Abstract
The European Prospective Into Cancer (EPIC) - Norfolk Study is a large UK observational study, with health and blood marker data. The study design facilitates analysis of incident cases of rheumatoid arthritis (RA). Novel markers of inflammation including the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) have been assessed in other cohorts, and we sought to characterise the inflammatory phase preceding disease onset.
Incident RA cases were validated in the EPIC-Norfolk study: age, sex, CRP, ferritin and fibrinogen were from the 1st health check (1993-1998), whilst NLR and PLR were calculated from the 3rd health check (2004-2011) due to data availability. NLR and PLR are respectively calculated as absolute neutrophil count/absolute lymphocyte count, and absolute platelet count/absolute lymphocyte count.
There are 415 cases of RA, including 206 incident cases, in a cohort of 25,636 participants. Linear model ANOVA testing on an unmatched population, identified a statistically significant difference between incident RA cases and non-RA cases for CRP (mean [SD] 6.32 [10.29] vs. 3.07 [6.23], n = 251), NLR (mean [SD] 1.02 [1.90] vs. 0.58 [1.32], n = 80), and PLR (mean [SD] 54.6 [94.2] vs 22.4 [70.8], n = 258); all p-values <0.001. There was also a significant difference in fibrinogen (mean [SD] 3.10 [0.95] vs 2.94 [0.99], p = 0.032), but no difference for ferritin (mean [SD] 78.31 [63.82] vs. 89.72 [75.34], p = 0.086). Higher CRP levels at enrolment were related to a shorter duration to diagnosis of incident RA (Table 1). A linear regression model demonstrates the negative association between CRP and duration till diagnosis of RA (p = <0.001); with a CRP reference level of 12.6, as the group variable increases, the expected CRP value decreases by 1.8. When adjusting for age and sex, this remains statistically significant (p < 0.001).
Our study adds to existing literature that there are additional blood markers of inflammation from routine blood tests, beyond CRP and ESR, which can be reviewed when assessing patients with possible RA. There exists a pre-disease inflammation risk that is detectable before disease onset, and our data suggest that there is a ‘window of opportunity’ 5-15 years before RA onset, where preventative strategies might be worthwhile implementing early.
P. Saha: None. J. Dainty: None. M. Yates: Grants/research support; NIHR, Versus Arthritis, Doris Hillier, PMRGCAuk, Health and Social Care Partners, Norfolk and Waveney Integrated Care Board, Norfolk and Norwich University Healthcare Trust Charitable Funds. Other; Advisory Board work - AbbVie, BioGen, Galapagos, Conference attendance - Lilly, AbbVie, UCB, Celltrion. A. MacGregor: None.
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