Heart Rate and Blood Pressure Variabilities in Salt-Sensitive Hypertension
In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P<.05) and of heart rate at rest (59.2±2.4 normalized units [NU], P<.001) than salt-resistant subjects (6.6±0.3 mm Hg2, 55.0±3.2 NU) and normotensive control subjects (5.1±0.5 mm Hg2, 41.6±2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P<.001) and the ratio of low- to high-power frequency (P<.001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0±0.7 to 17.5±0.7 ms/mm Hg, P<.001) and salt-resistant subjects (from 6.9±0.7 to 13.9±0.9, P<.05) but not in salt-sensitive subjects (7.4±0.3 to 7.9±0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.
Experimental evidence in spontaneously hypertensive rats and salt-sensitive hypertensive humans shows that a high sodium intake results in sympathetic hyperactivity and changes in baroreflex sensitivity.1 2 3 These two mechanisms could therefore be responsible for the onset and maintenance of high pressures in essential hypertension. We designed this study to determine whether sodium intake influences autonomic nervous system activity in salt-resistant and salt-sensitive hypertensive subjects. For this purpose, we studied HR and BP variabilities and baroreceptor sensitivity by power spectral analysis.
These two hypotheses need verifying for several reasons. First, plasma and urinary catecholamine levels merely indicate sympathetic efferent activity, supplying no information about receptor activity or its effect on the innervated organ.4 In addition, because plasma and urinary catecholamine levels also depend on efficient nerve terminal reuptake, the relation between norepinephrine release and sympathetic activity is nonlinear.5 Previous studies, however, have determined baroreflex activity with a neck chamber and low body pressure without phenylephrine testing.3 Even though phenylephrine testing is a more invasive and less selective method, it yields more reliable data that is less influenced by the psychological profile of the patient.
With this background knowledge, we sought to verify whether sodium-induced changes in autonomic nervous system control lead to changes in the spectral densities of HR and BP variabilities and baroreflex sensitivity. For this purpose, in salt-sensitive and salt-resistant hypertensive and normotensive subjects undergoing two dietary salt regimens, we studied power spectral densities of HR and BP and baroreflex sensitivity.
Nearly 15 years of research has established that the spectral density of 0.25 Hz, known as HF power, corresponds to HR and BP oscillations induced by respiratory activity. Hence, this spectral band provides a measure of parasympathetic activity.6 7 The power spectral density around 0.10 Hz, termed LF power, seems to be determined by sympathetic afferent activity on the cardiovascular system8 9 ; the LF/HF ratio of HR variability gives an index of cardiac sympathovagal balance activity.10 11
For study participants, we initially recruited a group of 52 subjects (45 men and 7 women) comprising 37 hypertensive (33 men and 4 women) and 15 normotensive (12 men and 3 women) individuals from our outpatient clinic. Hypertension was defined as DBP equal to or greater than 95 mm Hg. On recruitment, hypertensive subjects did not know they had hypertension; hence, none of them had received pharmacological treatment, none had other diseases or cardiovascular complications, and none had a history of raised BP. All subjects had been regularly attending the clinic for once-monthly BP readings, which had never detected raised pressure. Their clinic attendance depended solely on a family history of hypertension or cardiovascular disease. These criteria enabled us to select as many subjects as possible who had raised BPs of recent onset and thus to observe neuroautonomic activity in the earliest stages of arterial hypertension.
Subjects were excluded if they had a history or demonstrable evidence of cardiovascular, respiratory, renal (presence of proteinuria and creatinine >132.6 μmol/L), liver, or gastrointestinal diseases. Other exclusion criteria were DBP greater than 114 mm Hg, body mass index greater than 26 kg/m2, age greater than 55 years, smoking (more than five cigarettes per day), diabetes (presence of glycosuria or fasting glycemia >6.66 mmol/L or 6.10 mmol/L at 2 hours after glucose loading), plasma cholesterol greater than 5.7 mmol/L, arrhythmias or conduction abnormalities, ultrasound evidence of carotid stenosis of importance, or echocardiographic evidence of wall motion abnormalities of the left ventricle or valvular disease. The only ECG abnormalities allowed were signs of left ventricular hypertrophy. All subjects underwent Bruce protocol stress testing designed to eliminate from the study subjects with silent myocardial ischemia. Tests were considered valid only if the subject reached at least 90% of the maximal age-corrected frequency. Two-dimensional and M-mode echocardiograms were recorded from standard parasternal and apical windows with a commercially available ultrasound unit (ATL Ultramarks). Each variable was measured according to the conventions of the American Society of Echocardiography.12 Echocardiographic left ventricular mass was calculated from Penn convention standards according to the method described by Devereux and Reichek13 and was indexed for body surface area (LVMI). All subjects had sedentary occupations. No subject had taken part in a program of intense physical training or had received medication for at least 2 months before the study.
Subjects were assigned to a hypertensive group (>95 mm Hg) or a control normotensive group (<95 mm Hg) according to BP findings. On the day before BP readings, subjects underwent a urinary sodium excretion test.
All subjects were admitted to the hospital and underwent a 3-week period of controlled sodium intake during which they received a diet providing a total sodium content of about 20 mmol/d. During the first week (washout period), they received no oral sodium supplement, the daily sodium intake being only 20 mmol (Fig 1⇓). During the second week, sodium intake was increased in a double-blind manner. In addition to the controlled-sodium diet, subjects took a daily supplement consisting of four sodium capsules, each containing 50 mmol, supplying a total sodium intake of 220 mmol/d (Fig 1⇓). During the third week, they repeated the low sodium diet, supplying 20 mmol/d, this time supplemented with four placebo capsules (dextrose) daily (Fig 1⇓).
Sodium intake was checked by measurement of 24-hour urinary sodium excretion (>200 mmol/d during the high sodium diet and <35 mmol/d during the low sodium diet). To distinguish salt-sensitive from salt-resistant hypertensive subjects, we measured BP again after the second 1-week low sodium and placebo regimens (Fig 1⇑). Salt-sensitive hypertensive subjects were defined as those whose DBP measured after the 7-day high sodium regimen fell by more than 10 mm Hg after the low sodium regimen2 14 15 (Fig 1⇑).
During controlled-sodium regimens, BP was measured every morning, by traditional mercury sphygmomanometry, at 8 am after subjects had rested 15 minutes and when they were supine.
All subjects underwent two ECG recordings (Telemetria Battaglia Rangoni) of HR and beat-to-beat BP (Finapres) and two phenylephrine baroreflex sensitivity studies during two controlled dietary sodium regimens (Fig 1⇑): high sodium intake (220 mmol/d) and low sodium intake (placebo). Before each study day, subjects also underwent 24-hour urine collection for determination of sodium and norepinephrine excretion. HR and BP recordings obtained at baseline (rest) and after sympathetic stress (after tilt) were used for off-line spectral analysis of HR and BP variabilities. BP at rest and after tilt was measured with a sphygmomanometer. BP values used for comparisons among the three groups during the various sodium intake regimens were therefore read manually, whereas beat-to-beat BP values during spectral analysis were evaluated by a noninvasive volume-clamp device (Finapres, Ohmeda). HR and BP recordings for spectral analysis in all subjects took place according to the following protocol: At 8:30 am after BP measurement, in a quiet, comfortable environment (24°C), the subject rested supine for at least 30 minutes before undergoing a 15-minute ECG beat-to-beat BP and respiratory signal recording (rest). Afterwards, subjects underwent head-upright tilt testing, a passive orthostatic maneuver obtained with a motorized tilt table. During 15 minutes upright (90°), the subject underwent a second ECG beat-to-beat BP and respiratory recording (tilt). Transit from 0° to 90° took about 15 seconds. If hypotension (an SBP fall of 20 mm Hg) or if symptoms indicating the onset of syncope, nausea, or heartburn developed during tilt, testing was stopped and the subject was excluded from the study. Respiratory activity was measured with a thermistor probe. On the same morning at 7:30 am, 1 hour before HR and BP recordings, blood samples were drawn for determination of sodium and aldosterone levels and plasma renin activity. Plasma renin activity and aldosterone were assayed by radioimmunoassay. Plasma and urinary sodium levels were measured with standard laboratory methods. Twenty-four-hour urine samples were stored at −80°C until required for assay of 24-hour norepinephrine concentrations. Urinary norepinephrine was measured by high-performance reversed-phase liquid chromatography with electrochemical detection.
Off-line Analysis of HR and BP Variabilities
We used an autoregressive algorithm to compute power spectral densities from the ECG and beat-to-beat BP recordings. ECG beat-to-beat BP and respiratory signals were digitized, stored on hard disk, and sampled at a rate of 500 Hz, with 12 precision bits. From a series of 512 consecutive beats, the autocorrelation functions were applied to the complete RR, SBP, and DBP series; the Yule-Walker matrix (autocorrelation values matrix) was calculated with the method of Levinson-Durbin16 ; the matrix order was determined with the Anderson test16 and Akaike Information Criteria17 ; and the spectral decomposition method was then applied for estimation of the power and central frequency of each spectral component.18 Spectral power of HR is expressed in milliseconds squared; spectral power of BP is expressed in millimeters of mercury squared. The frequencies of the RR, SBP, and DBP oscillations divided by the mean RR interval, SBP, and DBP values, respectively, expressed in milliseconds and millimeters of mercury, were calculated in cycles per beat and then converted into hertz equivalents (Hz Eq). We also determined the TP of HR variability, of SBP, and of DBP as well as the total spectral density of these variables. For HR, SBP, and DBP, we calculated the following spectral power components: HF component, from 0.16 to 0.40 Hz Eq; LF component, from 0.04 to 0.15 Hz Eq; and VLF component, less than 0.04 Hz Eq (Fig 2⇓).
Power spectra from the respiratory trace were analyzed on the signal sampled once every cardiac cycle and used as a reference for identification of HR oscillations caused by respiratory sinus arrhythmia. The RR interval and respiratory signal recordings were also used for cross-spectral analysis. To avoid respiratory events that might influence LF power, we checked that subjects breathed at a rate of at least 9 breaths per minute (0.15 Hz).
The resulting spectral data of HR were transformed into the natural logarithm of the variable2 19 20 and LF and HF powers into NUs.2 6 10 11 Transforming data into NUs also helped to accentuate sympathetic/vagal balance activity. NUs were calculated as follows: LF NUs=(LF Power/TP−VLF Power)×100; HF NUs=(HF Power/TP−VLF Power)×100. Calculation of NUs annuls the effect of TP on the spectral profile. In other words, increased sympathetic activity corresponds to increased total HR variability and consequently lower TP. For this reason, despite a decrease in absolute LF spectral density, LF power will predominate.
After the ECG recording for spectral analysis of HR and beat-to-beat BP variabilities at rest and after tilt, we studied baroreflex sensitivity, calculated by relating the increase in pulse interval, measured in milliseconds, to the phenylephrine-induced surges in mean BP, measured in millimeters of mercury. The method has been described in detail by Korner et al.22 23
Statistical Methods and Data Analysis
All data were collected with the Lotus 1-2-3 database (Lotus Development Corp) and evaluated with Primit (McGraw-Hill) and SPSS PC+. All subjects were subdivided according to BP and salt sensitivity (salt sensitive or salt resistant). Data are expressed as mean±SE.
Because spectral data and baroreflex sensitivity from individual subjects were obtained under two controlled sodium conditions, we compared data from the salt-sensitive and salt-resistant hypertensive and normotensive subjects during high (220 mmol/d) and low (20 mmol/d) sodium intakes. ANOVA was used for comparison of general characteristics (including age, body mass index, urinary sodium concentrations, plasma renin activity, plasma aldosterone, arterial pressure, and HR); TP and VLF, LF, and HF powers; baroreflex sensitivity; and echocardiographic data in salt-sensitive and salt-resistant hypertensive and normotensive subjects. The Mann-Whitney test was used for comparison of LF NUs, HF NUs, and the LF/HF ratio in salt-sensitive and salt-resistant hypertensive and normotensive subjects. Student's paired t test was used for evaluation of differences between baseline and tilt values of arterial pressure; median RR interval; BP; TP; and VLF, LF, and HF powers. The Wilcoxon rank test was used for comparison of LF NUs, HF NUs, and the LF/HF ratio in the same subgroup before and after tilt.
The possible association between the spectral power components, the other variables studied, and LVMI was assessed during high sodium intake (220 mmol/d) in a stepwise multiple regression analysis considering LVMI as the dependent variable and the following as independent variables: 24-hour urinary sodium intake; 24-hour urinary norepinephrine excretion; plasma aldosterone; plasma renin activity; plasma sodium; baroreflex sensitivity, HR, SBP, and DBP at baseline and after tilt; and spectral data on HR and BP variabilities at baseline and after tilt.
A value of P<.05 was considered statistically significant.
Thirty-five subjects (32 men and 3 women) completed the study. Twenty-five (23 men and 2 women) were hypertensive and 10 (9 men and 1 woman) were normotensive. Seventeen subjects (13 men and 4 women), 3 (1 man and 2 women) normotensive and 14 (12 men and 2 women) hypertensive, were excluded. Two subjects initially designated as normotensive were later moved to the hypertensive group because their DBP values rose during the high sodium diet. Both of these subjects had DBP greater than 105 mm Hg. Follow-up clinic visits after the study confirmed raised BP on three occasions. Eight of the 17 (5 men and 3 women) were excluded because they had sodium excretion values outside the range of sodium intake, 4 (3 men and 1 woman) because DBPs of greater than 114 mm Hg developed during the study, and 5 (all men) because presyncope symptoms developed during the head-up tilt test. Twenty-four-hour urinary excretion rates did not differ significantly in the 35 subjects.
The three dietary sodium regimens identified 14 subjects (13 men and 1 woman) who had salt-sensitive hypertension, 11 (10 men and 1 woman) who had salt-resistant hypertension, and 10 (9 men and 1 woman) who were normotensive. Sex, age, height, and body mass index did not differ significantly among the three groups, but LVMI was significantly higher in salt-sensitive and salt-resistant subjects than in normotensive control subjects (P<.001) (Table 1⇓).
No statistically significant differences were found among the three groups for plasma and urinary sodium levels, plasma aldosterone, or plasma renin activity under the same experimental conditions of sodium intake (Table 2⇓). During the high sodium intake, salt-sensitive subjects had significantly higher urinary norepinephrine excretion rates (P<.05) than did salt-resistant or normotensive subjects (Table 2⇓).
Except in salt-resistant hypertensive subjects, changes in salt intake did not lead to changes in HR (Table 3⇓). During the high sodium intake, only salt-sensitive hypertensive subjects had significant changes in SBP (Table 4⇓).
During the switch from a high to a low sodium intake, salt-sensitive subjects had significantly higher DBPs at baseline and after tilt. During high sodium intake, both hypertensive groups had higher resting DBPs than normotensive control subjects (P<.001). During low sodium intake, salt-resistant hypertensive subjects had higher DBPs than normotensive control or salt-sensitive hypertensive subjects. Tilt almost invariably induced a significant increase in DBP; only the salt-resistant hypertensive subjects had nonsignificant increases (Table 5⇓).
HR Variability and Salt Intake During Rest
At rest, all subjects had significantly higher total HR variability, expressed as the natural logarithm of TP, during high sodium intake than during low sodium intake (Table 3⇑). The increased natural logarithm of TP was associated with an increase in all spectral components.
In the salt-sensitive (P<.001) and normotensive (P<.05) groups, the LF/HF ratio was significantly higher during high sodium than during low sodium intake. After the low sodium regimen, the LF/HF ratio remained significantly higher than that of control subjects (P<.001) only in the salt-resistant hypertensive group.
In salt-sensitive but not in salt-resistant hypertensive subjects, LF NUs at rest were significantly higher during high sodium than during low sodium intake (P<.001). In contrast, normotensive control subjects had higher LF NUs during low sodium intake (P<.05) (Fig 3⇓). The two hypertensive groups also had higher LF NUs at rest than normotensive control subjects during high sodium intake. However, LF NUs remained significantly higher than in normotensive control and salt-sensitive subjects also during the low sodium intake (Fig 3⇓). During high sodium intake, salt-sensitive hypertensive subjects had slightly higher LF NUs than salt-resistant and normotensive subjects (59.2±2.4 versus 55.0±3.2; control subjects, 41.6±2.9); during low sodium intake, salt-sensitive subjects had lower LF NUs than salt-resistant and normotensive subjects (48.4±1.6 versus 58.9±2.0; control subjects, 50.0±1.1) (Fig 3⇓).
HF NUs behaved in an opposite manner. In salt-sensitive subjects, HF NUs were significantly lower during high sodium than during low sodium intake (P<.001). By contrast, in normotensive subjects, HF NUs were significantly higher during high sodium intake. During high sodium intake, HF NUs were significantly lower in salt-sensitive than in salt-resistant hypertensive (P<.001) and control subjects. In particular, during high sodium intake, HF NUs at rest were lower in salt-sensitive subjects than in salt-resistant or normotensive subjects (36.4±2.2 versus 43.7±3.5; control subjects, 55.6±2.3). After the low sodium intake, they remained significantly lower only in salt-resistant subjects (P<.05). HF NUs measured at rest during low sodium intake were similar in hypertensive and control subjects (salt-sensitive, 47.2±1.4; salt-resistant, 38.3±2.2; control subjects, 46.5±1.8).
HR Variability and Salt Intake During Tilt
Comparison of spectral indexes at rest and during tilt showed that during both tilt and low sodium intake, all groups had significantly lower TP of HR variability, expressed as the natural logarithm of TP. Comparison of spectral power during the two sodium intakes showed that all groups had a significantly greater natural logarithm of TP during the high dietary sodium intake (Table 3⇑).
During high sodium intake, normotensive subjects had reduced HF power densities and hence a high LF/HF ratio (Table 3⇑). During low sodium intake, normotensive control subjects also had a higher LF/HF ratio than the hypertensive groups.
During high sodium intake in all subjects, LF NUs increased significantly between rest and tilt (Fig 3⇑). During low sodium intake, only normotensive control subjects (P<.001) had significantly increased post-tilt LF NUs (P<.001). During low sodium intake, normotensive control subjects also had higher post-tilt LF NUs than the two hypertensive groups (Fig 3⇑). However, only salt-sensitive subjects had markedly higher post-tilt LF NUs during high than during low sodium intake (salt-resistant subjects, 76.1±2.5 versus 51.3±1.4, P<.001; salt-sensitive subjects, 71.2±2.9 versus 62.2±3.8; control subjects, 79.0±2.5 versus 72.5±3.4).
Like the other spectral variables, HF NUs behaved in an opposite manner after tilt. In all groups, HF NUs declined significantly between rest and tilt after high sodium intake. But only in normotensive control subjects did HF NUs show this pattern also after low sodium intake. In addition, during high sodium intake, salt-sensitive subjects had significantly lower HF NUs than the other two groups. During high sodium intake, HF NUs differed in the three groups (salt-sensitive subjects, 36.4±2.2; salt-resistant subjects, 43.7±3.5; control subjects, 55.6±2.3). During low sodium intake, the three groups had similar HF NUs (salt-sensitive subjects, 47.2±1.4; salt-resistant subjects, 38.3±2.2; control subjects, 46.5±1.8).
SBP Variability During Rest and Tilt
Comparison of total variability, expressed as TP, in the two salt-intake conditions at rest showed that all 11 subjects had significantly higher TP values during the high sodium intake (Table 4⇑). During high sodium intake, salt-sensitive hypertensive subjects also had higher LF power than salt-resistant (P<.05) and control (P<.05) subjects (Table 4⇑). During low sodium intake, salt-resistant subjects had significantly higher LF power than the salt-sensitive (P<.05) and control (P<.05) subjects.
In all subjects, post-tilt TP was invariably significantly higher during high sodium intake, above all because of the increase in the VLF and LF components (Table 4⇑). During high sodium intake, the hypertensive subjects had significantly lower post-tilt LF power than normotensive control subjects.
DBP Variability During Rest and Tilt
DBP variability at rest did not differ significantly in the three groups. In all three groups, high sodium intake induced significantly higher TP.
In the two hypertensive groups during high sodium intake, tilt induced a reduction in resting TP. In all subjects during high sodium intake, tilt also significantly reduced resting LF power (P<.05). During low sodium intake, exactly the opposite happened so that in all subjects, resting LF power significantly increased (Table 5⇑).
During high sodium intake, normotensive control subjects showed significantly greater baroreceptor sensitivity than salt-sensitive (P<.001) and salt-resistant (P<.05) hypertensive subjects; salt-sensitive subjects had significantly lower sensitivity than salt-resistant subjects (P<.001) (salt-sensitive subjects, 7.9±0.4 ms/mm Hg; salt-resistant subjects, 13.9±0.9; control subjects, 17.5±0.7).
Salt-resistant (P<.001) and normotensive (P<.001) subjects had significantly higher baroreflex sensitivity during high sodium intake than during low sodium intake. During low sodium intake, normotensive control subjects (P<.05) showed greater baroreflex sensitivity than the two hypertensive groups (salt-sensitive subjects, 7.4±0.3 ms/mm Hg; salt-resistant subjects, 6.9±0.7; control subjects, 10.0±0.7).
Left Ventricular Mass Index
Multiple regression analysis showed that LVMI was associated with baroreflex sensitivity (β=−0.28, P=.0076), resting DBP (β=0.49, P=.0001), the natural logarithm of HF power of HR variability at rest (β=0.20, P=.04), the LF/HF ratio of HR variability at rest (β=0.25, P=.01), and VLF power of HR variability at rest (β=−0.25, P=.01; y=−4.47×Baroreflex Sensitivity [ms/mm Hg]+1.87×DBP [mm Hg]−8.43×HF Power [ms2]+10.26×LF/HF Ratio−14.26×ln VLF Power of HR Variability [ms2]; R2=0.76; F=19.6; P<.0001) (Fig 4⇓).
Effect of High Sodium Intake on HR and BP Variabilities at Rest
In this study, we have shown that in all subjects, a high sodium intake induced an increase in TP of HR and BP variabilities. LF power and the LF/HF ratio of HR and the LF power of SBP invariably tended to increase; therefore, this phenomenon could indicate increased cardiovascular sympathetic efferent activity during a high sodium intake.
The increased LF NUs and LF/HF ratio of HR variability show a sympathovagal activity imbalance toward adrenergic hyperactivity in both the salt-sensitive and salt-resistant hypertensive subjects. Our observation that the changeover to the low sodium intake caused LF NUs and the LF/HF ratio to decrease in the salt-sensitive subjects alone implies that cardiac sympathetic activity in this hypertensive group varies with sodium intake.
In the salt-resistant subjects, increased sympathetic activity could be compensated for by increased baroreceptor reflex sensitivity, which renders BP levels of the salt-resistant hypertensive subjects wholly independent of sodium intake. We based this interpretation on our observation that in the salt-resistant group, baroreflex sensitivity increased with salt intake. The same phenomenon occurred also in normotensive control subjects. The differences among groups could be the baroreflex pressure set point, which was much higher in salt-resistant hypertensive subjects and much lower in normotensive subjects.
The higher 24-hour norepinephrine concentrations during low sodium intake observed in all groups except the salt-sensitive subjects confirm the spectral data.
Effect of High Sodium Intake on HR and BP Variabilities After Tilt
In normotensive subjects, during all controlled salt regimens, tilt induced an increase in LF NUs, the LF/HF ratio, and the LF power of SBP variability, thus providing evidence of increased cardiovascular sympathetic activity. The LF power of DBP variability increased only during low sodium intake. In other words, in normotensive subjects, the increase in the LF power of DBP variability is inversely sodium dependent. During high sodium intake, because the sympathetic activity responsible for inducing the LF power of SBP variability is already high at baseline (rest), a further stimulus fails to increase it more. This is what happens normally in hypertensive subjects who have elevated pressor levels for a lengthy period.24
Neither salt-sensitive nor salt-resistant subjects managed to increase the LF power of HR variability, expressed in the absolute sense, during orthostatic stress, low sodium, or high sodium. Their LF NUs and LF/HF ratio, in contrast, behaved ambiguously toward salt intake; yet behavior was identical in the two groups. During high sodium intake, both hypertensive groups increased their LF NUs and LF/HF ratio, even though as other investigators have noted,2 25 the increase did not equal that of normotensive control subjects. In contrast, during low sodium intake, they could not increase these two variables. Notably, under the first condition, the salt-sensitive and salt-resistant hypertensive subjects achieved an increase in post-tilt LF NUs only half that of normotensive control subjects (see Fig 3⇑).
During low sodium intake, the two hypertensive groups appeared unable to increase either LF NUs or the LF/HF ratio. This observation contrasts with conclusions obtained with nonspectral methods.1 Our spectral data show that although all hypertensive subjects can augment sodium-induced sympathetic activity, only in salt-sensitive subjects does this hyperactivity lead to increased BP. One reason is that salt-sensitive subjects are less able to adapt baroreflex sensitivity.
Comparison With Previous Studies
It is difficult to compare our findings with those of other researchers. No published study of HR and BP variabilities has divided subjects according to salt sensitivity and analyzed spectral power during two controlled salt intakes. Hence, when published data and ours agree, study conditions were similar; when they disagree, study conditions were not similar. Although our findings broadly overlap with those of Guzzetti et al,25 26 Furlan et al,24 and our earlier preliminary study,2 they differ from those of Takalo et al,27 Parati et al,28 and Radaelli et al.10 The disagreement with Radaelli et al undoubtedly depends on the fundamental differences in study methods. Apart from salt intake, Radaelli et al included subjects who had already received pharmacological treatment. They also made shorter recordings (250 beats), tested subjects under conditions of parasympathetic stress (controlled breathing),6 and used a tilt test lasting only 10 minutes. To ensure that respiratory events did not influence the LF spectral density, these investigators recommended having subjects breathe at 15 breaths per minute (0.25 Hz). We believe that this engenders misleading data because controlled breathing leads not to a condition of sympathovagal balance but to parasympathetic stimulation. Data and conclusions thus obtained therefore cannot be compared with those obtained under free breathing conditions, also because of the nonlinear behavior of HR variability. To ensure that a subject's breathing activity does not influence LF power, respiratory activity should be monitored, and recordings including events with a frequency of less than nine respirations per minute (0.15 Hz) should be discarded. This never happened in our study, first because we asked subjects not to sleep and to breathe normally, and second because in subjects without cardiorespiratory diseases or complications, the normal respiratory rate always exceeds 0.15 Hz and never exceeds 0.40 Hz.
Relations Between Left Ventricular Hypertrophy, Spectral Data, and Other Variables
Even though we presume that our subjects had arterial diastolic hypertension of recent onset, even the presence of slight cardiac hypertrophy suggests that left ventricular hypertrophy depended not on prolonged exposure to raised BP but on increased sympathetic activity, which in salt-sensitive hypertensive subjects must be a sodium-dependent event. Our multiple regression analysis showed that BP levels and the index of sympathovagal balance associated with myocardial hypertrophy and that vagal activity expressed by baroreceptor sensitivity were negatively associated with the HF power of HR variability (Fig 4⇑). The physiological importance of the VLF power remains controversial. Some evidence supports a negative association between catecholamine concentrations29 and plasma renin activity.7 In addition, diminished VLF power may be a marker of sudden death in individuals with cardiovascular disease.20 Valuable information should be gained by studying these markers in the follow-up of hypertensive individuals with left ventricular hypertrophy.
Selected Abbreviations and Acronyms
|DBP||=||diastolic blood pressure|
|LF/HF ratio||=||ratio of low- to high-frequency powers of heart rate variability|
|LVMI||=||left ventricular mass index|
|SBP||=||systolic blood pressure|
We wish to thank Andrea Lo Verde (Bsc engineering) for his valuable technical support and Dr Sergio Morelli for doing the echocardiographic studies.
- Received May 7, 1996.
- Revision received June 17, 1996.
- Revision received July 9, 1996.
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