Lupus (2014) 23, 1460–1467 http://lup.sagepub.com

PAPER

Elevated C-reactive protein and self-reported disease activity in systemic lupus erythematosus AM Eudy1, AI Vines1, MA Dooley2, GS Cooper3 and CG Parks4 1

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA; 2 University of North Carolina, Chapel Hill, USA; 3National Center for Environmental Assessment, United States Environmental Protection Agency, Washington, DC, USA; and 4Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Durham, USA

C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased disease activity in rheumatoid arthritis. However, the association in systemic lupus erythematosus (SLE) remains unclear. We examined the association of CRP with self-reported disease activity in the Carolina Lupus Study and described differences by sociodemographic characteristics. The study included baseline and three-year follow-up data on 107 African-American and 69 Caucasian SLE patients enrolled at a median 13 months since diagnosis. Models estimated prevalence differences in the association of baseline CRP with self-reported flares, adjusting for age, sex, race and education. Active disease or flare was reported by 59% at baseline and 58% at follow-up. Higher CRP (>10 mg/ml vs. HS). Race/ethnicity, sex, education and age variables were centered so the intercept of regression models represented the average patient in the study (i.e. an African-American woman aged 42.5 years with some college education). Effect measure modifiers were determined by a likelihood ratio test ( ¼ 0.20). Confounding was defined as a 10% change-in-estimate of beta when included in the model. Age, sex, race and education were included in final models to adjust for confounding. Models stratified by education (i.e. HS or >HS) were also adjusted for education (HS n ¼ 99 n (%)

– – – –

– – – –

26 30 32 19

(24) (28) (30) (18)

7 14 27 21

(10) (20) (39) (30)

0.004

20 32 22 25 8

(19) (30) (21) (23) (7)

8 14 15 12 20

(12) (20) (22) (17) (29)

0.003

10 14 16 20 17

(13) (18) (21) (26) (22)

18 32 21 17 11

(18) (32) (21) (17) (11)

p-valuea

0.06

33 (31) 39 (36) 35 (33)

24 (35) 32 (46) 13 (19)

0.1

23 (30) 27 (35) 27 (35)

34 (34) 44 (44) 21 (21)

0.1

44 (42) 61 (58)

28 (41) 40 (59)

0.9

33 (43) 44 (57)

39 (41) 57 (59)

0.8

64 75 45 33

35 53 31 9

0.3 0.5 0.8 0.007

45 57 31 17

54 71 45 25

0.7 1.0 0.4 0.6

(65) (72) (44) (31)

43 (40) 64 (60) Mean (SD) 4.8 (2.9) 10.7 (5.7) 2.1 (2.0)

(56) (77) (46) (13)

29 (43) 38 (57) Mean (SD) 4.2 (2.5) 10.7 (4.7) 0.9 (1.2)

0.7 p-valuec 0.1 1.0 10 mg/ml). Reported active disease/flare at baseline and follow-up did not vary by race/ethnicity or educational attainment. AfricanAmericans were more likely to have lupus nephritis and a higher SDI score at follow-up (mean: 2.1) than Caucasians (mean: 0.9). No differences were seen by education. CRP and active disease at baseline Fifty-eight percent of patients reported active disease/flare at baseline (Table 2); of these, a greater proportion had arthritis compared with patients who did not report active disease/flare (80% vs. 65%), but no differences were seen for other clinical and immunologic features of SLE. Prevalence of arthritis and lupus nephritis did not increase with higher CPR levels. Serositis, however, was associated with higher CRP levels, with 59% of patients with CRP >10 mg/ml having serositis confirmed in their medical records at baseline, compared with 41% of patients with CRP 0.2). Baseline CRP and flare at follow-up The adjusted prevalence of flare at follow-up increased with higher baseline CRP (Table 3), from 46% for patients with a baseline CRP 10 mg/ml (PD: 26%; 95% CI: 9, 62%). Only 36% of participants reported both active disease/ flare at baseline and flare at follow-up, and the association of baseline CRP and flare at follow-up was not substantially attenuated after adjusting for baseline flare (results not shown). Among AfricanAmerican patients, there was a positive association of baseline CRP and prevalence of flare at followup. Prevalence differences for CRP levels of 3–10 mg/ml and >10 mg/ml compared with 0.2). The PGA of disease activity score at follow-up was significantly higher in patients reporting a recent flare than in those who did not report a flare (Table 4). PGA scores were significantly higher in patients with higher CRP; in linear models (not shown), for every 1 -mg/ml increase in lnCRP, there was a 0.4 unit increase in PGA score at follow-up. A similar pattern was seen for the SLAQ score, with patients who reported a flare at follow-up having a higher mean SLAQ score. No racial/ethnic or educational differences were seen for either disease activity score. Lupus

CRP and disease activity in SLE AM Eudy et al.

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Table 3

Association of baseline C-reactive protein with active disease/flare at baseline and follow-up (n ¼ 176) Active disease/flare at baseline

Baseline CRP (mg/ml)

CRP Mean  SD (mg/ml)

Na

Overall cohort 10 18.9  8.5 47 African-American 10 19.5  8.7 35 Caucasian 10 17.1  7.9 13 High school education or less 10 18.7  8.6 27 Greater than high school education 10 19.1  8.5 21

Flare at follow-up

Flares n (%)b

Adj. prev.c

PD (95% CI)c

Flares n (%)b

31 (54) 44 (64) 26 (55)

31% 39% 47%

0. (ref.) 8% (10, 26%) 17% (20, 53%)

26 (46) 42 (59) 34 (72)

46% 59% 72%

17 (52) 25 (66) 19 (56)

43% 54% 65%

0. (ref.) 11% (14, 35%) 22% (27, 70%)

13 (39) 26 (67) 25 (71)

62% 88% 114%

0. (ref.)d 26% (2, 50%) 52% (5, 99%)

14 (58) 19 (61) 7 (54)

21% 26% 32%

0. (ref.) 5% (22, 33%) 11% (44, 66%)

13 (57) 16 (50) 9 (75)

45% 40% 35%

0. (ref.) 5% (32, 21%) 11% (64, 43%)

11 (48) 19 (70) 14 (52)

26% 49% 71%

0. (ref.)e 23% (6, 51%) 45% (11, 102%)

10 (43) 16 (59) 20 (77)

63% 77% 91%

0. (ref.) 14% (14, 43%) 28% (28, 85%)

20 (59) 25 (60) 12 (60)

29% 30% 31%

0. (ref.) 1% (23, 24%) 1% (46, 48%)

16 (48) 26 (59) 14 (67)

38% 51% 64%

0. (ref.) 13% (10, 36%) 26% (20, 72%)

Adj. prev.c

PD (95% CI)c

0. (ref.) 13% (5, 31%) 26% (9, 62%)

a

Data missing for active disease/flare at baseline (n ¼ 3) and flare at follow-up (n ¼ 2). Row percentages. c Prevalence adjusted for age, sex, race and education. d Effect measure modification by race (likelihood ratio p-value ¼ 0.05). e Effect measure modification by education (likelihood ratio p-value ¼ 0.08). Adj. prev.: adjusted prevalence; CI: confidence interval; CRP: C-reactive protein; PD: prevalence difference; ref: reference; SD: standard deviation. b

Discussion Table 4 Mean distribution of Patient Global Assessment and SLE Activity Questionnaire scores (n ¼ 174)

Self-reported follow-up flare Yes No Race African-American Caucasian Education High school education or less Greater than high school Baseline CRP 10 a

PGA (0–10 scale)

SLAQ (0–24 scale)

Mean (SD) p-value

Mean (SD) p-value

5.8 (2.5) 2.9 (2.2)

Elevated C-reactive protein and self-reported disease activity in systemic lupus erythematosus.

C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased disease activity in rheumatoid arthritis. However, the assoc...
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