Geographical variations in blood pressure in British men and women

0895-4356/90 $3.00 + 0.00 copyright $$ 1990 Pergamon Pm8 plc

J Cb Epldmbl Vol. 43, No. 4, pp. 385-398, 1990 Printed in Great Britain. AU rights tescrval

GEOG,RAPHICAL VARIATIONS IN BLOOD PRESSURE BRITISH MEN AND WOMEN N. G. BRUCE,D. G.

COOK,

IN

A. G. SHAPERand A. G. THOMSON

Department of Clinical Epidemiology and General Practice, Royal Free Hospital School of Medicine,

Rowland Hill St, London NW3 2PF, England (Received in revised form 11 July 1989)

Abstract-Geographical variations in blood pressure have been studied using an automatic sphygmomanometer in 2596 men and women aged 25-29, 4044 and 55-59 living in nine British towns. In males aged 40-59, systolic blood pressure showed a range in age-adjusted town means of 9.0 mmHg (p c 0.05); in females the dilTerence of 8.6 mmHg was not significant (p = 0.14). Mean arterial pressure (MAP) and diastolic at age 40-59 were significantly different between towns for both sexes. Differences at age 25-29 were of a similar magnitude, and the mean town blood pressures at 25-29 correlated highly with those at 40-59 [systolic; males r = 0.74 (p < O.OS),females F = 0.65 @ = 0.05911. The ranking’of town blood pressures in an earlier study was reflected in the present study, but stronger associations were observed with cardiovascular mortality. It is concluded that geographical blood pressure variations in Britain are established by age 25-29 years. Blood pressure Hypertension Britain CVD mortality

Geography

INTRODUCTION The primary prevention of raised blood pressure is a critical public health goal, but its achievement depends on the identification of environmental factors that are important in aetiology as well as modifiable in populations. Mean levels of blood pressure and the rates of rise with age vary markedly between populations [l], and this observation has led to a number of international studies [2]. These international studies face considerable difficulties in the standardization of measurement, and the differing cultures of the populations studied introduce the potential for confounding by factors which may be poorly recognized and hard to measure [3]. The discovery of large variations in the blood pressure of middle-aged men in the 24 towns studied in the British Regional Heart Study (BRHS) [4] has provided an opportunity to conduct a comparative study within a well defined geographic region with a relatively homogeneous culture. The range of differences

Age

Automatic

sphygmomanometer

between the 24 BRHS towns was 16.6mmHg systolic and 12.5 mmHg diastolic, and the means showed correlations of 0.61 and 0.60 respectively with town standardized mortality ratios (SMR) for cardiovascular disease. It was therefore decided to conduct the Nine Towns Study, which would have three main objectives: (1) to substantiate the BRHS findings for middle-aged men, (2) to determine whether similar differences existed among middle-aged women, and (3) to examine a group of young adults (25-29) to establish whether town differences in blood pressure were already present in this age-group. This paper deals with the three main objectives and examines the strength of the evidence for geographical blood pressure variations in men and women, while giving due consideration to methodological issues which might bias the findings of this type of comparative study. The social, environmental and other causes for any such geographical variations as are established will be considered in a subsequent report. 385

N. G. BRUCEet al.

386 METHODS

The 24 BRHS towns surveyed in 1978-80 were each situated away from large conurbations, mostly having low proportions of immigrants and with resident populations of between 50,000 and 100,000 people. They were chosen to cover the full range of SMRs for cardiovascular disease in Britain, and to provide some representation of each of the 14 standard regions. The selection of towns for the present study was based on the mean levels of systolic and diastolic blood pressure found in the BRHS [4]. No more than 3 towns could reasonably have been classified as high, and 3 as low, the rest being more or less grouped in the middle. All 3 high, all 3 low, and 3 from the middle of the distribution of mean blood pressures were therefore chosen to make up the sample of 9 towns. Although it was evident that within each group of high, medium and low towns there was a wide spread of SMRs for cardiovascular disease, this did not influence the selection of towns. In order to minimize the possible effects of seasonal change, the towns were surveyed in 3 sets, each containing 1 low, 1 medium, and 1 high town. The fieldwork for each set was completed within 10 weeks. Sampling and jieldwork

The sampling frame used was the age-sex register of the same general practices as in the BRHS, practices which were originally chosen to reflect the social class composition of each town [5]. An age- and sex-stratified random sample of men and women in three 5-year age bands (25-29, 40-44, 55-59) was selected, excluding previous BRHS participants. This age structure was adopted to maximize the precision of the mean blood pressure estimates at the ends of the wide age range required for the present study. Two of these bands (40-44 and 55-59) allowed direct comparison with the BRHS (ages 40-59) since in that study both systolic and diastolic blood pressures rose linearly from 40 to 59 years of age. Subjects were excluded if pregnant, and if the general practitioner knew that someone was physically or mentally unable to participate. The latter criterion excluded no more than 2 or 3 subjects per town. The exclusion of pregnant women is only important for the youngest age group, and was considered necessary to avoid a systematic bias in absolute levels of mean blood pressure at 25-29 years. Since being pregnant at the time of the study

was unlikely to be associated with a women’s usual non-pregnant blood pressure level, the exclusion of pregnant women should not bias between-town comparisons within the youngest age group. Subjects were contacted with a letter signed by their general practitioner, including an appointment for the survey which in 6 of the towns took place on the practice premises, and on hospital or educational premises in the other three. Fieldwork was piloted in another BRHS town not selected for the new study, and the main study carried out between February and November 1987. The towns were visited in turn and 2 weeks spent in each. Two trained nurses conducted the interviews and examinations. The interview was conducted first and covered demography, medication, medical history, lifestyle and social factors. The questions on medication were carefully validated in the pilot town and it was found necessary to confirm the information given by all those respondents who were uncertain of their medication by checking the general practice records. The names of each drug were recorded and subsequently coded by reference to the British National Formulary (BNF) therapeutic categories [6]. Blood pressure measurement

Prior to examination, subjects were asked to empty their bladders. Blood pressure was measured with a Dinamap 1846SX automatic recorder in order to minimize observer variation [7]. This instrument was known to be accurate [8-121 and sufficiently reliable for epidemiological field studies [12]. Subjects were seated comfortably with the right arm supported on a foam cushion with the antecubital fossa at the level of the heart. The right upper arm circumference was measured and a cuff selected according to the manufacturer’s specifications [ 131 which are similar to those of the American Heart Association [14]. Room temperature and right mid-forearm skin temperatures were recorded using type-K thermocouple air and surface probes respectively (RS Components). The Dinamap was then set to measure blood pressure automatically five times in succession at 1 min intervals, and the mean of all five readings have been used for the analysis. The Dinamap operates on an oscillometric principle, and provides readings of systolic, mean arterial (MAP), and diastolic pressures. The static calibration of the single study instrument was checked each day against the mercury column of a standard Accoson sphygmomanometer, and

Geographical Variations in Blood Pressure in British Men and Women

was also compared in a sample of outpatients with a Hawksley Random Zero device at three stages during the survey. There was no evidence of any important drift in accuracy in either case. Response rate The response rate, after exclusion of those subsequently found to have moved, died or been pregnant, was similar in the two oldest age groups for both sexes (approximately 76%), but lower in the youngest age group (55%). The response rate also varied between towns. In the older two age groups the maximum difference in percentage response between towns was 19%, but was 35% in the 25-29 year old males, and 38% in the young females. In some towns, a high proportion of non-responders could be accounted for as having moved away through invitation letters returned by the Post Office and through local information received by practice staff. In other towns this was not so, and the true variation in response rate is therefore uncertain. Nevertheless, the possibility of marked variation in response rate between towns and age groups is of concern, and an attempt was therefore made to assess whether a serious non-response bias might have occurred. Accordingly, general practice records were examined, and the first blood pressure recording in each of the 5 years 1982-86 was extracted where available for each non-responding subject, and fey a responding control matched for sex, and for age within 5 years. Entries were found for a total of 137 male and 269 female responder/non-responder pairs, being 22 and 43% respectively of the total number of non-responders. The results of this study are presented below. Statistical methods Blood pressure levels for men and women in each town are presented separately for the oldest two age groups combined and for the youngest age group, and the means for both groups have been age-adjusted by linear regression. This grouping has been done for three reasons. First, comparison with the BRHS required separate consideration over the age range 40-59 years. Second, while the rise of blood pressure with age can (on the basis of BRHS data) be assumed to be linear for systolic and diastolic between 40 and 59 years, it is markedly non-linear (especially for systolic) over the whole age range of the Nine Towns Study. Third, the lower response rate in the 25-29 year olds

387

necessitatts separate examination of this group before an overall view of the data can be taken. Town blood pressures have also been calculated as medians, adjusted to take account of variations between towns in the proportions of subjects treated for high blood pressure, and for the effects of antihypertensive treatment on blood pressure levels. At ages 40-59, 11.4% of the men and 11.3% of the women reported taking medication in therapeutic categories that would lower blood pressure, and 7.0% (range between towns 2.7-11.3) of men and 6.8% (range 2.7-l 1.3) of women reported taking medication in the previous 48 hours which was classified in the BNF [6] specifically for the treatment of high blood pressure. In the oldest age group (55-59), 34% of those subjects who had taken specific antihypertensive treatment in the previous 48 hours had blood pressure values below the median for their age/sex cell. The adjustment has been made in the Nine Towns Study and in the BRHS (in the latter study only for the purposes of this paper) by ascribing blood pressure values well above the median to all subjects reporting regular antihypertensive medication taken in the previous 48 hours, and then recalculating the median. This could only be done for subjects who reported taking blood pressure-lowering drugs specifically for hypertension, since assumptions could not be made about pre-treatment levels in others who were on treatment for heart failure or angina. However, in the present study about 60% of all subjects on hypotensive drugs reported taking them for high blood pressure. In order to agestandardize the town medians for the combined age group 40-59, treatment-adjusted medians have been calculated for both 5-year age groups, and the average taken. A similar technique has recently been used in the analysis of the Intersalt study [2]. Although the method described should theoretically make a valid adjustment for treatment effects, it is dependent on the completeness and accuracy of information about treatment, and on certain assumptions about pre-treatment blood pressure values. For this reason, results for means are reported alongside those for treatment adjusted medians, so that comparison can be made. Other variables A number of other factors have been examined to assess their potential for biasing the between-town blood pressure comparisons, including observer effects, temperature, humidity

N. G. BRUCEet al.

388

and time of attendance. The study was designed to balance in a non-systematic way the numbers of subjects examined by each observer, and this was successful since overall both observers examined 50.0% of the subjects. Within towns, the most extreme deviation from a balanced allocation of subjects to observer for both men and women was 60/40%, but with most towns lying close to 50% for each observer. Overall observer effects after adjusting for age were small, with observer A reading 3.4 mmHg systolic lower than observer B for males (p < 0.0001) and 2.4 mmHg lower for females (p = 0.02). The differences for MAP and diastolic were much smaller and non-significant. The maximum effect of adjusting town means for observer effects was to increase the mean systolic value for Dunfermline by 0.4 mmHg in the men. Previous studies have identified effects of room temperature on blood pressure [15], and an association with skin temperature [16], and have suggested that the effect of season on blood pressure can be explained mainly by variations in external temperature [15, 171. However, in the present study no significant relationships between blood pressure and external or room temperature, or external humidity were detected after adjusting for age and town. External temperature and humidity were obtained from local meteorological offices for each hour during the survey work. Skin temperature showed significant associations only in males for MAP (-0.98 mmHg/“C; p = 0.01) and diastolic (-0.84 mmHg/“C; p < 0.01) after adjustment for age and town. Since the maximum difference in mean skin temperature between towns was

0.7”C, the effect on between-town comparisons in this study will have been no more than 0.68 mmHg MAP and 0.59 mmHg diastolic. Finally, time of attendance varied little between towns. No adjustments have been made to the data presented in the results section of this paper for any of these methodological factors. Of the 2615 respondents, 10 have been excluded as their ages were outside the specified ranges. A further 9 with inadequate blood pressure data were excluded; 1 due to a power cut, 2 as a result of failure by the Dinamap to record blood pressure (due to bradycardia), and 6 who did not have complete sets of five readings due to feeling faint and consequent termination by the nurses of the measurement cycle. Standardized mortality ratios (SMRs) are presented for cardiovascular disease (ICD 9th revision; 410-459) for ages 35-64 using 1979-83 data for the smallest areas defined by the Office of Population Censuses and Surveys that match the study towns. RESULTS

Evidence for non -response bias

The mean blood pressure values extracted from the practice records were slightly higher for the non-responders (95% CI -0.79 to 4.19 systolic, and -0.63 to 2.43 diastolic). Although the differences are small, the means for nonresponders are consistently greater in all age groups (Table 1). Although the town with the highest response (Carlisle) showed the greatest systolic difference between responders and non-responders, there was no other evidence of a systematic relationship between level of

Table 1. Mean systolic and diastolic blood pressures for the 5 years 1982--86 for nonresponders to the Nine Towns Study and for age and sex matched responding controls in the same study. The differences (non-responder minus responder) and r-values are also shown. All blood pressure values are taken from the general practice records Non-responders

Responders Pairs

Mean

@EM)?

Mean

(SEM)

Difference

209 91 106

120.1 130.0 141.8

(0.8) ii.:;

.

120.9 135.1 142.0

(0.9) (2.0) (1.8)

0.8 5.1 0.2

0.66 2.12’ 0.07

Total

406

128.0

(0.9)

129.7

(0.9)

1.7

1.34

(b) Diasrolic 25-29 40-44 55-59

209 91 106

73.9 80.1 85.1

I:$ (Ll)

14.4 81.4 86.5

(0.6) I:.:;

.

0.5 1.3 1.4

0.59 0.76 1.15

Total

406

78.2

(0.5)

79.1

(0.6)

0.9

1.15

Age group

r-Value

(a) Systolic

25-29 40-44 55-59

‘p < 0.05. tSEM = Standard error of the mean.

Geographical Variations in Blood F’ressurein British Men and Women

response and non-response bias. The mean blood pressures measured in the main study showed no association with the percentage response rate. Diflerences

between towns at age 40-59

years

Table 2 shows the age-adjusted mean systolic, MAP, and diastolic values for men and women aged 40-59 in the 9 towns. The ranges of mean town blood pressures for men are 9.0 mmHg systolic, 6.9 mmHg MAP, and 5.0 mmHg diastolic. Those for women are slightly smaller; 8.6mmHg systolic, 5.2mmHg MAP, and 4.5 mmHg diastolic. These between-town differences have been tested by one-way analysis of variance, and all reach significance with the exception of female systolic (Table 2). This is, in part, due to the greater variability among the oldest women, the systolic standard deviations for the 55-59 year age group being 20.62 mmHg (males) and 23.71 mmHg (females). D$erences

between towns at age 25-29

Table 3 shows the mean systolic, MAP, and diastolic results for the young men and women in the 9 towns. The range of differences between

389

towns is greater for the men than the women, and when tested by one-way analysis of variance the spread of towns is highly significant for all three measures of blood pressure in the men, but only significant (p = 0.02) for diastolic in the women. Similarity of male and female results

The pattern of town means is similar for the two sexes, and correlation coefficients for the associations between male and female ageadjusted means at 40-59 are; r = 0.76 (p < 0.05) systolic, r = 0.81 (p < 0.01) MAP, and r = 0.76 (p < 0.05) diastolic. The correlation coefficients for treatment-adjusted medians at age 40-59 (which take account of any differences between the sexes in levels of medication) are very similar; 0.70 (p < 0.05) for systolic, 0.91 (p < 0.001) for MAP, and 0.70 (p < 0.05) for diastolic. The association between male and female systolic medians, however, is dependent on the Guildford coordinate, that for diastolic somewhat less so, while Fig. 1 demonstrates that the stronger association for MAP is not dependent on any single town. For age 25-29 the correlation

Table 2. Age-adjusted mean blood pressures (and standard errors) for men and women (40-59) in the Nine Towns Study. These are presented in three sets, each of which contains a low, a medium, and a high town, classified according to the blood pressure levels in the BRHS. The ranges of the town means and the p-values for one-way analysis of variance are also shown Age adjusted mean for 40-59 years Town sets

BRHS status

Number of subjects

Systolic Mean (SEM)

Mean

MAP (SEM)

Diastolic Mean (SEM)

(a) Men Maidstone Exeter Carlisle

Low Medium High

106 92 99

142.7 140.0 139.2

it.2 &JO)

105.1 100.1 101.3

(1.37) ;t*:: .

84.5 79.5 80.4

‘,t$ (1:03)

Guildford Southport Dunfermline

Low Medium High

101 110 88

135.6 140.5 140.5

(1.88) (1.80) (2.01)

99.7 104.7 103.7

(1.40)

79.7 83.5 83.5

(1.02) (0.98) (1.10)

Suunthorpe

Low Medium High

84 81 106 867

140.1 143.3 144.6 140.7 9.0 0.05

103.5 106.6 106.5 103.5 6.9 0.001

(1.54) ;tz;

83.7 84.5 84.3 82.6 5.0 0.0001

(1.12) (1.14) (1.00)

Ayr Merthyr Total Range (mmHg) p-Value (ANOVA)

;::; (1:83)

::.::; .

.

(b) Women Maidstone Exeter Carlisle

Medium Low High

99 107 108

134.0 133.1 132.2

::::; (1:95)

95.3 99.0 97.4

(1.41) (1.36) (1.35)

74.1 78.1 76.9

K; (0:95)

Guildford southport Dunfermline

Medium Low High

111 113 96

129.5 136.6 134.3

(1.90) I:z

100.1 95.4 100.2

I:.::; (1.32)

.

74.6 78.4 78.6

$z; (1:OO)

Scunthorpe Ayr Merthyr

Low Medium High

97 :

134.2 134.1 138.1

(2.05) (2.08) (2.03)

98.3 98.1 100.5

77.1 76.3 77.3

925

134.0

98.2

76.8 4.5 0.006

Total Range (mmHg) p-Value (ANOVA)

.

N. G. BRUCEet al.

390

Table 3. Age-adjusted mean blood pressures (and standard errors) for men and women aged 25-29 in the Nine Towns Study These are presented in three sets, each of which contains a low, a medium, and a high town, classified according to thk’blood pressure levels in the BRHS. The ranges of the town means and the p-values for one-way analysis of variance are also shown Age-adjusted mean for 25-29 years Number of subjects

Town sets

BRHS status

Exeter Maidstone Carlisle

Low Medium High

42 35 57

134.5 137.7 135.3

Guildford Southport Dunfermline

Low Medium High

43 54 51

Scunthorpe Ayr Merthyr

Low Medium High

51 30 51

Systolic Mean (SEM)

MAP

Diastolic Mean (SEM)

Mean

(SEM)

(2.16) (2.36) (1.89)

93.8 92.8 91.5

(1.45) (1.59) (1.27)

73.4 70.0 69.5

(1.30) (1.42) (1.14)

128.3 138.1 135.1

(2.14) (1.92) (1.99)

89.9 96.7 94.2

(1.44) (1.29) (1.34)

70.5 76.0 72.5

(1.29) (1.16) (1.20)

134.9 142.8 137.6

(1.97) (2.56) (1.96)

93.1 100.1 95.5

(1.33) (1.72) (1.32)

71.5 77.4 73.2

(1.19) (1.54) (1.18)

(a) Men

414

Total Range (mmHg) p-Value (ANOVA)

94.0 10.2 0.0002

135.8 14.5 0.004

72.5 7.9 0.0001

(b) Women

Exeter Maidstone Carlisle

Low Medium High

45 22 59

121.4 121.1 121.9

(1.98) (2.83) (1.76)

87.4 83.1 87.7

(1.35) (1.94) (1.21)

69.3 64.6 70.0

(1.13) (1.62) (1.01)

Guildford Southport Dunfermline

Low Medium High

33 54 52

115.9 121.7 121.1

(2.32) (1.82) (1.84)

84.2

(1.58)

89.1 87.9

It::;

68.0 72.0 70.6

(1.32) (1.04) (1.05)

Scunthorpe

Low Medium High

42 30 53

120.2 124.1 122.2

(2.06) (2.41) (1.81)

85.9 89.1 87.6

(1.41) (1.65) (1.24)

68.5 70.9 69.4

(1.18)

390

121.2 8.2 0.52

Ayr Merthyr Total Range (mmHg) p-Value (ANOVA)

between male and female ageadjusted means (treatment-adjusted medians not being required at this age) are 0.92 (p < 0.001) for systolic, 0.70 (p < 0.05) for MAP, and 0.66 for diastolic.

coefficients

Mean Arterial Female treatment-adj

87.2 6.0 0.14

69.6 7.4 0.022

Relationship to previous BRHS findings

The results of the Nine Towns Study and the BRHS have been compared by correlation and scatter plots, and although there are no data for

Pressure;

age 40-59

median (mmHgj

102 r=O.Q (p~O.001)

100 -

99 -

96 -

Q2/ 95

97

99

101

Male treatment-adj

103

105

107

109

median (mmHg)

Fig. 1. Association between male and female treatment-adjusted median blood pressures at age 40-59 in the Nine Towns Study (A = Guildford).

391

Geographical Variations in Blood Pressure in BritJsh Men and Women Table 4. Correlation coefficients bscllvan tnota%tantadjusted median blood pressurea in the BRAS (males aged 40-59) and the Nine Towns Study (malea and fm aged 25-29 and 40-59). The same cortelations using age-ad@ted mean blood pressures for both studies are also shown BRHS (ma& 40-59) Nine Towns Study

Diastolic Median Meall

systolic Median Mean

40-59

Male Female

0.66f 0.55

0.33 0.57

0.01 0.21

-0.17 0.25

25-29

Male Female

0.52 0.75’

0.45 0.55

0.22 0.30

-0.19 0.20

*p < 0.05.

females in the BRHS, this method of comparison does allow examination of whether the original pattern of between-town differences in men is similar to that for women in the new study. In view of expected changes in the detection and management of high blood pressure in the community over the last g-10 years, treatment-adjusted medians are probably the more valid measure for comparing the

Wings of the new study and the BRHS, but the results for means are also given. MAP is not included since direct measurement of this is not available from the BRHS. The correlation coefficients (Table 4) show that there are positive relationships between the median town values in the two studies for systolic in older and younger men and women, but that the diastolic relationships are very weak. The male 40-59 age group associations are representative of the data for medians in all subjects (Fig. 2), and illustrate the dependence of the systolic correlations on one town, Guildford. Relationships to cardiovascular mortality There are three important reasons for studying the relationships between the findings of the new study and the mortality experience from cardiovascular disease in the survey towns. First, the BRHS was originally established to investigate regional variations in cardiovascular mortality in Britain, and SMRs were critical in

Systolic Blood Pressure BRHS 154 -

treatment-adj median

(mmHp)

r=0.66 (~~0.06) A

h

150 A 148 -

A

142 -

A

138 -

aa

134 -

A

A

130 131

133

19s

137

139

3 Towns treatment-adj

141

I43

14s

147

median (minH3)

Diastolic Blood Pressure BRHS treatment-ad1

90

median (mmHe)

r=O.Ol

I

t A

A

86 1 A

82

78 A

77

70

81

0 Towna

treatment-rdi

83

86

07

: 09

median bunHo)

Fig. 2. Associations between male treatment-adjusted median blood pressures at age 40-59 in the Nine Towns Study and the British Regional Heart Siudy (A = Guildford).

N. G. BRUCEet al.

392

Table 5. Correlation coefficients for relationships between the SMRs for cardiovascular disease (ages 35-64, 1979-83) and treatmentadjusted median blood pressures. Correlations using age-adjusted mean blood pressures for the Nine Towns Study at ages 40-59 and 25-29 are also shown Correlation with CVD SMR Nine Towns Study blood pressure by age group

Males Median Mean

Females Median Mean

Age 40-59 Systolic MAP Diastolic

og1** 0.91*** 0.87**

0.69’ 0.77* 0.72,

0.41 0.74* 0.55

0.61 0.72* 0.58

Age 2529 Systolic MAP Diastolic

0.74* 0.702 0.56

0.64 0.67* 0.52

0.78* 0.63 0.54

0.75* 0.75* 0.61

*p < 0.05; ?? *p < 0.01; ***p< 0.001.

the selection of the 24 study towns. Second, SMRs provide an important source of external validation for the findings of the present study, particularly for women since the selection of high, medium, and low towns was based solely on the mean blood pressure values in an exclusively male sample. Third, SMRs for a given town are likely to be estimated with more precision than are the mean town blood pressure levels in the BRHS which are open to measurement bias as well as sampling error. Each town SMR for cardiovascular disease has a 95% CI of approximately + 5 with a range of 62 males and 115 for females, while the BRHS town means have 95% CIs of k2.4 mmHg systolic with a range of 16.6 mmHg. Table 5 shows that for the men aged 40-59 there are consistent and strong relationships between the treatment-adjusted medians for all three measures of blood pressure and the cardiovascular SMRs. The relationships for women aged 40-59 are also consistent across the same three measures of blood pressure, though weaker than for the men. With the exception of female systolic, these associations are not dependent on one town, and this is illustrated for MAP in Fig. 3. The results for the young age group are very similar, again with female systolic being the only association dependent on the Guildford coordinate. The pattern of change between the two studies A number of factors will have influenced the levels of blood pressure found in the 9 towns on the two separate occasions, including regression to the mean of towns chosen for their extreme positions, and random error and bias inevitably associated with the sampling and methodology.

The strong association with SMRs described above also suggests that the level of a particular town may have adopted a position closer to what might be expected given the cardiovascular mortality experience. Figure 4 illustrates the movement of the treatment-adjusted town medians between the two studies. It is restricted to males aged 40-59, as no data on females or younger people is available from the BRHS. The vertical dotted line at 0 mmHg represents the mean for both studies. Methodology differed in the two studies, so a comparison of actual blood pressure values would not be helpful; instead it has been assumed that the true mean blood pressure over all 9 towns in both studies has remained constant, and for each town the difference between the town value and the average for all towns in that study has been plotted. Thus movement towards the vertical line represents regression to the mean. The dashed (oblique) line has been calculated by regressing the treatment-adjusted median blood pressure values in the BRHS on the SMRs for all 24 towns. Movement towards this line represents adoption of a value closer to that expected on the basis of cardiovascular mortality. Figure 4 shows that in many cases movements could be either regression to the mean, or movement towards the SMR predicted value, or indeed both. But for both systolic and diastolic the scatter around the regression line is reduced in the present study, and there are some towns which have clearly moved away from the mean to take up a position closer to the regression line. This has occurred for Ayr (systolic), and for Ayr, Merthyr Tydfil and Maidstone (diastolic), and it can be seen that these towns lie where the regression line and mean are

Geographical Variations in Blood Reasure in British Men and Women

393

Males; MAP SMR CVD W-64) 146

1978 - 6s

r-O.01 (ptO.001) A A A

126

A

A

106

OS 101 Treatment-adj

lO8

K)6

107

median MAP (mmno)

Females; MAP SMR CVD (36-64) 190

1979-63

r-O.74 (~~0.05)

A

AA A

94

06 Treatmmt-ad]

96

100

102

median MAP (mmHg)

Fig. 3. Associations between treatment-adjusted median MAP at age 40-59 in the Nine Towns Study and SMRs for cardiovascular disease (age 3544) for the period 197943 (A = Guildford).

becoming divergent. It appears that regression to the mean is not the only explanation for the change between the two studies, and that the scatter has been reduced consistent with towns adopting positions closer to those predicted from local cardiovascular mortality. Geographical dlrerences

by age group

Evidence from the Nine Towns Study has been presented which suggests that there are geographical variations in blood pressure in both young adults and middle-aged people in Britain. One of the key questions to be addressed by this study is whether towns with high mean blood pressures in middle-age were also high at 25-29 years, and if so by how much. Table 6 shows the correlation coefficients between age-adjusted mean blood pressures at age 25-29 and at 40-59, which indicate that the associations between mean blood pressures in

young adulthood and middle-age are consistent and quite strong for both men and women. Figure 5 illustrates the associations between young and middle-aged subjects for MAP, and demonstrates that this finding is generally consistent across the 9 towns, and is not confined to one or two outliers. Regression slopes of blood pressure on age have been calculated for all 9 towns using mean MAP (Fig. 6). MAP was chosen since it has the most consistently linear rise with age, and was thus more suitable for the regression model. No significant differences between the rates of rise of MAP. with age in individual towns were found for either sex, although it is recognized that the power to detect such differences in this study is limited. It is nevertheless clear that the differences in blood pressure between high and low town groups are of similar magnitude across the whole age range of the study. There

N. G. BRUCEet al.

394

Males; Systolic SMR CVD (35-64)

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Fig. 4. Change of male treatment-adjusted median blood pressures between the BRHS and the Nine Towns Study. For full explanation see text. BRHS medians are represented by (A), Nine Towns Study medians by (e), and the arrows illustrate the changes that occurred between the two studies. The vertical dotted line represents the mean for both studies, the oblique dashed line the predicted blood pressure of a town based on its cardiovascular SMR. Key for towns; M = Maidstone, E = Exeter, C = Carlisle, Sp = Southport, G = Guildford, D = Dunfermline, A = Ayr, Sc = Scunthorpe, MT = Merthyr Tydfil.

Table 6. Correlation coefficients for relationships between age-adjusted mean blood pressures at 25-29 and at 40-59 in the Nine Towns Study. Correlations using treatment-adjusted median blood pressures are also shown Age 40-59 Systolic Median Mean

Age 25-29

0.74* 0.65

0.52 0.75*

systolic

Male Female

MAP

Male Female

-

Diastolic

Male Female

-

‘p < 0.05; **p < 0.01; ***p < 0.001.

Mean

MAP Median -

0.83** 0.79*

Diastolic Mean Median -

0.65 0.92*** -

0.7@ 0.78;

0.63 0.59

Geographical Variations in Blood Pressure in British Men and Women

395

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mean MAP at 25-29 and at 40-59 in the Nine Towns Study (A = Guildford).

are no important differences seen when the age trends in treatment-adjusted medians are examined instead to take account of the increasing proportion of subjects on antihypertensive treatment at older ages. DISCUSSION

This study shows that there are clear geographical variations in blood pressure in British men aged 40-59 years and at 25-29 years, and that similar though less marked variations are to be found among women of the same age. These town blood pressures show consistent associations with SMRs for cardiovascular disease at ages 35-64 for the period 1979433; the associations with the findings for middle-aged men in the British Regional Heart Study are less strong.

In the Nine Towns Study, the response rate varied by age group and- between towns, although greater difficulty was experienced in some towns in ascertaining who had moved or left the practice, so the true extent of variation in response rate is uncertain. However, evidence drawn from the practice records of blood pressure suggests that bias arising from nonresponse would not seriously influence the conclusions drawn. One other study, which compared early responders with those who were examined only after one or more reminders, also concluded that non-response does not introduce a serious bias into community surveys of blood pressure [18]. Of the other methodological factors considered, none appear likely to have biased the results to any significant degree.

N. G. BRUCE et al.

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Males; Mean Arterial Pressure MAP (mmHg) 115

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t 20

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Age (yeare)

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95

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i 25

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Age (yeara)

Fig. 6. Regression slopes of mean arterial pressure (MAP) on age for men and women for all towns in the Nine Towns Study.

Similarity of results in young adults and in middle age

Further evidence supporting the validity of the data in the 25-29 year age group is that, despite the higher response rate in the older two age groups, the pattern of between town differences, and associations with cardiovascular disease SMRs and with the BRHS results are very similar in the young adults and in middle-age. Since subjects in all 3 age groups were examined within any given town during the same 2 week period, it is theoretically possible that associations of this nature could arise at least in part spuriously if some measurement

bias were to have operated differentially between the 9 towns. However, the strong associations with cardiovascular disease SMRs (Table 5 and Figs 3 and 4) would argue against this explanation, since the direction and extent of measurement bias in specific towns would not be expected to reproduce so consistently the ecological relationship between risk level (blood pressure mean) and outcome (SMR). This observation is emphasized here for the support it lends to the validity of the Nine Towns Study findings, and is not meant to imply that blood pressure differences necessarily explain the geographical patterns of cardiovascular disease in Britain. Nevertheless, evidence from the BRHS suggests that of the three major risk

Geographical Variations

in Bl6od F%aurc in British Men and Women

factors, it is smoking and blood pressure, and not blood cholesterol, that contribute .t,o geographical variations in cardiovascular disease in Britain [19]. One town, Guildford, plays an important though not exclusive role in the positive findings presented. No methodological problems have been identified that could explain its tendency towards an outlying position. Powerful independent corroborative evidence of the validity of the position of Guildford comes from a parallel study of blood pressure in 5-7 year old children examined in the same 9 towns [20]. This study, which utilized a completely different sampling frame (schools) and was carried out on a separate occasion, also found a markedly lower blood pressure level in the Guildford sample. Comparative population studies of blood pressure within single countries

A review of the literature has yielded no other culturally homogeneous within-country studies involving more than two or three centres, where measurement of blood pressure has included young men and women and been carefully standardized. Among studies that have been carried out in Britain, a survey of the Hebridean Island of Time and two Scottish mainland samples [21] showed evidence of statistically significantly higher levels on the island in men and women aged 30 and above, and the data suggest that the geographical differences probably do extend down (though non-significant) to the youngest age group (15-19) for systolic in both sexes and for diastolic in males. However, differing sampling frames were used, blood pressure was measured with an ordinary sphygmomanometer rather than a Hawksley Random Zero or other bias reducing device, and ambient temperature was not recorded. The Health and Lifestyle Survey, a national study of adults age 18 and over which utilized an automated oscillometric blood pressure recorder (not the Dinamap), has also shown regional variations in the prevalence of hypertension [22].The general pattern for males is consistent with the findings of the Nine Towns Study, the lowest prevalence being in the South and East, the highest in the North, North West and Wales. For women the results are not consistent, with Wales being among the lowest, and the South East among the highest. Direct comparison of this study with the Nine Towns Study should be made

391

with eau@ou, since the former represented whole ‘regions,the latter single towns, and there may be wide variations within any one region. Another British study carried out in the Rho&da Fach and Vale of Glamorgan in South Wales showed no evidence of differences between the two neighbouring populations [23]. A number of within-country studies have also been conducted outside Britain [24-261, and those in Japan have established that there are important regional differences in blood pressure which correspond to some extent with the death rates from cerebrovascular disease [24]. One national study of Japanese railway employees has shown blood pressures in Osaka to be lower at all ages, while separate local studies tend to support the findings of regional variations with data extending down to 35 years [24]. It has been argued that a reduction of the whole blood pressure distribution by even a few mmHg w$#;have ~p@tant consequences in reducing #ttMutable mortality [271.The popula&+ di@ercnces detected in the Nine Towns Stidy are therefore important in public health terms. The key question then centres around the explanations for these differences. This report has concentrated on presenting the evidence for geographical differences in blood pressure, and on assessing the validity of that evidence by considering the sources of bias that might arise in a comparative population study. Detailed analysis of the possible aetiological explanations for these variations will be addressed in a subsequent report.

CONCLUSION

There is growing evidence that blood pressure varies signiticantly within populations in a number of countries, The results of the British Regional Heart Study [4],the present study, and of one other study [22] indicate that Britain is one such country, and furthermore that there is an association between population levels of blood pressure and cardiovascular mortality. The Nine Towns Study has demonstrated that geographical blood pressure differences in Britain are well established by age 25-29, certainly in men, and probably also in women, and a recent study of young children in the same communities has provided some evidence that geographical differences are already present at age 5-7 [20].

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Acknowfedgemenls-The Regional Heart Study is a British Heart Foundation Research Group. The Nine Towns Study was funded by grants from the British Heart Foundation and the Scottish Hospitals Endowment Research Trust. NGB was supported by a grant from the Medical Research Council. We thank Sarah Burke RGN and Stenhanie Kershaw RGN for their hard work in the data coll&ion, and for their commitment throughout the study. We are grateful to all the general practitioners and their staff for their generous support, and to Trusthouse Forte for assistance with accommodation.

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