TY - JOUR
AU - Sukitawut,, W.
AB - Abstract Although peripheral and central nervous system involvement have been well recognized in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), autonomic nervous system (ANS) involvement has rarely been studied, and has shown conflicting results. We performed cardiovascular ANS assessment in 34 RA and 37 SLE patients, using standard cardiovascular reflex tests. The results in each patient were compared with age- and sex-matched healthy controls. Forty-seven percent of the RA patients and 19% of the SLE patients had symptoms suggesting ANS dysfunction. The heart rate variation in response to deep breathing was significantly decreased in both the RA and SLE patients (p=0.001). This diminished heart rate response showed no correlation with the disease duration, the number of swollen joints, the Ritchie articular index, ESR, or rheumatoid factor in the RA group, or the disease duration, the SLEDAI score or ESR in the SLE group. The clinical significance of the diminished cardiovascular ANS response needs to be investigated. Introduction Although involvement of the peripheral nervous system (PNS) and central nervous system (CNS) in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) has been well described, autonomic nervous system (ANS) involvement in RA and SLE has rarely been described in standard textbooks of rheumatology.1–3 The ANS can be assessed by several tests including cardiovascular, sweating, pupillary reflex and skin tests. However, cardiovascular reflex tests have been most widely used as they are non-invasive, and results are easy to reproduce. The purpose of this study was to evaluate cardiovascular ANS function in patients with RA and SLE, and to correlate the ANS function with clinical features. As the ANS function has been reported to deteriorate with age,4 we used age- and sex-matched healthy controls. Methods The patients studied were in- and out-patients with RA and SLE at the Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai University. The diagnoses of RA and SLE were made by using the criteria developed by the American College of Rheumatology.5,6 Control subjects were selected from healthy hospital staff who did not have symptoms of ANS dysfunction and were not taking any medications. These controls had never been studied before. All patients were checked for symptoms and signs of possible ANS dysfunction, including orthostatic hypotension (lightheadedness, blurred vision, sensation of weakness and unsteadiness, fainting or syncope upon standing), perspiration, palpitation and Raynaud's phenomenon. The criterion for age matching was an age difference of <3 years for each matched pair. Patients were excluded from the study if they (i) had <10 g/dl haemoglobin; (ii) were pregnant; (iii) had diseases interfering with the autonomic nervous system, including diabetes mellitus, renal and liver diseases, Parkinson's disease, porphyria and amyloidosis; (iv) had cardiovascular diseases including hypertension, ischaemic heart disease, congestive heart failure, valvular heart disease, cardiomyopathy and cardiac arrhythmia; or (v) had neurological diseases including multiple sclerosis, polyneuropathy or Guillain-Barré syndrome. Patients taking drugs that interfered with the ANS including antihypertensive, diuretic, adrenergic inhibitor, vasodilator, anti-arrhythmic, sedative, hypnotic and anti-epileptic drugs were also excluded from the study. Cardiovascular ANS function assessment was performed by one of us, PR, using the standard technique described by Ewing et al.7 Two tests, the heart rate response to deep breathing and the immediate heart rate response to standing (or the R-R ratio), were performed to measure heart rate changes, reflecting the parasympathetic nerve function. The other two tests, the systolic blood pressure response to standing and the diastolic blood pressure response to sustained handgrip, were done to measure changes in blood pressure, reflecting the sympathetic nerve function. All patients and controls were confirmed to have a normal sinus rhythm, without evidence of a conduction defect in a standard electrocardiograph (ECG). The tests were performed under standardized conditions, in the morning, after a period of relaxation. Tobacco, alcohol and medications were not allowed before the tests. RA activity was determined by using the number of swollen joints, the joint tenderness scores determined by the Ritchie articular index, the rheumatoid factor (RF) determined by the latex agglutination test and erythrocyte sedimentation rate (ESR). An RF titre of 1 : 80 or more was considered significant. The activity of SLE was determined by ESR and the SLEDAI score.8 The SLEDAI score was modified in this study, as the DNA binding assay was not available at our hospital, and its score was not counted as part of our SLEDAI score. Thus our maximum modified SLEDAI score was 103. Statistical analysis Test values are reported as means±SD. Student's t test for paired samples was used to compare these means. Wilcoxon matched-pairs signed-ranks test was used for non-parametric values. Regression analysis was used to find the correlation between the cardiovascular ANS function test and disease activity or dosage of medication. A p value <0.05 was considered statistically significant. Statistical analysis used the SPSS for Windows program, release 7.0. Results Thirty-four RA and 37 SLE patients were included in this study. The characteristics of these patients are given in Table 1. Nineteen RA patients (55.8%) had positive RF (≥1 : 80). Their mean number of swollen joints, the Ritchie articular index and the ESR were 15.50±10.46, 11.59±6.08, and 35.22±18.27 mm/h, respectively. None had rheumatoid vasculitis or peripheral neuropathy. All RA patients were taking non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs at the standard dosage. The mean modified SLEDAI score and ESR in SLE patients were 4.65±5.77, and 27.65±11.67 mm/h, respectively. A past history of vasculitis, CNS lupus and peripheral neuropathy was documented in 12, six and two patients, respectively. Among the patients with CNS lupus, there were seizures in three, organic brain syndrome in one, transverse myelitis in one and aseptic meningitis in one. Two patients who had peripheral neuropathy had had mononeuritis multiplex. At the time of the study, four patients had cutaneous vasculitis and one had a residual ulnar neuropathy from her previous neuropathy. Anti-nuclear antibody test, using the indirect immunofluorescent method, was positive in 31 and was negative in six cases. There were 62 healthy controls (50 females and 12 males). Each RA and SLE patient was matched for age with these controls, and for sex where possible. The mean±SD ages of the control groups for RA and SLE were 47.0±10.6 and 30.3±7.9 years, respectively (p>0.05); the percentages of sex-matched control patients in the RA and SLE groups were 76% and 81%, respectively. Results of the cardiovascular ANS function assessment in RA and SLE patients and their age- and sex-matched controls are shown in Table 2. The heart rate response to deep breathing was significantly diminished in both RA and SLE groups when compared with controls (p=0.001). There was no correlation between the diminished heart rate response to deep breathing and number of swollen joints, the Ritchie articular index or ESR or RF titre in RA patients, nor to the modified SLEDAI score or ESR in SLE patients. There was no significant correlation between the extent to which the systolic blood pressure fell and the orthostatic hypotension symptoms, nor between the heart rate variation in response to deep breathing or the R-R ratio and palpitation in both RA and SLE groups. A significant correlation between the diminished heart rate response to deep breathing and the dosage of chloroquine used in RA patients was observed (p<0.05), but this correlation disappeared on multiple regression analysis. Discussion In this study, we used non-invasive cardiovascular reflex tests to evaluate cardiovascular ANS function. The heart rate response to deep breathing was found to be significantly diminished in both RA and SLE groups compared to their age- and sex-matched healthy controls. This diminished heart rate response showed no correlation to the duration of the disease, the disease activity, or the dosage of the medication used in both RA and SLE. Unfortunately, we did not study the correlation between the presence of ANS dysfunction and the degree of articular destruction in our RA patients. Forty-seven percent of our RA and 19% of our SLE patients had symptoms suggesting ANS dysfunction. The high incidence of ANS dysfunction symptoms seen in our RA patients might have been related to their advanced age group. In this study, control subjects were recruited from healthy hospital staff. They were in general health-conscious. Thus, they might not represent the population from which the patients were drawn. As the controls had no symptoms of ANS dysfunction, it is not known whether the ANS dysfunction symptoms seen in both our RA and SLE patients are more common than those of the general population. Cardiovascular ANS assessment in RA has been studied by several investigators, and there have been conflicting results because of the way in which controls were selected and the criteria used to determine ANS dysfunction. Tests measuring heart rate variation have been most commonly employed, and these have usually given abnormal results. Edmonds et al.9 demonstrated abnormalities in parasympathetic cardiovascular reflexes in nine of their 27 RA patients (33%). Four of nine patients with abnormal tests had symptoms suggesting ANS dysfunction. However, more than 50% of their patients with abnormal tests had evidence of peripheral neuropathy. Tan et al.10 also found abnormal heart rate response to deep breathing in eight of their 30 RA patients (27%). Five of these eight had had clinical symptoms of dysautonomia. Nine patients had evidence of peripheral neuropathy, of whom five had clinical symptoms of dysautonomia. Leden et al.11 studied 17 RA patients and found an increase in resting heart rate in all patients, and an abnormal heart rate response to standing in all seven patients who had severe RA. An increase in resting heart rate in RA was confirmed by Piha et al.12 but they found no abnormalities in parasympathetic cardiovascular reflex tests. This increased heart rate was independent of severity of the disease, pain and ESR. They concluded that the increase in resting heart rate might have been related to vascular inflammation, accelerated atherosclerosis and poor physical condition. Parasympathetic cardiovascular ANS dysfunction was confirmed by Toussirot et al.13 who demonstrated that 60% of their 50 RA patients had ANS dysfunction, defined by abnormal results on two of the three cardiovascular reflex tests. However, ANS dysfunction showed no correlation with the duration of the disease, inflammatory syndrome, RF titre or articular destruction. Approximately 50% of their patients had severe disease and showed some degree of articular destruction. Geenen et al.14 found diminished ANS function in RA patients who had had the disease for <1 year. This diminished ANS function was related to severity of pain and might have been related to the pathophysiological mechanisms in RA. In contrast to previous studies, Bekkelund et al.15 found no cardiovascular ANS abnormality in their 43 RA patients, who had no ANS symptoms. An abnormal cardiovascular ANS function in SLE has also been found in several studies. Gledhill et al.16 found that 13 of their 14 SLE patients (93%) without autonomic symptoms had cardiovascular ANS dysfunction. However, 12 of these patients had evidence of peripheral neuropathy. The reason for the high incidence of autonomic neuropathy in their study is not clear. Liote et al.17 found that 88% of their 17 SLE patients with mild disease activity had at least one abnormal cardiovascular reflex test. Both the standing heart rate ratio and the fall in standing systolic blood pressure were abnormal, reflecting abnormalities in both the parasympathetic and the sympathetic nervous system. In contrast to Gledhill's study,16 no relationship between autonomic neuropathy and peripheral neuropathy was found. Straub et al.18 found that three of their 31 SLE patients (9.7%) had cardiovascular ANS dysfunction defined by abnormal results in two of the five cardiovascular reflex tests. The systolic blood pressure response to standing was abnormal in 29%. A significant correlation between disease activity and the number of abnormal cardiovascular reflex tests was observed. Recently Lagana et al.19 and Laversuch et al.20 used 24-h ECG monitoring in addition to the standard cardiovascular reflex tests to evaluate cardiovascular ANS function and showed that a significant decreased heart rate variability occurred in SLE patients, especially at night when the parasympathetic nerve function is prominent, when compared with controls. Twenty-two percent of Laversuch's,20 but none of Lagana's19 patients had symptoms of dysautonomia. The diminished heart rate variability showed no correlation with the disease duration, the disease activity or serology. In contrast to the above studies, Omdal et al.21 found no abnormality in the cardiovascular ANS function in their 34 SLE patients when using age- and sex-matched controls. The diminished heart rate response to deep breathing in RA and SLE seen in this study is in line with previous studies. However, many of the previous studies had some limitations, such as selection of controls and statistical analyses. Although the ages of patients were matched to those of controls, they compared means of the group rather than the age-matched pairs used by Laversuch et al.,20 Omdal et al.,21 Stein et al.,22 and our study. Moreover, some studies used the standard-age reference values as controls. As the ANS has been shown to deteriorate with age,4 it is crucial to correct for age, and if possible for sex, to strengthen results of the statistical analysis. Although 26% of our RA and 95% of our SLE patients took low doses of corticosteroids, the diminished heart rate response to deep breathing seen in our patients showed no correlation with the dosage of prednisolone used. This diminished heart rate variability has been previously demonstrated to be independent of the use of corticosteroids.22 Most of our SLE patients had mild disease activity, with an average modified SLEDAI score of 4.65, similar to those of Loite et al.,17 Laversuch et al.,20 and Stein et al.22 Patients with more severe disease tended to have renal involvement, be anaemic, have high blood pressure or to have conditions or be taking drugs which were excluded from our study. It might be of interest to study the cardiovascular ANS function in the more severe SLE patients. There have been substantial advances in the assessment of autonomic function, particularly of the cardiovascular system.23 However, the Ewing approach, which has been used to assess ANS function in clinical research for many years remains satisfactory.7,9,15,17,20,21 A 24-h ECG record has been recently used to evaluate heart rate variability in combination with the standard cardiovascular reflex tests as it is more sensitive in detecting the parasympathetic nervous system dysfunction, but an analysis of the time and frequency domain for an evaluation of the heart rate variation from a 24-h ECG recording is mathematically complex and perhaps cannot be done at a general hospital. Moreover, there is a good correlation between the high frequency 24-h heart rate variability, which is influenced by the parasympathetic nervous system, and the heart rate variation in response to deep breathing.20 Note the fall in the systolic blood pressure, at a mean of 10 mmHg in RA and SLE groups versus 8 and 6 mmHg, respectively, in the controls. The large standard deviation indicates that there were great variations, implying that our subjects were heterogeneous. The fall in systolic blood pressure showed no correlation with the orthostatic hypotension symptoms in both groups. However, there is no agreement for the normal range for the postural change, and a decrease of as much as 25 mmHg can be normal.24 At the time of study, none of our RA patients had vasculitis or numbness that was suggestive of sensory neuropathy. Four lupus patients had cutaneous vasculitis and one had residual sensory and motor ulnar neuropathy. As we did not do a peripheral nerve conduction study, it is difficult to rule out the absence of peripheral neuropathy in these patients. Peripheral neuropathy, especially sensory, can affect responses in some of the tests, in particular cold stimulation. However, this test was not used in our study. The pathogenesis of the ANS dysfunction in patients with RA and SLE is not clearly understood. Vasculitis of the vasa nervorum and secondary amyloidosis has been proposed.13 The pathogenesis may have an immune component. This is supported by improvement of acute autonomic neuropathy after treatment with immunosuppressive drugs in a patient with SLE.25 The presence of circulating auto-antibodies against nerve growth factor, cervical ganglia and the vagus nerve has been recently demonstrated in RA and SLE patients who had cardiovascular ANS dysfunction.26,27 The significance of these auto-antibodies in the pathogenesis of ANS dysfunction remains to be determined. In summary, cardiovascular ANS dysfunction, particularly the parasympathetic nervous system, occurs in RA and SLE. It is usually not evident unless one specifically tests for it, by using the standard cardiovascular reflex tests, before overt symptoms of ANS dysfunction occur. The significance of asymptomatic cardiovascular ANS dysfunction in clinical practice remains to be investigated. One should be cautious in prescribing drugs that have effects on the cardiovascular ANS in patients with RA and SLE with possible autonomic dysfunction. Table 1 Characteristics of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients Data are either numbers, or means±SD. RA (n=34) SLE (n=37) Sex (F : M) 30 : 4 34 : 3 Age (years) 47.2±10.5 30.4±8.1 Duration (years)  5.1±3.6  3.1±2.2 Medication: n (dosage) Prednisolone (mg/day)  9 (4.45±1.10) 35 (17.03±13.59) Chloroquine (mg/day) 20 (168.45±61.17) 21 (202.33±71.10) Methotrexate (mg/week) 11 (4.55±1.51) – Cyclophosphamide (mg/day) – 13 (50.00±17.68) ANS symptoms Orthostatic hypotension 16  7 Palpitation 12  7 Raynaud's symptom  5  5 Perspiration  4  5 Data are either numbers, or means±SD. RA (n=34) SLE (n=37) Sex (F : M) 30 : 4 34 : 3 Age (years) 47.2±10.5 30.4±8.1 Duration (years)  5.1±3.6  3.1±2.2 Medication: n (dosage) Prednisolone (mg/day)  9 (4.45±1.10) 35 (17.03±13.59) Chloroquine (mg/day) 20 (168.45±61.17) 21 (202.33±71.10) Methotrexate (mg/week) 11 (4.55±1.51) – Cyclophosphamide (mg/day) – 13 (50.00±17.68) ANS symptoms Orthostatic hypotension 16  7 Palpitation 12  7 Raynaud's symptom  5  5 Perspiration  4  5 Open in new tab Table 1 Characteristics of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients Data are either numbers, or means±SD. RA (n=34) SLE (n=37) Sex (F : M) 30 : 4 34 : 3 Age (years) 47.2±10.5 30.4±8.1 Duration (years)  5.1±3.6  3.1±2.2 Medication: n (dosage) Prednisolone (mg/day)  9 (4.45±1.10) 35 (17.03±13.59) Chloroquine (mg/day) 20 (168.45±61.17) 21 (202.33±71.10) Methotrexate (mg/week) 11 (4.55±1.51) – Cyclophosphamide (mg/day) – 13 (50.00±17.68) ANS symptoms Orthostatic hypotension 16  7 Palpitation 12  7 Raynaud's symptom  5  5 Perspiration  4  5 Data are either numbers, or means±SD. RA (n=34) SLE (n=37) Sex (F : M) 30 : 4 34 : 3 Age (years) 47.2±10.5 30.4±8.1 Duration (years)  5.1±3.6  3.1±2.2 Medication: n (dosage) Prednisolone (mg/day)  9 (4.45±1.10) 35 (17.03±13.59) Chloroquine (mg/day) 20 (168.45±61.17) 21 (202.33±71.10) Methotrexate (mg/week) 11 (4.55±1.51) – Cyclophosphamide (mg/day) – 13 (50.00±17.68) ANS symptoms Orthostatic hypotension 16  7 Palpitation 12  7 Raynaud's symptom  5  5 Perspiration  4  5 Open in new tab Table 2 Results of cardiovascular autonomic assessment in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) Values are means±SD. HRmax, maximum heart rate during deep breathing; HRmin, minimum heart rate during deep breathing; HRvar, the difference between HRmax and HRmin; R-R 15, R-R interval at 15th heart beat after standing; R-R 30, R-R interval at 30th heart beat after standing; R-R ratio, the ratio of R-R 30 to R-R 15; BPs baseline, systolic blood pressure while supine; BPs stimulated, lowest systolic blood pressure while standing; BPs decrease, BPs baseline—BPs stimulated; BPd baseline, diastolic blood pressure before handgrip; BPd stimulated, highest diastolic blood pressure during handgrip exercise; BPd increase, BPd stimulated−BPd baseline. Parameter RA patients (n=34) RA controls (n=34) p SLE patients (n=37) SLE controls (n=37) p HRmax (beats/min)  91.59±15.80  84.91±12.00 100.57±15.46  90.95±11.80 HRmin (beats/min)  77.38±16.06  65.38±11.16  81.19±15.51  64.43±9.92 HRvar (beats/min)  14.20±7.57  19.52±6.83 0.001  19.37±7.93  26.51±8.22 0.001 R-R15 (mm)  16.19±2.23  17.59±3.57  14.43±2.83  17.03±2.77 R-R30 (mm)  16.19±2.51  18.27±3.01  14.76±2.68  18.05±2.47 R-R ratio   1.08±0.11   1.05±0.12 0.21   1.02±0.08   1.07±0.12 0.18 BPs baseline (mmHg) 125.06±16.71 118.44±14.00 124.32±14.99 115.32±13.04 BPs stimulated (mmHg) 114.65±17.70 110.85±13.41 113.78±13.04 109.16±12.81 BPs decrease  10.41±11.48   7.58±9.22 0.30  10.54±8.97   6.16±7.89 0.06 BPd baseline (mmHg)  76.65±12.39  76.21±7.91  78.60±10.40  75.24±9.66 BPd stimulated (mmHg)  87.00±11.49  84.91±8.22  91.94±12.34  84.70±10.15 BPd increase  10.35±6.55   8.70±3.92 0.25  13.35±8.57   9.45±9.00 0.06 Values are means±SD. HRmax, maximum heart rate during deep breathing; HRmin, minimum heart rate during deep breathing; HRvar, the difference between HRmax and HRmin; R-R 15, R-R interval at 15th heart beat after standing; R-R 30, R-R interval at 30th heart beat after standing; R-R ratio, the ratio of R-R 30 to R-R 15; BPs baseline, systolic blood pressure while supine; BPs stimulated, lowest systolic blood pressure while standing; BPs decrease, BPs baseline—BPs stimulated; BPd baseline, diastolic blood pressure before handgrip; BPd stimulated, highest diastolic blood pressure during handgrip exercise; BPd increase, BPd stimulated−BPd baseline. Parameter RA patients (n=34) RA controls (n=34) p SLE patients (n=37) SLE controls (n=37) p HRmax (beats/min)  91.59±15.80  84.91±12.00 100.57±15.46  90.95±11.80 HRmin (beats/min)  77.38±16.06  65.38±11.16  81.19±15.51  64.43±9.92 HRvar (beats/min)  14.20±7.57  19.52±6.83 0.001  19.37±7.93  26.51±8.22 0.001 R-R15 (mm)  16.19±2.23  17.59±3.57  14.43±2.83  17.03±2.77 R-R30 (mm)  16.19±2.51  18.27±3.01  14.76±2.68  18.05±2.47 R-R ratio   1.08±0.11   1.05±0.12 0.21   1.02±0.08   1.07±0.12 0.18 BPs baseline (mmHg) 125.06±16.71 118.44±14.00 124.32±14.99 115.32±13.04 BPs stimulated (mmHg) 114.65±17.70 110.85±13.41 113.78±13.04 109.16±12.81 BPs decrease  10.41±11.48   7.58±9.22 0.30  10.54±8.97   6.16±7.89 0.06 BPd baseline (mmHg)  76.65±12.39  76.21±7.91  78.60±10.40  75.24±9.66 BPd stimulated (mmHg)  87.00±11.49  84.91±8.22  91.94±12.34  84.70±10.15 BPd increase  10.35±6.55   8.70±3.92 0.25  13.35±8.57   9.45±9.00 0.06 Open in new tab Table 2 Results of cardiovascular autonomic assessment in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) Values are means±SD. HRmax, maximum heart rate during deep breathing; HRmin, minimum heart rate during deep breathing; HRvar, the difference between HRmax and HRmin; R-R 15, R-R interval at 15th heart beat after standing; R-R 30, R-R interval at 30th heart beat after standing; R-R ratio, the ratio of R-R 30 to R-R 15; BPs baseline, systolic blood pressure while supine; BPs stimulated, lowest systolic blood pressure while standing; BPs decrease, BPs baseline—BPs stimulated; BPd baseline, diastolic blood pressure before handgrip; BPd stimulated, highest diastolic blood pressure during handgrip exercise; BPd increase, BPd stimulated−BPd baseline. Parameter RA patients (n=34) RA controls (n=34) p SLE patients (n=37) SLE controls (n=37) p HRmax (beats/min)  91.59±15.80  84.91±12.00 100.57±15.46  90.95±11.80 HRmin (beats/min)  77.38±16.06  65.38±11.16  81.19±15.51  64.43±9.92 HRvar (beats/min)  14.20±7.57  19.52±6.83 0.001  19.37±7.93  26.51±8.22 0.001 R-R15 (mm)  16.19±2.23  17.59±3.57  14.43±2.83  17.03±2.77 R-R30 (mm)  16.19±2.51  18.27±3.01  14.76±2.68  18.05±2.47 R-R ratio   1.08±0.11   1.05±0.12 0.21   1.02±0.08   1.07±0.12 0.18 BPs baseline (mmHg) 125.06±16.71 118.44±14.00 124.32±14.99 115.32±13.04 BPs stimulated (mmHg) 114.65±17.70 110.85±13.41 113.78±13.04 109.16±12.81 BPs decrease  10.41±11.48   7.58±9.22 0.30  10.54±8.97   6.16±7.89 0.06 BPd baseline (mmHg)  76.65±12.39  76.21±7.91  78.60±10.40  75.24±9.66 BPd stimulated (mmHg)  87.00±11.49  84.91±8.22  91.94±12.34  84.70±10.15 BPd increase  10.35±6.55   8.70±3.92 0.25  13.35±8.57   9.45±9.00 0.06 Values are means±SD. HRmax, maximum heart rate during deep breathing; HRmin, minimum heart rate during deep breathing; HRvar, the difference between HRmax and HRmin; R-R 15, R-R interval at 15th heart beat after standing; R-R 30, R-R interval at 30th heart beat after standing; R-R ratio, the ratio of R-R 30 to R-R 15; BPs baseline, systolic blood pressure while supine; BPs stimulated, lowest systolic blood pressure while standing; BPs decrease, BPs baseline—BPs stimulated; BPd baseline, diastolic blood pressure before handgrip; BPd stimulated, highest diastolic blood pressure during handgrip exercise; BPd increase, BPd stimulated−BPd baseline. Parameter RA patients (n=34) RA controls (n=34) p SLE patients (n=37) SLE controls (n=37) p HRmax (beats/min)  91.59±15.80  84.91±12.00 100.57±15.46  90.95±11.80 HRmin (beats/min)  77.38±16.06  65.38±11.16  81.19±15.51  64.43±9.92 HRvar (beats/min)  14.20±7.57  19.52±6.83 0.001  19.37±7.93  26.51±8.22 0.001 R-R15 (mm)  16.19±2.23  17.59±3.57  14.43±2.83  17.03±2.77 R-R30 (mm)  16.19±2.51  18.27±3.01  14.76±2.68  18.05±2.47 R-R ratio   1.08±0.11   1.05±0.12 0.21   1.02±0.08   1.07±0.12 0.18 BPs baseline (mmHg) 125.06±16.71 118.44±14.00 124.32±14.99 115.32±13.04 BPs stimulated (mmHg) 114.65±17.70 110.85±13.41 113.78±13.04 109.16±12.81 BPs decrease  10.41±11.48   7.58±9.22 0.30  10.54±8.97   6.16±7.89 0.06 BPd baseline (mmHg)  76.65±12.39  76.21±7.91  78.60±10.40  75.24±9.66 BPd stimulated (mmHg)  87.00±11.49  84.91±8.22  91.94±12.34  84.70±10.15 BPd increase  10.35±6.55   8.70±3.92 0.25  13.35±8.57   9.45±9.00 0.06 Open in new tab References 1 Conn DL. Rheumatoid neuropathy. 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TI - Cardiovascular autonomic nervous system dysfunction in patients with rheumatoid arthritis and systemic lupus erythematosus
JF - QJM: An International Journal of Medicine
DO - 10.1093/qjmed/92.2.97
DA - 1999-02-01
UR - https://www.deepdyve.com/lp/oxford-university-press/cardiovascular-autonomic-nervous-system-dysfunction-in-patients-with-ij3zRcGsrU
SP - 97
EP - 102
VL - 92
IS - 2
DP - DeepDyve
ER -