University of Groningen. Isolated systolic hypertension Heesen, Willem Frederik

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1 University of Groningen Isolated systolic hypertension Heesen, Willem Frederik IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 1998 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Heesen, W. F. (1998). Isolated systolic hypertension: pathophysiology and effects of treatment Groningen: s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 REVALENCE OF ISH CHAPTER 4 HIGH PREVALENCE AND INCIDENCE OF ISOLATED SYSTOLIC HYPERTENSION a b a c Wilfred F Heesen MD ; Frank W Beltman MD,PhD ; Johan F May MD,PhD ; cd cde Andries J Smit MD,PhD ; Pieter A de Graeff MD,PhD ; Tjeerd K Havinga c c c MD,PhD ; Enno van der Veur PhD ; Frits H Schuurman PhD ; Pieter J de Kam, a b a MSc ; Betty Meyboom-de Jong MD,PhD ; Kong I Lie MD,PhD Submitted a b d e Departments of Cardiology, General Practice, Internal Medicine and Clinical c Pharmacology, University of Groningen and Groningen Hypertension Service Groningen, The Netherlands This investigation was supported by the "Praeventiefonds", grant number

3 CHAPTER ABSTRACT Introduction In the past, most attention in treatment studies in hypertension has focused on diastolic hypertension, despite the known higher prognostic risk of systolic hypertension. The beneficial results of the SHEP- and SYST-EUR trials have brought about a revival of interest in isolated systolic hypertension (ISH). Reports on prevalence of ISH show a wide variety in rates, while studies on incidence of ISH and controbuting factors are scarce. Methods An unselected population of elderly was screened, and this was repeated after two years. Prevalence and incidence of different subtypes of hypertension were determined. The influence of initial blood pressure on changes in blood pressure during follow-up was analysed using Oldham s plotting method, taking into account the regression to the meanphenomenon. Results Among 2356 attendants (rate 55%) at the first screening, ISH was the most prevalent subtype of hypertension. Among definite cases (> 3 measurements) of untreated subjects, rate of ISH was 10%. This prevalence increased strongly with age. In two years follow-up, overall systolic BP increased with 4 mm Hg, while diastolic BP did not change significantly. The increase in systolic BP was highest among those with consistently high systolic blood pressures (r=0.20; P< 0.05). This correlation was much less for diastolic hypertension, while results for pulse pressure were intermediate. After two year follow-up, 20% of initially normotensives had become hypertensive, among which the majority (13% of total) had ISH. Multiple regression analysis showed that initial systolic BP itself was the strongest predictor for an increase of systolic BP in follow-up. Conclusion. This study shows that among elderly isolated systolic hypertension is the most prevalent hypertensive subtype, both at initial screening and the incidence in follow-up. The high rate of development of new cases warrants regular control of BP in the elderly. Among factors related to this incidence, systolic hypertension itself appears to be a main contributing factor. -88-

4 REVALENCE OF ISH INTRODUCTION While in the past decades (seventies and eighties) most attention in the treatment of hypertension focused on elevated diastolic blood pressure, systolic hypertension has regained new interest. Elevated systolic blood pressure is known for long to be an important cardiovascular risk factor, being a stronger predictor of cardiovascular morbidity and mortality than diastolic hypertension. Less evidence was available on the benefits of treatment of systolic hypertension, especially isolated systolic hypertension (ISH). With 6 the recent published beneficial results of the SYST-EUR trial, confirming 7 those of the SHEP-trial, this evidence now appears to be solid. Revision of the importance of ISH is therefore necessary. 8 Several reports are available on the prevalence of ISH, showing a wide variety ranging from 1 to 41 %, differing between males and females Less is known about the incidence of ISH, as few of these studies included follow-up analysis. This would be important for daily practice, as the occurrence of ISH is known to increase with age, as a consequence of several factors. First, systolic blood pressure increases after the age of 60, while diastolic blood pressure remains unchanged or even decreases. Reasons for this increase in systolic blood pressure with age might be related to the normal determinants of high blood pressure, such as sodium intake, serum cholesterol, cigarette smoking, glucose intolerance, body weight, physical exercise and alcohol consumption. A more specific contributing factor is less distensibility of the large arteries. A decreased distensibility of the aorta and other large arteries, or the loss of the Windkessel-function, is known to be the main pathophysiologic feature of ISH. Interestingly, systolic blood pressure itself is one of the determinants of aortic distensibility. This may lead to the hypothesis of a vicious circle of high systolic blood pressure decreasing aortic distensibility which in itself increases systolic blood pressure: systolic hypertension begets systolic hypertension. -89-

5 CHAPTER Aim of this study was to investigate the hypertensive pattern in an elderly population, in particular the contribution of (isolated) systolic hypertension. Prevalence at first screening of ISH, and incidence at two year follow-up were determined in a large population screening program of elderly aged 60 and over. The influence of the initial blood pressure level on increase of blood pressure during follow-up was analyzed along with other factors such as age, to investigate the hypothesis whether an increased systolic blood pressure itself contributes to a further increase of blood pressure in follow-up. -90-

6 REVALENCE OF ISH METHODS Study population and blood pressure measurements A population screening program was conducted in a rural municipality (Achtkarspelen) in The Netherlands in All inhabitants aged 60 years of age and over were invited to participate by mailed personal invitation cards, preceded by general mailing and advertising announcements. Blood pressure was measured in schools and community centers as close to the homes as possible. Elderly homes were also visited to measure those not able to attend the screening centers. After five minutes rest, the sitting blood pressure (BP) was measured by trained volunteers using a sphygmomanometer. When BP was elevated (systolic BP: > 160 mm Hg, diastolic > BP 95 mm Hg) its measurement was repeated by a physician. When BP remained elevated, the patient was invited for a third and fourth measurement on two separate occasions. A fourth measurement was not done in those receiving antihypertensive treatment, and in elderly aged 75 years and over. All subjects were asked whether they were currently treated for hypertension. Subjects were defined to have isolated systolic hypertension (ISH) if untreated systolic BP was > 160 mmhg at each measurement, with diastolic BP <95 mmhg on at least the last two occasions, and average diastolic BP less than 95 mmhg. The definition of isolated diastolic hypertension (IDH) was DBP of 95 mmhg or more, with normal systolic BP (< 160 mm Hg). In case of both elevated diastolic and systolic BP (> 160 mm Hg and > 95 mm Hg, resp.), subjects were defined as systolo-diastolic hypertension (SDH). All categories were considered to be definite when at least three BP measurements were available. When less measurements were available the classification was based on those results of available measurements ( average ISH, IDH or SDH). For analysis of changes in blood pressures in follow-up, all measurements were used. All participants were asked whether they were currently treated for hypertension, had a history of hypertension, or a family history of hypertension. Furthermore, all participants received an extensive questionnaire with questions on presence of other cardiovascular risk factors such as high cholesterol, diabetes, smoking, and exercise capacity as assessed with the Duke Activity Status Index questionnaire. 25 The screening program was repeated in 1995, two years after the initial screening, in the same population and in the same season. The procedure of BP measurement and of definition of hypertensive categories were the same as in the original investigation. All results of BP measurements had been sent -91-

7 CHAPTER to the treating general practitioners, who were free in their decision to install treatment. Also, a number of untreated hypertensive subjects was investigated in a drug intervention trial between both screenings. Statistical analysis The influence of regression to the mean is assessed by Oldham s plotting 26 method. In this method, the relation between the average of two measurements, and the difference between both measurements is plotted. If the slope of the correlation line in the plot of this relation differs from horizontal, a relation between initial measurement and the change in time is present. The statistical significance of this slope between initial measurement and change in time is calculated with univariate analysis. Also, Pearsons coefficient of correlation is calculated. Furthermore, multiple logistic regression analysis is performed to analyse which (other) factors are related to changes in systolic blood pressure at follow-up. The procedure used is backward removal of insignificant factors. Factors analysed are age and sex, results of the initial blood pressure and heart rate measurements, and cardiovascular risk factors as obtained from the questionnaire. The (uncorrected) regression to the mean-phenomenon itself was analyzed also, by division of the initial measurements into quartiles, and assessment of the change in time per quartile. Continuous data are reported as mean + S.D.. Logistic or categorical variables are reported as frequencies (%). Difference between categories, as between males and females, are analyzed with Student t-test for continuous variables, and with Chi-square testing for logistic or categorical variables. All analyses are done with SAS statistical software analysis (SAS statistical software V 6.12, Cary, N.C.). All differences are considered statistically significant when the two-sided P-value <

8 REVALENCE OF ISH RESULTS Initial screening Of the 4251 inhabitants aged 60 years and over 2356 (55%) attended the first screening, with equal attendance among males and females (table 1). As shown in table, 1, attending females had slightly higher age and systolic BP, were more often treated for hypertension, and had more frequently diabetes or high cholesterol, whereas males were more often smokers. The blood pressure values presented (first measurement) cover all subjects including those receiving antihypertensive treatment. In table 2 the hypertensive categories are given, according to 5-years age group, for untreated and treated subjects. Among the untreated subjects, the percentage normotensive subjects is almost 70% in the youngest age-group, declining with higher age to values under 50% after the age of 75 years. ISH is the most prevalent subtype of hypertension among all age groups except for the youngest, where it equals prevalence of combined or systolo-diastolic N= attendance (%) age (years) systolic BP (mm Hg) diastolic BP (mm Hg) heart rate (bpm) treated for hypertension (%) previous hypertension (%) familial hypertension (%) weight (kg) smoking (%) diabetes (%) high cholesterol (%) exercise capacity (DASI-score) males females * * * 38 * 32 * * 13 * 9 * 7 * * Table 1. Baseline characteristics according to gender (first screening, N= 2356) Abbreviations: BP = blood pressure; bpm = beats per minute. *: significantly different between males and females (P< 0.05) -93-

9 CHAPTER -94- untreated subjects (%): Age: > 90 Total N = normotensive (%) - ISH (%) - SDH (%) - IDH (%) treated subjects: males females age category (years) > > N= normotensive (%) - ISH (%) - SDH (%) - IDH (%) Figure 1. Relation between blood pressure (BP) and age First BP measurement of first screening, untreated subjects only (N=1878). Bars represent pulse pressures (top: systolic BP, bottom: diastolic BP). Table 2. Prevalences (%) of hypertensive categories at first screening according to age (5-years categories) in untreated and treated subjects Abbreviations: ISH = isolated systolic hypertension; IDH = isolated diastolic hypertension ; SDH = systolo-diastolic hypertension pulse pressure (mmhg)

10 REVALENCE OF ISH DH 0,7% normot 78,1% SDH 11,5% ISH 9,6% Figure 2. Hypertensive patterns (%) at first screening of untreated subjects (Definite cases only, N=1158) Abbreviations: normot= normotensives, IDH = isolated diastolic hypertension, ISH = isolated systolic hypertension, SDH = systolo-diastolic hypertension (definitions: see text). -95-

11 CHAPTER hypertension (SDH). Isolated diastolic hypertension (IDH) is very rare in this population. A similar predominance of ISH can be seen among the subjects who were on antihypertensive treatment, reaching an overall percentage of 40%. The percentage of normotensives among these treated subjects is just over 25%, the remaining 75% still being hypertensive. The changes of blood pressure with age are depicted in figure 1 (first measurements, only untreated subjects). In males, systolic blood pressure increases with age, while diastolic blood pressure decreases slightly. The same pattern is observed, although increase of systolic blood pressure may level off at higher age. No significant differences were found between males and females for these changes. The pulse pressure of males in the age category years appears to be higher, but this was based on a relatively low number of measurements (52). The hypertensive categories in table 2 are based on definite and average results: 720 subjects had less than 3 measurements and were classified according to average results. As this may influence the analysis of hypertensive categories, the results of definite cases only (and untreated, N=1158) are presented separately, in figure 2. When these cases are analyzed, prevalence of ISH was again high, comparable to SDH, while prevalence of IDH was less than 1%. Follow-up screening Attendance at the second screening after two years was 2212 persons (50.5%). Of these, 1632 subjects were untreated, of whom 66.1% was normotensive, 22.8% had ISH, 9.1% SDH, and 2.0% IDH. The remaining 580 were treated for hypertension, of which 27.1 % was normotensive, 46.9% had ISH, 24.5 % SDH and 1.6% IDH. Combined results from first and second screening were available from 1403 subjects, enabling evaluation of blood pressure changes. Figure 3 shows what happened with those subjects who were normotensive and untreated at the initial screening (N=873). Less than 80% of these initially normotensive subjects were still normotensive after two years. Among those who had become hypertensive, ISH was the most frequently classified hypertensive category, accounting for over 60% of the cases. IDH was again a rare classification, occurring in less than one percent. A comparable predominance of ISH and SDH could be seen among those who were meanwhile treated for hypertension (Figure 3: smaller circle). -96-

12 REVALENCE OF ISH IDH 0,9% ISH 13,2% SDH 3,2% treated 4,0% SDH 8,6% ISH 25,7% normot 78,7% normot 65,7% Figure 3: Incidence of hypertension (%) at two year follow-up among subjects normotensive and untreated at first screening (N= 873). Abbreviation: see previous figure Changes in blood pressure and estimation of regression to the mean-effect The main results of analysis of changes in blood pressure patterns are given in figure 4, as Oldham s plots correcting for regression to the mean by plotting the average of both values against the differences between both values. In these figures, the results are plotted of first measurements of initial and follow-up screening, of untreated subjects only. As figure 4.A shows, there is a relation between the height of the systolic blood pressure and change over time: the higher the blood pressure, the higher the increase in time from first to second screening period. This relation is significant, with a Pearson coefficient of correlation 0.20 (P< 0.01). The slope of the line is 0.18, significanty different from zero, thus systolic BP increases 1.8 mm Hg for each 10 mm Hg of average systolic BP. The absolute increase (horizontal line) is 3.9 (+ 17.5) mm Hg at two year follow-up. For diastolic blood pressure, no such relation is observed (figure 4.B): the slope of the regression line is nearly horizontal, not significantly different from zero. In absolute change, virtually no change over time is seen (+0.1 mmhg). The results of pulse pressure (figure not shown) were intermediate -97-

13 CHAPTER Figure 4. Oldham s plots for change in systolic (SBP - top) and diastolic blood pressure (DBP) Results plotted are first measurements of untreated subjects both at first and second screening (N= 1153). The sloped (solid) line shows the correlation line between average measurements and change during follow-up, the horizontal line (dotted) shows the absolute change in follow-up (for statistics, see text). -98-

14 REVALENCE OF ISH between those of systolic and diastolic BP. The regression to the mean-phenomenon itself was analyzed by division of the initial measurements into quartiles, and assessment of the change in time per quartile. For systolic blood pressure the following results were observed: in the lowest quartile there was an increase of 9.3 mmhg, changing from mmhg in the second and mmhg in the third quartile to a decrease in the fourth quartile of highest initial systolic blood pressures: mmhg. In multiple regression analysis, all factors as depicted in table 1 were investigated, to examine predictive factors for the increase of systolic BP during follow-up. Factors not significantly related were removed, starting with the least significant (backward procedure). In the final model, Initial systolic blood pressure was the strongest predictor (P= ). Other factors included in the model were initial diastolic BP (P= 0.01), familial history of hypertension (0.03), and weight ( 0.03). Age was also kept in the model, because of marginal signficance (0.06). -99-

15 CHAPTER DISCUSSION This study shows that almost all cases of elevated blood pressure in the elderly are due to systolic hypertension, either alone (ISH) or in combination with diastolic hypertension while isolated diastolic hypertension occurs only infrequently. Prevalence of ISH is about 10% in males and females over the age of 60, increasing up to the highest ages. Perhaps of even greater clinical importance are the results on new cases or incidence of hypertension in the elderly. Two years after the initial screening almost 20% of initially normotensive subjects became hypertensive, of whom the majority showed ISH. Even while actual changes in blood pressure in time were not always that pronounced, this high incidence of new cases of ISH is of considerable clinical interest. One implication could be that blood pressure screening in the elderly should be performed regularly, even in those with normal blood pressure values. This high incidence of ISH in the elderly could be related to its pathophysiology. The mechanism of elevation of systolic blood pressure is a decrease of distensibility of the large arteries. Since systolic hypertension itself also negatively influences aortic distensibility, a vicious circle may develop: of systolic hypertension itself contributing to a further increase in systolic blood pressure ( systolic hypertension begets systolic hypertension ). Support for this hypothesis can be drawn from the observation that the change of systolic blood pressure depends on the height of the initial value. A problem of such analysis may be the regression to the mean-effect. Measurements selected on high initial values are likely to show a decrease while low values tend to increase. As shown in our study, the regression to the mean-phenomenon is present: the group with the highest initial systolic blood pressure showed a decrease during follow-up, and the group with the lowest initial results an increase. However, both intermediate groups also showed an increase of SBP in follow-up, suggesting an overall increase of SBP. A method to correct for the regression to the mean is Oldham s plotting method, which compares the average of the results of both screenings with the change during follow-up. Those subjects who have consistent high (or low) values are taken together, thus avoiding some of the variation due to the regression to the mean-phenomenon. As the plots show, a high SBP is related to a higher increase of SBP during follow-up, confirming the earlier hypothesis of systolic blood pressure itself contributing to (further) increase of systolic blood pressure. It is also shown that such a relation is not present for

16 REVALENCE OF ISH diastolic BP. Finally, multiple regression analysis also showed that initial systolic BP was by far the strongest predictor of change of SBP during followup. Comparing these results with other reports, a comparable predominance of ISH in a community-dwelling elderly population has been observed by Ekpo 29 et al.. One of the differences between these results and ours is that a decline of prevalence in ISH and of systolic blood pressure was observed after the age of 80 years. As shown, the prevalence in ISH in our study increases up until 30 the highest age groups, a pattern observed also in other studies. Another main difference is that the report of Elko et al. lacked a follow-up, therefore our results of newly developed cases of hypertension can not be compared. Another study which does present comparable information on the development of (systolic) hypertension is a report from the Framingham 31 study. It was observed that the majority (80%) of subjects with borderline systolic hypertension (SBP , with diastolic < 90 mmhg) progressed to definite hypertension, as opposed to 47% of those with lower blood pressures. However, this progression was seen after 20 years follow-up. As the present study shows, the rate of development of new cases in the elderly may be much faster, although the observations in the present study would be strengthened if more than one follow-up screening would have been performed. Another potential problem of our study is the problem of selection or voluntary bias, i.e. the phenomenon that more healthy and health-minded subjects are likely to attend such screening projects. We did try to estimate the magnitude of this problem, by conducting an investigation among nonresponders as part of an investigation for prevalence of chronic disorders in the same population. In approximately 200 non-attenders, blood pressure was somewhat lower: 153/80 versus 163/87 mm Hg in responders (P< 0.05 for systolic BP). However, some of this difference might be due to the fact that blood pressure measurements were doone at home, instead of at sreening sessions. In conclusion, this study shows that in an unselected population of elderly systolic hypertension is the predominant pattern of hypertension, either isolated or combined with diastolic hypertension. After two years follow-up, ISH is also the predominant subtype of hypertension. The highest risk for development of ISH is among those with higher initial values of systolic blood pressure, which may raise the hypothesis that (isolated) systolic hypertension begets systolic hypertension. This high rate of development of new cases of hypertension may warrant a regular blood pressure control in the elderly. In general, knowing the favourable effects of treatment, ISH

17 CHAPTER probably should derive more attention than is given so far in daily practice. Taking into consideration the increased proportion of elderly in our Western population, management of ISH will present a major challenge both in terms of medical and socio-economical burden

18 REVALENCE OF ISH References 1. Kannel WB. Hypertension and other risk factors in coronary heart disease. Am Heart J 1987;114: Shekelle RB, Ostfeld AM, Klawans HL. Hypertension and risks of stroke in an elderly population. Stroke 1974;5: Mann SJ. Systolic hypertension in the elderly. Pathophysiology and management (Review). Arch Intern Med 1992;152: Staessen J, Amery A, Fagard R. Editorial review: Isolated systolic hypertension in the elderly. J Hypertens 1990;8: Applegate WB. Hypertension in elderly patients (review). Ann Intern Med 1989;110: Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhäger WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A, for the Systolic Hypertension in Europe (SYST-EUR) trial investigators. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997;350: The SHEP cooperative research group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1991;265: Smulyan H, Safar ME. Systolic blood pressure revisited. J Am Coll Cardiol 1997;29: Silagy C, McNeil JJ. Epidemiologic aspects of isolated systolic hypertension and implications for future research. Am J Cardiol 1992;69: Amery A, Fagard R, Guo C, Staessen J, Lutgarde T. Isolated systolic hypertension in the elderly: an epidemiologic review. Am J Med 1991;90 (Suppl. 3A):64S-74S 11. Kannel WB, Dawber TR, McDee DL. Perspectives on systolic hypertension. The Framingham Study. Circulation 1980;61: National center for health statistics. Blood pressure levels of persons 6-74 years. United States, Rockville, MD: National center for health statistics, (Vital and health statistics, series 11: Data from the National Health Survey no. 203) 13. Garland C, Barrett-Connor E, Suarez L, Criqui MH. Isolated systolic hypertension and mortality after age 60 years. Am J Epidemiol 1983;118: Cubb JD, Borhani NO, Entwisle G, Tung B, Kass E, Schnaper H, Williams W, Berman R. Isolated systolic hypertension in 14 communities. Am J Epidemiol 1985;121: Staessen RB, Ostfeld AM, Klawans HL Jr. Hypertension and risk of stroke in an elderly population. Stroke 1974;5:

19 CHAPTER 16. Psaty BK, Furberg CD, Kuller LH et al. Isolated systolic hypertension and subclinical cardiovascular disease in the elderly: initial findings from the Cardiovascular Health Study. JAMA 1992;268: Rutan GH, Kuller LH, Neaton JD, Wentworth DN, McDonald RH, Smith WM. Mortality associated with diastolic hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial. Circulation 1988;77: Amery A, Fagard R, Guo C, Staessen J, Lutgarde T. Isolated systolic hypertension in the elderly: an epidemiologic review. Am J Med 1991;90 (Suppl. 3A):64S-74S 19. Wilking SV, Belanger A, Kannel WB, D Agostino RB, Steel K. Determinants of isolated systolic hypertension. JAMA 1988;260: Fletcher A, Bulpitt C. Epidemiology of hypertension in the elderly. J of Hypertens 1994;12 (Suppl. 6):S3-S5 21. Van Wilking SB, Belanger A, Kannel WB, D Agostino RB, Steel K. Determinants of isolated systolic hypertension. JAMA 1988;260: Smulyan H, Safar ME. Systolic blood pressure revisited. J Am Coll Cardiol 1997;29: Meaney E, Soltero E, Samaniego V, Alva F, Moguel R, Vela A, Gonzales V. Vascular dynamics in isolated systolic arterial hypertension. Clin Cardiol 1995;18: Muntinga JHJ, Schut JK, Visser KR. Age-related differences in elastic properties of the upper arm vascular bed in healthy adults. J Vasc Res 1997;34(2): Hlatky MA, Boineau RE, Higginbotham MB, Lee KL, Mark DB, Califf RM, Cobb FR, Pryor DB, A brief self-administered questionnaire to determine functional capacity (The Duke Activity Status Index). Am J Cardiol; 1989; 64: Hayes RJ. Methods for assessing whether change depends on initial value. Statistics in Medicine 1988;7: Meaney E, Soltero E, Samaniego V, Alva F, Moguel R, Vela A, Gonzales V. Vascular dynamics in isolated systolic arterial hypertension. Clin Cardiol 1995;18: Muntinga JHJ, Schut JK, Visser KR. Age-related differences in elastic properties of the upper arm vascular bed in healthy adults. J Vasc Res 1997;34(2): Ekpo EB, Ashworth IN, Frenando MU, White AD, Shah IU. Prevalence of mixed hypertension, isolated systolic hypertension and isolated diastolic hypertension in the elderly population in the community. J Hum Hypertens 1994;8: Kannel WB, Dawber TR, McGee DL. Perspectives on systolic hypertension. Circulation 1980;61: Sagie A, Larson MG, Levy D. The natural history of borderline isolated systolic hypertension. N Engl J Med 1993;329:

20 REVALENCE OF ISH

21 CHAPTER LAW NR. IV: THE PATIENT IS THE ONE WITH THE DISEASE