Spurious systolic hypertension 143

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1 Spurious systolic hypertension in youth Michael F O Rourke a, Charalambos Vlachopoulos a and Robert M Graham b Abstract: Six young men diagnosed with systolic hypertension had normal carotid pressure wave contours, normal synthesized aortic pressure wave contours and normal diastolic and mean pressures in upper limb arteries. Elevated brachial systolic pressure was caused by a high narrow systolic peak of the pressure wave. This was attributed to amplification of the pressure wave between the ascending aorta and upper limb (radial and brachial) arteries that is associated with attainment of full body length and very distensible arteries. These young men were not truly hypertensive. Exaggeration of the upper limb systolic peak represented an extreme of the normal pressure wave pattern in youth, where amplification is greater than in childhood or in older subjects. This phenomenon accounts for the rapid increase in systolic pressure between the ages of 5 and 20 years, and the relative plateau in systolic pressure between the ages of 20 and 45 years that is seen in population studies. Key words: amplification; arterial compliance; body length; pulse pressure Introduction It is not uncommon to have young healthy adults aged 15 to 25 years referred to us with elevated systolic, but normal diastolic pressure. Investigations reveal no abnormality, and no satisfactory explanation can be given to the subject or to anxious parents. On the basis of the Systolic Hypertension in the Elderly Program Cooperative Research Group (SHEP), one is tempted to offer antihypertensive therapy. 1 It is well known from the records of life insurance companies of young adults who take up policies that diastolic pressure is a better guide to cardiovascular events than systolic pressure. 2 However, the reverse is true in persons over 50 years of age. 3 The Framingham Study, the Multiple Risk Factor Intervention Trial (MRFIT) and the SHEP study have all shown that in older humans, systolic pressure is a better predictor than diastolic pressure for cardiovascular risk. 1,4,5 No satisfactory explanation for this disparity has yet been offered. We suggest that all findings can be explained on the basis of wave transmission to the brachial artery, with unusually high amplification of the pressure pulse in young adults, which causes systolic pressure to be considerably higher in upper limb arteries than in the ascending aorta and left ventricle. This sometimes leads to the inappropriate diagnosis of systolic hypertension. We suggest that such subjects are not truly hypertensive, and that their central aortic systolic pressure is normal. Patients and results Six young, otherwise healthy male subjects aged from 14 to 23 years had elevated systolic pressure measured repeata Medical Professorial Unit, University of NSW, Sydney, Australia; b Victor Chang Cardiac Research Institute, St Vincent s Clinic, Sydney, Australia Address for correspondence: Professor MF O Rourke, University of New South Wales, Medical Professorial Unit, St Vincent s Clinic, Darlinghurst, Sydney, NSW 2010, Australia. edly by sphygmomanometer cuff in the brachial artery (Table 1). All previous investigations had been normal and the subjects were referred for further assessment. This included measurement of radial and carotid artery waveforms with applanation tonometry, and synthesis of ascending aortic pressure waveforms using generalized transfer functions as previously described. 6 Diastolic pressure was normal. In each, elevation in systolic pressure was associated with, and due to, a high narrow peak of the pressure wave recorded by tonometry in the upper limb (Figure 1). Integrated mean pressure was normal. The synthesized ascending aortic pressure wave was of normal amplitude and contour, with normal aortic systolic pressure ( 126 mmhg). Carotid pulse contour was normal for age (Figure 2) 4 ; ascending aortic wave contour, synthesized from this (Figure 2), was virtually identical to the aortic wave contour synthesized from the radial pulse. Discussion Normal young adults Pressure waves recorded in these six subjects were similar to those normally recorded in the radial artery of young adults (Figure 3), 7 and their systolic peak was in the upper range of that seen in this age group (2nd to 3rd decade). Wave contour in this age group is, however, different to that recorded in older subjects and children (Figure 3) 7 9 : at older and younger ages the initial peak is of relatively low amplitude compared with the second systolic peak. Pulse waveform in young children and older adults has been attributed to an earlier return of wave reflection from the lower body in children because of shorter body length and in older adults because of higher aortic pulse wave velocity. 6 9 It appears that amplification of the brachial and radial pressure waves, relative to the aortic one, is greater in adolescents than in children or in older adults. This is a consequence of a relatively late return of wave reflection from peripheral sites, which is dependent on attainment of Arnold X(00)VM332OA

2 142 MF O Rourke et al Table 1 Subjects with pseudo-systolic hypertension. Subject A B C D E F Age (years) Weight (kg) Height (cm) Blood pressure (on referral) 150/80 160/55 165/60 160/70 176/82 155/85 (mmhg) full body length, but still in the presence of very distensible arteries with low aortic pulse wave velocity. 7 9 The hypothesis that emerges is that spurious systolic hypertension in young adults represents an extreme of the normal situation for this age group, where elevated brachial and radial systolic pressure represent nothing more than an unusually high amplification of the initial pressure wave. If the above mechanism is correct, one would expect to see this more commonly in tall subjects with low aortic pulse wave velocity, and in young adult males rather than young adult females because they are generally taller. 10 One would also expect to see an effect of the phenomenon in population studies. Population studies If the hypothesis and postulated mechanism is correct, then systolic pressure should be unusually high in all young adults, and more so in males (who are taller) than in females. Population studies support this proposition. The 1977 USA National Health Survey (Figure 4a) showed (for males) a steep rise in brachial systolic pressure from the age of 5 to 20 years, with a plateau between ages 20 and 40 years, then a progressive rise thereafter. The latest (1992) USA survey reports data only for adults, but shows the same plateau from ages 20 to 40 years with a progressive rise over 40 years of age. 11 The same plateau is seen in the Australian National Heart Foundation study for male adults (Figure 4b). 12 When combined with a similarly large study in children, this showed the same steep rise to age 20 that was seen in the 1977 USA study (Figure 4b). 13 The large INTERSALT study also supports the hypothesis. 14 The rise in systolic pressure from the pooled sample in the decade between age 25 and 35 years was just 2.6 mmhg, and considerably lower than the rise per decade for younger and older subjects in this and other studies. In the USA and Australian studies, data for young adult females was similar to males, though the variations are were not so marked. These findings were consistent with a lower average height in women than men. 10 Further support of this concept comes from studies of blood pressure from birth to adulthood 15 and from pooled population studies. 16 Implications are further supported by the most recent data from the Framingham Heart Study. 17 These data confirm that upper limb pulse pressure in young adults has no value in predicting cardiovascular events, whereas in older adults (where brachial pulse pressure approximates aortic) this is of greater predictive value than brachial systolic or diastolic pressure. In Figure 4, a dotted line is drawn to denote the predicted increase in aortic systolic pressure with age, which is consistent with the known progressive increase in aortic pulse wave velocity from childhood to old age. 18 Reservations The proposition advanced will not be proven until young subjects with elevated systolic pressure are shown to have normal systolic pressure in the ascending aorta. Since this requires aortic cannulation, and carries some risk, it is unlikely to be performed unless other special indications exist. For the moment there is sufficient circumstantial evidence for young people to be reassured, provided (a) their radial or brachial pressure wave shows a narrow initial systolic peak of high amplitude, (b) the synthesized ascending aortic or measured carotid arterial pressure pulse is of normal amplitude, and (c) brachial diastolic and integrated mean pressures are normal. Reassurance is also based on recent Framingham finding 17 of an inverse relationship between brachial pulse pressure and coronary events in males under age 40 years. In conclusion, high peripheral systolic pressure in young subjects may represent an extreme of the normal pressure wave pattern in youth, where the normally existing high amplification between central and peripheral arteries leads to peripheral systolic values that exaggerate central aortic ones. Pulse wave analysis has the potential to enhance our diagnostic abilities and to aid decision-making and management is such cases. Potential conflicts of interest Michael O Rourke has an interest in PWV Medical (Australia) and EMTS (USA), companies associated with pulse analysis systems.

3 Spurious systolic hypertension 143 Figure 1 Pressure waves recorded non-invasively by applanation tonometry from the radial artery (left panels) of six young adults (aged 14 to 23 years) referred to our group with the diagnosis of systolic hypertension together (right panels) with pressure waves synthesized for the ascending aorta. 6 BP, blood pressure; ED, ejection duration.

4 144 MF O Rourke et al Figure 2 Pressure waves recorded non-invasively by applanation tonometry from the carotid artery (left panels) of the same subjects as Figure 1, together with (right panels) pressure waves synthesized for the ascending aorta. 6 BP, blood pressure; ED, ejection duration.

5 Spurious systolic hypertension 145 Figure 3 Ensemble-averaged radial artery pressure waves at different ages in a group of 420 normal subjects studied by Kelly et al. 7 Reproduced from ref. 7 with permission. References 1 SHEP The Systolic Hypertension in the Elderly Program Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265(24): Pickering G. High blood pressure (2nd edition). London: J & A Churchill, Franklin SS, Weber MA. Measuring hypertensive cardiovascular risk: the vascular overload concept. Am Heart J 1994; 128(4): Kannel WB, Wolf PA, McGee DL, Dawber TR, McNamara P, Castelli WP. Systolic blood pressure, arterial rigidity and risk of stroke: The Framingham Study. JAMA 1981; 245: Rutan GH, Kuller LH, Neaton JD, Wentworth DN, McDonald RH, McFate-Smith WM. Mortality associated with diastolic hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial. Circulation 1988; 77(3): O Rourke MF, Kelly RP. Wave reflection in the systemic circulation and its implication in ventricular function. J Hypertens 1993; 11: Kelly RP, Hayward C, Avolio A, O Rourke M. Non-invasive determination of age-related changes in the human arterial pulse. Circulation 1989; 80: Hsieh KY, O Rourke MF. Pressure wave contour in the ascending aorta of children paradoxical similarity to the elderly. Aust NZ J Med 1989; 19: Gevers L. Arterial pressure waveforms in newborn infants: invasive measurements in clinical practice [PhD thesis]. Utrecht: Elinkwyk BV, London GM, Guerin AP, Pannier B, Marchais SJ, Stimpel M. Influence of sex on arterial hemodynamics and blood pressure: role of body height. Hypertension 1995; 26: Burt VL, Whelton P, Roccella EJ et al. Prevalence of hypertension in the Figure 4 Sphygmomanometric blood pressure values (solid lines) for males at different ages, from (A) the 1977 USA National Health Survey (DHEW Publication No. (HRA) (1977)) and (B) the 1989 Australian National Heart Foundation survey of adults 12 combined with a study using similar methods for Australian male children. 13 The dotted lines represent the estimated ascending aortic pressure values from the same cohort, based on known aortic aging changes. Reproduced from ref. 18 with permission. US adult population. Results from the Third National Health and Nutrition Examination Survey Hypertension 1995; 25(3): Risk Factor Prevalence Study Management Committee. Preliminary survey analysis. In: Risk Factor Prevalence Study: Survey No 3. Canberra: National Heart Foundation of Australia, Roy LP, Tiller DJ, Jones DL. The range of blood pressures in Australian children. Med J Aust 1984; 141(1): Rodriguez BL, Labarthe DR, Huang B, Lopez-Gomez J. Rise of blood pressure with age; new evidence of population differences. Hypertension 1994; 24: Uiterwaal CSPM, Anthony S, Launer LJ et al. Birth weight, growth and blood pressure: an annual follow-up of children aged 5 through 21 years. Hypertension 1997; 30: O Rourke MF. Isolated systolic hypertension, pulse pressure, and arterial stiffness as risk factors for cardiovascular disease. Cur Hyperten Reports 1999; 3: Franklin S, Khan S, Wong N, Larson M, Lev D. The relation of blood pressure to coronary heart disease risk as a function of age: The Framingham Heart Study. J Am Coll Cardiol 2000; 35 (Suppl A): Nichols WW, O Rourke MF. McDonald s blood flow in arteries (3rd edition). London: Edward Arnold, 1990.