C-Reactive Protein-to-Albumin Ratio: A Novel Inflammatory Marker and Disease Activity Sign in Early Rheumatoid Arthritis

Abstract

Objective A novel inflammation-based score, C-reactive protein (CRP)-to-albumin ratio (CAR), has been shown to have an association with the inflammatory status in several diseases. We aimed to analyse the association between CAR and disease activity in patients with early rheumatoid arthritis (RA) and to determine the cut-off value of CAR in early and established RA.

Methods A total of 177 patients with RA and 111 age and gender-matched healthy controls were included in this study. Cases with a disease duration of less than 1 year were classified as early RA. Serum albumin, CRP, erythrocyte sedimentation rate (ESR), Disease Activity Score-28 (DAS-28-ESR), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores were recorded.

Results CAR was 2.44 (0.21–30.83) in the RA group and 0.45 (0.21–10.47) in the control group (p<0.001). Eighty-seven (49.15%) of the RA cases were classified as early RA. The analyses indicated that the ESR, CRP and CAR values were higher in patients with early RA than in those with established RA and controls. CAR was correlated with albumin, CRP, ESH, DAS-28 and HAQ scores in both early RA and established RA groups. The receiver operating characteristic curves revealed a CAR cut-off value of 2.67 (80% sensitivity and 85% specificity) and 1.63 (77% sensitivity and 72% specificity) for the prediction of early and established RA, respectively.

Conclusion CAR, a formulated ratio, has been described as a predictor for disease activity in patients with early RA as well as in those with established RA. However, CAR has higher sensitivity and specificity for early RA than for established RA.

Zusammenfassung

Ziel der Arbeit Das C-reaktive Protein (CRP)-zu-Albumin-Verhältnis (CAR), ein neuartiger entzündungsbasierter Score, zeigte eine Korrelation mit dem Entzündungsstatus bei verschiedenen Krankheiten. Unser Ziel war es, die Assoziation zwischen CAR und Krankheitsaktivität bei Patienten mit früher rheumatoider Arthritis (RA) zu analysieren und den cut-off-Wert von CAR bei früher und etablierter RA zu bestimmen.

Methoden Insgesamt wurden 177 Patienten mit RA zu 111 alters- und geschlechtsgematchten gesunden Personen in diese Studie aufgenommen. Fälle mit einer Krankheitsdauer von weniger als 1 Jahr wurden als frühe RA klassifiziert. Die Werte für Serumalbumin, CRP, Erythrozytensedimentationsrate (ESR), Disease Activity Score-28 (DAS-28-ESR), Clinical Disease Activity Index (CDAI) und Health Assessment Questionnaire (HAQ) wurden aufgezeichnet.

Ergebnisse CAR war 2,44 (0,21–30,83) in der RA-Gruppe und 0,45 (0,21–10,47) in der Kontrollgruppe (p<0,001). Siebenundachtzig (49,15%) der RA-Fälle wurden als frühe RA klassifiziert. Die Analysen zeigten, dass die ESR-, CRP- und CAR-Werte der Patienten mit früher RA höher waren als die der Patienten mit etablierter RA und die der Kontrollpersonen. CAR korrelierte mit Albumin, CRP, ESH, DAS-28 und HAQ-Scores sowohl in den Gruppen mit früher RA als auch mit etablierter RA. Die Empfängerkennlinien ergaben einen cut-off-Wert für CAR von 2,67 (80% Sensitivität und 85% Spezifität) und von 1,63 (77% Sensitivität und 72% Spezifität) für die Vorhersage einer frühen bzw. etablierten RA.

Schlussfolgerung CAR, ein formulierter Quotient, wird als Vorhersagewert für die Krankheitsaktivität sowohl bei Patienten mit früher RA als auch bei Patienten mit etablierter RA beschrieben. CAR hat jedoch eine höhere Sensitivität und Spezifität für frühe RA als für etablierte RA.

Key words

C-reactive protein - albumin - inflammation - rheumatoid arthritis

Schlüsselwörter

C-reaktives Protein - albumin - entzündung - rheumatoide arthritis

Publication History

Article published online:
12 November 2021

• References

• 1 Firestein GS, McInnes IB. Immunopathogenesis of Rheumatoid Arthritis. Immunity 2017; 46: 183-196 DOI: 10.1016/j.immuni.2017.02.006.
• 2 Chen S, Ying H, Du J. et al. The association between albumin-dNLR score and disease activity in patients with rheumatoid arthritis. J Clin Lab Anal 2019; 33: e22695 DOI: 10.1002/jcla.22695.
• 3 Afifi N, Medhat BM, Abdel Ghani AM. et al. Value of Albumin-Fibrinogen Ratio and CRP-Albumin Ratio as Predictor Marker of Disease Activity in Egyptian RA Patients, Correlated with Musculoskeletal Sonography. Open Access Rheumatol 2020; 12: 241-248 DOI: 10.2147/OARRR.S268668.
• 4 Yang WM, Zhang WH, Ying HQ. et al. Two new inflammatory markers associated with disease activity score-28 in patients with rheumatoid arthritis: Albumin to fibrinogen ratio and C-reactive protein to albumin ratio. Int Immunopharmacol 2018; 62: 293-298 DOI: 10.1016/j.intimp.2018.07.007.
• 5 Hobbs KF, Cohen MD. Rheumatoid arthritis disease measurement: a new old idea. Rheumatology (Oxford) 2012; 51: vi21-vi27 DOI: 10.1093/rheumatology/kes282.
• 6 Mercan R, Bitik B, Tufan A. et al. The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheumatoid Arthritis and Ankylosing Spondylitis. J Clin Lab Anal 2016; 30: 597-601 DOI: 10.1002/jcla.21908.
• 7 Kisacik B, Tufan A, Kalyoncu U. et al. Mean platelet volume (MPV) as an inflammatory marker in ankylosing spondylitis and rheumatoid arthritis. Joint Bone Spine 2008; 75: 291-294 DOI: 10.1016/j.jbspin.2007.06.016.
• 8 Kinoshita H, Watanabe K, Azma T. et al. Human serum albumin and oxidative stress in preeclamptic women and the mechanism of albumin for stress reduction. Heliyon 2017; 3: e00369 DOI: 10.1016/j.heliyon.2017.e00369.
• 9 Tominaga T, Nonaka T, Sumida Y. et al. The C-Reactive Protein to Albumin Ratio as a Predictor of Severe Side Effects of Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients. PLoS One 2016; 11: e0167967 DOI: 10.1371/journal.pone.0167967.
• 10 Ishizuka M, Nagata H, Takagi K. et al. Clinical Significance of the C-Reactive Protein to Albumin Ratio for Survival After Surgery for Colorectal Cancer. Ann Surg Oncol 2016; 23: 900-907 DOI: 10.1245/s10434-015-4948-7.
• 11 Juhász P, Mester A, Biró AJ. et al. Clinical and radiological dissociation of anti-TNF plus methotrexate treatment in early rheumatoid arthritis in routine care: results from the ABRAB study. BMC Musculoskelet Disord 2014; 15: 251 DOI: 10.1186/1471-2474-15-251.
• 12 Nam JL, Catrina AI, Emery P. Early Arthritis. In: JW Bijlsma, Hachulla E (eds) EULAR Textbook on Rheumatic Diseases. 2nd edn. London: BMJ Publishing Group; 2015: 265-275
• 13 van der Heijde DM, van’t Hof M, van Riel PL. et al. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol 1993; 20: 579-581
• 14 Prevoo ML, van’t Hof MA, Kuper HH. et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 44-48 DOI: 10.1002/art.1780380107.
• 15 Aletaha D, Nell VP, Stamm T. et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score. Arthritis Res Ther 2005; 7: R796-R806 DOI: 10.1186/ar1740. Epub 2005 Apr 7. PMID: 15987481; PMCID: PMC1175030.
• 16 Greenwood MC, Doyle DV, Ensor M. Does the Stanford Health Assessment Questionnaire have potential as a monitoring tool for subjects with rheumatoid arthritis?. Ann Rheum Dis 2001; 60: 344-348 DOI: 10.1136/ard.60.4.344.
• 17 Singh HV, Shrivastava AK, Raizada A. et al. Atherogenic lipid profile and high sensitive C-reactive protein in patients with rheumatoid arthritis. Clin Biochem 2013; 46: 1007-1012 DOI: 10.1016/j.clinbiochem.2013.03.023.
• 18 Hayashi H, Satoi K, Sato-Mito N. et al. Nutritional status in relation to adipokines and oxidative stress is associated with disease activity in patients with rheumatoid arthritis. Nutrition 2012; 28: 1109-1114 DOI: 10.1016/j.nut.2012.02.009.
• 19 Byeon HJ, Min SY, Kim I. et al. Human serum albumin-TRAIL conjugate for the treatment of rheumatoid arthritis. Bioconjug Chem 2014; 25: 2212-2221 DOI: 10.1021/bc500427g.
• 20 Ishizuka M, Nagata H, Takagi K. et al. Clinical Significance of the C-Reactive Protein to Albumin Ratio for Survival After Surgery for Colorectal Cancer. Ann Surg Oncol 2016; 23: 900-907 DOI: 10.1245/s10434-015-4948-7.
• 21 Kinoshita A, Onoda H, Imai N. et al. The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma. Ann Surg Oncol 2015; 22: 803-810 DOI: 10.1245/s10434-014-4048-0.
• 22 Sen D, Brasington R. Tight disease control in early RA. Rheum Dis Clin North Am 2012; 38: 327-343 DOI: 10.1016/j.rdc.2012.04.004.
• 23 Buzatu C, Moots RJ. Measuring disease activity and response to treatment in rheumatoid arthritis. Expert Rev Clin Immunol 2019; 15: 135-145 DOI: 10.1080/1744666X.2019.1559050.
• 24 Castrejon I. Evaluation and monitoring of established rheumatoid arthritis. Best Practice & Research Clinical Rheumatology 2019; 33: 101480 DOI: 10.1016/j.berh.2019.101480.
• 25 Hammer HB, Michelsen B, Provan SA. et al. Tender Joint Count and Inflammatory Activity in Patients With Established Rheumatoid Arthritis: Results From a Longitudinal Study. Arthritis Care Res (Hoboken) 2020; 72: 27-35 DOI: 10.1002/acr.23815.