(Hypertension. 1997;29:22.)
© 1997 American Heart Association, Inc.
Research Articles (Issue 1, Part 1) |
Prediction of Cardiac Structure and Function by Repeated Clinic and Ambulatory Blood Pressure
the Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven KUL (Belgium).
Correspondence to R. Fagard, MD, PhD, UZ Pellenberg, Weligerveld 1, B-3212 Pellenberg, Belgium.
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Abstract |
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We performed imaging echocardiography, Doppler velocimetry, and repeated clinic and ambulatory blood pressure measurements in 74 hypertensive individuals to clarify why reports differ on the strength of the relationships of left ventricular characteristics with clinic blood pressure, on the superiority of ambulatory over clinic pressure, and on the importance of daytime and nighttime pressures. Clinic pressure was measured five times with an automated device and five times with the conventional technique on 2 different days. The partial correlation coefficients of left ventricular mass and wall thickness with the first automated systolic and diastolic clinic pressures amounted to .38 to .45 (P<.001), improved with increasing numbers of measurements, and reached .56 to .58 for the average of 10 automated pressure determinations. Similar trends were observed for conventional clinic pressures. Average 24-hour pressures were significantly related to mass and wall thickness (partial r=.50 to .61, P<.001) and explained 3% to 6% (systolic) and 5% to 12% (diastolic) of the variance of cardiac structure in addition to the first automated or conventional clinic pressure (P<.05). However, when 10 clinic measurements were averaged, only diastolic 24-hour pressure added information over and above clinic pressure (P<.05); the additional explained variance was larger with regard to the conventional (+4% for mass and +7% for wall thickness) rather than the automated (+3% for wall thickness only) pressures. Mass and wall thickness were more closely related to daytime than nighttime pressures and were not independently related to day-night differences in pressure, except when men and women were considered separately; the results were similar when four different definitions of day and night were applied. Finally, the weak association of left ventricular diastolic function with blood pressure did not improve on repeated clinic or ambulatory blood pressure measurements. In conclusion, increasing numbers of measurements strengthen the relationships of clinic pressure with left ventricular mass and wall thickness and, conversely, diminish the additional predictive power of 24-hour blood pressure. The importance of nighttime pressure and of the nighttime pressure fall does not seem to depend on the definition of day and night but differs in men and women.
Key Words: echocardiography • hypertrophy, heart • blood pressure monitoring
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Introduction |
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The strength of the relationship of echocardiographic LVM with CBP varies considerably among studies; correlation coefficients have ranged from close to zero to around .5 at the highest.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Apart from differences in echocardiographic methodology and in characteristics of the studied populations, discrepancies in the literature could be related to variable numbers, conditions, and standardization of the CBP measurements. However, published studies do not allow one to test this assertion because of the lack of details on CBP in many reports.17 ABP is, on average, more closely related to LVM than is CBP,1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 but the gain in predictive power has been variable among reports, appearing to be most pronounced in studies in which the relationship with CBP was weak, possibly because of poor standardization of the CBP measurement.17 Apart from the average 24-hour ABP value, there has been a lot of interest in daytime and nighttime BPs and in day-night differences in BP. However, the results on the relationships of LVM with daytime and nighttime ABPs1 2 3 5 7 8 9 10 11 12 13 14 15 and with the day-night differences in BP5 7 9 10 11 12 13 14 15 16 18 19 have not been consistent,20 which could be related to the variable definitions of day and night.20 21 22 23 BP is also a significant determinant of LV diastolic function,24 25 26 but relationships with different types of BP measurements have not often been explored.3 8 In the present study, we sought to clarify discrepancies in the literature (1) by relating echocardiographic measures of LV structure and function to increasing numbers of BP measurements in the clinic, (2) by assessing the variance of the echocardiographic variables that can be explained by 24-hour ABP in addition to differing numbers of CBP measurements, and (3) by studying the influence of the definition of day and night on the relationships of the echocardiographic variables with daytime and nighttime BP and with the day-night BP difference.
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Methods |
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Protocol
Previously treated or untreated patients referred for evaluation of hypertension were eligible for the study when no underlying disease could be detected, when organ damage was limited to World Health Organization stages I or II,27 and when their echocardiogram was judged to be of good quality by two investigators. Antihypertensive treatment was interrupted in patients willing to participate. They were invited for two study visits, always in the morning, within the next 6 weeks, with 2 to 3 weeks between visits. The study period could be shortened in patients with severe BP elevation. The study was approved by the Ethics Committee of the Faculty of Medicine, and participants gave informed consent.
Clinic BP
After arrival in the laboratory, patients were left alone in a quiet room, where they rested in the supine position. Ten minutes later, an automated device (Dinamap 845) was started for measurement of BP and pulse rate five times at 2-minute intervals. Thereafter, conventional CBP was measured five times by sphygmomanometry and auscultation (Korotkoff phases I and V) by one of two observers, who remained blinded to the automated BP measurements. Pulse rate was assessed by palpation of the radial artery during 30 seconds. Mean BP was calculated as Diastolic BP+(Systolic BP-Diastolic BP)/3.
Echocardiography
M-mode and Doppler echocardiographic measurements were made with control of the two-dimensional image by one of two operators, under the supervision of the same third investigator, by use of an Ultra-Imager (Honeywell Inc) or CV 750 device (Vingmed), as described in detail previously.28 The following measurements were obtained from LV M-mode echocardiography: (1) LV end-diastolic and end-systolic internal diameters (LVIDd and LVIDs, in millimeters) and (2) end-diastolic posterior wall and interventricular septal thicknesses (PWT and IVST, in millimeters). Several indexes were derived from these measurements: (1) end-diastolic MWT (in millimeters), as the average of PWT and IVST; (2) LVM (in grams) and LVM index (in grams per meter squared); (3) relative wall thickness, as the ratio of MWT to the internal radius (LVIDd/2); and (4) fractional shortening of the LV internal diameter (percent). LV inflow Doppler echocardiography gave the peak velocities of the early filling curve and atrial contraction curve (both in millimeters per second); the AE ratio was derived from these measurements.
ABP Monitoring
ABP was monitored for 24 hours with the SpaceLabs 5250 or 90202 device (SpaceLabs Inc) between the two study visits. The monitor was usually applied in the morning. The recorders were programmed to obtain measurements every 15 minutes from 6 AM to midnight and every 30 minutes from midnight to 6 AM. The ABP recordings were not edited; ie, readings were excluded only if the monitor did not successfully complete them. Only 1.8% of the individual recordings were eligible for exclusion according to previously published criteria.29 Subjects were excluded from further analysis when no valid measurements were obtained in any 2-hour period. Several time-weighted average BP values were derived from the 24-hour recordings of the remaining subjects, as described23 : (1) the average 24-hour BP; (2) the average high and low BP of two alternating contiguous periods of high and low BP, respectively, considered to represent the day and night, by use of the square-wave method30 adapted for noninvasive, intermittent measurements by the implementation of restrictions; the high-pressure and low-pressure periods had to last at least 10 and 6 hours, respectively, and solutions in which the time of monitor application fell within the low-pressure period were rejected23 ; (3) the average BP of the 6-hour periods of highest (crest) and lowest (trough) BP, considered to be included in the day and night, respectively, by use of the cumulative sum technique31 ; and (4) analysis by clock time performed with two methods. The "wide" method covered the full 24 hours and defined daytime as the period from 7 AM to 10 PM and nighttime from 10 PM to 7 AM.32 In the "narrow" approach, the morning and evening intervals were excluded from the analysis; daytime lasted from 10 AM to 8 PM and nighttime from midnight to 6 AM.29 33 Day-night BP differences were calculated from the average daytime and nighttime BP values obtained by the various analytic methods.
Statistical Analysis
Database management and statistical analyses were performed with SAS software (SAS Institute Inc). Group data are reported as mean (SD) or median and range; data for men and women were compared by use of the unpaired Student's t test. Results were analyzed by single and multiple regression analyses. The strengths of relationships between echocardiographic variables and BP are given as partial correlation coefficients, unless stated otherwise. The equality of correlations of two independent samples and within one single sample was tested as described.34 The variances of echocardiographic variables, which can be explained by ABP over and above CBP, were assessed with forced inclusion of CBP and significant covariates in the regression models. A two-tailed value of P
.05 was considered significant, except for the comparison of correlations, for which a one-tailed test was applied.
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Results |
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Patient Characteristics
Seventy-four patients were investigated at the first study visit (49 men and 25 women). Age averaged 43.6±10.0 years; weight, 75.3±12.5 kg; height, 1.71±0.09 m; and body mass index, 25.6±3.2 kg/m2. Age and body mass index were not different between men and women; women were smaller and weighed less than men (P<.001). Forty-one patients had never been treated or had not taken antihypertensive treatment for more than 4 weeks in the previous year; treatment had been interrupted for a median of 9 weeks (range, 3 to 43) in the other 33 patients. Known duration of hypertension ranged from 1.5 to 300 months (median, 49). Three patients dropped out before the second visit.
Heart rate at the time of echocardiography was 65.4±8.3 beats per minute and was 4.8 beats per minute higher in women than men (P<.05). LVM averaged 231±69 g; LVM index, 123±32 g/m2; LVIDd, 46.0±4.9 mm; and IVST, PWT, and MWT, 13.4±2.8, 12.4±2.2, and 12.9±2.3 mm, respectively. Relative wall thickness averaged 0.57±0.12. These structural echocardiographic variables, except relative wall thickness, were smaller in women than men (P<.05). Fractional shortening averaged 31.3±6.5%. Transmitral peak velocities amounted to 460±96 and 557±118 mm/s for late and early LV inflow, respectively. The AE ratio averaged 0.86±0.23 and was not different between men and women. Echocardiographic data were the averages of the two visits, except in the three patients who were seen only once.
Conventional CBP was measured five times on two occasions in 71 patients; because of occasional technical failure, the automated CBP measurements were complete in only 68 patients. The first CBP measurement at the first study visit averaged 157±16/97±13 mm Hg for the automated method and 161±20/103±12 for the conventional technique. The averages of the 10 CBP measurements amounted to 155±16/96±12 and 159±19/102±13 mm Hg for the automated and conventional techniques, respectively. Analysis of the ABP data was restricted to the 41 men and 22 women in whom there was no single 2-hour period without BP measurement. Mean 24-hour ABP averaged 141±16/91±12 mm Hg; there were 66±12 valid measurements. The results of the average systolic and diastolic ABPs for the various definitions of daytime and nighttime and the day-night differences are given in Table 1. ABP was lower during the nighttime than daytime hours in all subjects. None of the CBP or ABP values differed significantly between men and women.
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Determinants of Echocardiographic LV Characteristics
Demographic, anthropometric, and clinical determinants of LV structural and functional characteristics were identified by use of stepwise multiple regression analysis (Table 2). LVM and MWT were independently and positively related to weight and mean CBP and negatively to height; both variables were significantly lower in women than men. In addition, MWT was inversely related to LV internal diameter. The AE ratio increased with age, heart rate, and mean CBP and was not independently related to LV structural characteristics. Duration of hypertension and previous antihypertensive treatment did not enter the equations. LV internal diameter and its fractional shortening were not related to BP.
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Relationships Between LV Characteristics and CBP
Fig 1 gives the partial correlation coefficients of LVM, MWT, and the AE ratio with the automated CBP measurements after controlling for significant covariates. The correlation coefficient of the relationship of LVM with the first automated measurement of systolic CBP was .43 (P<.001); the r value increased to .50 when the five CBP values of the first visit were averaged. When the first systolic CBP measurements of two visits were averaged, the coefficient was .53. It reached .56 for the average of six CBP measurements, ie, three CBP measurements taken on two different occasions and .57 for the average of ten CBP measurements, ie, five CBP measurements, taken on two different occasions; the latter r values were significantly different from the correlation coefficient with the first CBP measurement (P<.05). The results were similar for MWT. None of the combinations of the various systolic automated CBP measurements was significantly related to the AE ratio. The relationships of the first diastolic CBP measurement with LVM and MWT were significant though somewhat weaker than for systolic CBP; the partial correlation coefficients increased with increasing numbers of measurements or visits, or both (P<.05). The AE ratio was significantly related to diastolic CBP, but the strength of the relationships did not improve when more measurements were averaged. Fig 2 illustrates the results for conventional CBP measurements. The partial correlation coefficients between the LV structural characteristics and the first conventional CBP measurement were in general slightly higher than with the first automated measurement, but the gains obtained with increasing numbers of CBP measurements were less pronounced and not significant. Only diastolic CBP correlated significantly with the AE ratio, and there was no improvement on repeated CBP measurement.
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The partial correlation coefficients between LVM and CBP, after controlling for height and weight, were not significantly different between men and women. For example, the partial r values between LVM and the average of 10 conventional CBP measurements were .66 (systolic BP) and .51 (diastolic BP) in men, and .51 and .50 in women, respectively.
Relationships Between LV Characteristics and ABP
The partial correlation coefficients of LVM, MWT, and AE ratio with systolic and diastolic 24-hour ABPs and with the various daytime and nighttime ABPs were significant, except for the relationship of systolic ABP with the AE ratio (Table 3). There were no significant differences in the strength of the relationships of the daytime ABP values, obtained by the various methods of analysis, with LV characteristics; this was also the case for nighttime ABP values. Within each analytic approach, the correlation coefficients of the LV structural characteristics were somewhat higher for daytime than for nighttime ABP, but the differences were not statistically significant. Nighttime ABP did not contribute independently to the variances of LVM, MWT, and AE ratio over and above the daytime ABP. The partial correlation coefficients of the relationships of LVM with the various day-night differences in BP were significant only for the square-wave method (.25 for systolic BP and .26 for diastolic BP, P<.05) and ranged from .21 to .24 for the other methods. MWT was related (P<.05) to the day-night difference in systolic BP derived from the square-wave method (partial r=.26) and from cumulative sum analysis (partial r=.27) but not when other definitions were used (.15<r<.23). However, none of these relationships was significant after further adjustment for mean 24-hour ABP. The AE ratio was not significantly related to any day-night difference in BP.
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When the associations of LVM with ABP were analyzed separately in men and women, there were no significant gender differences in the strength of the relationships of LVM with 24-hour ABP and with the various daytime and nighttime ABP values, although the partial r values tended to be higher for daytime ABP than for nighttime ABP in men and vice versa in women. In men, nighttime ABP did not contribute independently to the variance of LVM over and above daytime ABP, but in women, the additional contribution of nighttime ABP was significant for diastolic BP (P<.05) and ranged from 6.2% to 10.2% for the various analytic methods. Table 4 summarizes the relationships of LVM with the various day-night differences in systolic and diastolic BPs in men and women. After control for body size, the partial correlation coefficients were significant and positive in men; after additional adjustment for mean 24-hour ABP, the correlations remained significant for the diastolic day-night BP difference. In women, the inverse associations between LVM and the day-night differences in BP did not reach statistical significance, at least partly because of the smaller number of participants. However, comparison of the partial correlation coefficients of men and women revealed that the opposite associations were significantly different between the two sexes. There were no substantial differences among the various methods of analysis.
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Relationships of LVM Index With CBP and ABP
Fig 3 illustrates the relationships of LVM index with the averages of 10 conventional systolic and diastolic CBP values and with mean 24-hour ABP in the 63 patients with complete ABP recordings. There were no significant differences among the single correlation coefficients, which ranged from .53 to .58. The r values were not significantly different between men and women.
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Variance of LV Characteristics Explained by 24-Hour BP in addition to CBP
ABP did not add any significant information to CBP with regard to the AE ratio. Fig 4 illustrates the variance of LVM and MWT that is explained by the average 24-hour ABP in addition to significant covariates and the averages of increasing numbers of automated CBP measurements. Systolic and diastolic 24-hour ABP values did add significant information to the first automated CBP measurement of the first study visit, but the additional explained variance decreased with increasing numbers of measurements or visits, or both. When the results of two visits were combined, only diastolic 24-hour ABP added information over and above automated CBP with regard to MWT (P<.05), but the additional explained variance was only 3%. There was no significant and independent contribution of systolic 24-hour ABP over and above repeated conventional CBP measurements, but diastolic 24-hour ABP added 4% (P<.05) to the variance of LVM and 7% (P<.01) to that of MWT on top of the variance explained by the average of 10 conventional CBP values (Fig 5).
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Discussion |
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The present study assessed the relationships of 24-hour, daytime, and nighttime ABPs and of repeated CBP measurements with echocardiographic LV characteristics known to be associated with BP. We confirmed that BP is a significant and independent determinant of LVM and MWT and to a lesser extent of the AE ratio, a crude index of LV diastolic function. LV internal dimension and its fractional shortening, a measure of systolic function, were not independently related to BP in the present study population.
The strength of the reported associations of LVM with CBP has varied greatly, with correlation coefficients ranging from close to zero to about .5.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Our speculation that differences among studies might be partly attributed to variable degrees of standardization, to different numbers of CBP measurements, or to both17 seems to be supported by the results of the present study. The partial correlation coefficients of LVM and MWT with the first automated BP measurement at the first study visit in the clinic were already highly significant and amounted to about .45 for systolic CBP and .40 for diastolic CBP (Fig 1). The relatively strong predictive power of this single CBP measurement compared with data from the literature may be related to the familiarity of the patients with investigators and laboratory conditions and the standardization of the CBP measurements but also to the reduced imprecision of echocardiographic measurements by averaging results of two separate recordings. Increasing the number of CBP measurements at one visit further improved the strength of the relationships, but adding CBP values of a second visit appeared to be more informative in this respect. For example, the partial correlation coefficients were higher for the average of the first measurements of two visits than for the first two measurements of the first visit. The data seem to indicate that a plateau is reached when six CBPs, that is, three measurements taken on two different occasions, are averaged. Although we have not studied the effect of a third visit, these results support recommendations that CBP be measured at least twice on at least two different occasions with regard to the classification and management of hypertensive patients.27 35 The results obtained with conventional CBP measurements showed similar trends (Fig 2), but several differences emerged compared with the automated technique, that is, the somewhat higher partial correlation coefficients of the LV structural characteristics with the first CBP measurement and the lesser improvement on repeated CBP measurements. Possible factors are the different methodology (an automated oscillometric versus traditional auscultatory technique), the fixed protocol in which the automated measurements always came first, the fact that an investigator may be biased by preceding measurements whereas a machine is not, and the influence of the investigator's presence on the patient's BP.
LVM and MWT were significantly and independently related to the average 24-hour systolic and diastolic ABPs (Table 3). For comparison with most previous studies, we also assessed the single correlation coefficients of LVM index with ABP (Fig 3). These coefficients amounted to .57 for systolic ABP and .58 for diastolic ABP, which is somewhat higher than the weighted averages from 19 reports in the literature, that is, .50 for systolic ABP and .44 for diastolic ABP.17 The strength of the relationships was similar in men and women. An important question is whether ABP adds significant independent information to explain the variance of LV structural characteristics over and above CBP. Most authors have reported that LVM correlates better with ABP than with CBP, but the significance of the difference was usually not assessed in individual studies.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Our meta-analysis17 showed that the average weighted correlation coefficient of LVM with systolic 24-hour ABP (r=.50) was significantly larger (P<.001) than that with systolic CBP (r=.35). However, the meta-analysis also indicated that the improvement of the correlation was most pronounced in studies that found a weak relationship with CBP and that there was little or no obvious gain from ABP when the correlation coefficient with CBP was already around .5. These observations led us to hypothesize that the relationship of LVM to ABP is not necessarily superior to CBP when an adequate number of BP measurements are taken in well-standardized conditions in the clinic. However, this assertion is difficult to prove from data in the literature because details of the CBP measurements in terms of methodology and conditions, number of observers involved, number of pressure measurements and visits, and time of day often have not been reported.17 The results of the present study seem to support the above-mentioned hypothesis. As shown in Figs 4 and 5, 24-hour ABP does add independent explanatory information to the first automated and conventional CBP measurement. However, when more pressures from the same visit or from two visits were averaged, the independent predictive power of 24-hour ABP decreased progressively. The small remaining independent information from 24-hour ABP was limited to diastolic BP and was more important for MWT than for LVM. In addition, ABP added more information to CBP measured by an observer than to automated CBP measurements.
Reports in the literature differ on the strength of the associations between LVM and daytime and nighttime ABPs.1 2 3 5 7 8 9 10 11 12 13 14 15 However, there is no consensus concerning the definitions of these pressures, and about 10 different time schedules have been used.20 21 22 23 We examined the possibility that the strength of the relationships of LV structural characteristics with daytime and nighttime ABPs might depend on the definitions of these periods by applying four selected methods, that is, two clock time–independent methods and two methods based on fixed time intervals.23 Within each approach, we used one "wide" method, which divides the full 24 hours into two periods,30 32 and one "narrow" method, with more restricted windows and exclusion of morning and evening intervals or transition periods.29 31 33 The results show that the partial correlation coefficients of LVM and MWT with daytime and nighttime ABPs, respectively, do not vary according to definitions of day and night (Table 3). The similarity of the results may have to do with the presumably normal awake-asleep pattern of our patients, as suggested by the times of awakening (between 5:30 and 10 AM) and going to bed (between 10:10 PM and 12:30 AM) noted by 23 patients who filled in a questionnaire, and by the fact that ABP was lower during the night than during the day in all subjects. The present study also shows that within each method of analysis, LV structural characteristics correlate somewhat more strongly with daytime ABP than with nighttime ABP and that nighttime ABP does not add to the variance explained by daytime ABP, except for diastolic BP in women. Several authors reported that a small or absent day-night BP difference is associated with a larger LVM,5 10 12 14 16 but others did not find this.7 9 11 13 15 Differences in the selection of participants with regard to sex, BP status, severity of hypertension, and degree of target-organ damage may have contributed to the divergent results among studies. Most reports5 7 9 10 12 13 14 15 16 combined the data for men and women, which may not be appropriate in view of recent findings that the associations between LVM and the day-night BP difference may differ between men and women.18 19 In the present study, LVM was not independently related to the day-night BP difference in the overall analysis, but we found that the results differed significantly according to sex. A larger decrease in nighttime ABP was associated with a greater LVM in men and smaller LVM in women. The opposite relationships remained significantly different after controlling for average 24-hour ABP. Our results are consistent with reports that female nondippers have a larger LVM than female dippers18 19 ; whereas these studies18 19 reported no association between LVM and nighttime BP fall in men, we observed an opposite relationship in men. Our results furthermore suggest that discrepancies concerning the importance of the dipping phenomenon for LVM probably cannot be explained by different definitions of day and night, at least not in the present study population.
In addition to LV structure, we assessed functional characteristics of the left ventricle. Whereas the fractional shortening of the LV internal diameter, an index of systolic function, was not independently related to BP, the AE ratio, an index of diastolic function, did depend on diastolic BP.24 25 26 However, the independent association with automated and conventional CBP measurements was rather weak, and its strength did not improve with repeated CBP measurements or with ABP monitoring. Also, Marabotti et al8 found that the single correlation coefficients of the AE ratio with BP were similar for ABP and the average of three CBP measurements. White et al3 reported that rapid LV filling (radionuclide technique) correlated somewhat better with ABP than with casual BP, but details of the latter measurement were not described.
An important limitation of the present study is that we examined only so-called surrogate end points. Although LVM has been associated with prognosis,36 37 our results should be confirmed with regard to the relative importance of CBP and ABP for the incidence of cardiovascular morbidity and mortality. Perloff et al38 reported that repeated semiautomated ABP measurements during the day are an independent predictor of cardiovascular complications, and Mann et al39 and Verdecchia et al40 observed that fully automated ABP measurements added prognostic precision to CBP measurements. We would suggest critical examination of the quality of CBP measurements in published and future reports on the prognostic importance of ABP compared with CBP measurements.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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R. Fagard is holder of the Prof A. Amery Chair in Hypertension Research, founded by M.S.D., Belgium. The authors gratefully acknowledge the secretarial assistance of N. Ausseloos.
Received June 14, 1996;
first decision July 11, 1996; first decision August 27, 1996;
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References |
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