Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis

TY - JOUR

T1 - Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis

AU - Adlan, Ahmed M

AU - Paton, Julian F R

AU - Lip, Gregory Y H

AU - Kitas, George D

AU - Fisher, James P

N1 - This article is protected by copyright. All rights reserved.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood-borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesised that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts/min) compared to NC (22 ± 9 bursts/min; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), while cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients (5[3-8], 4[2-7], 6[4-9] ms/mmHg) compared to NC (11[8-15] ms/mmHg; P = 0.002). HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events. This article is protected by copyright. All rights reserved.

AB - Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood-borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesised that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts/min) compared to NC (22 ± 9 bursts/min; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), while cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients (5[3-8], 4[2-7], 6[4-9] ms/mmHg) compared to NC (11[8-15] ms/mmHg; P = 0.002). HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events. This article is protected by copyright. All rights reserved.

KW - autonomic nervous system

KW - cytokine

KW - inflammation

KW - pain

U2 - 10.1113/JP272944

DO - 10.1113/JP272944

M3 - Article

C2 - 27561790

VL - 595

SP - 967

EP - 981

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 3

ER -