Sex Differences in Pulse Pressure Trends With Age Are
Cross-Cultural
Joan H. Skurnick, Mordechay Aladjem, Abraham Aviv
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
Abstract—Sex differences in systolic and diastolic blood pressure levels and trends with age have been consistently
observed in both industrialized and unindustrialized populations. However, the impact of sex on pulse pressure, an index
of vascular aging, in unindustrialized populations has not been addressed. The objective of this report was to characterize
sex differences in aging trends of pulse pressure within unindustrialized populations. Using PubMed and Medline, we
identified 60 articles with blood pressure data from unacculturated or partially acculturated populations. Data on 27
populations from 22 articles were included for analysis, on the basis of adequate description of study design and blood
pressure measurement. Blood pressure means of adult age groups were modeled by linear and polynomial regression.
The pulse pressure levels of women were lower than those of men in early adulthood and higher in older ages. Women
had a steeper, steady increase in pulse pressure with age than men (P⬍0.001), whereas men had a stronger curvilinear
upswing in pulse pressure with age (P⫽0.006). Partially acculturated populations had higher pulse pressures than
unacculturated populations. Sex had a stronger effect on pulse pressure than acculturation. Pulse pressure trajectories of
unindustrialized populations were slightly attenuated compared with those seen in National Health and Nutritional
Examination Surveys III and IV of the US population. A sex effect on pulse pressure trends with age prevails across
unacculturated and acculturated populations. Accordingly, the biological principles of arterial aging, as expressed in
pulse pressure, are the same in all humans, regardless of demography. (Hypertension. 2010;55:00-00.)
Key Words: blood pressure 䡲 aging 䡲 sex factors 䡲 hypertension 䡲 humans
S
ex differences in age-dependent systolic blood pressure
(SBP) and diastolic blood pressure (DBP) trends have
been consistently observed in modern industrialized populations.1,2 That men and women in less industrialized populations also have different age trends in SBP and DBP has been
reported in numerous studies.3–5 Despite this wealth of
literature, aging trends of pulse pressure (PP) in less industrialized populations have not been addressed.
In this study, we explicitly investigated the sex differences
in PP trajectories in less industrialized populations. The focus
on PP stems from its recently recognized importance as a risk
factor for cardiovascular diseases.6 –13 In the Framingham
Heart Study, neither SBP nor DBP added to the predictive
value of PP for coronary heart disease.9 A study of French
men demonstrated that PP predicted cardiovascular mortality
independently of mean arterial pressure,11 although a meta-analysis of Japanese studies found PP to be less predictive of stroke
and myocardial infarction than SBP and mean blood pressure.14
PP is a surrogate of arterial stiffness and, hence, an indicator of
arterial aging in modern societies.15 Should less industrialized
populations also exhibit sex differences in PP trends with age, as
seen in industrialized societies, this would suggest physiological
sex differences in arterial aging that are relatively impervious to
changes in environment or lifestyle, with implications for sexspecific differences in cardiovascular risk.
Methods
Study Selection
Using PubMed and Medline, followed by cross-references, we identified 60 articles in which blood pressure data were available for
populations that were judged as unacculturated or partially acculturated.
Unacculturated societies were defined as remote, with minimal or no
contact with industrialized or Westernized (“acculturated”) societies.
Partially unacculturated societies were defined as maintaining some contact
with acculturated societies. For instance, their locations were within walking
distances from major roads, towns, hospitals, or missions.
We selected by consensus of the authors 22 articles3,16 –36 with
data on 27 populations for inclusion in our analysis. Articles were
required to specify how the study population was selected, methods
for determination of a participant’s age, and a description of
procedures for obtaining blood pressure measurements. To be
included in the analysis, data were required to specify SBP and DBP
means by sex, with sample size, for ⱖ3 adult age ranges (ⱖ18 years
of age), and which included individuals ⱖ50 years. Table 1 presents
the articles and populations selected for analysis. The data were
obtained from field studies between the years 1937 and 1983. The
remaining articles and the reasons for their exclusion are presented in
Table S1 (available in the online Data Supplement, at
http://hyper.ahajournals.org).
Received July 20, 2009; first decision August 3, 2009; revision accepted October 19, 2009.
From the Department of Preventive Medicine and Community Health (J.H.S.) and Center of Human Development and Aging (A.A.), University of
Medicine and Dentistry, New Jersey-New Jersey Medical School, Newark, N.J.; Assaf Harofe Medical Center (M.A.), Sackler School of Medicine, Tel
Aviv University, Zerifin, Israel.
Correspondence to Joan H. Skurnick, Medical Sciences Building-F506, 185 South Orange Ave, Department of Preventive Medicine and Community
Health, UMDNJ-New Jersey Medical School, Newark, NJ 07101-1709. E-mail [email protected]
© 2009 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.109.139477
1
2
Hypertension
Table 1.
January 2010
Twenty-Seven Unacculturated Societies With SBP and DBP by Age Groups
Publication
Year
Source
Murphy34
1955
Whyte29
1958
Padmavati and Gupta28
Kaminer and Lutz24
Lowenstein3
1960
1961
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Maddocks30
1961
Hunter36
1962
Mann et al22
1962
Fulmer and Roberts26
35
Barnes
1963
1965
Maddocks and Rovin17
27
Maddocks31
1967
Prior et al18
1968
Stanhope32
1968
23
Shaper and Saxton
Williams25
Truswell et al20
1965
1967
Kapur and Patt
Oliver et al16
1959
1969
1969
1972
1975
Population
Sex
Degree of
Acculturation*
N†
Oldest Age
Group‡
No. of Age
Groups
Pukapuka,
Female
Not
108
65
3
Cook Islands
Male
Not
96
65
3
Southern Coastal
Female
Partly
69
50
4
Papua New Guinea
Male
Partly
120
50
4
Central Highlands,
Female
Not
145
60
5
Papua New Guinea
Male
Not
197
60
5
Rural Delhi State,
Female
Partly
349
60
5
India
Male
Partly
225
60
5
Bushmen, Kalahari
Female
Partly
29
60
3
Desert, Botswana
Male
Partly
38
60
3
Carajas,
Female
Not
41
61
5
Brazil
Male
Not
39
61
5
Mundurucus,
Female
Partly
34
51
4
Brazil
Male
Partly
36
51
4
Abaiang, Gilbert
Female
Partly
481
70
6
Islands, Micronesia
Male
Partly
451
70
6
Gau,
Female
Partly
393
70
6
Fiji Islands
Male
Partly
345
70
6
Atiu and Mitiaro,
Female
Not
69
70
6
Cook Islands
Male
Not
216
70
6
Pygmies, Democratic
Female
Not
81
50
4
Republic of the Congo
Male
Not
81
50
4
Navajo, New Mexico,
Female
Partly
90
55
4
United States
Male
Partly
159
55
6
Bomai, Papua
Female
Not
53
51
4
New Guinea
Male
Not
83
51
4
Chimbu, Papua
Female
Not
161
60
5
New Guinea
Male
Not
268
60
5
Todas,
Female
Not
21
70
5
India
Male
Not
33
70
6
Purari Delta, Papua
Female
Not
168
50
4
New Guinea
Male
Not
126
50
4
Hanuabada, Papua
Female
Partly
166
60
5
New Guinea
Male
Partly
139
60
5
Mainland region,
Female
Not
255
50
4
Papua New Guinea
Male
Not
238
50
4
Pukapuka,
Female
Not
169
60
5
Cook Islands
Male
Not
188
70
6
Highland villages,
Female
Not
109
50
4
Papua New Guinea
Male
Not
99
50
4
Baganda,
Female
Not
227
75
6
Uganda
Male
Not
216
75
6
Kikuyu,
Female
Partly
289
83
14
Kenya
Male
Partly
239
83
14
!Kung,
Female
Not
68
70
6
Botswana
Male
Not
76
70
6
Yanomamo, Brazil and
Female
Not
130
50
4
Venezuela
Male
Not
122
50
4
(Continued)
Table 1.
Skurnick et al
Cross-Cultural Sex Differences in Pulse Pressure
3
Publication
Year
Population
Sex
1979
Rural Tanzania
Female
Not
275
55
4
Male
Not
333
55
4
Continued
Source
Vaughan33
Poulter et al19
1984
Zein and Assefa21
Luo, Kenya
1986
Degree of
Acculturation*
Oldest Age
Group‡
N†
No. of Age
Groups
Female
Partly
597
65
6
Male
Partly
264
65
6
Rural northwestern
Female
Partly
182
50
4
Ethiopian community
Male
Partly
202
50
4
*Not indicates unacculturated; partly, partially acculturated.
†Data show the sample size.
‡Data show the bottom of the age range.
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Statistical Analysis
Regressions Pooled Across Populations
PP means were presented by age group for 4 populations. For the
remainder, mean PP was computed as the mean SBP minus the mean
DBP, with identical sample sizes, indicating that the same individuals provided both SBP and DBP.
To summarize the overall trends of BP with age, a second set of
analyses pooled data across all populations. Mixed-model analyses
of covariance tested sex, acculturation, and their interaction as
factors in BP trends with age. The linear models included random
population-specific intercepts and slopes to model population variability in BP patterns. Polynomial regression analyses also included
a 2nd-degree age term (age squared) for curvature and were centered
at age 40 years, the approximate overall mean age.
For comparison with PP trends in modern society, regression analyses
were performed on National Health and Nutritional Examination Surveys (NHANES) III (1988 –1994) and IV (1999 –2002)37 BP measurements for men and women aged ⱖ20 years, applying the NHANES
sample weights to achieve representation of the US population.
Means are presented with 95% confidence limits. A P value ⬍0.05
is considered significant. SAS 9.1 software (SAS Institute) was used
for computations.
Linear Regressions Within Populations
Linear regression analyses were performed within each population,
stratified by sex. SBP, DBP, and PP age group means were regressed
on the midpoint of the age interval, weighted by the age-group
sample size. Where the oldest age group was unbounded, a midpoint
was imputed on the basis of the intervals between lower bounds. BP
at age 20 years, a nominal onset of adulthood, was used as the
intercept. The null hypotheses were as follows: (1) no differences in
PP (or SBP or DBP) slopes between men and women within
unacculturated and partially acculturated societies; (2) no difference
in PP slopes between unacculturated and partially acculturated
societies; and (3) no acculturation effect on sex differences in the
change in PP with age. Within-population differences between
parameters for men and women were used to test for sex effects,
given the paired structure of the data. Univariate comparisons of sexand population-specific parameters were performed by t tests or rank
tests. Within most populations, there were too few age groups to
perform polynomial regression.
Results
Regression Slopes by Population
Table 2 presents the estimated BP at age 20 years and the
slopes, summarized by sex and degree of acculturation. SBP
at age 20 years among women was lower than among men,
Table 2. Change in Blood Pressure/Year of Aging: Linear Regression Slopes Within Unacculturated and Partially
Acculturated Populations
Blood Pressure at Age 20 y, mm Hg
Slope: Annual Change in Blood Pressure, mm Hg/y
Degree of Acculturation*
N†
Sex
Minimum
Median
Maximum
Mean
Minimum
Systolic
Not
16
Female
98.6
111.4
124.1
110.8
⫺0.08
0.24
0.79
0.28
13
Male
91.8
117.5
127.2
115.9
⫺0.56
⫺0.05
0.66
⫺0.01
56
Female
98.2
110.2
126.1
110.0
0.05
0.44
0.94
0.40
0
Male
108.3
116.1
133.9
117.3
⫺0.24
0.13
0.43
0.14
18
Female
62.4
73.0
82.3
72.3
⫺0.23
0.06
0.41
0.05
44
Male
68.7
75.3
86.2
75.4
⫺0.34
⫺0.08
0.26
⫺0.07
75
Female
62.2
72.9
81.8
71.5
⫺0.26
0.08
0.26
0.09
9
Male
65.6
78.2
81.7
75.0
⫺0.11
0.02
0.16
0.02
27
Female
32.2
38.0
50.4
38.5
⫺0.16
0.23
0.55
0.24
6
Male
20.2
40.6
49.2
40.3
⫺0.47
0.03
0.55
0.07
44
Partly
Diastolic
Not;
Partly
Pulse pressure
Not
Partly
11
16
11
16
11
Median
Maximum
Mean
Percentage
⬍0, %
Variable
Female
25.3
37.8
47.2
38.5
⫺0.03
0.23
0.72
0.31
9
Male
31.4
40.0
55.5
42.3
⫺0.21
0.11
0.54
0.12
18
Linear regression slopes weighted by number of observations per age group.
*Not indicates unacculturated; partly, partially acculturated.
†Data show the number of populations.
4
Hypertension
January 2010
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whereas SBP slopes among women were consistently higher
than those among men. There was considerable heterogeneity
in slopes, within sex and acculturation category. The withinpopulation differences of women’s minus men’s SBP at age
20 years (mean difference: ⫺6.0 mm Hg [95% CI: ⫺8.0 to
⫺4.0 mm Hg]) and the differences in the slopes of women’s
minus men’s (mean difference: 0.28 mm Hg/y [95% CI: 0.16
to 0.40 mm Hg/y]) were significantly different across populations (P⬍0.001 and P⬍0.001) and also when stratified by
acculturation (all Ps ⬍0.01).
Women’s mean DBP at age 20 years was ⫺3.3 mm Hg
lower than the mean for men (95% CI: ⫺4.6 to ⫺1.9 mm Hg;
P⬍0.001). The median and mean slopes of DBP among men
showed little or no increase with age. The mean DBP slopes
(change per year of age) of women were higher than those of
men (mean difference: 0.10 mm Hg/y [95% CI: 0.05 to
0.14 mm Hg/y]; P⬍0.001) but also showed little DBP increase with age. Higher DBP slopes and lower mean DBP at
age 20 years among women than among men were also seen
among the subgroup of 16 unacculturated populations (both P
values ⬍0.001). Among the 11 partially acculturated populations, women’s DBP slopes were higher but not significantly (P⫽0.12), and women’s mean DBPs at age 20 years
were lower (P⫽0.030).
The regression lines for PP are a composite reflection of
the joint trends in SBP and DBP. Mean PP at age 20 years
was lower among women than among men (mean difference:
⫺2.6 mm Hg [95% CI: ⫺4.6 to ⫺0.6 mm Hg]; P⫽0.014). PP
slopes of women were significantly higher than those of men
(mean difference: 0.18 mm Hg/y [95% CI: 0.07 to
0.29 mm Hg/y]; P⫽0.002). Within acculturation strata,
women had higher PP slopes and lower mean PPs at age 20
years, although the age 20 difference among unacculturated
women was not significant (unacculturated: difference at age
20, P⫽0.20 and slope, P⫽0.030; partially acculturated:
difference at age 20, P⫽0.022 and slope, P⫽0.042).
Unacculturated and partially acculturated populations did
not differ in SBP, DBP, or PP levels at age 20 years when
tested within sexes. Partially acculturated populations showed
higher SBP, DBP, and PP slopes than unacculturated populations within both sexes, but the differences were not
significant.
Linear Regressions Pooled Across Populations
To examine further the differences in slopes and BP at age 20
years, linear regressions were performed on BP levels pooled
across all of the populations. Table 3 again displays that
women had lower SBP, DBP, and PP at age 20 years and
greater increases with age within each acculturation group of
populations. Sex, degree of acculturation, and their interaction were tested jointly as factors affecting age trends in all of
the populations, pooled across sexes. SBP and DBP at age 20
years were both lower among women than men (P⫽0.001;
P⬍0.001) by 2 to 5 mm Hg. Women had significantly higher
slopes of increase in SBP and DBP with age (P⬍0.001 and
P⫽0.006, respectively), although the slopes for DBP were
close to 0. The difference in men’s and women’s PP at age 20
years was not significant. However, women’s greater increase
Table 3. Analysis of Covariance Linear Regression Parameters
for Change in SBP, DBP, and PP With Age, From Data Pooled
Across Populations
Blood Pressure
at Age 20 y,
mm Hg
Slope: Annual
Change in
Blood Pressure,
mm Hg/y
Variable
Degree of
Acculturation*
Sex
Systolic
Not
Female
111.5†
0.244‡
Male
114.7
0.066
Partly
Female
111.8
0.330
Male
116.7
0.181
Not
Female
72.8§
Male
75.6
⫺0.074
Partly
Female
72.5
0.049
Male
75.2
0.016
Not
Female
38.5
0.227¶
Male
38.9
0.149
Female
39.3
0.282
Male
41.5
0.167
Diastolic
Pulse
Pressure
Partly
0.025㛳
Model includes sex, acculturation, and sex-acculturation interaction as fixed
effects on blood pressure at age 20 years and on slope, and population and
population-age interaction as random effects.
*Not indicates unacculturated; partly, partially acculturated.
†Data show significant effects on SBP at age 20: sex (P⫽0.001).
‡Data show significant effects on SBP slope: sex (P⬍0.001).
§Data show significant effects on DBP at age 20: sex (P⬍0.001).
㛳Data show significant effects on DBP slope: sex (P⬍0.001).
¶Data show significant effects on PP slope: sex (P⫽0.005).
in SBP with age carried over to a greater increase in PP per
year in women than in men (P⫽0.005).
Unacculturated and partially acculturated populations did
not differ in SBP, DBP, or PP levels at age 20 years. Partially
acculturated populations had more positive SBP and DBP
slopes than unacculturated populations, but the differences
were not statistically significant. There was no synergistic
effect of sex and acculturation on age trends in SBP, DBP,
or PP.
Polynomial Regression Parameters Pooled
Across Populations
Figure 1 presents plots of PP age-group means from all of the
unacculturated and partially acculturated populations. Each
panel distinguishes men and women separately for unacculturated and partially acculturated populations. These PP plots
reveal upswing patterns not fully represented by straight-line
regression, as also observed in modern populations, for
example, the Framingham Heart Study.10 Polynomial regressions were performed on all of the data, pooled across
populations, anchored at age 40 years, the approximate mean
age of the populations. Table 4 presents the resulting estimates of BP at age 40 years, change per year (slope), and
change per year2 (curvature) for each sex and acculturation
category.
The polynomial regressions of SBP, DBP, and PP pooled
across sex and acculturation all indicated that, in the presence
of significant curvature with age, effects of sex and acculturation on BP levels were significant and in some cases
Skurnick et al
A
80
Women
Women
PP (mmHg)
60
Comparison With a US Population Survey
50
40
30
20
20
30
40
50
60
Age (years)
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Women
Women
80
70
80
Men
Men
70
PP (mmHg)
5
age (P⫽0.006). The upswing was somewhat greater among
partially acculturated populations (interaction: P⫽0.046). As
can be discerned from Table 4, sex was a more influential
factor in age-related trends in SBP, DBP, and PP than
acculturation.
Men
Men
70
B
Cross-Cultural Sex Differences in Pulse Pressure
60
50
40
For comparison with a modern population, analogous polynomial regressions were performed on NHANES III and IV
data. Table 4 includes the parameter estimates for the
NHANES population. Figure 2 presents the fitted NHANES
PP polynomial regression and the PP polynomial regression
obtained by pooling the unacculturated and partially acculturated populations. The NHANES parameters define PP
trajectories that, at younger ages, are similar to those of the
less acculturated populations. However, PP in NHANES
swings upward more rapidly from age 40 years for both
sexes. Above approximately age 50 years, the mean PP of US
men and women surpassed the means of the less acculturated
populations. The PP levels of US women overtook those of
US men at approximately age 45 years and widened gradually
to ⬇7 mm Hg at age 80 years. In comparison, in less
acculturated populations, women had higher PP levels by age
40 years, with differences of ⬇4 mm Hg from age 50 years
and above.
Discussion
30
20
20
30
40
50
60
Age (years)
70
80
Figure 1. Mean PP by age group from 16 unacculturated and
11 partially acculturated populations. Polynomial regression
curves are fitted within sex and acculturation group. A, Unacculturated populations: women, PP⫽43.4⫹(age⫺40)*0.275⫹
(age⫺40)2*0.0019; men, PP⫽40.6⫺(age⫺40)*(0.003)⫹
(age⫺40)2*0.0092. B, Partially acculturated populations:
women, PP⫽43.8⫹(age⫺40)*0.245⫹(age⫺40)2*0.0083; men,
PP⫽43.1⫹(age⫺40)*0.041⫹(age⫺40)2*0.0099.
interactive. SBP levels at age 40 years were higher among
unacculturated women than men, but SBP was higher among
men than women in partially acculturated populations (interaction P⫽0.002). Women had a significantly greater slope of
SBP with age than men (P⬍0.001), whereas men had a
greater curvilinear upswing in SBP with age (P⫽0.013).
Women had lower DBP at age 40 years (P⬍0.001) and a
significantly more positive linear increase in DBP
(P⬍0.001).
The consequent age patterns of PP resulted in significant
curvilinear upswings in PP with age. The curves in Figure 1
illustrate that mean PP levels for women were lower than
men’s in early adulthood and then surpassed those of men
through older ages. The PP of women at age 40 years was
significantly higher than that of men (P⫽0.001), somewhat
less so among partially acculturated populations (interaction
P⫽0.007). Women had a significantly steeper steady increase
in PP with age than men (P⬍0.001), with little curvilinear
upswing. In contrast, men had a stronger upswing in PP with
Our findings underscore the similarity of age-dependent PP
trajectories in all societies, suggesting that, regardless of
culture or demography, the biological principles of arterial
aging are the same in all humans. Moreover, the sex effect on
these PP trajectories points to different patterns of arterial
aging in women and men.
On the basis of anthropological studies, it has been proposed that blood pressure may not increase or may increase
only slightly with age during adulthood in some isolated
societies.18 This phenomenon has been attributed primarily to
low salt consumption.16 –20 However, questions have been
raised about causality, particularly in unacculturated societies.38 – 40 In this context, the Intersalt Study was undertaken to
focus on the relationship of blood pressure with sodium and
potassium urinary excretion, which reflected salt intake, and
with lifestyle factors in 52 populations across 32 countries.41
Population differences in the increase of SBP with age were
associated with sodium excretion, but the diversity was only
partially attributable to salt intake; climate, physical activity,
and societal factors were presumed confounders.41 These
findings of the Intersalt Study have contributed to the
protracted debate about “salt sensitivity,”17,28,29 which centers
on the premise that, in humans, the effect of a “high” salt
intake is ultimately and almost singularly expressed by blood
pressure elevation.
The findings that monogenic forms of human hypertension
arise from major mutations in genes encoding sodium transport proteins in the renal tubules42 have only served to bolster
the idea that a high salt intake causes hypertension in the
general population. However, sodium is vital to diverse
networks of biological pathways that are integral components
of growth, development, and, therefore, aging. Because aging
6
Hypertension
Table 4.
January 2010
Polynomial Regression Parameters for Change in SBP, DBP, and PP With Age
NHANES Parameters
Degree of
Acculturation*
Sex
Systolic
Not
Female
117.0†
Male
115.2
⫺0.056
0.00542
Partly
Female
117.4
0.379
0.00469
Male
119.2
0.082
0.00685
Combined
Female
116.8
0.341
0.00175
115.1
0.612
0.0055
Male
116.8
⫺0.003
0.00684
122.0
0.380
0.0044
Diastolic
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Pulse pressure
BP at age 40 y,
mm Hg
Slope: Change in
BP/y, mm Hg/y
Curvature: Change
in BP/y2, mm Hg/y2
0.333‡
⫺0.00276§
0.069¶
BP at Age 40 y,
mm Hg
Change in BP/y,
mm Hg/y
Change in BP/y2,
mm Hg/y2
Variable
⫺0.00396
Not
Female
73.7㛳
Male
74.7
⫺0.038
⫺0.00345
Partly
Female
73.9
0.142
⫺0.00358
Male
76.0
0.039
⫺0.00303
Combined
Female
73.7
0.100
⫺0.00385
73.2
0.275
⫺0.0080
Male
75.2
⫺0.009
⫺0.00299
78.7
0.252
⫺0.0103
Not
Female
43.4#
Male
40.5
⫺0.012
0.00896
Partly
Female
43.5
0.238
0.00827
Male
43.3
0.044
0.00988
Combined
Female
43.1
0.246
0.00557
41.9
0.34
0.0135
Male
41.6
0.010
0.00982
43.4
0.13
0.0147
0.271**
0.00122††
Model includes sex, acculturation, and sex-acculturation interaction as fixed effects on blood pressure at age 20 years, slope and curvature, and population and
population-age interaction as random effects.
*Not indicates unacculturated; partly, partially acculturated.
†Data show significant effects on SBP at age 40 years: sex-acculturation interaction (P⫽0.002).
‡Data show significant effects on SBP slope: sex (P⬍0.001).
§Data show significant effects on SBP curvature: sex (P⫽0.01).
㛳Data show significant effects on DBP at age 40: sex (P⬍0.001).
¶Data show significant effects on DBP slope: sex (P⬍0.001).
#Data show significant effects on PP at age 40: sex (P⫽0.001) and sex-acculturation interaction (P⫽0.007).
**Data show significant effects on PP slope: sex (P⬍0.001).
††Data show significant effects on PP curvature: sex (P⫽0.006) and acculturation (P⫽0.046).
in industrialized societies is frequently accompanied by a rise
in SBP and PP, the question that matters most is whether the
influence of sodium on human biology should be defined in
terms of blood pressure effects or within the framework of the
potential relationship between sodium and biological aging.
Another salient matter is how much of the effect of salt can
be explained in genetic terms.
The genetic argument in support of the role of salt in
human biology is that our genetic makeup has been shaped
primarily by natural selection during the preagricultural era,
when individuals with avid renal sodium absorption capacity
enjoyed an evolutionary advantage. The argument goes on to
suggest that salt-mediated blood pressure elevation is a
modern affliction of a subset of the human population with
genetic predilection to retain sodium, because sodium intake
of contemporary humans well exceeds the low-sodium/highpotassium diet of their Stone Age ancestors.18 However,
Paleolithic diet evolved to meet nutritional needs of humans
with an average life span of ⬍30 years.
A central feature of evolution is that natural selection
largely operates during the reproductive period. The upper
boundary of this period is ⬇50 years, reflecting the onset of
menopause. However, essential hypertension primarily oc-
curs during the postreproductive years, among upper middle
aged and elderly persons. Thus, essential hypertension is a
modern problem, because humans live much longer than ever
before. Moreover, approximately two thirds of patients with
essential hypertension manifest systolic hypertension and,
hence, a high PP.43– 45 The aging factor is, hence, relevant to
understanding age-dependent PP trajectories. Accordingly, if
salt intake impacted age-dependent blood pressure trajectories, its effect might largely be by accelerating the pace of
arterial aging. Indeed, salt might exert a cardiovascular effect
independent of that on blood pressure.46,47
Our findings suggest that, in populations not yet industrialized, women and men differ in their patterns of increasing
PP with age. Broadly, regardless of acculturation, women
tend to have lower SBP in early adulthood and to have a more
rapid rise of this variable with age, resulting in a steeper
climb of PP in women than in men. We have illustrated that
the NHANES III/IV broad survey of the US population
exhibits a similar crossover of women’s and men’s PP trends.
In the Asklepios survey of healthy middle-aged Belgians, the
PP age trend among women also crosses over that of men at
age 50 years.48 A sex difference in blood pressure trends with
age is seen despite the variety of populations and study
Skurnick et al
A
80
PP (mmHg)
70
Women
Women
Men
Men
60
50
40
30
20
20
B
30
80
40
Women
50
60
Age (years)
80
70
80
Men
70
PP (mmHg)
Downloaded from http://hyper.ahajournals.org/ by guest on June 17, 2017
70
60
50
40
30
20
20
30
40
50
60
Age (years)
Figure 2. Polynomial regression curves fitted to A. Mean PP by
age group across 27 unacculturated and partially acculturated
populations. Women: PP⫽43.1⫹(age⫺40)*0.246⫹(age⫺40)2*
0.0056. Men: PP⫽41.6⫹(age⫺40)*0.010⫹(age⫺40)2*0.0098. B,
NHANES III and IV PP readings among adults. Women: PP⫽
41.9⫹(age⫺40)*0.337⫹(age⫺40)2*0.0136. Men: PP⫽43.4⫹
(age⫺40)*0.128⫹(age⫺40)2*0.0147.
designs, underscoring the robustness of the sex effect. Although not all 27 of the within-population estimates show
higher PP in women aged 20 years than in men or in PP slope,
the within-population sex differences are significant, within
and across acculturation classes. Most population subsets
contain only a few age levels, with some relatively small
sample sizes. We would expect, because of statistical variability alone, that not all of the observed within-population
results would track overall trends.
Trajectories on the basis of longitudinal follow-up of
individuals in these populations might not have shown the
same aging patterns. As noted by Pearson et al,49 crosssectional aging trends may reflect selective mortality. The
longitudinal Framingham Heart Study reported PP trends for
healthy or untreated hypertensive women that were lower at
a younger age and then converged or slightly overtook the PP
levels of comparable men.10 The Baltimore Longitudinal
Study of Aging of healthy volunteers observed little difference in results from cross-sectional and longitudinal analyses.
Women had consistently lower SBP and DBP levels. Although SBP increased with age, the gap narrowed between
Cross-Cultural Sex Differences in Pulse Pressure
7
men’s higher SBP and women’s lower SBP because of
steeper SBP increases in women up to age 70 years. With a
smaller sex difference in DBP levels and flatter trajectories,49
the narrowing of the SBP differences would be reflected in PP
trends, albeit without crossover.
We underscore limitations of our study. Our regression
analyses are “ecological,” in that the observations are agegroup means, rather than individual BP measurements. We
nevertheless have compared our trend results with those from
well-known cross-sectional studies of individuals. Our designation of populations as unacculturated versus partially
acculturated is subjective and crude. We note that degree of
acculturation may be a surrogate for or confounded by
differences in diet, cultural practices, and study procedures,
particularly in measurement of blood pressure. We were
unable to classify with any confidence the population diets.
We cannot rule out the possibility that sex differences in PP
trends are consequences of sex differences in a time-varying
exposure to a covariate. However, the regression patterns, if
indirect, would be attenuated from the underlying covariate
trends, which would imply very strong covariate effects on
PP. Furthermore, such sex-specific covariate effects and time
trends would have to be consistent across our diverse populations to produce such an effect. It is more likely that the sex
differences in PP trends seen cross-culturally in less acculturated and modern societies do not depend on external
confounders such as lifestyle and diet. Although there is no
doubt that PP and vascular stiffness are related to salt intake,
a phenomenon that is clearly evident in the elderly,47 it is
unlikely that the age-related PP trajectory and its modification by sex can be solely explained by salt intake. PP may
nevertheless be a surrogate for sex-dependent physiological
differences, which is salient to our interpretation of the
results.
Finally, our study has focused on societies untouched by
environmental confounders of modern times, an undertaking
no longer feasible, as so few populations remain truly remote.
For this reason alone, recognition that a sex effect on PP
trajectories, and, by implication, arterial aging, is independent
of acculturation is highly relevant to perspectives on essential
hypertension and cardiovascular risk.
Perspectives
Among less acculturated populations, an effect of sex on the
PP trajectory was observed regardless of interpopulation
variations in environmental exposures, including salt intake.
Thus, the age-dependent differences in PP trajectories between women and men seen across societies most likely stem
from sex-related differences in arterial aging. It follows, then,
that if a high salt intake increases the likelihood of cardiovascular disease, its effect is primarily mediated by accelerating arterial aging. To tackle the problem of age-dependent
rises in PP, we must confront the underlying biology of the
aging process itself.
Acknowledgments
We thank Eileen Crimmins and Jung Ki Kim (Andrus Gerontology
Center, University of Southern California, Los Angeles) for their
assistance in the analysis of the NHANES data.
8
Hypertension
January 2010
Disclosures
None.
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Sex Differences in Pulse Pressure Trends With Age Are Cross-Cultural
Joan H. Skurnick, Mordechay Aladjem and Abraham Aviv
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ONLINE SUPPLEMENT
Sex Differences in Pulse Pressure Trends with Age Are Cross-Cultural
Joan H. Skurnick, PhD*, Mordechay Aladjem, MD†, Abraham Aviv, MD‡
*Department of Preventive Medicine and Community Health, University of Medicine and
Dentistry-New Jersey Medical School, Newark, NJ, †Assaf Harofe Medical Center,
Sackler School of Medicine, Tel Aviv University, Zerifin, Israel, ‡Center of Human
Development and Aging, University of Medicine and Dentistry-New Jersey Medical
School, Newark, NJ.
Address inquiries to:
Joan Skurnick, Medical Sciences Building – F506, 185 South Orange Avenue,
Department of Preventive Medicine and Community Health, UMDNJ-New Jersey
Medical School, Newark, NJ 07101-1709
E-mail: [email protected]
1
______________________________________________________________________
Table S1. Articles Excluded from Analyses
______________________________________________________________________
Populations deemed acculturated, not rural or isolated
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Dubey VD. A study of blood pressure amongst industrial workers of Kanpur. J Indian
Med Assoc.1964;23:495-498.
Fleming WD. Blood chemistry and blood pressure standards. The effect of tropical
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Lovell RRH, Maddocks I, Rogerson GW. The casual arterial pressure of Fijians and
Indians. Australas Ann Med. 1960;9:4-17.
Lygonis C. Arterial blood pressure in a Faroese fishing community. Dan Med Bull.
1967;14:82-83.
Makela M, Barton SA, Schull WJ, Weidman W, Rothhammer F. The multinational
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Mathur K, Wahi PN, Gahlaut D. Blood pressure studies in the adult population of Agra,
India. Amer J Cardiol. 1963;11:61-65
.
Page LB, Vandevert DE, Nader K, Lubin NK, Page JR. Blood pressure of Qash’qai
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rural Zulu. J Epidemiol Community Health. 1982;36:256-261.
2
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the Philippines, Japan and Korea. Philipp J Cardiol. 1983;9:1-10.
Blood pressure values not presented as mean, N per age group
Becker BJP. Cardiovascular disease in the Bantu and coloured races of South Africa. S
Afr J Med Sci. 1946;11:107-120.
Casley-Smith JR. Blood pressure in Australian aborigines. Med J Aust. 1959;9:627-633.
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Mann GV, Shaffer RD, Anderson RS, Sandstead HH. Cardiovascular disease in the
Masai. J Atheroscler Res. 1964;4:289-312.
Marvin HP, Smith ER. Hypertensive cardiovascular disease in Panamanians and West
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88:1559-1560.
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Data presented graphically
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Solomon Islands societies. Circulation. 1974;49:1132-1146.
3
Pandey MR. Upadhyaya LR, Dhungel S, Pillai KK, Regmi HN, Neupane RP. Prevalence
of hypertension in a rural community in Nepal. Indian Heart J. 1981;33:284-289.
Sinnett PF, Whyte MH. Epidemiologic studies in a total highland population, Tukisenta,
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Data not presented by sex
Morse WR, McGill MD, Beh YT. Blood pressure amongst aboriginal ethnic groups of
Szechwan province, West China. Lancet. 1937;I:966-967.
Data for males only
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Shaper AG, Williams AW, Spencer P. Blood-pressure and body build in an African tribe
living on a diet of milk and meat. East Afr Med J. 1961;38:569-580.
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Exclusion of subjects with hypertension
Murrill RI. A blood pressure study of the natives of Ponape Island, Eastern Carolines.
Human Biol. 1949;21:47-59.
Data presented in other publications
Poulter NR, Lury JD, Thompson AV. Blood pressures higher in the home than in the
clinic in rural Kenya. J Epidemiol Community Health. 1986;40:186-187.
Review articles with no original data
Huizinga J. Casual blood pressure in populations. In: The Human Biology of
Environmental Change: Proceedings of a Conference held in Blantyre, Malawi, April 512, 1971. London: International Biological Programme; 1972:164-167.
Lovell RRH. The relationship between blood pressure and age in various races of
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______________________________________________________________________
4