Abstract
Background
Blood pressure (BP) variability can be evaluated by 24-hour ambulatory BPmonitoring (24h-ABPM), but its concordance with results from finger BPmeasurement (FBPM) has not been established yet.
Objective
The aim of this study was to compare parameters of short-term (24h-ABPM) withvery short-term BP variability (FBPM) in healthy (C) anddiabetic-hypertensive (DH) subjects.
Methods
Cross-sectional study with 51 DH subjects and 12 C subjects who underwent24h-ABPM [extracting time-rate, standard deviation (SD), coefficient ofvariation (CV)] and short-term beat-to-beat recording at rest and afterstanding-up maneuvers [FBPM, extracting BP and heart rate (HR) variabilityparameters in the frequency domain, autoregressive spectral analysis].Spearman correlation coefficient was used to correlate BP and HR variabilityparameters obtained from both FBPM and 24h-ABPM (divided into daytime,nighttime, and total). Statistical significance was set at p < 0.05.
Results
There was a circadian variation of BP levels in C and DH groups; systolic BPand time-rate were higher in DH subjects in all periods evaluated. In Csubjects, high positive correlations were shown between time-rate index(24h-ABPM) and LF component of short-term variability (FBPM, total, R =0.591, p = 0.043); standard deviation (24h-ABPM) with LF component BPV(FBPM, total, R = 0.608, p = 0.036), coefficient of variation (24h-ABPM)with total BPV (FBPM, daytime, -0.585, p = 0.046) and alpha index (FBPM,daytime, -0.592, p = 0.043), time rate (24h-ABPM) and delta LF/HF (FBPM,total, R = 0.636, p = 0.026; daytime R = 0,857, p < 0.001). Recordsobtained from DH showed weak positive correlations.
Conclusions
Indices obtained from 24h-ABPM (total, daytime) reflect BP and HRvariability evaluated by FBPM in healthy individuals. This does not applyfor DH subjects.
Keywords: Hypertension; Diabetes Mellitus, Type 2; Autonomic Nervous System; Blood Pressure Monitoring, Ambulatory
Introduction
Blood pressure (BP) variability results from the interplay between externalenvironmental stimuli, vascular system, and biological autonomic regulation ofcirculation.1 Abnormalitiesin BP variability, evaluated by continuous intra-arterial ambulatory BP monitoring,are associated with poor outcomes in normotensive and hypertensivesubjects.2-4 Noninvasive methods such as finger BP measurement(FBPM) are good alternatives to invasive BP monitoring, as they are accuratenon-invasive estimates of beat-to-beat radial BP, providing data that can estimatevery short-term BP variability.5,6 In addition, beat-to-beat recordsallow the extraction of information regarding heart rate (HR) variability that isdirectly related to cardiac autonomic control impairment7,8 andassociated with poor outcomes in both general9 and diabetic populations.10 However, due to practical and economic reasons,this method cannot be routinely used in the evaluation of outpatients.
The development of noninvasive 24-hour ambulatory BP monitoring (24h-ABPM), withmultiple readings throughout day and night, has made short-term BP variabilityestimate through several indices possible.11 However, there are major differences between BP variabilityobtained from beat-to-beat records and that obtained by 24h-ABPM. Besides theduration of the series-very short- (FBPM) or short-term (24h-ABPM)-, BP seriesobtained by FBPM allows studying beat-to-beat variability, while 24h-ABPM series aresampled every 10-15 minutes within 24 hours.6 While non-invasive beat-to-beat methods allow detecting fastoscillations resulting from inter-beat variations, it is inefficient to access veryslow waves in short series; 24h-ABPM, in turn, detects slow variationsonly.12,13 As both methods provide information about BPsignals originating from the same cardiovascular system, a correlation betweenoscillatory components of overlapping bands obtained from FBPM and 24h-ABPM isexpected; however, studies on the association between BP variability evaluated by24h-ABPM indices and target organ damage have shown contradictory results.4,14
Our report was aimed to compare three different parameters of short-term BPvariability in 24h-ABPM, with very short-term BP variability measured by indicesobtained from the FBPM in healthy subjects and in a population at highcardiovascular risk comprised of diabetic hypertensive subjects.
Methods
Study design and population
This cross-sectional study was conducted at the outpatient clinic of the Hospitalde Clínicas de Porto Alegre (Porto Alegre, RS, Brazil), a tertiaryteaching hospital, and Instituto de Cardiologia do Rio Grande do Sul,Fundação Universitária de Cardiologia, from January 2009 toDecember 2012. The study was approved by the Ethics Committee of bothInstitutions (nº 0469.0.001.000-08 and 4313/09, respectively), which isaccredited by the Office of Human Research Protections as an InstitutionalReview Board, in agreement with the principles outlined in the Declaration ofHelsinki. After protocol approval, all subjects signed a written informedconsent for participation. Adult patients of both genders, aged 18-65 years, andwith hypertension and type 2 diabetes mellitus were invited to participate (DHgroup). Control group (C) consisted of healthy subjects, that is, withoutdiagnosis or medication for hypertension and diabetes.
Clinical evaluation
Patients underwent demographic and clinical baseline data collection. Diabetesmellitus was defined by two fasting plasma glucose ≥ 126 mg/dl or use ofantidiabetic agents or personal history of diabetes. Blood pressure was measuredwith an office aneroid sphygmomanometer and the mean values were estimated afteran two measures on average. The cuff size was selected according to armcircumference. Hypertension was defined by mean blood pressure ≥ 140/90mmHg or use of antihypertensive medication. After baseline data collection,subjects were randomly assigned to evaluations, being first submitted to24h-ABPM or to FBPM. The interval between the two examinations was of no morethan 15 days.
Short-term blood pressure variability evaluation (24h-ABPM)
All individuals were submitted to a 24h-ABPM in a usual working day, using amonitor (Spacelabs 90207, Spacelabs, Redmond, WA). Measurements were obtainedevery 15 minutes from 7 a.m. to 11 p.m., and every 20 minutes from 11 p.m. to 7a.m. to complete 24 hours of the period studied. Cuff size was selectedaccording to subjects' arm circumference.14
Based on the results of 24h-ABPM, the mean 24-hour systolic (SBP) and diastolic(DBP) blood pressures were calculated for each patient. Three differentparameters of SBP variability were calculated: 1) time-rate index (rate ofchange in SBP over time in mmHg/min, defined as the first derivative values ofSBP by time); 2) coefficient of variation of systolic BP within 24 hours(SD/mean pressure x 100%); and 3) mean of standard deviation of 24-hour systolicBP. The time-rate index allows the calculation of angular coefficients' sum andaims to measure how fast or slow and in which direction SBP values change. Themeasure was calculated using the following formula, where r is the rate of BPvariability over time (considering the differences between BP measurements ateach time interval) and N is the number of recordings:15
In addition, considering circadian variations of BP and possible differencesbetween daytime and nighttime 24h-ABPM parameters, data were divided intodaytime and nighttime according to patients' reports and were also analyzedseparately, considering both periods. Circadian behavior differences werecalculated by subtracting nighttime from daytime values for each parameter.
Very short-term blood pressure variability evaluation (FBPM)
Blood pressure was recorded continuously, on a beat-to-beat basis, using theFINAPRES system (Ohmeda 2300, Monitoring Systems, Englewood, CO, USA).16 In this method, the pressurewave can be continuously monitored by a sensor placed on the patient'snon-dominant middle finger, detecting small oscillations only. The experimentalprotocol had measurements at two different stages: ten minutes at rest in asitting position and ten minutes after standing-up maneuver (sympatheticactivation).
The BP signal was digitized by the CODAS system (Computer Operated DataAcquisition Software; DATAQ, Instruments, AKRON, OH, USA), sampling at 1 kHz andanalyzed for each condition. Pulse interval (PI) tachogram and systolic arterial(SA) systogram series were constructed through the algorithm of Windaq/DATAQ,which identifies systolic peaks from BP waves. Systogram and tachogram serieswere analyzed by spectral analysis (frequency domain analysis) using anautoregressive model, applied to stationary intervals, which were selected ineach segment condition. The stationarity of each time series was tested aspreviously reported.17Short-term BP and HR variabilities were evaluated based on systogram andtachogram analyses, respectively.
In humans, the frequency domain analysis considers three distinct bands: highfrequency (HF), which includes the interval between 0.15 and 0.4 Hz; lowfrequency (LF) between 0.04 and 0.15 Hz; and very low frequency (VLF), lowerthan 0.04 Hz.18,19 The same analysis was appliedto tachogram series. Among parameters obtained by frequency domain analysis, LFand HF components are distinguished by physiological significance. They aremainly related to sympathetic and parasympathetic cardiac modulations,respectively; the relation between them-LF/HF index-is related tosympathetic-vagal balance;20and the absolute powers of LF and VLF components are predominantly related tovascular sympathetic modulation and to renin-angiotensin system modulation onSBP, respectively.1 The alphaindex was obtained from the square root of the ratio between the LF component oftachogram and systogram when coherence, assessed by cross-spectral analysis,exceeded 0.5 in these bands21and expressed spontaneous baroreflex sensitivity. All series were analyzed by atrained researcher who was also blinded to conditions and subjects.
Delta indices were calculated for HR variability (HRV), LF/HF index and LFcomponent of BPV, using variable values before (rest) and after standing-upmaneuver (sympathetic activation, SA) for normalization, as follows:
These indices had been previously proposed in order to quantify autonomicresponses to standing-up maneuver.22,23
Biochemical measurements
Venous blood samples for biochemical measurements were drawn after 12-hourfasting. Plasma glucose was determined by the glucose oxidase method, serumcreatinine by Jaffé's reaction, and glycated hemoglobin (HbA1c) byion-exchange HPLC (Merck-Hitachi L-9100 HbA1c analyzer; Merck,Darmstadt, Germany). Serum cholesterol and triglycerides were measured byenzymatic-colorimetric methods (Merck Diagnostica, Darmstadt, Germany;Boehringer Mannheim, Buenos Aires, Argentina), and HDL cholesterol by ahomogeneous direct method (autoanalyzer, ADVIA 1650). Low-density lipoprotein(LDL) cholesterol was calculated using Friedewald's formula.24
Statistical analyses
Data are expressed as mean ± standard deviation (SD) or medians andinterquartile intervals, according to normality plots with tests andpercentages. Pearson's chi-square, unpaired Student's t-test, Mann-Whitney ranksum test, two-way repeated measures ANOVA or Friedman repeated measures analysisof variance on rank, post hoc Student-Newman-Keuls were usedwhen variables were compared between groups, as indicated. The correlationbetween the different indices obtained by 24h-ABPM and by FBPM were analyzed bythe Spearman's correlation coefficient. Correlations were considered fordiscussion only if they were statistically significant and representedlarge-effect sizes, as defined by a correlation coefficient of 0.50 orhigher.25 Allstatistical analyses were performed using the SPSS statistical software packageversion 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Statistical significancewas set at p < 0.05.
Results
Twelve healthy subjects (C) and 73 diabetic-hypertensive patients (DH) were selected;all C and 51 DH had complete data from 24h-ABPM and FBPM. Controls were 51.7± 8.1 years old and 50% were men; DH were 57.3 ± 8.1 years-old, 12%were men, 54.9% had their office BP well-controlled (< 130/80 mmHg) and 35.8% hadgood metabolic control (HbA1c < 7.0%). Clinical characteristics are shown inTable 1.
Table 1.
Clinical characteristics of controls (C) and diabetic-hypertensive (DH)subjects.
Variables | Controls (n = 12) | Diabetic-hypertensive (n = 51) | p |
---|---|---|---|
Age (years) | 51.6 ± 4.4 | 57.3 ± 8.1 | 0.011 |
Male gender | 6 (50.0) | 11 (20.8) | 0.065 |
BMI (Kg/m2) | 23.5 ± 2.3 | 30.5 ± 4.2 | < 0.001 |
Office SBP (mmHg) | 116.0 ± 8.2 | 139.2 ± 17.2 | < 0.001 |
Office DBP (mmHg) | 77.0 ± 5.0 | 80.9 ± 11.9 | 0.086 |
Duration of diabetes (years) | - | 6.9 (3.0-10.0) | |
Fasting plasma glucose (mg/dL) | - | 156.5 ± 55.1 | |
HbA1c (%) | - | 8.2 ± 2.0 | |
Total cholesterol (mg/dl) | - | 181. 2 ± 32.6 | |
HDL cholesterol (mg/dl) | - | 42.6 ± 13.2 | |
Triglycerides (mg/dl) | - | 180.5 (132.8 - 248.5) | |
Creatinine (mg/dl) | - | 0.82 ± 0.2 | |
Microalbuminuria (> 17 µg/min) | - | 14 (27.4) |
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BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic bloodpressure, HbA1c: glycated hemoglobin, HDL: high-density lipoprotein;FBPM: Short-Term Blood Pressure. Continuous variables are expressed asmean ± standard deviation or median and interquartile range(p25-p75) and percentiles. Categorical variables are expressed as number(%). Comparisons were tested by Pearson's χ2 test and Student's ttest.
Short-term BP variability (24h-ABPM) results are displayed in Figure 1. There were differences among the indices obtained fromtotal, daytime, and nighttime periods for both C and DH groups, confirming theexpected circadian variations and justifying the division into periods. Comparisonsbetween C and DH groups are represented by the bar graph, which shows that higherSBP and time-rate obtained from SBP in DH group for all periods evaluated. The meanof the standard deviation and the coefficient of variation of 24-hour SBP weredifferent between C and DH in daytime only. Circadian behavior differences,calculated by subtracting nighttime from daytime values, show a lower reduction ofmean SBP at night in DH patients as compared to controls. The differences obtainedfor the coefficient of variation and mean of standard deviation of 24-hour systolicBP were positive in DH, negative in C, and different between groups.
Very short-term BP variability and HR variability (FBPM) results obtained by spectralanalysis are displayed in Table 2. Asexpected, BP was higher in DH vs. C at rest and after standing-upmaneuver. Heart rate variability, LF component of HRV, and alpha index were lower inDH vs. C. The standing-up maneuver, applied to induce sympatheticactivation, resulted in differences for all HR variability components, showing theexpected response to this maneuver in both groups. However, BP variability did notchange after the maneuver in DH subjects, and the alpha index (spontaneousbaroreflex sensitivity) was lower at rest and after the maneuver in this group whencompared to controls.
Table 2.
Very short-term blood pressure variability and heart rate variability (FBPM)at rest and after standing-up maneuver.
Variable | C (n = 12) | DH (n = 51) | P | ||||
---|---|---|---|---|---|---|---|
At rest | Standing up | At rest | Standing up | Group | Condition | Interaction | |
Mean BP (mmHg) | 114.6 ± 23.6 | 112.6 ± 18.2 | 129.4 ± 17.7 | 123.8 ± 21.6 | 0.019 | 0.494 | 0.147 |
Very short-term BPV (mmHg2) | 21.57 ± 12.20 | 37.17 ± 16.12* | 25.27 ± 20.08 | 25.23 ± 23.04 | 0.504 | 0.058 | 0.047 |
LF component of BPV (mmHg2) | 1.80 ± 1.13 | 13.84 ± 11.93 | 4.59 ± 6.02 | 9.26 ± 10.61 | 0.879 | < 0.001 | 0.060 |
HF component of BPV (mmHg2) | 1.40 ± 1.57 | 3.73 ± 3.02* | 3.44 ± 3.46# | 2.25 ± 1.64* | 0.538 | 0.323 | < 0.001 |
Mean HR (bpm) | 66.2 ± 9.3 | 77.8 ± 8.7* | 70.8 ± 11.9 | 77.2 ± 13.9* | 0.419 | < 0.001 | 0.016 |
HRV (s2) | 1.47 ± 1.71 | 1.07 ± 0.78 | 0.73 ± 0.79 | 0.45 ± 0.42 | 0.005 | 0.010 | 0.658 |
LF component of HRV (nu) | 40.77 ± 16.84 | 61.48 ± 16.90 | 31.08 ± 21.07# | 40.69 ± 23.62 | 0.014 | < 0.001 | 0.339 |
HF component of HRV (nu) | 50.65 ± 14.79 | 30.07 ± 15.33 | 49.91 ± 22.35 | 36.19 ± 20.48 | 0.842 | < 0.001 | 0.464 |
LF/HF index | 0.99 ± 0.76 | 3.33 ± 3.16 | 1.09 ± 1.54 | 2.69 ± 4.13 | 0.902 | 0.001 | 0.744 |
Alpha index (ms/mmHg) | 15.04 ± 9.75 | 6.43 ± 5.24* | 8.24 ± 7.70# | 4.72 ± 3.89* | < 0.001 | < 0.001 | 0.003 |
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Data are shown as mean ± SD. HR: heart rate, HRV: heart ratevariability, BP: blood pressure, BPV: BP variability, LF: low frequencycomponent, HF: high frequency component.
*
p < 0.05 vs. rest condition;
#
p < 0.05 vs. C; FBPM: Short-Term Blood Pressure. Two-way repeatedmeasures ANOVA. Post hoc Student-Newman-Keuls.
Autonomic response to standing-up maneuver assessed by delta indices (Figure 2) had a lower response for LF/HF ratio inDH group as compared to C group. Changes in delta HRV and delta_LF/HF variability(BPV) were not different.
Correlations between very short- and short-term BP variabilities are shown in Tables 3 (C group) and 4 (DH group). In C group, some correlations were found at rest,and some after the standing-up maneuver. At rest, standard deviation of 24-hoursystolic BP (24h-ABPM) was positively correlated with the LF component of BPvariability (FBPM) in 24-hour evaluation; the coefficient of variation (24h-ABPM)was negatively correlated with total BP variability and alpha index (FBPM) duringdaytime. After standing-up maneuver, time-rate (24h-ABPM) was positively correlatedwith the LF component of BP variability (FBPM, 24 hours, and daytime). Time-rate(24h-ABPM) was correlated with delta_LF/HF (FBPM, 24 hours, and daytime). In DHgroup, although some correlations were statistically significant, none of themrepresented large-effect sizes (correlation coefficient of 0.50 or higher).Moderate-effect sizes (correlation coefficient near 0.50) were shown for total BPvariability (24h-ABPM), coefficient of variation, and standard deviation (FBPM, 24hours, and daytime). There was no correlation between short-term (24h-ABPM) and veryshort-term variability (FBPM) parameters, considering delta indices for DHsubjects.
Table 3.
Correlation between very short- (FBPM) and short-term (24h-ABPM) BPvariability parameters - Control group.
24-hour | Daytime | Nighttime | |||||||
---|---|---|---|---|---|---|---|---|---|
Time-rate | Coefficient of variation | Standard deviation | Time-rate | Coefficient of variation | Standard deviation | Time-rate | Coefficient of variation | Standard deviation | |
AT REST | |||||||||
Total BPV R | 0.236 | -0.042 | -0.007 | -0.247 | -0.585 | -0.315 | 0.555 | 0.210 | 0.301 |
(P) | 0.461 | 0.897 | 0.983 | 0.439 | 0.046 | 0.319 | 0.061 | 0.513 | 0.341 |
LF component BPV R | 0.373 | 0.538 | 0.608 | 0.370 | 0.445 | 0.559 | 0.021 | 0.343 | 0.438 |
(P) | 0.233 | 0.071 | 0.036 | 0.236 | 0.147 | 0.059 | 0.948 | 0.276 | 0.155 |
Alpha index R | -0.127 | -0.357 | -0.322 | -0.483 | -0.592 | -0.524 | 0.290 | -0.056 | 0.063 |
(P) | 0.695 | 0.255 | 0.308 | 0.111 | 0.043 | 0.080 | 0.361 | 0.863 | 0.846 |
AFTER SYMPATHETIC ACTIVATION(Standing‑upmaneuver) | |||||||||
Total BPV R | 0.418 | 0.350 | 0.427 | 0.138 | -0.172 | 0.084 | 0.180 | 0.392 | 0.424 |
(P) | 0.176 | 0.265 | 0.167 | 0.670 | 0.594 | 0.795 | 0.575 | 0.208 | 0.170 |
LF component BPV R | 0.591 | 0.322 | 0.385 | 0.649 | 0.329 | 0.413 | -0.074 | 0.315 | 0.263 |
(P) | 0.043 | 0.308 | 0.217 | 0.022 | 0.296 | 0.183 | 0.819 | 0.319 | 0.409 |
Alpha index R | -0.116 | -0.392 | -0.322 | -0.346 | -0.312 | -0.322 | 0.191 | -0.503 | -0.270 |
(P) | 0.720 | 0.208 | 0.308 | 0.271 | 0.324 | 0.308 | 0.552 | 0.095 | 0.397 |
DELTA INDEXES (AT REST/AFTER SYMPATHETICACTIVATION) | |||||||||
Delta_HRV R | -0.056 | -0.070 | -0.105 | 0.353 | 0.081 | -0.042 | -0.541 | -0.168 | -0.340 |
(P) | 0.862 | 0.829 | 0.746 | 0.261 | 0.803 | 0.897 | 0.070 | 0.602 | 0.280 |
Delta_LF/HF R | 0.636 | 0.000 | 0.217 | 0.857 | 0.385 | 0.392 | -0.233 | -0.126 | 0.088 |
(P) | 0.026 | 1.000 | 0.499 | 0.000 | 0.216 | 0.208 | 0.466 | 0.697 | 0.787 |
Delta LF_BPV R | 0.299 | -0.091 | -0.077 | 0.282 | 0.011 | -0.035 | -0.170 | -0.035 | -0.217 |
(P) | 0.346 | 0.779 | 0.812 | 0.374 | 0.974 | 0.914 | 0.598 | 0.914 | 0.498 |
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BPV: blood pressure variability, LF: low frequency, LF_BPV: LF componentof BPV; FBPM: Short-Term Blood Pressure. Statistic correlation expressedas correlation coefficient (R) and significance (P), obtained bySpearman's test.
Table 4.
Correlation between very short- (FBPM) and short-term (24h-ABPM) BPvariability parameters - DH group.
24-hour | Daytime | Nighttime | |||||||
---|---|---|---|---|---|---|---|---|---|
Time-rate | Coefficient of variation | Standard deviation | Time-rate | Coefficient of variation | Standard deviation | Time-rate | Coefficient of variation | Standard deviation | |
AT REST | |||||||||
Total BPV R | 0.03 | 0.280 | 0.240 | 0.210 | 0.261 | 0.286 | -0.036 | 0.026 | 0.103 |
(P) | 0.486 | 0.046 | 0.090 | 0.152 | 0.064 | 0.042 | 0.807 | 0.857 | 0.471 |
LF component BPV R | 0.330 | 0.356 | 0.347 | 0.332 | 0.185 | 0.259 | 0.234 | 0.278 | 0.337 |
(P) | 0.022 | 0.010 | 0.013 | 0.021 | 0.194 | 0.066 | 0.110 | 0.048 | 0.016 |
Alpha index R | -0.371 | -0.250 | -0.264 | -0.420 | -0.171 | -0.222 | -0.158 | -0.151 | -0.220 |
(P) | 0.009 | 0.076 | 0.062 | 0.003 | 0.229 | 0.117 | 0.283 | 0.289 | 0.122 |
AFTER SYMPATHETIC ACTIVATION (Standing‑upmaneuver) | |||||||||
Total BPV R | 0.192 | 0.403 | 0.413 | 0.269 | 0.447 | 0.486 | 0.033 | 0.029 | 0.176 |
(P) | 0.191 | 0.003 | 0.003 | 0.065 | 0.001 | 0.000 | 0.826 | 0.841 | 0.218 |
LF component BPV R | 0.140 | 0.274 | 0.283 | 0.156 | 0.166 | 0.245 | 0.042 | 0.090 | 0.134 |
(P) | 0.341 | 0.052 | 0.044 | 0.290 | 0.244 | 0.083 | 0.777 | 0.532 | 0.349 |
Alpha index R | -0.359 | -0.206 | -0.263 | -0.405 | -0.098 | -0.192 | -0.172 | -0.306 | -0.336 |
(P) | 0.012 | 0.146 | 0.063 | 0.004 | 0.493 | 0.177 | 0.243 | 0.029 | 0.016 |
DELTA INDEXES (AT REST/AFTERSYMPATHETICACTIVATION) | |||||||||
Delta_HRV R | 0.054 | 0.018 | -0.011 | -0.003 | -0.045 | -0.058 | 0.055 | 0.106 | 0.059 |
(P) | 0.714 | 0.901 | 0.938 | 0.985 | 0.754 | 0.688 | 0.711 | 0.460 | 0.679 |
Delta_LF/HF R | -0.015 | -0.152 | -0.099 | -0.037 | -0.215 | -0.190 | 0.088 | 0.097 | 0.083 |
(P) | 0.922 | 0.291 | 0.492 | 0.807 | 0.134 | 0.186 | 0.557 | 0.501 | 0.568 |
Delta LF_BPV R | -0.162 | -0.105 | -0.077 | -0.210 | -0.093 | -0.070 | -0.069 | -0.070 | -0.097 |
(P) | 0.271 | 0.464 | 0.590 | 0.152 | 0.515 | 0.623 | 0.643 | 0.623 | 0.500 |
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BPV: blood pressure variability, LF: low frequency, LF_BPV: LF componentof BPV; DH: Diabetic-Hypertensive. Statistic correlation expressed ascorrelation coefficient (R) and significance (P), obtained by Spearman'stest
Discussion
BP and HR variabilities were assessed in healthy and diabetic-hypertensiveindividuals by two well-known methods-24h-ABPM and FBPM-, seeking potentialconcordance between results of each method, which was indeed observed. Correlationsbetween indices of BP variability (time rate with LF component BPV, standarddeviation with LF component BPV, and coefficient of variation with total BPV andalpha index) and indices of HR variability (time rate with delta_LF/HF) were highand significant in controls. On the other hand, few moderate correlations wereobserved in diabetic-hypertensive patients only after sympathetic activation.
As expected, there were differences between 24h-ABPM indices obtained in total,daytime, and nighttime periods because of the well-known circadian variations of BPlevels26,27 which occurred in both healthy anddiabetic-hypertensive subjects. This leads us to conclude that data were adequatelycollected. Moreover, periods division showed differences between groups only whendata collection included the day period, in accordance with previousreports.28,29
Additionally, indices obtained from FBPM had lower HRV, LF component of HRV, andalpha index (at rest and after standing-up maneuver) in DH vs. Cgroup. This finding suggests the presence of autonomic neuropathy in the diabeticpopulation, as expected and previously demonstrated by evaluating similarindices.30,31
In controls, correlations between very short- and short-term BP variability werepresent with FBPM data at rest and after the standing-up maneuver, but only whendaytime data were included. This probably occurs because both methods are evaluatingBP signals in similar situations, as 24h-ABPM provides data obtained mostly duringroutine activities in standing-up position (mean duration of nighttime period~6.9h). The most significant correlations were those between time-rate index(24h-ABPM) and LF component of BP variability and delta_LF/HF (FBPM); also betweenthe coefficient of variation (24h-ABPM) and between total BPV and the alpha index inall periods that included daytime data. The time-rate index obtained by 24h-ABPM(24-hour or daytime period) in healthy individuals is expected to reflect what thereference standard (FBPM) would show, considering LF component of BP variability anddelta_LF/HF.
The weak correlations observed between 24h-ABPM and FBPM indices in thediabetic-hypertensive group depict a very different pattern, which is certainlyrelated to their disease. Moreover, there was no correlation between short-termvariability parameters and delta indices. These correlations are weak even thoughfour times more patients were evaluated, which would show significant correlationsif they in fact existed. We cannot exclude that one or both methods employed mayprovide false results for this specific population once FBPM, for example, dependson attaining good BP signals, and quality of such information was not good becauseof vascular disorders common to this population.32 Therefore, we do not recommend 24h-ABPM to estimate veryshort-term BP variability parameters based on short-term variability indices fordiabetic-hypertensive individuals.
Currently, the evaluation of BP variability across the several indices that can beobtained from 24h-ABPM or home blood pressure monitoring is not recommended byguidelines,14,33 for predicting cardiovascularrisk, or as additional goal for antihypertensive therapy, because literature has noconsensus on these issues.4,14,34,35 It is possiblethat evidence available is not strong enough to support this use because the toolsused are not so reliable. We suggest that equations derived from the 24h-ABPMmeasurement for non-diabetic subjects would be useful for risk prediction, but notfor diabetic-hypertensive patients. It is unknown, though, whether this patternoccurs in hypertensive-only populations. The use of BP variability reduction as anew target to explore in further intervention trials related to hypertension shouldonly be considered after this information is validated.
Considering the high prevalence of autonomic neuropathy in diabetes,36,37 and characteristic changes of this complication detected inthe diabetic-hypertensive group (circadian behavior differences, lower spontaneousbaroreflex sensitivity, HR variability and lower responses to stand-up in the LF/HFratio vs. controls), we attributed to this complication some of the differencesobserved in other indices between groups. The standing-up maneuver is usuallyapplied to induce sympathetic activation in very short-term BP variabilityevaluation, and in fact it induced the expected cardiac autonomic response for manyindices in controls, but not for most of them in diabetic-hypertensiveindividuals.
Taking clinical characteristics of diabetic-hypertensive subjects into account andbearing in mind that the sample studied was obtained from a tertiary center, manypatients were not adequately monitored (BP and metabolic control), indicating ahigh-risk group. Perhaps in this high-risk population, variability found in 24h-ABPMor other home BP evaluation methods may not successfully qualify highercardiovascular risk beyond absolute systolic or diastolic BP, as previouslydescribed.34,38 Also, the age differences foundcould, at least partially, overestimate the differences between groups, andtherefore configure a limitation of this study.
Conclusions
In summary, short-term BP variability measured by time-rate index, standard deviationor coefficient of variation in 24h-ABPM are correlated with LF component BPV anddelta_LF/HF obtained from FBPM in nondiabetic individuals. Such findings should beevaluated in further cohort studies adequately designed for this purpose, alsoseeking relations with hard outcomes. This correlation was not well established indiabetic-hypertensive subjects. Some indices obtained from FBPM for diabeticsubjects are promising tools for the diagnosis of diabetic autonomic neuropathy.Considering a standard reference for the diagnosis of autonomic neuropathy, theseindices and cutoff values should be evaluated in further studies adequately designedfor this purpose.
Footnotes
Sources of Funding
This study was funded by CNPq and FIPE (Hospital de Clínicas de PortoAlegre).
Study Association
This study is not associated with any thesis or dissertation work.
Ethics approval and consent to participate
This study was approved by the Ethics Committee of the Hospital deClínicas de Porto Alegre (RS) and Instituto de Cardiologia do Rio Grandedo Sul / Fundação Universitária de Cardiologia under theprotocol number 0469.0.001.000-08 and 4313/09. All the procedures in this studywere in accordance with the 1975 Helsinki Declaration, updated in 2013. Informedconsent was obtained from all participants included in the study.
Author contributions
Conception and design of the research and Analysis and interpretation of thedata: Casali KR, Schaan B, Montano N, Massierer D, Neto FMF, Teló G,Ledur PS, Reinheimer M, Sbruzzi G, Gus M; Acquisition of data: Casali KR, SchaanB, Montano N, Massierer D, Teló G, Ledur PS, Reinheimer M, Sbruzzi G, GusM; Statistical analysis: Casali KR, Teló G, Gus M; Obtaining financing:Schaan B, Gus M; Writing of the manuscript: Casali KR; Critical revision of themanuscript for intellectual content: Schaan B, Montano N, Massierer D, Neto FMF,Teló G, Ledur PS, Reinheimer M, Sbruzzi G, Gus M.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
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