DEFINING NORMAL AMBULATORY PRESSURE

Defining Normal Ambulatory Blood Pressure Eoin O'Brien, Neil Afkins, and Kevin O'Mally

Providing normal reference values and the means to interpret such values in practice is an urgent issue re- quiring consensus. Five basic approaches to defining normalcy for 24 h blood pressures (BP) are consid- ered: 1) the relationship of ambulatory blood pres- sure (ABP) to morbidity and mortality, 2) the rela- tionship of ABP to end-organ involvement, 3) ABP levels in normal populations, 4) the relationship of ABP to clinic BP, and 5) the relationship of 24 h indi- ces to risk. Although there now is considerable evi- dence demonstrating that ambulatory measurement correlates more strongly with endsrgan damage, the first two approaches are scientifically the best. It will

be some time before levels of normalcy can be de- rived. There is a large volume of data on population samples permitting derivation of normalcy for clini- cal practice. Rounded upper limits of normal can be calculated as 140190 mm Hg for 24 h ambulatory pres- sure, 150190 mm Hg for daytime pressure, and 13W80 mm Hg for nighttime pressure. There are, however, considerable differences for age and gender which need to be taken into consideration. Am J Hypertens 1993;6201S-206s

KEYWORDS: Ambulatory blood pressure, normal levels, population studies.

T he importance of establishing normal refer- ence values for blood pressure (BP) levels throughout the 24 h period is of paramount importance if the technique of 24 h ambula-

tory monitoring is to become established in clinical practice. The most fundamental need of the technique is the establishment of normal reference values. Ab- normality cannot be defined without first having es- tablished normalcy.

It is evident in Ewope that the technique of 24 h am- bulatory measurement is rapidly moving away from the research arena, to which it had been confined foi the past 15 years. Pharmaceutical companies in partic- ular are providing ambulatory systems for use in gen- eral practice. There is little point in lamenting the inev- itability of this development by claiming it to be pre- mature; market forces often dictate the pace of pro- gress. What is important, however, is for those with

Prom The Blood Pressure Unit, Beaumont Hospital, Dublin, Iteland

Address d reprint requests to Eoin (YBrien, MD, The Bbod F%esmm Unit, Beaumont Haspid, Dublin 9, Ireknd.

expertise in ambulatory blood pressure (ABP) meas- urement to provide the essential information neces- sary to ensure that the technique is used in practice to enhance patient management, and not abused for fis- cal advantage. Just as important, we want to ensure that the large amount of data provided by 24 h BP measurement is not misinterpreted because of unfa- miliarity with a new methodology.

The need, therefore, for providing normal reference values and the means to interpret such values in prac- tice is an urgent issue requiring consensus. It must be recogruzed that our present state of knowledge may not permit us to provide the reference values to fulfill the precise dictates that scientific methodology re- quires. It is important for us to use the knowledge we possess (and this is considerable) to establish guide- lines for normalcy in clinical practice, recognizing that we may have to adjust these figures slightly as infor- mation from longitudinal studies accumulates. We cannot, however, retreat to a position which was once afforded to us when ambulatory measurement was confined solely to research, by opting to tread &en- tiiic waters until the information necessary to make a

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d a t i v e statement on normalcy becomes available. Research has shown us the important contribution that ambulatory measurement may make to managing hy- pertensive patienk. The exigencies of developments in ambulatory measurement, primarily the techno- ,logical advances in equipment design and research, have rnadea working definition of normal 24 h BPS mandatory.

REVIEW OF AVAILABLE METHODS

The following are five basic approaches to defining normalcy for 24 h BPS that can be considered.

Relationship of ABP to Morbidity and Mortality First, we can relate BP to risk of heart attack, stroke, and death in longitudinal studies. The classical epi- demiological approach, used in studies such as the Framinghaml and Multiple Risk Factor Intervention Trial2 studies relating risk to the level of clinic BP, is the ideal one to adopt for ABP. There has been, how- ever, only one such study performed to date. This study was first reported by Dr. Maurice Sokolow's group in 196e3 and subsequently in the intervening years.' This study showed that the relationship be- tween risk and BP is steeper for ABP than for clinic pressure. The results of the study were consistent with the prediction that h e BP would be distinct from dinic BP? The Office Versus Ambulatory (OVA) trial in Europe

is attempting longitudinally to relate the outcome of managing BP on the basis of clinic BP v ABPP The as- sumption, which awaits confinnation, is that hy- pertedve s u m managed on the basis of ABPs will have at least as good an outcome as those managed on clinic BP. In addition, subjects may have the advantage of needing less antihypertensive medication, and therefore, may enjoy a better quality of life.

In the Syst-Eur trial,' another multicenter longitudi- nal study examining antih-ve medication in isolated systolic hypertension, a side project on ABP measurement should provide information on the rela- tionship between 24 h ambulatory measurement and the risk in elderly subjects. There is evidence that pa- tients diagnosed as having isolated systolic hyperten- sion by conventional measurement may not experi- ence the phenomenon when BP is measured over the 24 h period? It is hoped that the implications of this observation will be demonstrated in the Syst-Eur trial.

The approach of relating 24 h ABP to outcome is the most ideal one from a scientific viewpoint. This should enable us to relate actual levels of 24 h BP and variations of the pattern of 24 h pressure, such as blunting of the normal nocturnal p a t t e d to the ulti- mate cardiovascular consequences of hypertension. The major problem with longitudinal studies is that they take time, usually decades, before pmvid-

I I # /Ibrt AtbCk 8 Stroke m

FIGURE 1. Plan ofthe rrlptimhips of clinic blood prnsun and anlbufatory BP to tmgd organ dmnngc, morbidity, and mortality. Left-hand arrows indicate the ~stoblished relationship clinic BP and targcf organ damage, and morbidity and mortality. Right-hand arrorus'indicatt the established relationship of 24 h BP with t a w organ damage and tk likely, but not as ye^ funy p r m , relationship with morbidity and mortality.

ing answers. Moreover, theinterpretation of resulk is not always as straightforward as it might seem to be; study design, the effects of other risk factom, and management strategies often prove to be confound- ing factors.

Relationship of ABP to End-Organ Involvement An- other approach in relating 24 h ABP to risk is to substi- tute the m g a t e end-points of end-organ involve ment for the classical end-points of death and morbid- ity. n\is technique would establish an association with risk in a shorter period of time. This approach has been followed in a number o'

studies in which the relatiortship of ABP to end-orp involvement as determined in the h-10 kidney,a blood vesseIs,m and brain1' has been shown to be m perior to climc blood pressure. Indeed, with the in aeasing development of techniques for assessing end. organ involvement in hypertension, it can only be a matter of time before the evidence becomes irrefutable However, two important issues need to be clarified.

First, one can ask if it is acceptable to substitute sur rogate end-points for the more substantial end-points of morbid events and death In respomk, we mi@ apply the scheme of reasoning outlined in Figure 2. Clinic BP depicted on the left predicts end-organ in- volvement in addition to morbidity and death. There- fore, associating end-organ involvement with morbid- ity and death may be seen as a stepping stone to the ultimate cardiovascular insults of stroke, heart attack and death. If we accept that ABP is a better predictor of end-organ involvement (shown on the right) than clinic BP, it is difficult to escape the conclusion that ABP also must provide us with a sensitive means of predicting outcome in terms of morbidity and death,

204s O'BRWErAL AJH-)WE 2 9 S V a 6, NO. 6, PART 2

TABLE 2 MEAN f SD, MEDIAN, AND 9 5 M PER-= AND COEFFICIENTS OF VARXATION FOR OFFICE AND 24 h AMBUTORY BLOOD PRESSURE IN 8l5 PEOPLE BY AGE (AIB S h d f l

Men All Women All Men Women Both

17-29 30-39 4049 -79 17-79 17-29 30-39 40-49 -79 17-79 17-79 (101) (123) (109) (60) 099) (174) (149) (55) (35) (416) (S5)

Office measurements SBP (mm Hg)

Mean f SD 121 f 12 122k 11 125 f 16 133 + 15 124 f 14 110 f 11 113 k 10 121 + 17 130 f 24 115 f 15 119 f 15 Median 121 122 122 130 122 110 113 116 123 114 118 95th percentile 140 142 153 160 150 130 131 154 193 139 145 Coeff. var. 10 9 13 11 I1 10 9 14 19 13 13

DBP (mm Hg) Mean f SD 7 3 f 9 7 7 f 8 8 l i l O Sf11 782 10 7lf 8 Rf 8 7 8 f 9 81f 12 73f 9 76f 10 Median 73 77 80 EM 78 70 72 76 80 72 75 95th percentile 89 90 99 110 % 83 84 % 103 88 93 Coeff. var. 12 10 I3 13 13 11 11 12 15 12 13

Ambulatory measurements Daytime SBP (rnm Hg)

Mean f SD 12958 128f9 129f12 132f12 129f 10 l l 8 f 8 117f8 l2lf l2.126f18 118f 10 l24f l2 Median 129 128 127 l34 128 118 116 lu) 122 118 l23 95th pacmtile 144 - 143 150 155 146 131 132 150 I77 135 143 Coeff. var. 6 7 9 9 8 7 7 10 14 9 9

DBP (mm Hg) Mean f SD 7 7 f 7 8 0 f 6 8329 84f9 8 1 f 8 7456 7 5 f 7 7 6 f 9 7 8 f 9 7 5 f 7 7 8 f 7 ~ e d i a n 77 80 82 8s 80 73 74 74 76 74 n 95th -tile 88 91 98 103 92 83 85 94 97 88 91 Gdf. var. 8 8 10 11 10 8 9 l2 l2 10 10

Nighttime- -

SBP (mm HG) Mean f SD 110f9 108f8 109f 12 1l3fl3 110f 10 102f9 1Mf9 103f l l 108fl2 102f9 106f11 Median 110 108 107 110 109 101 100 101 I 1M 105 95th prantile 125 121 128 140 126 117 116 125 l33 120 123 CoeEf. var. 8 8 11 11 9 9 8 10 11 9 10

DBP (mm Hg) ~ 6 a . n f SD 5 9 f 6 6 2 f 6 66f10 68f9 63f8 5 7 f 6 5 8 f 7 6 1 f 8 6 3 f 7 5 8 f 7 6 1 f 8 Median 59 61 65 66 62 56 57 59 63 57 60 95th p e r ~ m t i l ~ 70 n 80 90 n 68 n 77 75 R 75 C d . var. 10 9 15 14 13 10 11 13 10 12 l3

24h SBP (mrn Hg) Mean f SD 123i8 lZI f8 122fll l26fl2 122f10 112f7 l l l f 8 114f10 I20515 113f9 118f l l Median 123 120 122 125 122 112 110 112 118 112 117 95th percentile 136 133 136 151 137 125 126 141 160 129 134 Coeff. var. 6 7 9 9 8 7 7 9 13 8 9

DBP (mm Hg) Mean f SD 7 l f 5 7 4 f 5 7 7 i 8 79f9 75f7 68f5 69f6 7 1 f 8 73f8 6 9 f 6 7 2 f 7 Median 71 74 76 n 74 67 68 69 72 68 n 95th percentile 81 82 89 98 86 78 78 87 87 82 84 Cwff. var. 8 7 11 11 10 8 9 11 10 9 10

Nunlkrs am indimld in pmtthcscs. SBP, systdk blood prrssun; DBP, Diastolic Mood pterrurr; Caf. m., ~ c m t l of tuription.

AIH-IUNE 1993-VOL 6, NO. 6, PART 2 NORMAL AMBULATORY BP 205s

this study is that the relationship belwcwn ambulatory 10.

and office measurements is derived f ron~ 522 subjects comprised of normotensives, borderline, mild, moder- ate, and severe hypertensives. Other weaknesses are that the hypertensive subjects greatly outnumber the ll. normotensive subjects, the hypertensive subjects are older than the normotensive subjects, and the ambula- tory measurements were performed with three ambu- latory systems, at least one of which had not met the current criteria for accuracy.2s The conclusion that the 12. disparity between office and ABP was unrelated to age and gender would need to be examined more closely. -

13. Relationship of 24 h Indices to Risk It is possible to examine the relationship of a number of indices of 24 h BP to risk. These indices might include measures of 14- BP load on the 24 h pressure profile,29 or measures of excessive reduction in BP (leese effect30), and measures of the variability of 24 h BP, such as standard devia- tions, coefficients of variation, cumulative sums, IS. Fourier analysis, and spectral analysis. Any of the lat- ter measures may prove to be more sensitive predic- tors of cardiovascular risk than absolute levels of 16. Bp.15.1631

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