Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
Hypertension is common in rheumatoid arthritis (RA), but it is unclear whether this prevalence is due to RA-related medications or to the disease process itself. Prior work in first-degree relatives (FDR) of RA patients without clinically apparent RA, and thus without RA-related medications, has shown that markers of endothelial dysfunction were associated with antibodies to citrullinated protein antigens (ACPA), suggesting that ACPA may be involved in vascular injury. Thus, we sought to investigate associations between ACPA and systolic and diastolic blood pressure in FDRs.
Methods
In the Studies of the Etiology of RA (SERA) (a multicenter prospective study of preclinical RA), we evaluated associations between ACPA and systolic (SBP) and diastolic blood pressure (DBP) in 89 FDRs of RA patients. A panel of 15 ACPA were measured using a Bio-Plex bead-based assay; and were dichotomized as positive/negative based on pre-specified cut-offs in 200 RA patients and 98 blood bank controls. These cutoffs were developed using receiver operating characteristic (ROC) curves giving >90% specificity. Seventeen FDRs lacked ACPA measurements and were excluded, leaving 72 FDRs for analysis. SBP and DBP were measured 3 times and averaged. ANCOVA was used to evaluate associations between ACPA positivity and SBP and DBP, adjusting for age, sex, race, body mass index (BMI), pack-years of smoking, high sensitivity C-reactive protein (CRP), and current use of anti-hypertensive medications.
Results
Average age was 51 years, and 69% were female. Mean SBP was 119 ± 18 and DBP was 74 ± 9 mmHg. 46% of FDRs were positive for any ACPA; these individuals were younger and had lower BMI, more pack-years of smoking, and higher levels of hsCRP, and had marginally higher DBP. (Table) Positivity for antibodies to cit-fibrinogen A (211-230) was associated with 11.52 mmHg higher SBP; to cit-filaggrin was associated with 13.9 mmHg higher SBP; to cit-clusterin, cit-filaggrin, and cit-vimentin were associated with 7-8 mmHg higher DBP. Positivity for each additional ACPA was significantly associated with a 0.98 mmHg increase in SBP, and a 0.66 mmHg increase in DBP.
Conclusion
In FDRs without RA, ACPA positivity is associated with higher SBP and DBP, independent of risk factors and medications for hypertension. While cit-fib and cit-vimentin have been implicated in subclinical CVD in RA, these findings suggest ACPA play a role in the vascular changes leading to hypertension prior to RA.
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Table. Proportion of SERA FDRs with ACPA, and associations of ACPA with blood pressure |
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n (%) positive
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Systolic Blood Pressure
|
Diastolic Blood Pressure
|
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|
|
β (SD) |
p |
β (SD) |
p |
|
|
Any ACPA positivity
|
33 (45.8) |
4.79 (3.40) |
0.164 |
3.79 (2.17) |
0.085 |
|
Apolipo E (277-296) cit2 cyclic
|
10 (13.9) |
5.30 (4.89) |
0.283 |
1.83 (3.16) |
0.565 |
|
Biglycan (247-266) cit cyclic
|
9 (12.5) |
8.28 (5.43) |
0.133 |
6.47 (3.46) |
0.066 |
|
Clusterin (221-240) cit
|
8 (11.1) |
8.38 (5.33) |
0.122 |
7.67 (3.35)
|
0.026
|
|
Enolase (5-21) cit
|
8 (11.1) |
3.39 (5.44) |
0.536 |
3.70 (3.47) |
0.290 |
|
Fibrinogen A (211-230) cit cyclic
|
10 (13.9) |
11.52 (4.89)
|
0.022
|
4.89 (3.22) |
0.135 |
|
Fibrinogen A (41-60) cit3 cyclic
|
10 (13.9) |
9.53 (5.05) |
0.064 |
4.74 (3.28) |
0.153 |
|
Fibrinogen A (556-575) cit cyclic
|
11 (15.3) |
9.27 (4.78) |
0.058 |
5.80 (3.08) |
0.064 |
|
Fibrinogen A (616-635) cit3 cyclic
|
5 (6.9) |
6.07 (6.65) |
0.365 |
3.71 (4.27) |
0.388 |
|
Fibrinogen A cit
|
11 (15.3) |
0.40 (4.71) |
0.932 |
0.75 (3.03) |
0.805 |
|
Filaggrin (48-65) cit2 cyclic
|
7 (9.7) |
13.90 (5.67)
|
0.017
|
7.47 (3.69)
|
0.048
|
|
Histone 2A (1-20) cit cyclic
|
13 (18.1) |
6.85 (4.56) |
0.138 |
3.42 (2.95) |
0.251 |
|
Histone 2B (62-81) cit cyclic
|
13 (18.1) |
5.49 (4.49) |
0.226 |
5.31 (2.83) |
0.066 |
|
Histone 2B-cit
|
5 (6.9) |
5.54 (6.64) |
0.408 |
5.54 (4.23) |
0.195 |
|
Vimentin cit
|
8 (11.1) |
6.22 (5.48) |
0.261 |
6.89 (3.44)
|
0.050
|
|
Vimentin (58-77) cit3 cyclic
|
3 (4.2) |
16.02 (8.54) |
0.066 |
10.09 (5.49) |
0.071 |
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Number of ACPA, mean (SD)
|
1.88 (3.59) |
0.98 (0.48)
|
0.045
|
0.66 (0.30)
|
0.035
|
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*adjusted for age, sex, race, BMI, pack-years of smoking, high sensitivity C-reactive protein, and current use of anti-hypertensive medications |
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Disclosure:
J. M. Hughes-Austin,
None;
R. W. Gan,
None;
K. D. Deane,
None;
P. K. Gregersen,
None;
M. H. Weisman,
None;
J. H. Ix,
None;
J. Sokolove,
None;
W. H. Robinson,
None;
V. M. Holers,
None;
J. M. Norris,
None.
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