duration of <10 years or >10 years (Log-rank test: p=0.82). Time-averaged DAS28 was significantly associated with CVD (p=0.002) after correction for confounders. CONCLUSIONS Disease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.
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Affiliation(s)
- Elke E A Arts
- Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Jaap Fransen
- Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | | | - Calin D Popa
- Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Piet L C M van Riel
- Department of Rheumatology, Radboud University Medical Centre, Nijmegen, The Netherlands
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Nurmohamed M, Bao Y, Signorovitch J, Trahey A, Mulani P, Furst DE. Longer durations of antitumour necrosis factor treatment are associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis. RMD Open 2015; 1:e000080. [PMID: 26535138 PMCID: PMC4612693 DOI: 10.1136/rmdopen-2015-000080] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/23/2015] [Accepted: 04/27/2015] [Indexed: 12/20/2022] Open
Abstract
Objective To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA). Methods We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with ≥1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models. Results Of 113 677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6 months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6 months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged ≥50 years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3 years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively. Conclusions Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.
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Affiliation(s)
- Michael Nurmohamed
- Departments of Internal Medicine and Rheumatology , VU University Medical Centre , Amsterdam , The Netherlands
| | - Yanjun Bao
- Health Economics and Outcomes Research, AbbVie , North Chicago, Illinois , USA
| | | | - Alex Trahey
- The Analysis Group , Boston, Massachusetts , USA
| | - Parvez Mulani
- Health Economics and Outcomes Research, AbbVie , North Chicago, Illinois , USA
| | - Daniel E Furst
- University of California-Los Angeles (UCLA) , Los Angeles, California , USA
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Skeoch S, Bruce IN. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat Rev Rheumatol 2015; 11:390-400. [PMID: 25825281 DOI: 10.1038/nrrheum.2015.40] [Citation(s) in RCA: 217] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Rheumatoid arthritis (RA) has long been associated with increased cardiovascular risk, but despite substantial improvements in disease management, mortality remains high. Atherosclerosis is more prevalent in RA than in the general population, and atherosclerotic lesions progress at a faster rate and might be more prone to rupture, causing clinical events. Cells and cytokines implicated in RA pathogenesis are also involved in the development and progression of atherosclerosis, which is generally recognized as an inflammatory condition. The two diseases also share genetic and environmental risk factors, which suggests that patients who develop RA might also be predisposed to developing cardiovascular disease. In RA, inflammation and atherosclerosis are closely linked. Inflammation mediates its effects on atherosclerosis both through modulation of traditional risk factors and by directly affecting the vessel wall. Treatments such as TNF inhibitors might have a beneficial effect on cardiovascular risk. However, whether this benefit is attributable to effective control of inflammation or whether targeting specific cytokines, implicated in atherosclerosis, provides additional risk reduction is unclear. Further knowledge of the predictors of cardiovascular risk, the effects of early control of inflammation and of drug-specific effects are likely to improve the recognition and management of cardiovascular risk in patients with RA.
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Affiliation(s)
- Sarah Skeoch
- Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Brunswick Street, Manchester M13 9PL, UK
| | - Ian N Bruce
- NIHR Manchester Musculoskeletal Biomedical Research Unit, and Kellgren Centre for Rheumatology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
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Humphreys JH, Warner A, Chipping J, Marshall T, Lunt M, Symmons DPM, Verstappen SMM. Mortality trends in patients with early rheumatoid arthritis over 20 years: results from the Norfolk Arthritis Register. Arthritis Care Res (Hoboken) 2014; 66:1296-301. [PMID: 24497371 PMCID: PMC4226330 DOI: 10.1002/acr.22296] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 01/28/2014] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To examine mortality rates in UK patients with early rheumatoid arthritis (RA) from 1990-2011 and compare with population trends. METHODS The Norfolk Arthritis Register (NOAR) recruited adults with ≥2 swollen joints for ≥4 weeks: cohort 1 (1990-1994), cohort 2 (1995-1999), and cohort 3 (2000-2004). At baseline, serum rheumatoid factor and anti-citrullinated protein antibody were measured and the 2010 American College of Rheumatology/European League Against Rheumatism RA classification criteria were applied. Patients were followed for 7 years, until emigration or death. The UK Office for National Statistics notified the NOAR of the date and cause of deaths, and provided mortality rates for the Norfolk population. All-cause and cardiovascular-specific standardized mortality ratios (SMRs) were calculated. Poisson regression was used to compare mortality rate ratios (MRRs) between cohorts and then, with cubic splines, to model rates by calendar year. Analyses were performed in patients 1) with early inflammatory arthritis, 2) classified as having RA, and 3) autoantibody positive. RESULTS A total of 2,517 patients were included, with 1,639 women (65%) and median age 55 years, and 1,419 (56%) fulfilled the 2010 RA criteria. All-cause and cardiovascular-specific SMRs were significantly elevated in the antibody-positive groups. There was no change in mortality rates over time after accounting for changes in the population rates. In RA patients, all-cause MRRs, compared to cohort 1, were 1.13 (95% confidence interval [95% CI] 0.84-1.52) and 1.00 (95% CI 0.70-1.43) in cohorts 2 and 3, respectively. CONCLUSION Mortality rates were increased in patients with RA and SMRs were particularly elevated in those who were autoantibody positive. Compared to the general population, mortality rates have not improved over the past 20 years.
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Affiliation(s)
- J H Humphreys
- Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
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Arnold MB, Bykerk VP, Boire G, Haraoui BP, Hitchon C, Thorne C, Keystone EC, Pope JE. Are there differences between young- and older-onset early inflammatory arthritis and do these impact outcomes? An analysis from the CATCH cohort. Rheumatology (Oxford) 2014; 53:1075-86. [DOI: 10.1093/rheumatology/ket449] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Kerola AM, Kerola T, Kauppi MJ, Kautiainen H, Virta LJ, Puolakka K, Nieminen TVM. Cardiovascular comorbidities antedating the diagnosis of rheumatoid arthritis. Ann Rheum Dis 2013; 72:1826-9. [PMID: 23178207 DOI: 10.1136/annrheumdis-2012-202398] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
OBJECTIVES To assess the prevalence of coronary heart disease (CHD) and chronic hypertension among patients with rheumatoid arthritis (RA) at the time of diagnosis, in comparison with age-specific and sex-specific non-RA subjects. Furthermore, the impacts of age at the onset of RA, as well as gender and the presence of rheumatoid factor (RF) on the risk of these comorbidities, were evaluated. METHODS A cohort of 7209 RA patients diagnosed between January 2004 and December 2007 was identified, based on a Finnish nationwide register on special reimbursements for medication costs. The presence of CHD and chronic hypertension antedating the diagnosis of RA was identified from the same register. The prevalence of the cardiovascular comorbidities was compared with the general Finnish population, and a standardised rate ratio (SRR) for both these cardiovascular diseases was calculated. RESULTS The risk of having CHD at RA diagnosis was slightly elevated, the SRR being 1.10 (95% CI 1.01 to 1.20). Younger age at the onset of RA seemed to be related with higher SRR for CHD. In a subset analysis, an increased prevalence of hypertension (SRR 1.19, 95% CI 1.10 to 1.30) and CHD (SRR 1.15, 95% CI 1.00 to 1.32) was apparent only among the RF negative RA cases. CONCLUSIONS The SRR for CHD is augmented in RA patients already at disease onset, and more pronouncedly in early onset RA. The findings highlight the importance of early prevention of atherosclerosis, regardless of RF status.
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Affiliation(s)
- Anne M Kerola
- Medical School, University of Helsinki, , Helsinki, Finland
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Ntatsaki E, Mooney J, Scott DGI, Watts RA. Systemic rheumatoid vasculitis in the era of modern immunosuppressive therapy. Rheumatology (Oxford) 2013; 53:145-52. [DOI: 10.1093/rheumatology/ket326] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Postpublication validation of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: where do we stand? Curr Opin Rheumatol 2013; 25:157-63. [PMID: 23274519 DOI: 10.1097/bor.0b013e32835cfc41] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW To summarise the results of the validation studies testing the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) to date and highlight the areas for future research. RECENT FINDINGS The 2010 ACR/EULAR classification criteria for RA were developed aiming to identify patients early in the natural history of the disease. Validation studies conducted since their publication have demonstrated that, compared with the 1987 ACR criteria for RA, the 2010 criteria identify more patients earlier in the disease course. Sensitivity for the initiation of disease-modifying antirheumatic drugs and persistent disease is increased, with decreased specificity. Patients who are seronegative may not satisfy the 2010 criteria despite meeting the 1987 criteria at presentation. The 2010 criteria may also incorrectly classify some patients with self-limiting disease as RA. SUMMARY The 2010 criteria appear to be superior to the 1987 criteria in terms of identifying individuals with early RA. Their validity in established disease and their ability to predict worse prognosis in the long term have yet to be determined.
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van den Oever IAM, van Sijl AM, Nurmohamed MT. Management of cardiovascular risk in patients with rheumatoid arthritis: evidence and expert opinion. Ther Adv Musculoskelet Dis 2013; 5:166-81. [PMID: 23904862 DOI: 10.1177/1759720x13491025] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The risk of cardiovascular morbidity and mortality is increased in rheumatoid arthritis. The classical cardiovascular risk factors, including smoking, hypertension, dyslipidaemia, insulin resistance and diabetes mellitus, obesity and physical inactivity do not appear to explain the excess cardiovascular risk in rheumatoid arthritis, although they do contribute, albeit in a different way or to a lesser extent, to rheumatoid arthritis in comparison with the general population. A very important link between rheumatoid arthritis and cardiovascular disease is inflammation as it plays a key role in all stages of atherosclerosis: from endothelial dysfunction to plaque rupture and thrombosis. It also has an influence on and accentuates some traditional cardiovascular risk factors, such as dyslipidaemia, obesity and insulin resistance. To date, the exact pathophysiologic mechanism by which this relation between cardiovascular disease and rheumatoid arthritis can be explained is not completely clear. Cardiovascular risk management in rheumatoid arthritis is mandatory. Unfortunately, the way this should be done remains a point of discussion. In this review issues regarding cardiovascular risk in rheumatoid arthritis and its management will be addressed, according to evidence presented in the latest studies and our own experience-based opinion.
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Affiliation(s)
- Inge A M van den Oever
- Jan van Breemen Research Institute Reade, Amsterdam, Netherlands and Department of Internal Medicine, VU University Medical Centre, Amsterdam, Netherlands
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26
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Abstract
Rheumatoid arthritis is characterized by early and accelerated atherosclerosis leading to increased cardiovascular morbidity and mortality. Beyond traditional cardiovascular risk factors, several pathogenetic mechanisms have been proposed, including emerging inflammatory and autoimmune mechanisms. Inflammatory stimuli are now believed to cause vascular damage, which can be estimated by well-established noninvasive techniques. Carotid intima-media thickness, pulse-wave velocity and flow-mediated dilatation, markers of subclinical atherosclerosis, arterial stiffness, and endothelial function, respectively, have been recently used to detect vascular dysfunction in the wide spectrum of autoimmune diseases. The role of anti-tumor necrosis factor α and novel biologic agents remains unclear, although early control of the inflammatory process seems crucial for reducing cardiovascular risk. Considering the importance of cardiovascular risk management, further well-designed studies are warranted to clarify the potential benefits and harms of anti-inflammatory treatment.
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Kerola AM, Kauppi MJ, Kerola T, Nieminen TVM. How early in the course of rheumatoid arthritis does the excess cardiovascular risk appear? Ann Rheum Dis 2012; 71:1606-15. [PMID: 22736093 DOI: 10.1136/annrheumdis-2012-201334] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease which is associated with an increased cardiovascular (CV) burden. Whether the risk is already present at the time of RA diagnosis remains a key area of debate. The aim of this review was to evaluate the existence of both subclinical CV changes, including endothelial dysfunction and atherosclerosis, CV risk factors, as well as CV disease manifestations such as coronary heart disease, myocardial infarction, congestive heart failure and CV death prior to RA diagnosis and during the first few years of the disease. The state of the endothelial function remains controversial in patients with newly diagnosed RA. Studies with impaired brachial artery vasodilatory responses at baseline showed a reversal of the dysfunction after 6-12 months of anti-inflammatory therapy. Morphological evidence of arterial wall atherosclerosis, measured by carotid artery intima-media thickness or the prevalence of carotid plaques, was already present during the first year following RA diagnosis. The risk of coronary heart disease and myocardial infarction is increased even prior to and, at the latest, within 1 year of the clinical onset of RA. The prevalence of hypertension was similar among patients with RA and controls. CV mortality may not increase within the first years of RA diagnosis. In conclusion, the CV risk seems to increase sooner after the RA diagnosis than previously thought. In addition to systematic CV risk assessment, patients with early RA might benefit from being targeted with stricter than conventional CV risk prevention and intervention.
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Affiliation(s)
- Anne M Kerola
- Correspondence to Dr Tuomo V M Nieminen, Division of Cardiology, Helsinki University Central Hospital, P O Box 340, Helsinki FI-00029, Finland
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Fairweather D, Petri MA, Coronado MJ, Cooper LT. Autoimmune heart disease: role of sex hormones and autoantibodies in disease pathogenesis. Expert Rev Clin Immunol 2012; 8:269-84. [PMID: 22390491 DOI: 10.1586/eci.12.10] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cardiovascular disease (CVD) and autoimmune diseases (ADs) are the first and third highest causes of death in the USA, respectively. Men have an increased incidence of the majority of CVDs, including atherosclerosis, myocarditis, dilated cardiomyopathy and heart failure. By contrast, nearly 80% of all ADs occur in women. However, in one category of ADs, rheumatic diseases, CVD is the main cause of death. Factors that link rheumatic ADs to CVD are inflammation and the presence of autoantibodies. In this review we will examine recent findings regarding sex differences in the immunopathogenesis of CVD and ADs, explore possible reasons for the increased occurrence of CVD within rheumatic ADs and discuss whether autoantibodies, including rheumatoid factor, could be involved in disease pathogenesis.
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Affiliation(s)
- DeLisa Fairweather
- Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
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29
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Feeny D, Huguet N, McFarland BH, Kaplan MS, Orpana H, Eckstrom E. Hearing, mobility, and pain predict mortality: a longitudinal population-based study. J Clin Epidemiol 2012; 65:764-77. [PMID: 22521576 DOI: 10.1016/j.jclinepi.2012.01.003] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Revised: 01/08/2012] [Accepted: 01/22/2012] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Measures of health-related quality of life (HRQL), including the Health Utilities Index Mark 3 (HUI3) are predictive of mortality. HUI3 includes eight attributes, vision, hearing, speech, ambulation, dexterity, cognition, emotion, and pain and discomfort, with five or six levels per attribute that vary from no to severe disability. This study examined associations between individual HUI3 attributes and mortality. STUDY DESIGN AND SETTING Baseline data and 12 years of follow-up data from a closed longitudinal cohort study, the 1994/95 Canadian National Population Health Survey, consisting of 12,375 women and men aged 18 and older. A priori hypotheses were that ambulation, cognition, emotion, and pain would predict mortality. Cox proportional hazards regression models were applied controlling for standard determinants of health and risk factors. RESULTS Single-attribute utility scores for ambulation (hazard ratio [HR]=0.10; 0.04-0.22), hearing (HR=0.18; 0.06-0.57), and pain (HR=0.53; 0.29-0.96) were statistically significantly associated with an increased risk of mortality; ambulation and hearing were predictive for the 60+ cohort. CONCLUSION Few studies have identified hearing or pain as risk factors for mortality. This study is innovative because it identifies specific components of HRQL that predict mortality. Further research is needed to understand better the mechanisms through which deficits in hearing and pain affect mortality risks.
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Affiliation(s)
- David Feeny
- Kaiser Permanente Northwest Center for Health Research, Portland, OR 97204-1030, USA.
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30
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Mirjafari H, Farragher TM, Verstappen SMM, Yates A, Bunn D, Marshall T, Lunt M, Symmons DPM, Bruce IN. Seropositivity is associated with insulin resistance in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register (NOAR): an observational study. Arthritis Res Ther 2011; 13:R159. [PMID: 21959060 PMCID: PMC3308090 DOI: 10.1186/ar3476] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Revised: 08/24/2011] [Accepted: 09/29/2011] [Indexed: 12/28/2022] Open
Abstract
Introduction Cardiovascular disease (CVD) is the leading cause of death in patients with inflammatory polyarthritis (IP), especially in seropositive disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is increased and associated with CVD. We investigated factors associated with IR in an inception cohort of patients with early IP. Methods Patients with early IP (two or more swollen joints for four or more weeks), aged 18 to 65 years, seen within 24 months of symptom onset were recruited from the Norfolk Arthritis Register (NOAR), a primary-care-based inception cohort. Assessment included joint examination, current and prior therapy and completion of the Health Assessment Questionnaire. Fasting blood was taken for measurement of CVD risk factors, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), C-reactive protein (CRP), and insulin levels. IR was calculated using the homeostatic model assessment (HOMA-IR). We examined factors associated with IR using univariate and multivariable linear regression models. Results A total of 196 patients, including 59 (30%) males, were studied with a median (interquartile range, IQR) age and IP symptom duration of 49 (40 to 57) years and 6.7 (4.6 to 10.7) months, respectively. After age and gender adjustment, HOMA-IR was associated with obesity, (β-Coefficient (95% CI); 1.60 (0.96, 2.24)), higher systolic and diastolic blood pressure (0.03 (0.01, 0.05) and 0.04 (0.01, 0.08) respectively), triglycerides (1.06 (0.54, 1.57)), and HDL (-1.38 (-2.17,-0.58)). HOMA-IR was associated with serological status and this association persisted after adjustment for classic CVD risk factors and other IP-related variables (RF β-Coefficient (95% CI); 0.87 (0.20, 1.53) and ACPA β-Coefficient (95% CI); 1.42 (0.70, 2.15)). Conclusions Seropositivity for RF or ACPA was associated with IR in this early IP cohort. This association may, in part, explain why seropositive patients have excess CVD mortality.
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Affiliation(s)
- Hoda Mirjafari
- Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Sciences Centre, Oxford Road, Manchester, M13 9PT, UK
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Verstappen SM, Symmons DP. What is the outcome of RA in 2011 and can we predict it? Best Pract Res Clin Rheumatol 2011; 25:485-96. [DOI: 10.1016/j.berh.2011.10.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Symmons DPM, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol 2011; 7:399-408. [PMID: 21629241 DOI: 10.1038/nrrheum.2011.75] [Citation(s) in RCA: 277] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The excess risk of cardiovascular disease (CVD) associated with inflammatory rheumatic diseases has long been recognized. Patients with established rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) have higher mortality compared with the general population. Over 50% of premature deaths in RA are attributable to CVD. Excess mortality in SLE follows a bimodal pattern, with the early peak predominantly a consequence of active lupus or its complications, and the later peak largely attributable to atherosclerosis. Patients with RA or SLE are also at increased risk of nonfatal ischemic heart disease. The management and outcome of myocardial infarction and congestive heart failure in patients with RA or SLE differs from that in the general population. Traditional CVD risk factors (TRF) include increasing age, male gender, smoking, hypertension, hypercholesterolemia and diabetes. Whereas some TRFs are elevated in patients with RA or SLE, several are not, and others exhibit paradoxical relationships. Risk scores developed for the general population based on TRFs are likely, therefore, to underestimate CVD risk in RA and SLE. Until additional research and disease-specific risk prediction tools are available, current evidence supports aggressive treatment of disease activity, and careful screening for and management of TRFs.
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Affiliation(s)
- Deborah P M Symmons
- Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Center, University of Manchester, Oxford Road, Manchester M13 0PT, UK. deborah.symmons@ manchester.ac.uk
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33
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Crowson CS, Gabriel SE. Towards improving cardiovascular risk management in patients with rheumatoid arthritis: the need for accurate risk assessment. Ann Rheum Dis 2011; 70:719-21. [PMID: 21345812 PMCID: PMC3907170 DOI: 10.1136/ard.2010.145482] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Cynthia S. Crowson
- Department of Health Sciences Research, Mayo Clinic, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Sherine E. Gabriel
- Department of Health Sciences Research, Mayo Clinic, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
- Division of Rheumatology, Mayo Clinic, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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34
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35
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Sander O. [The safety of biologics : a risk-benefit assessment of treating rheumatoid arthritis with biologics based on registry data on mortality]. Z Rheumatol 2010; 69:788-94. [PMID: 21063827 DOI: 10.1007/s00393-010-0641-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The aim of this study is a risk-benefit assessment of treating rheumatoid arthritis with biologics based on registry data on mortality.UK, Sweden and Spain have published evaluable data on mortality. A parallel control group was conducted in the UK. Sweden and Spain used an historical cohort for comparison.Central registries supported British and Swedish research by sending details on all deaths. The variety of possible confounders prevents direct comparisons of the registers and safe predictions for individual patients.The death rate in TNF-inhibitor-treated patients is higher than in the general population but lower than in the control groups with RA. Thus comorbidities are not balanced, the weighted mortality rate scaled down the difference between exposed patients and controls. When TNF-inhibitors are given for the usual indication, mortality is reduced compared to conventional therapy.
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Affiliation(s)
- O Sander
- Klinik für Endokrinologie, Diabetologie und Rheumatologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf.
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36
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Franklin J, Farragher TM, Lunt M, Camacho EM, Bunn D, Marshall T, Symmons DPM. Excess risk of hospital admission for cardiovascular disease within the first 7 years from onset of inflammatory polyarthritis. Ann Rheum Dis 2010; 69:1660-4. [PMID: 20498206 PMCID: PMC2938882 DOI: 10.1136/ard.2009.121871] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2010] [Indexed: 11/06/2022]
Abstract
OBJECTIVES SUBJECTS with rheumatoid factor positive inflammatory polyarthritis (IP) are known to have increased mortality from cardiovascular disease (CVD). A study was undertaken to examine the risk and baseline predictors of admission with CVD in patients with recent-onset IP. METHODS Subjects are recruited by the Norfolk Arthritis Register if they present to primary or secondary care with > or =2 swollen joints lasting > or =4 weeks. This analysis includes subjects recruited between 1995 and 1999. Baseline data on lifestyle, demographic characteristics, disease and treatment characteristics were collected. CVD admissions were identified through record linkage with the only acute care hospital in the study region. First-episode hospitalisation rates were compared with those of the general population. Poisson regression was used to calculate the relative risk (RR) of admission for patients with IP (overall and for each risk factor). Death certificates were obtained from the national death register. RESULTS 800 patients with recent-onset IP were followed for a median of 7.0 years. 64 CVD-related hospitalisations were observed (11.7 per 1000 person-years). Patients with IP were twice as likely (RR=2.0; 95% CI 1.5 to 2.5) to be hospitalised for CVD as the general population. Difficulty walking at baseline was a significant predictor of CVD admission and baseline non-steroidal anti-inflammatory drug use was associated with a reduced risk of CVD admission. CONCLUSIONS Patients with IP are at increased risk of CVD-related hospitalisation, within 7 years of symptom onset. Informing patients about lifestyle modification may reduce the risk of CVD.
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Affiliation(s)
- Jarrod Franklin
- arc Epidemiology Unit, The University of Manchester, Manchester, UK
| | | | - Mark Lunt
- arc Epidemiology Unit, The University of Manchester, Manchester, UK
| | | | - Diane Bunn
- arc Epidemiology Unit, The University of Manchester, Manchester, UK
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
| | - Tarnya Marshall
- Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
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37
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Bartoloni E, Alunno A, Bistoni O, Gerli R. How early is the atherosclerotic risk in rheumatoid arthritis? Autoimmun Rev 2010; 9:701-7. [DOI: 10.1016/j.autrev.2010.06.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2010] [Accepted: 06/02/2010] [Indexed: 12/25/2022]
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Mikuls TR, Fay BT, Michaud K, Sayles H, Thiele GM, Caplan L, Johnson D, Richards JS, Kerr GS, Cannon GW, Reimold A. Associations of disease activity and treatments with mortality in men with rheumatoid arthritis: results from the VARA registry. Rheumatology (Oxford) 2010; 50:101-9. [PMID: 20659916 DOI: 10.1093/rheumatology/keq232] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES To examine the all-cause mortality rate and factors associated with mortality in US veteran men with RA. METHODS Men with RA were enrolled and followed until death or censoring. Vital status was ascertained through systematic record review and standardized mortality ratios (SMRs) were calculated using US life tables for men. Multivariate Cox proportional hazards regression was used to examine the independent associations of patient factors including socio-demographics, comorbidity, measures of RA disease activity/severity and medication use with mortality. Measures of RA disease activity and medications were examined as time-varying factors. RESULTS A total of 138 deaths were observed during 2314 patient-years of follow-up (n=1015 patients), corresponding to a crude morality rate of 5.9 deaths per 100 patient-years (95% CI 5.0, 7.0) and an SMR of 2.1 (95% CI 1.8, 2.5). After multivariate adjustment, factors independently associated with higher mortality risk in men with RA included older age, Caucasian race, low body weight, an increased frequency of rheumatology visits, higher ESR and RF concentrations, increased DAS28, subcutaneous nodules and prednisone use. In contrast, MTX use [hazard ratio (HR) 0.63; 95% CI 0.42, 0.96] was associated with ∼40% lower mortality risk. CONCLUSION Mortality rates among US male veterans with RA are more than twice those of age-matched men in the general population. These results suggest that optimizing disease control, particularly with regimens that include MTX and minimize glucocorticoid exposure, could improve long-term survival in this population.
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Affiliation(s)
- Ted R Mikuls
- Department of Medicine, Omaha Veterans Affairs Medical Center (VAMC), University of Nebraska, Omaha, NE 68198-6270, USA.
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Soubrier M, Mathieu S, Bruckert E. Risque cardiovasculaire en rhumatologie : critères et scores. ACTA ACUST UNITED AC 2010. [DOI: 10.1016/j.monrhu.2010.01.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Crilly MA, Clark HJ, Kumar V, Scott NW, MacDonald AG, Williams DJ. Relationship between arterial stiffness and Stanford Health Assessment Questionnaire disability in rheumatoid arthritis patients without overt arterial disease. J Rheumatol 2010; 37:946-52. [PMID: 20231203 DOI: 10.3899/jrheum.091052] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVE To quantify the relationship between Stanford Health Assessment Questionnaire (HAQ) disability and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS A consecutive series of 114 patients with RA but without overt arterial disease, aged 40-65 years, were recruited from rheumatology clinics. A research nurse measured blood pressure (BP), arterial stiffness (heart rate-adjusted augmentation index), fasting lipids, glucose, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). A self-completed patient questionnaire included HAQ, damaged joint count, EuroQol measure of health outcome, and Godin physical activity score. Multiple linear regression (MLR) adjusted for age, sex, smoking pack-years, cholesterol, mean arterial BP, physical activity, daily fruit and vegetable consumption, arthritis duration, ESR, and RA criteria. RESULTS Mean age was 54 years (81% women) with a median HAQ of 1.13 (interquartile range 0.50; 1.75). Median RA duration was 10 years, 83% were RF-positive, and median ESR was 16 mm/h. Mean arterial stiffness was 31.5 (SD 7.7), BP 125/82 mm Hg, cholesterol 5.3 mmol/l, and 24% were current smokers. Current therapy included RA disease-modifying agents (90%), prednisolone (11%), and antihypertensive therapy (18%). Arterial stiffness was positively correlated with HAQ (r = 0.42; 95% CI 0.25 to 0.56). On MLR, a 1-point increase in HAQ disability was associated with a 2.8 increase (95% CI 1.1 to 4.4; p = 0.001) in arterial stiffness. Each additional damaged joint was associated with a 0.17 point increase (95% CI 0.04 to 0.29; p = 0.009) in arterial stiffness. The relationship between EuroQol and arterial stiffness was not statistically significant. CONCLUSION In patients with RA who are free of overt arterial disease, higher RA disability is associated with increased arterial stiffness independently of traditional cardiovascular risk factors and RA characteristics.
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Affiliation(s)
- Michael A Crilly
- Institute of Applied Health Sciences, Section of Population Health, Aberdeen University Medical School, Aberdeen, Scotland.
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41
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Peters MJL, Symmons DPM, McCarey D, Dijkmans BAC, Nicola P, Kvien TK, McInnes IB, Haentzschel H, Gonzalez-Gay MA, Provan S, Semb A, Sidiropoulos P, Kitas G, Smulders YM, Soubrier M, Szekanecz Z, Sattar N, Nurmohamed MT. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010; 69:325-31. [PMID: 19773290 DOI: 10.1136/ard.2009.113696] [Citation(s) in RCA: 1031] [Impact Index Per Article: 68.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVES To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. RESULTS Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. CONCLUSIONS Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.
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Affiliation(s)
- M J L Peters
- Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands
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John H, Kitas G, Toms T, Goodson N. Cardiovascular co-morbidity in early rheumatoid arthritis. Best Pract Res Clin Rheumatol 2009; 23:71-82. [DOI: 10.1016/j.berh.2008.11.007] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Abstract
PURPOSE OF REVIEW Our aim was to review recent studies that address the increased risk of atherosclerosis and coronary heart disease in patients with rheumatoid arthritis and systemic lupus erythematosus. We examine the strength of this association, how inflammation mediates this increased risk and what impact therapies may have. RECENT FINDINGS Atherosclerosis is more prevalent and accelerated in both conditions. Indeed the process may actually precede the onset of clinical inflammatory disease. Metabolic alterations include insulin resistance and the generation of proinflammatory HDL. In addition, inflammatory mechanisms central to both rheumatoid arthritis and systemic lupus erythematosus such as macrophage activation, interferon-1 and complement deficiency may contribute to atherogenesis. There is still no consensus as to the value of primary preventive strategies in these conditions. However, drugs such as hydroxychloroquine seem to modify coronary heart disease risk and may improve survival. The recently developed antitumour necrosis factor drugs may also reduce coronary heart disease risk but biomarker studies to date have been inconclusive. SUMMARY There is an urgent need for clinical trials to examine both the lipid-lowering and inflammatory hypotheses of atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Novel targeted therapies in development may also have a major impact on future coronary heart disease risk in these conditions.
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Affiliation(s)
- Sahena Haque
- arc Epidemiology Unit, School of Translational Medicine, The University of Manchester, UK
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