Dynamic changes in CBC-derived inflammatory indices before and during acute coronary syndrome in patients with rheumatoid arthritis: a within-patient paired study.
Wang Y, Zhang Y, et al. • Frontiers in immunology • 2026
Among patients with RA who developed ACS, CBC-derived inflammatory indices were higher than in a healthy comparison cohort before the event and increased further within the first 24 hours of ACS.
Key Findings
Results
Pre-event CBC-derived inflammatory indices in RA patients were elevated compared to healthy controls even before the onset of acute coronary syndrome.
Pre-event log(NLR), log(SII), and log(SIRI) were all higher in the RA cohort than in healthy controls (n=110)
Differences remained statistically significant after adjustment for age and sex (all P < 0.001)
Age- and sex-adjusted analyses were used because residual demographic imbalance was present between cohorts
Pre-event CBCs were defined as the most recent routine measurements obtained more than 14 days before the ACS event
Results
Within-patient analyses demonstrated significant increases in all three CBC-derived inflammatory indices during acute coronary syndrome compared to each patient's own pre-event values.
Mean Δlog values were 0.466 for NLR, 0.508 for SII, and 0.381 for SIRI
All changes were statistically significant after Benjamini-Hochberg multiple comparison correction (all q < 0.001)
Acute-phase CBCs were obtained within 24 hours after symptom onset
The paired design quantifies change relative to each patient's own pre-event value, with 89 patients contributing qualifying paired measurements
Results
The prevalence of neutrophilia increased markedly from the pre-event period to the acute phase of ACS in RA patients.
Neutrophilia was present in 11.2% of patients before the event and rose to 41.6% during ACS
This increase was statistically significant (McNemar P < 0.001)
McNemar's test was used to account for the paired, within-patient nature of the comparison
Results
Exploratory subgroup analyses showed heterogeneous and non-monotonic estimates, and inflammatory index changes did not differ materially between RA disease activity groups.
Subgroup estimates were described as 'heterogeneous and non-monotonic across several small strata'
Changes in inflammatory indices did not differ materially between remission/low and moderate/high RA disease activity groups
The authors note that small subgroup sizes limit the reliability of subgroup-level conclusions
Methods
The study identified 89 RA patients with clinician-confirmed ACS and qualifying paired CBC measurements from a base population of 3,960 hospitalized RA patients over approximately 90 months.
Hospital records were reviewed from July 1, 2018, to December 30, 2025, at a single center
Of 3,960 hospitalized RA patients, 89 had both clinician-confirmed ACS and qualifying paired CBC measurements
This was a retrospective, single-center, within-patient paired study design
NLR, SII, and SIRI were calculated and natural log-transformed for analysis
Discussion
The study cannot establish RA-specific inflammatory priming or a causal chronic-to-acute mechanism due to the absence of a non-RA ACS comparator group.
The authors explicitly state: 'Without a non-RA ACS comparator, however, the study cannot establish RA-specific inflammatory priming or a causal chronic-to-acute mechanism'
The authors call for 'prospective studies with serial sampling and clinical outcomes'
The single-center retrospective design and reliance on available clinical CBCs are noted as additional limitations
What This Means
This research suggests that in patients with rheumatoid arthritis (RA), markers of inflammation measurable from a routine blood count (called CBC-derived inflammatory indices — specifically the NLR, SII, and SIRI) are already elevated compared to healthy individuals even before a heart attack or acute coronary syndrome (ACS) occurs. When these same patients then experienced ACS, their inflammatory markers rose even further within the first 24 hours. The proportion of patients with abnormally high neutrophil counts (a type of white blood cell that rises during inflammation and infection) jumped from about 1 in 9 patients before the event to nearly 1 in 2 patients during the acute event. The study's key strength is its paired design — comparing each person to their own earlier measurements — which eliminates the influence of individual differences between people.
This research suggests that the chronic inflammation of RA may create a background state of heightened immune activity, on top of which the acute inflammatory response of a heart attack is then layered. However, because the study had no comparison group of heart attack patients without RA, it is not possible to conclude that what was observed is unique to RA rather than simply a normal response to ACS seen in any patient. The findings also could not confirm whether the level of RA disease activity (remission versus active disease) influenced how much the inflammatory markers changed during ACS.
Practically, this research suggests that standard blood count tests, which are inexpensive and widely available, may capture meaningful inflammatory signals in RA patients both before and during cardiac events. However, the authors caution that larger prospective studies with repeated blood sampling over time and tracking of clinical outcomes are needed before any clinical use of these markers for predicting or managing cardiac events in RA patients can be considered.
Wang Y, Zhang Y, Zhang J, Nie W, Wang X, Su F, et al.. (2026). Dynamic changes in CBC-derived inflammatory indices before and during acute coronary syndrome in patients with rheumatoid arthritis: a within-patient paired study.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1833991