NPAR Predicts Low Muscle Mass in Rheumatoid Arthritis
Key Takeaways
- Among hospitalized adults with RA, DXA-defined low muscle mass was observed in a substantial subset.
- Higher NPAR was independently associated with greater odds of low muscle mass and followed a positive linear pattern.
- NPAR discriminated low muscle mass better than the comparator inflammatory markers and showed an identifiable operating threshold.
- The same directional association appeared in U.S. NHANES participants with RA, and higher NPAR was also linked to poorer survival among those with low muscle mass.
Investigators in the Frontiers in Immunology study of NPAR, low muscle mass, and mortality in rheumatoid arthritis performed a cross-sectional analysis of first admissions among adults hospitalized at the Second Affiliated Hospital of Zhejiang Chinese Medical University from January 2021 through December 2025. They screened 1,356 rheumatoid arthritis hospitalizations and included 659 patients after exclusions, defining low muscle mass by dual-energy X-ray absorptiometry (DXA) with Asian Working Group for Sarcopenia (AWGS) 2019 appendicular skeletal muscle index (ASMI) thresholds of <7.0 kg/m² for men and <5.4 kg/m² for women.
NPAR was modeled mainly as a continuous exposure. A parallel U.S. National Health and Nutrition Examination Survey (NHANES) cohort included 375 participants with self-reported physician-diagnosed rheumatoid arthritis, used a European Working Group on Sarcopenia in Older People (EWGSOP)-based low muscle mass definition, and linked mortality through December 31, 2019.
Low muscle mass was present in 167 of 659 hospitalized participants with rheumatoid arthritis. After full adjustment, each 1-unit higher NPAR was associated with greater odds of low muscle mass at odds ratio (OR) 1.20 (95% confidence interval [CI] 1.09-1.31; P<0.001), and restricted cubic spline analysis showed a positive linear relationship.
NPAR showed the highest discrimination among the tested inflammatory markers, with area under the curve (AUC) 0.80 (95% CI 0.76-0.84). The optimal cutoff was 9.55, with 72% sensitivity and 76.5% specificity.
In the NHANES validation of NPAR in rheumatoid arthritis, the fully adjusted association with low muscle mass remained present at OR 1.28 (95% CI 1.09-1.49; P=0.003). Among rheumatoid arthritis participants with low muscle mass, higher NPAR was also associated with all-cause mortality over a median 8.3 years (HR 1.12, 95% CI 1.02-1.22; P=0.013), although this NHANES analysis was based on only 21 deaths. The association also persisted across major subgroups, appeared stronger with longer disease duration, and remained after excluding clinical infection or markedly elevated C-reactive protein.
Because the derivation cohort was cross-sectional, the analysis could not determine whether higher NPAR contributes to muscle loss or reflects the inflammatory and nutritional context surrounding it. Residual confounding remained possible because disease activity scores, cumulative glucocorticoid exposure, and direct nutritional assessment were not available. Low muscle mass was also defined differently across cohorts, and rheumatoid arthritis status in NHANES was self-reported, so NPAR is better read as an accessible adjunct risk-stratification signal than as a stand-alone diagnostic test. The derivation cohort came from a single Chinese hospital, whereas the validation and mortality analyses came from U.S. NHANES participants.
The authors concluded that higher NPAR tracked with DXA-defined low muscle mass in hospitalized rheumatoid arthritis and showed the same directional signal in NHANES. They described the marker as a practical inflammation-nutrition measure that may help identify patients at higher likelihood of low muscle mass, while prospective and multicenter confirmation is still needed.
Clinician Questions
How do the hospital and NHANES rheumatoid arthritis cohorts differ in ways that affect how NPAR findings should be applied?
The derivation cohort comprised hospitalized adults with rheumatoid arthritis at a single Chinese center, whereas the validation cohort came from U.S. NHANES participants with self-reported physician-diagnosed rheumatoid arthritis. Low muscle mass was defined differently across the two cohorts, and the authors also cited differences in racial composition. That means the validation mainly supports the direction of the NPAR signal rather than one-to-one interchangeability of absolute risk estimates or thresholds.
Which rheumatoid arthritis subgroups showed a stronger association between NPAR and low muscle mass?
In the hospital cohort, the positive association between higher NPAR and low muscle mass persisted across sex, age, body mass index, smoking status, alcohol use, and disease-duration strata. The authors reported stronger estimates in participants with longer rheumatoid arthritis duration, especially in the 11-20 year and >20 year strata. The subgroup pattern therefore pointed more toward longstanding disease than toward a signal confined to any one demographic category.
What did the sensitivity analysis excluding infection or markedly elevated CRP show about the NPAR-low muscle mass relationship?
After excluding hospitalized rheumatoid arthritis patients with clinical infection or C-reactive protein above 100 mg/L, the association between higher NPAR and low muscle mass remained and appeared stronger. The authors interpreted that pattern as support that the relationship was not driven only by acute inflammatory states, although the smaller sample leaves more uncertainty.
What remains unresolved before NPAR can be viewed as a stable cutoff-based or prognostic marker in rheumatoid arthritis?
Several issues remain unresolved before NPAR can be treated as a stable cutoff-based or prognostic marker in rheumatoid arthritis. The hospital analysis was cross-sectional, disease activity scores and cumulative glucocorticoid exposure were unavailable, direct nutritional assessment was lacking, and rheumatoid arthritis status in NHANES was self-reported. The authors also said the 9.55 cutoff requires prospective multicenter validation and described NPAR as an adjunct risk-stratification marker rather than a stand-alone diagnostic test.
Recommended Reading
- For more on hospitalized RA cohorts: RA Cohort Links Heart Failure to 10-Year CV Burden