Hemoglobin May Protect Against Inflammation From Rheumatoid Arthritis

Hemoglobin (Hb) is considered a protective factor against C-reactive protein (CRP) in patients with rheumatoid arthritis (RA), suggesting that regulating Hb levels could help reduce CRP levels and slow RA progression.¹

The authors of the Scientific Reports study explained that patients with RA experience various extra-articular manifestations and complications due to their chronic inflammation, with anemia being the most common.^2,3

Although CRP is a common marker of inflammation and RA activity, no in-depth statistical analysis has examined the relationship between Hb and CRP levels in patients with RA.¹ To address this gap, the researchers investigated the association between Hb, CRP, and mortality in patients with RA using data from the National Health and Nutrition Examination Database (NHANES).

Regulating hemoglobin levels could help reduce inflammation and improve rheumatoid arthritis management. | Image Credit: Andrea Danti - stock.adobe.com

The study population consisted of all individuals aged 18 and older in NHANES between 1999 and 2018 who self-reported that they were diagnosed with RA by a health professional. Conversely, the researchers excluded pregnant women and individuals who lacked the necessary data.

The primary outcome of interest was all-cause mortality. The researchers determined which individuals died using data from the NHANES Public Use Associated Mortality Document, which the National Center for Health Statistics linked to the National Mortality Index and followed up until December 31, 2015. The case definition of potential cause of death was based on codes from the International Classification of Diseases, Tenth Revision. Additionally, they assessed the association of numerous covariates, such as age, gender, and race.

Based on the inclusion criteria, the researchers recruited 610 subjects. They split the sample into 2 groups: the low-CRP group with levels less than 3 mg/L (n = 285) and the high-CRP group with levels greater than 3 mg/L. These groups differed by gender, poverty-to-income ratio, hypertension, body mass index, Hb, hematocrit, mean corpuscular Hb, and red cell distribution width (P < .05).

To better investigate the link between Hb and CRP, the researchers constructed sequential multifactorial generalized linear models. Model 1 was unadjusted; model 2 was adjusted for age, gender, and race; and model 3 was adjusted for other covariates.

A significant correlation between Hb and CRP was found in both models 1 (OR, 0.791; 95% CI, 0.699-0.895; P = .000364) and 2 (OR, 0.84; 95% CI, 0.737-0.958; P = .0102). After a thorough adjustment for variables in model 3, this link remained statistically significant (OR, 0.821; 95% CI, 0.713-0.946; P = .00749), indicating that other factors did not significantly impact the effect of Hb on CRP. Similarly, stratified analyses showed that there was still a significant association between Hb and CRP in patients with RA.

According to World Health Organization data, the researchers classified Hb levels as low or high, using cutoffs of 13 g/dL for males and 12 g/dL for females. They determined the link between Hb and all-cause mortality in patients with RA by analyzing the survival difference between the 2 groups using a Kaplan-Meier survival analysis.

The analysis found that male patients with RA and low Hb levels had significantly worse survival outcomes; this difference was statistically significant (P < .0001). In contrast, female patients with RA and low Hb levels had worse survival outcomes, but the difference was not statistically significant (P = .13).

Additionally, the restricted cubic spline analysis determined that the relationship between Hb and all-cause mortality is nonlinear, suggesting a complex pattern as Hb levels fluctuate (P = .0005). Among male patients with RA, Hb exhibited a protective effect within the range of approximately 14 to 16 g/dL but became a risk factor outside this range. Similarly, for female patients with RA, Hb acted as a protective factor between approximately 13 and 17 g/dL.

Lastly, both male and female patients demonstrated a threshold of around 15 g/dL. Therefore, Hb levels above this point were associated with smaller HRs, while levels below this threshold corresponded to higher HRs.

The researchers acknowledged their study’s limitations, including that its cross-sectional nature prevented causality between Hb and CRP levels from being inferred. Also, not all plausible confounding factors were available for inclusion in the multiple regression models. Despite these limitations, they expressed confidence in their findings.

“The results of our study estimated Hb as a protective factor against CRP in RA patients,” the authors concluded. “Therefore, regulating Hb levels might be a potential strategy for reducing CRP levels and managing the progression of RA.”

References

1. Liu D, Yan J, Luo T, Yang L. Association between C-reactive protein and hemoglobin in US rheumatoid arthritis patients based on NHANES data analysis. Sci Rep. 2025;15(1):8905. doi:10.1038/s41598-025-93720-z
2. Giles JT. Extra-articular manifestations and comorbidity in rheumatoid arthritis: potential impact of pre–rheumatoid arthritis prevention. Clin Therap. 2019;41(7):1246-1255. doi:10.1016/j.clinthera.2019.04.018
3. Pereira ICP, Sousa NCF, Pereira DMS, et al. Treatment with either leflunomide or adalimumab reduces anaemia in patients with rheumatoid arthritis. An Acad Bras Cienc. 2018;90(2 suppl 1):2161-2166. doi:10.1590/0001-3765201820170091