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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 6, November/December 2015
AFRICA
215
NY, USA) with a sampling rate of 1 024 Hz was performed on
all subjects enrolled in the study. The HRV was automatically
analysed with software of the same device.
Standard deviation of all R–R intervals (SDNN), standard
deviation of the successive N–N differences (SDSD), standard
deviation of the averages of the R–R intervals in all five-minute
segments of R–R intervals (SDANN), the mean of all the five-
minute standard deviations of N–N (normal R–R) intervals
during the 24-hour period (SDNN index), the mean square
root of the difference of successive R–R intervals (RMSSD),
successive N–N intervals differing more than 50 ms (NN50
count), and the proportion of adjacent normal R–R intervals
<
50 ms (pNN50) were defined as the time-domain variables of
HRV analysis. HRV analyses of the patients with primary RP
were compared with those of healthy controls.
Statistical analysis
The data were tested for normal distributions using the
Kolmogorov–Smirnov test. The continuous variables are
presented as means
±
standard deviation (SD) and the categorical
variables as percentages. The chi-square test was used to compare
categorical data and the independent-samples
t-
test was used to
compare quantitative data. Spearman’s and Pearson’s correlation
coefficients were used to perform univariate correlation. A
p
-value
<
0.05 was considered statistically significant. All
statistical analyses and calculations were performed using the
Statistical Package for Social Sciences version 20.0 (SPSS,
Chicago, Illinois, USA).
Results
Thirty patients (median age 21 years, IQR: 2) in whom the
three-phase cold test was positive, were diagnosed as primary
RP and enrolled in the study. The average duration of primary
RP patients’ symptoms was 3 (2.13) years [median (IQR)]. The
control group consisted of 31 healthy subjects (median age 21
years, IQR: 3). There was no statistically significant difference
between primary RP patients and healthy control subjects
regarding basal demographic characteristics (Table 1).
All participants were in sinus rhythmwithout any arrhythmias.
Statistical analysis of the HRV analyses showed a significant
decrease in time-domain variables of SDNN, RMSDD, NN50
count, PNN50 and SDNN index between the two groups (
p
<
0.05 for all) (Table 2).
Univariate correlation analysis showed that the presence of
primary RP was moderately correlated with SDNN (
r
=
0.287,
p
=
0.025), RMSDD (
r
=
0.297,
p
=
0.020), NN50 count (
r
=
0.340,
p
=
0.007), PNN50 count (
r
=
0.281,
p
=
0.028) and SDNN index
(
r
=
0.409,
p
=
0.001). We did not find any significant correlation
between the duration of Raynaud’s phenomenon and the time-
domain HRV indices (
p
>
0.05 for all).
To demonstrate the independent effect of time-domain
HRV indices on the presence of primary RP, we performed a
multivariate logistic regression analysis using the LR method,
based on independent variables likely to affect the level of mean
platelet volume. In multivariate analysis, SDNN index (
β =
1.138,
95.0% CI
=
1.049–1.235,
p
=
0.002) and PNN50 (
β =
0.881, 95.0%
CI
=
0.785–0.989,
p
=
0.032) were the only independent variables
(Table 3).
Discussion
The pathogenesis of primary RP appears to be multifactorial.
The endothelium, smooth muscle, circulating mediators, and
autonomic and sensory nerves play a pivotal role in maintaining
vasomotor homeostasis. Disturbance in these factors may lead
to vasospasm of the small arteries and arterioles and to the
manifestation of RP.
Since Maurice Raynaud, a French physician, first described
Raynaud’s phenomenon in 1862, sympathetic nervous system
over-reactivity has been suggested as the most common cause
of the disease. Besides sympathetic up-regulation, impaired
parasympathetic activation has also been blamed.
5
Therefore, it
is suggested that the autonomic nervous system seems to have
a pivotal role in the pathogenesis of Raynaud’s phenomenon.
6-8
However, it should be noted that the autonomic nervous system
may not be affected to the same degree in all patients with RP.
The cyclic changes in the sinus node rate over time are defined
as heart rate variability. HRV analysis provides information on the
balance between sympathetic and parasympathetic innervation of
the heart and has been extensively used as an indirect method for
the determination of cardiac autonomic function.
9
Physical and
mental stress, exercise, and respiratory and metabolic changes are
associated with autonomic tone of heart rate.
10,11
Table 2. Comparison of time-domain HRV indices
between the two groups
Primary RP
(
n
=
30)
Control
(
n
=
31)
p-
value
Mean heart rate (bpm)
76.80
±
12.99
76.22
±
11.74 0.857
SDNN (ms)
145.09
±
40.65
177.55
±
66.18 0.025
SDSD (ms)
46.43
±
24.03
63.40
±
42.04 0.059
NN50 count (%)
11085.53
±
10246.89 19302.74
±
12717.30 0.007
RMSDD (ms)
42.58
±
22.76
63.39
±
42.04 0.020
SDANN (ms)
93.33
±
65.78
79.06
±
75.89 0.437
SDNN index
55.71
±
24.50
82.03
±
34.25 0.001
pNN50
13.30
±
12.74
21.92
±
16.86 0.028
SDNN: standard deviation of all R–R intervals, SDSD: standard devia-
tion of the successive N–N differences, NN50 count: successive N–N
intervals differing more than 50 ms, RMSSD: the mean square root of
the difference of successive R–R intervals, SDANN: standard devia-
tion of the averages of the R–R intervals in all five-minute segments of
R–R intervals, SDNN index: the mean of all the five-minute standard
deviations of N–N (normal R–R) intervals during the 24-hour period,
pNN50: the proportion of adjacent normal R–R intervals
<
50 ms.
Table 1. Basal demographic and clinical
characteristics of the two groups
Primary RP
(
n
=
30)
Control
(
n
=
31)
p-
value
Age (years), median (IQR)* 21 (2)
21 (3)
0.381
Male,
n
(%)
30 (100)
31 (100)
NA
SBP (mmHg)
116.76
±
10.45 119.41
±
10.13 0.318
DBP (mmHg)
74.43
±
7.81 75.54
±
9.30 0.615
Smoking,
n
(%)
10 (33.3)
7 (22.6)
0.258
Duration of primary RP
(years), median (IQR)*
3 (2.13)
–
NA
*Data without normal distribution were expressed as median (inter-
quartile range).
RP: Reynaud’s phenomenon, SBP: systolic blood pressure, DBP:
diastolic blood pressure IQR: interquartile range.