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C HAPTER 1 7 / Heart Rate Variability 393
near-normal cardiac-specific sympathetic nerve firing. This find- correlations between peak estrogen levels at ovulation and LF
ing suggests insufficient or dysfunctional reinnervation of the car- power (p .05), HF power (p .05), and total power (p .05)
diac muscle, and particularly the SA node with respect to ANS lend modest support for the claim that estrogen has cardioprotec-
nerve fiber communication. 34 tive effects. 61
Biventricular pacing enhanced ANS functioning in a study of
13 patients with heart failure and ventricular conduction distur- Genetics
46
bances. In this surgical procedure, chronic cardiac resynchroniza-
tion is achieved through the permanent implanting of a pacemaker. Genetic factors influence many aspects of health, including
Significant increases were found in several measures of HRV, al- HRV. 62–64 Genetic components are estimated to contribute 13% to
though not in LF power. Larger samples and survival impact analy- 23% of the variance in HRV measures. 63 Genetic testing provides
sis are needed to confirm these early but positive findings. suggestive but nonsignificant evidence linking LF power to chro-
Other cardiac procedures have been explored with respect to mosome 2 at 153 cM and linking very low-frequency power to
64
HRV. Transmyocardial laser revascularization 47 and percutaneous chromosome 15 at 62 cM. Increased HRV is also associated with
transluminal angioplasty 48 are not associated with a significant the genotype factor described as polymorphisms in angiotensin-
change in HRV after procedure, but left ventricular reduction is converting enzyme gene. 62
associated with significant reduction in HRV. 47
Noncardiac surgeries can also have an impact on postoperative Sleep and Wake
HRV patterns. Reduced 24-hour HRV is found in the postopera-
49
tive period after major abdominal surgery. Significantly improved Significant autonomic activity differences between wake and sleep
HRV has been noted in patients receiving kidney transplants and and within different sleep states have been identified. HRV is nor-
for those patients with kidney–pancreas transplants. 50 Measures of mally characterized by greater variability during sleep than wake
HRV may provide an indication of recovery in transplantation as- in adults 65 and children. 66 This sleep-associated increase in vari-
sociated with disorders of autonomic neuropathy. ability persists even after controlling for behavioral rhythms, 67
daytime physical activity, posture, 68 and shift work. 69
Sleep is characterized by two major states: nonrapid eye move-
FACTORS INFLUENCING HRV ment (NREM) sleep and rapid eye movement (REM) sleep.
NREM sleep is further divided into three stages, generally charac-
terized by progressively lower-frequency and higher-amplitude
Several factors have been found to influence HRV and are im- 70
portant considerations for HRV interpretation. The following brain wave activity. Low-voltage, mixed-frequency brain wave
section provides a summary of the influences of age, sex, genet- activity, rapid saccadic eye movements, and CNS-invoked low
ics, sleep and wake, body position, general health, and acute and skeletal muscle tone denote REM sleep. Individuals typically cy-
chronic disorders on HRV. Readers should refer to Chapter 8 for cle between NREM and REM sleep approximately five times over
a detailed review of sleep. the course of the night, with the proportion of REM sleep in-
creasing across the night.
Not surprisingly, HRV patterns differ between NREM and
Age
REM sleep. NREM sleep is characterized by a low LF:HF, inter-
HRV tends to decrease with increasing age. 51–54 This decline is preted to reflect PSNS predominance. 71 Researchers report a pro-
72
caused by decreases in absolute PSNS and SNS activity and by re- gressive increase in vagal activity across NREM sleep stages. The
ductions in their relative dominance. 9,55 Premature very low- higher LF:HF seen during REM sleep is similar to that of wake-
birthweight infants have a better developed SNS but an underde- fulness and reflects a higher sympathetic tone. 71,73,74 During peri-
veloped PSNS. 56 ods of acute psychophysiological stress, the normal increase in
Stimulus challenge tests, such as active standing, are frequently PSNS across NREM is blunted and SNS power is higher and this
included in assessments of ANS function. Test results should be in- increase in sympathetic activity during NREM is associated with
terpreted within the context of the patient’s age because responses to greater difficulties in sleep maintenance. 75
sympatho-excitatory (i.e., active standing) and sympatho-inhibitory Sleep is scored in terms of discrete stages in 30-second epochs,
(i.e., cold face challenge) stimuli decrease with age. 57 but there is a range in the amount of delta (slow wave) activity
present within these stages. Findings suggest that mixed SNS and
Sex and Sex Hormones PSNS activity (LF:HF) is negatively dependent on the amount of
delta activity, whereas PSNS activity (HF) is independent of delta
Sex and the interaction of sex and age appear to influence HRV. activity. 76
Healthy women typically have higher heart rates and less HRV A final consideration for HRV patterns in sleep is arousal ac-
than healthy men. 53,58,59 Young men are reported to exhibit par- tivity. Electroencephalography-defined arousals occur with a
ticularly high values in vagal-related indices (rmsSD, SDNN). 58 movement to a lower sleep stage or to wake. These arousals are as-
77
Other studies support that lower sympathetic predominance (low sociated with increased LF power in the cardiac signal. Although
LF) and higher vagal activity (high HF) are seen in middle-aged more subtle, NREM sleep is also characterized by two arousal
women. 55,60 Sex disparities in HRV values diminish with increas- rhythms. These NREM rhythms include a state of sustained
ing age, 58 disappearing entirely by 60 years of age, 59,60 and possi- arousal instability known as cyclic alternating pattern (CAP) and
bly as early as 40 years of age. 21 a stable arousal condition known as non-CAP. The percentage of
The impact of endogenous sex hormones on ANS activity has LF power is greater in CAP, and HF power is greater in non-CAP
been explored. HRV is not significantly different across menstrual within NREM stage 2 sleep and NREM slow-wave sleep. 78 Peri-
phases, although heart rate is increased at ovulation. Positive odic leg movements in sleep are frequently associated with