{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:53:36Z","timestamp":1790351616063,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic inflammatory disorder that leads to joint damage, cartilage and bone destruction, and functional disability. The C-Reactive Protein to Albumin Ratio (CAR), an emerging biomarker reflecting systemic inflammation and nutritional status, has demonstrated prognostic value in various diseases. However, its utility in predicting clinical outcomes in RA patients remains underexplored, warranting further investigation to assess its potential role in disease management and prognosis. This cross-sectional study investigates the potential relationship between CAR and RA in United States adults, develops a clinical prediction model, and validates its effectiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the association between the CAR and RA using data from the National Health and Nutrition Examination Survey (NHANES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This large-scale, cross-sectional study analyzed data from the NHANES database between 1999 and 2018 (excluding 2011\u20132014). The CAR was calculated as the ratio of C-reactive protein (CRP) to albumin (ALB) levels. RA status was identified through self-reported questionnaire data. Weighted multivariate regression models and subgroup analyses were used to examine the association between CAR and RA. Restricted cubic splines (RCS) were employed to evaluate potential non-linear relationships, and sensitivity analyses were conducted to assess the robustness of the results. Least absolute shrinkage and selection operator (LASSO) were utilized for variable selection in the prediction model. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curve analysis were applied to assess the predictive performance of the models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study included a total of 20,733 patients, among whom 1,744 individuals (4.95%) were diagnosed with RA. After controlling for all covariates, the results of multivariate logistic regression analysis indicated a statistically significant correlation between higher Ln(CAR) levels and the increased incidence of RA (OR:1.77 (95% CI, 1.39\u20132.25); <jats:italic>p<\/jats:italic> &amp;lt; 0.001). The interaction test results showed that there was no statistically significant influence in this specific association. RCS regression modeling demonstrated a linear relationship between Ln-CAR and RA risk. After variable screening, we constructed an RA prediction model incorporating CAR, and the results were visualized using a nomogram. The area under the curve (AUC) was 0.749 (95% CI, 0.738\u20130.760), and DCA indicated that the model holds clinical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that CAR may serve as a promising inflammatory biomarker for predicting the presence of RA. In the RA prediction model incorporating CAR, we validated the effectiveness and clinical utility of this model, providing evidence that CAR can serve as a biomarker for RA risk prediction. Further prospective studies are warranted to validate its clinical utility in RA risk stratification and management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1624527","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T05:24:17Z","timestamp":1752816257000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The C-reactive protein-to-albumin ratio as a diagnostic biomarker for rheumatoid arthritis: a cross-sectional NHANES analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis.","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis.","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1007\/s10198-007-0088-8","article-title":"The burden of rheumatoid arthritis and access to treatment: Health burden and costs.","volume":"8","author":"Lundkvist","year":"2008","journal-title":"Eur J Health Econ."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1136\/annrheumdis-2019-215920","article-title":"Global, regional and national burden of rheumatoid arthritis 1990-2017: A systematic analysis of the Global burden of disease study 2017.","volume":"78","author":"Safiri","year":"2019","journal-title":"Ann Rheum Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"551","DOI":"10.7326\/0003-4819-93-4-551","article-title":"Work disability in rheumatoid arthritis: Effects of disease, social, and work factors.","volume":"93","author":"Yelin","year":"1980","journal-title":"Ann Intern Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"259","DOI":"10.5114\/ceji.2017.70968","article-title":"Autoantibodies, C-reactive protein, erythrocyte sedimentation rate and serum cytokine profiling in monitoring of early treatment.","volume":"42","author":"Brzustewicz","year":"2017","journal-title":"Cent Eur J Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis.","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA."},{"key":"B8","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.pop.2018.02.010","article-title":"Early diagnosis and treatment of rheumatoid arthritis.","volume":"45","author":"Littlejohn","year":"2018","journal-title":"Prim Care Clin Off Pract."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e13877","DOI":"10.1111\/eci.13877","article-title":"Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio and disease activity in rheumatoid arthritis: A systematic review and meta-analysis.","volume":"53","author":"Zinellu","year":"2023","journal-title":"Eur J Clin Invest."},{"key":"B10","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13075-023-03018-6","article-title":"The association between systemic immune-inflammation index and rheumatoid arthritis: evidence from NHANES 1999-2018.","volume":"25","author":"Liu","year":"2023","journal-title":"Arthritis Res Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"754","DOI":"10.3389\/fimmu.2018.00754","article-title":"Role of C-reactive protein at sites of inflammation and infection.","volume":"9","author":"Sproston","year":"2018","journal-title":"Front Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.jhep.2014.04.012","article-title":"Human serum albumin, systemic inflammation, and cirrhosis.","volume":"61","author":"Arroyo","year":"2014","journal-title":"J Hepatol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3390\/tropicalmed7080186","article-title":"C-reactive protein-to-albumin ratio and clinical outcomes in COVID-19 patients: A systematic review and meta-analysis.","volume":"7","author":"Zavalaga-Zegarra","year":"2022","journal-title":"Trop Med Infect Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e0132109","DOI":"10.1371\/journal.pone.0132109","article-title":"The C-reactive protein\/albumin ratio as an independent predictor of mortality in patients with severe sepsis or septic shock treated with early goal-directed therapy.","volume":"10","author":"Kim","year":"2015","journal-title":"PLoS One."},{"key":"B15","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1515\/biol-2021-0011","article-title":"Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive c-reactive protein to albumin ratio and fibrinogen to albumin ratio.","volume":"16","author":"Luo","year":"2021","journal-title":"Open Life Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.3389\/fneur.2019.01186","article-title":"C-Reactive protein\/albumin ratio correlates with disease severity and predicts outcome in patients with aneurysmal subarachnoid hemorrhage.","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.intimp.2018.07.007","article-title":"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.","volume":"62","author":"Yang","year":"2018","journal-title":"Int Immunopharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2959","DOI":"10.1007\/s10067-023-06703-8","article-title":"Is the C-reactive protein-to-albumin ratio the most remarkable simple inflammatory marker showing active disease in patients with axial spondyloarthritis, psoriatic arthritis, and rheumatoid arthritis?","volume":"42","author":"Kaplan","year":"2023","journal-title":"Clin Rheumatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ypmed.2015.08.014","article-title":"Dose\u2013response association of moderate-to-vigorous physical activity with cardiovascular biomarkers and all-cause mortality: Considerations by individual sports, exercise and recreational physical activities.","volume":"81","author":"Loprinzi","year":"2015","journal-title":"Prev Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.intimp.2016.04.006","article-title":"Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus.","volume":"36","author":"Wu","year":"2016","journal-title":"Int Immunopharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1471-2474-10-41","article-title":"Disease activity level, remission and response in established rheumatoid arthritis: Performance of various criteria sets in an observational cohort, treated with anti-TNF agents.","volume":"10","author":"Gulfe","year":"2009","journal-title":"BMC Musculoskelet Disord."},{"key":"B22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3810\/pgm.1998.02.310","article-title":"Laboratory testing for systemic rheumatic diseases.","volume":"103","author":"Ward","year":"1998","journal-title":"Postgrad Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/jcla.21908","article-title":"The association between neutrophil-to-lymphocyte ratio and disease activity in rheumatoid arthritis.","volume":"30","author":"Liu","year":"2015","journal-title":"J Clin Lab Anal."},{"key":"B24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1097\/00002281-200005000-00007","article-title":"Markers of disease in rheumatoid arthritis.","volume":"12","author":"Wollheim","year":"2000","journal-title":"Curr Opin Rheumatol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.3389\/fimmu.2020.01613","article-title":"HLA-G expressing immune cells in immune mediated diseases.","volume":"11","author":"Contini","year":"2020","journal-title":"Front Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e0167967","DOI":"10.1371\/journal.pone.0167967","article-title":"The C-reactive protein to albumin ratio as a predictor of severe side effects of adjuvant chemotherapy in stage III colorectal cancer patients.","volume":"11","author":"Tominaga","year":"2016","journal-title":"PLoS One."},{"key":"B27","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1245\/s10434-015-4948-7","article-title":"Clinical significance of the C-reactive protein to albumin ratio for survival after surgery for colorectal cancer.","volume":"23","author":"Ishizuka","year":"2016","journal-title":"Ann Surg Oncol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"757123","DOI":"10.1155\/2014\/757123","article-title":"C-reactive protein and coronary heart disease: All said\u2013is not it?","volume":"2014","author":"Strang","year":"2014","journal-title":"Mediators Inflamm."},{"key":"B29","doi-asserted-by":"publisher","first-page":"s18","DOI":"10.2450\/2013.005s","article-title":"Clinical use of albumin.","volume":"11","author":"Caraceni","year":"2013","journal-title":"Blood Transfus."},{"key":"B30","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1475-2891-9-69","article-title":"Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature.","volume":"9","author":"Gupta","year":"2010","journal-title":"Nutr J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.jhep.2020.08.021","article-title":"On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites.","volume":"74","author":"Caraceni","year":"2021","journal-title":"J Hepatol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.23736\/S0375-9393.19.13625-5","article-title":"Prognostic value of C-reactive protein\/albumin ratio in neurocritically Ill patients.","volume":"85","author":"Bai","year":"2019","journal-title":"Minerva Anestesiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1186\/s12885-017-3220-x","article-title":"The prognostic value of the preoperative C-reactive protein\/albumin ratio in ovarian cancer.","volume":"17","author":"Liu","year":"2017","journal-title":"BMC Cancer."},{"key":"B34","doi-asserted-by":"publisher","first-page":"20573","DOI":"10.1038\/s41598-024-71754-z","article-title":"Association between the C-reactive protein to albumin ratio with asthma and mortality in adult: A population-based study.","volume":"14","author":"You","year":"2024","journal-title":"Sci Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e59321","DOI":"10.1371\/journal.pone.0059321","article-title":"C-reactive protein\/albumin ratio predicts 90-day mortality of septic patients.","volume":"8","author":"Ranzani","year":"2013","journal-title":"PLoS One."},{"key":"B36","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.ijbiomac.2021.06.140","article-title":"Serum albumin levels and inflammation.","volume":"184","author":"Sheinenzon","year":"2021","journal-title":"Int J Biol Macromol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1624527\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T05:24:18Z","timestamp":1752816258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1624527\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":36,"alternative-id":["10.3389\/fmed.2025.1624527"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1624527","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]},"article-number":"1624527"}}