Hypertension

Predictors of New-Onset Diastolic and Systolic Hypertension

The Framingham Heart Study
Stanley S. Franklin, MD; Jose R. Pio, BS; Nathan D. Wong, PhD; Martin G. Larson, ScD;
Eric P. Leip, MS; Ramachandran S. Vasan, MD; Daniel Levy, MD
BackgroundFactors leading differentially to the development of isolated diastolic (IDH), systolic-diastolic (SDH), and
isolated systolic (ISH) hypertension are poorly understood. We examined the relations of blood pressure (BP) and
clinical risk factors to the new onset of the 3 forms of hypertension.
Methods and ResultsParticipants in the Framingham Heart Study were included if they had undergone 2 biennial
examinations between 1953 and 1957 and were free of antihypertensive therapy and cardiovascular disease. Compared
with optimal BP (SBP 120 and DBP 80 mm Hg), the adjusted hazard ratios (HRs) for developing new-onset IDH
over the ensuing 10 years were 2.75 for normal BP, 3.29 for high-normal BP (both P0.0001), 1.31 (P0.40) for SDH,
and 0.61 (P0.36) for ISH. The HRs of developing new-onset SDH were 3.32, 7.96, 7.10, and 23.12 for the normal BP,
high-normal BP, ISH, and IDH groups, respectively (all P0.0001). The HRs of developing ISH were 3.26 for normal
and 4.82 for high-normal BP (both P0.0001), 1.39 (P0.24) for IDH, and 1.69 (P0.01) for SDH. Increased body
mass index (BMI) during follow-up predicted new-onset IDH and SDH. Other predictors of IDH were younger age,
male sex, and BMI at baseline. Predictors of ISH included older age, female sex, and increased BMI during follow-up.
ConclusionGiven the propensity for increased baseline BMI and weight gain to predict new-onset IDH and the high
probability of IDH to transition to SDH, it is likely that IDH is not a benign condition. ISH arises more commonly from
normal and high-normal BP than from burned-out diastolic hypertension. (Circulation. 2005;111:1121-1127.)
Key Words: blood pressure hypertension aging obesity epidemiology

iastolic hypertension, defined as a diastolic blood pressure (DBP) of 90 mm Hg or higher, often occurs in
conjunction with a systolic blood pressure (SBP)
140 mm Hg: so-called systolic-diastolic hypertension
(SDH).1 When diastolic hypertension occurs with an SBP
140 mm Hg, it is called isolated diastolic hypertension
(IDH).2 Isolated systolic hypertension (ISH) is defined as an
SBP 140 and a DBP of 90 mm Hg.1 We previously
described the age-related longitudinal tracking of DBP and
SBP in the original Framingham Heart cohort,3 but the
pathways leading to and the risk factors that predispose to the
development of the new-onset hypertension subtypes have
not been fully characterized.

See p 1094
In younger adults, IDH is more common than SDH.4
Indeed, the Third National Health and Nutrition Examination
Survey (NHANES III, 1988 to 1991)5 showed that IDH was
the most frequent form of diastolic hypertension in young
adults 40 years old and comparable to SDH in prevalence
from age 40 to 49 years. Together, IDH and SDH accounted

for more than 75% of younger adult individuals with untreated hypertension.5 Surprisingly, despite its frequency in
young hypertensive individuals, IDH has been considered by
some to be an artifact of measurement6 or to be of no clinical
importance.2
In contrast, ISH becomes the dominant form of hypertension from the sixth decade of life and beyond.5,7 NHANES III
data also showed that 3 out of 4 adults with hypertension were
50 years of age or older, and approximately 80% of untreated
and inadequately treated individuals with hypertension age 50
years and older have ISH.5 It is unclear, however, whether the
majority of ISH in older people arises from younger people
with burned-out diastolic hypertension rather than de novo
in persons with nonhypertensive BP.
The first goal of the present study was to determine, by use
of longitudinal follow-up in the original Framingham Heart
Study cohort from 1963 to 1967, the risk for the development
of IDH, SDH, and ISH among nonhypertensive subjects and
from hypertension subtypes other than the specific outcome
analyzed. For example, when the outcome analyzed was IDH,
subjects with IDH were excluded from the baseline popula-

Received July 17, 2004; revision received October 22, 2004; accepted December 20, 2004.
From the Heart Disease Prevention Program, University of California, Irvine (S.S.F., J.R.P., N.D.W.); the Framingham Heart Study, Framingham, Mass
(M.G.L., E.P.L., R.S.V., D.L.); and the National Heart, Lung, and Blood Institute, Bethesda, Md (D.L.).
Guest Editor for this article was Roberto Bolli, MD.
Correspondence to Stanley S. Franklin, MD, Heart Disease Prevention Program, C240 Medical Sciences, University of California, Irvine, CA 92697.
E-mail ssfranklinmd@earthlink.net
2005 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org

DOI: 10.1161/01.CIR.0000157159.39889.EC

1121
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TABLE 1.

March 8, 2005
Mean Values of Selected Risk Factors by Blood Pressure Groups at Baseline
Blood Pressure Group
Optimal
(n1133)

Risk Factor

Normal
(n927)

High Normal
(n695)

IDH
(n193)

ISH
(n349)

Female, n (%)

701 (61.9)

499 (53.8)

344 (49.5)

349 (56.5)

229 (65.6)

Age, y

45.37.6

47.48.3

49.18.0

45.76.5

52.77.7

54.47.6

BMI, kg/m2

24.03.1

25.23.3

26.13.6

28.04.1

28.14.6

26.53.9

Total cholesterol, mg/dL

67 (34.7)

SDH
(n618)

223.239.4

229.539.6

239.040.0

232.842.2

247.042.0

244.742.6

Blood glucose, mg/dL

79.520.4

79.913.1

82.819.1

80.313.6

85.430.8

87.723.0

Smoker, n (%)

683 (60.3)

504 (54.4)

353 (50.8)

110 (57.0)

271 (43.9)

144 (41.3)

Systolic blood pressure, mm Hg

111.35.6

123.04.2

131.95.1

133.64.7

161.017.3

149.58.8

Diastolic blood pressure, mm Hg

72.24.5

78.64.3

83.84.4

92.92.8

99.07.9

84.05.5

Heart rate, bpm

73.610.5

74.811.2

76.711.6

78.311.7

80.812.8

76.612.0

Values are meanSD or n (%). Patients on hypertension medication or with myocardial infarctions, cerebral vascular accidents,
or congestive heart failure were eliminated at baseline.
P0.0001 across groups for all risk factors.

tion. The second goal was to identify clinical risk factors that
predispose differentially to the development of new-onset
IDH, SDH, and ISH. The Framingham Heart Study is
uniquely suited to explore these questions because it provides
an opportunity to characterize the natural history of largely
untreated BP during the early years of the study, thus
minimizing treatment bias.

Methods
Overview
The Framingham Heart Study began in 1948 with the enrollment of
5209 men and women, 28 to 62 years of age at entry, with all
subjects undergoing an extensive cardiovascular history, physical
examination, 12-lead ECG, and various blood chemistry tests.
Detailed descriptions of study design, the method of determining BP
measurements, and the method of classifying cardiovascular end
points have been published elsewhere.3,8

Study Sample
Participants in the original Framingham Heart Study cohort were
included in this investigation if they (1) had undergone both biennial
examinations 3 and 4 (1953 to 1957); (2) were not receiving
antihypertensive treatment; (3) were free of previous cardiovascular
disease, such as myocardial infarction, stroke, or heart failure (the
advent of a cardiovascular event may interrupt the natural history of
the normal transition from one BP category to another); and (4) were
not classified as having the hypertension outcome of interest at
baseline. Values from the first and second biennial examinations
were not used because both SBP and DBP on these examinations
were slightly higher than those recorded on subsequent examinations. This finding was consistent with an early-visit white-coat
hypertensive effect. Follow-up was through biennial examination 9
(19651967). We used 1953 to 1967 as our follow-up period because
a more contemporary one would have resulted in a substantial
increase in subjects receiving antihypertensive therapy and/or experiencing cardiovascular events (because of older age) and thus
limiting our ability to draw conclusions about the natural history of
new-onset IDH, SDH, and ISH. The term new-onset is a categoryspecific term that refers to the first time that the specific hypertension
subtype of interest develops in someone who did not previously have
it; it does not include subsequent additional transitions to other
hypertension subtypes.

Blood Pressure Classification

Those qualifying for the study were classified according to the Sixth
Report of the Joint National Committee on Detection, Evaluation,

and Treatment of High Blood Pressure (JNC-VI).9 Subjects were

divided into 6 categories (Table 1) on the basis of similar BP groups
on both examinations 3 and 4 or on the average of BP from
examinations 3 and 4, as follows: group 1, optimal BP (SBP 120
and DBP 80 mm Hg); group 2, normal BP (SBP 120 to 129 or DBP
80 to 84 mm Hg); group 3, high-normal BP (SBP 130 to 139 or DBP
85 to 89 mm Hg); group 4, IDH (SBP 140 and DBP 90 mm Hg);
group 5, SDH (SBP 140 and DBP 90 mm Hg); and group 6, ISH
(SBP 140 and DBP 90 mm Hg). Those who met the above
qualifications were followed up for a mean of 10 years through
biennial examination 9 (1965 to 1967) for the development of
new-onset IDH, SDH, and ISH, defined as occurring on 2 consecutive biennial examinations or the average of BP from 2 consecutive
biennial examinations. Thus, criteria for defining (1) baseline BP
groups, (2) baseline BP exclusions, and (3) new-onset BP end points
were identical.

Data Analysis
Incidence rates for new-onset IDH, SDH, and ISH (per 1000
person-years) were determined from baseline through examination 9,
both unadjusted and after adjustment for age and sex. Cox
proportional-hazards regression was performed, providing hazard
ratios10 for developing IDH, SDH, or ISH for each baseline BP
category, using those with optimal BP as a reference group. We
adjusted for covariates that were related to the development of
hypertension in a previous Framingham heart Study investigation11
as follows: age, sex, body mass index (BMI in kg/m2) at baseline and
change in BMI (as a time-dependent covariate), total cholesterol
(mg/dL), blood glucose (mg/dL), heart rate (bpm), and current
smoking. Similarly, Cox regression analysis was performed to
provide standardized hazard ratios for 1-SD increments in risk
factors at baseline in the prediction of incident hypertension subtypes. The development of new-onset IDH, SDH, and ISH was
determined at the follow-up examinations occurring at any time
during the 3, 5, 7, 9, and 11 years of follow-up after the baseline
examinations. Individuals were censored if they started antihypertensive medication or if they sustained a myocardial infarction,
stroke, or heart failure before developing the new-onset hypertension
subtype of interest. SAS statistical software (SAS Institute)12 was
used. A probability value of P0.05 was considered significant.

Results
Demographic and Clinical Characteristics
Of the original 5209 Framingham Heart Study participants,
1027 did not attend both examinations 3 and 4, 155 were
receiving antihypertensive therapy, and 112 had experienced

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TABLE 2. Incidence of New-Onset IDH, SDH, and ISH During Follow-Up, Unadjusted and
Adjusted for Age and Sex
Blood Pressure Group
Optimal

Normal

High Normal

SDH

ISH

IDH

1133

927

695

618

349

31

72

64

21

10.3

9.9

9.7

9.4

9.9

Unadjusted: incidence of IDH per 1000

person-y

2.6

7.9

9.5

3.6

1.2

Adjusted for age and sex: incidence of IDH

per 1000 person-y

2.1

7.5

9.2

3.8

2.1

1133

927

695

349

193

52

131

189

75

106

10.3

9.7

8.8

8.6

6.7

Unadjusted: incidence of SDH per 1000

person-y

4.5

14.6

30.9

25.1

82.0

Adjusted for age and sex: incidence of

SDH per 1000 person-y

4.3

14.6

31.6

32.3

84.8

1133

927

695

618

193
19

Incidence of new-onset IDH

Population within group
No. of people who develop IDH
Mean follow-up time, y

Incidence of new-onset SDH

No. of subjects
No. who developed SDH
Mean follow-up, y

Incidence of new-onset ISH

No. of subjects
No. who developed ISH

77

200

216

93

10.3

9.5

8.8

8.9

9.8

Unadjusted: incidence of ISH per 1000

person-y

6.6

22.8

35.4

16.9

10.0

Adjusted for age and sex: incidence of ISH

per 1000 person-y

8.1

24.3

36.1

13.6

12.1

Mean follow-up, y

All tables censored for those receiving hypertension medication and for those sustaining myocardial infarction,
cerebral vascular accident, or congestive heart failure.

a previous cardiovascular event. There remained 3915 subjects who met the inclusion criteria and were eligible for this
study, comprising 1726 men and 2189 women; the mean age
was 48.5 years. Table 1 shows the mean values of selected
risk factors by BP groupings at baseline. There was a
predominance of women in all BP groupings except for IDH,
in which younger men accounted for 65% of the subjects, and
high-normal BP, in which there were equal numbers of men
and women.

Incidence Rates
Of the subjects who met the inclusion criteria, 193 were
classified as having IDH at baseline (54 on both biennial
examination 3 or 4 and 139 from the average of examinations
3 and 4). Among the 3722 participants without IDH at
baseline, 240 developed new-onset IDH during follow-up. Of
these, 48 were censored (23 for starting antihypertensive
therapy, 18 for sustaining cardiovascular events, and 7 for
meeting both exclusion criteria), leaving 192 individuals (111
men and 82 women, 5.2% of the baseline sample) who
qualified as new onset of IDH (Table 2). After adjustment for
age and sex, incidence rates of IDH (per 1000 person-years)
were 2.1, 7.5, 9.2, 3.8, and 2.1 from optimal BP, normal BP,
high-normal BP, SDH, and ISH, respectively. At the time of
diagnosis of IDH, the mean age was 50.3 years and the mean
BP was 131.7/93.4 mm Hg.

Of the subjects who met the inclusion criteria, 618 were

classified as having SDH at baseline (416 on both biennial
examination 3 and 4 and 202 from the average of examinations 3 and 4). Among the remaining 3297 participants
without SDH at baseline, 685 developed new-onset SDH
during follow-up. Of these, 132 were censored (58 for
starting antihypertensive therapy, 67 for sustaining cardiovascular events previously, and 7 for fulfilling both exclusions),
leaving 553 individuals (254 men and 299 women, 16.8% of
the baseline sample) who qualified as having new onset of
SDH (Table 2). After adjustment for age and sex, incidence
rates of SDH (per 1000 person-years) were 4.3, 14.7, 31.7,
32.3, and 79.5 from optimal BP, normal BP, high-normal BP,
IDH, and ISH, respectively. At the time of diagnosis of SDH,
the mean age was 53.4 years and the mean BP was
152.5/96.2 mm Hg.
Of the subjects who met the inclusion criteria, 349 were
classified as having ISH at baseline (137 on the basis of BP
on both biennial examination 3 and 4 and 212 by the average
of BP on examination 3 and 4). Of the remaining 3566
subjects without ISH at baseline, 808 developed new-onset
ISH during follow-up. Of these, 203 individuals were censored (127 for starting antihypertensive therapy, 51 for
sustaining a cardiovascular event, and 25 for having both
exclusion criteria before developing ISH), leaving 605 indi-

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March 8, 2005

TABLE 3.

Hazard Ratios for New-Onset IDH, SDH, and ISH According to Baseline Blood Pressure Groups
Baseline Blood Pressure Group
Normal

High Normal

SDH

ISH

IDH

Age- and sex-adjusted hazard ratio (95% CI)

3.11 (2.044.74)

4.01 (2.606.21)

Age-, sex-, and risk factoradjusted* hazard

ratio (95% CI)

2.75 (1.794.23)

3.29 (2.095.19)

1.89 (1.073.33)

0.71 (0.252.04)

1.31 (0.702.43)

0.61 (0.211.76)

Age- and sex-adjusted hazard ratio (95% CI)

3.35 (2.434.63)

7.19 (5.279.82)

Age-, sex-, and risk factoradjusted* hazard

ratio (95% CI)

3.32 (2.384.62)

7.96 (5.7311.04)

5.97 (4.128.63)

18.43 (13.1625.80)

7.10 (4.8010.50)

23.12 (15.8533.71)

Age- and sex-adjusted hazard ratio (95% CI)

3.12 (2.404.06)

Age-, sex-, and risk factoradjusted* hazard

ratio (95% CI)

3.26 (2.484.29)

4.51 (3.465.86)

1.67 (1.232.28)

1.63 (0.982.69)

4.82 (3.656.37)

1.69 (1.212.37)

1.39 (0.802.43)

Hazard ratio for new-onset IDH

Hazard ratio for new-onset SDH

Hazard ratio for new-onset ISH

Patients on hypertension medication or with myocardial infarctions, cerebral vascular accidents, or congestive heart failure were censored.
*Risk factors include BMI (kg/m2) at baseline, change in BMI during follow-up, total cholesterol (mg/dL), blood glucose (mg/dL), heart rate (bpm), and smoking
prevalence.
P0.01, P0.0001 vs optimal.

viduals (238 men and 367 women, 17.0% of the baseline

population) who developed ISH (Table 2). After adjustment
for age and sex, incidence rates of ISH (per 1000 personyears) were 8.1, 24.3, 36.1, 12.1, and 13.6 for optimal BP,
normal BP, high-normal BP, IDH, and SDH, respectively.
The mean age at diagnosis of ISH was 58.6 years, and the
mean BP was 149.4/82.6 mm Hg.

Hazard Ratios for Developing Outcome Variables

With persons with optimal BP at the baseline visit used as a
reference group, hazard ratios (HRs) and 95% CIs for
developing IDH, SDH, and ISH are shown in Table 3. After
adjustment for age, sex, baseline BMI, change in BMI during
follow-up, total cholesterol, blood glucose, heart rate, and
smoking, the HRs for developing IDH were 2.75 (95% CI,
1.79 to 4.23) for normal BP, 3.29 (95% CI, 2.09 to 5.19) for
high-normal BP (both probability values 0.0001), and 1.31
(95% CI, 0.70 to 2.43, P0.40) for SDH and 0.61 (95% CI,
0.21 to 1.76, P0.36) for ISH.
The HRs for developing SDH, after adjustment for risk
factors as above, were 3.32 (95% CI, 2.38 to 4.62) for normal
BP, 7.96 (95% CI, 5.73 to 11.04) for high-normal BP, 7.10
(95% CI, 4.80 to 10.50) for ISH, and 23.12 (95% CI, 15.85 to
33.71) for IDH (all probability values 0.0001).
The HRs for developing ISH, after adjustment for risk
factors as above, were 3.26 (95% CI, 2.48 to 4.29) for normal
BP, 4.82 (95% CI, 3.65 to 6.37) for high-normal BP (both
probability values 0.0001), 1.39 (95% CI, 0.80 to 2.43,
P0.24) for IDH, and 1.69 (95% CI, 1.21 to 2.37, P0.01)
for SDH.
By use of dummy variables for the prediction of new-onset
IDH, all categories were significantly different from each
other except for the comparison between normal and highnormal BP and between normal BP and ISH. For the
prediction of new-onset SDH, all categories were significantly different from each other except for the comparison
between high-normal BP and SDH and between high-normal

BP and ISH. For the prediction of new-onset ISH, all

categories were significantly different from each other except
for the comparison between optimal BP and IDH and between IDH and SDH (data not shown for IDH, SDH, or ISH
subtypes).

Risk Factors for Development of Hypertension

HRs of risk factors for the development of IDH, SDH, and
ISH are shown in Table 4. After adjustment for baseline BP
groups, HRs for developing IDH were 0.62 (95% CI, 0.52 to
0.74) for each 1 SD of age, 0.54 (95% CI, 0.39 to 0.74) for
female sex, 1.24 (95% CI, 1.06 to 1.44) for each 1 SD of
baseline BMI, and 1.28 (95% CI, 1.06 to 1.55) for each 1-SD
increase in BMI over time. Baseline heart rate, total cholesterol, blood glucose, and smoking were not predictive of IDH
incidence.
After adjustment for baseline BP groups, the HR for
developing SDH was 1.92 (95% CI, 1.72 to 2.15) for each 1
SD of increase in BMI during follow-up. Baseline age, sex,
baseline BMI, heart rate, total cholesterol, blood glucose, and
smoking were not predictive of SDH incidence.
After adjustment for baseline BP groups, HRs for developing ISH were 1.82 (95% CI, 1.66 to 1.99) for 1 SD of age,
1.40 (95% CI, 1.16 to 1.68) for female sex, and 1.15 (95% CI,
1.04 to 1.28) for an increase in BMI during follow-up. BMI
at baseline was not associated with an increased likelihood of
ISH. In separate models, BMI at baseline did not predict
new-onset ISH in younger (age 50 years, P0.22) or older
subjects (age 50 years, P0.31), in men (P0.71) or
women (P0.91). Baseline heart rate, total cholesterol, blood
glucose, and smoking were not predictive of ISH incidence.

Average Maximum DBP Values Reached Before

the Development of ISH
Of subjects who developed ISH, 59% did not have antecedent
diastolic hypertension either at baseline or at any examination
before ISH onset (average maximum DBP of 80.8 mm Hg),

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TABLE 4. Standardized Risk Factor Prediction of New-Onset IDH, SDH, and ISH According to
Baseline Blood Pressure Group
*

Per 1 SD

SEM

Hazard Ratio

95% CI

Risk factors for IDH

Age, y

8.5

Sex, female vs male

Heart rate, bpm

0.483

0.092

0.62

0.520.74

0.0001

0.625

0.163

0.54

0.390.74

0.0001

0.117

0.077

1.12

0.971.31

0.128

11.7

Total cholesterol, mg/dL

41.2

0.033

0.081

1.03

0.881.21

0.685

Blood glucose, mg/dL

21.3

0.061

0.111

0.94

0.761.17

0.585

0.265

0.160

0.77

0.561.05

0.099

BMI, baseline

3.9

0.211

0.078

1.24

1.061.44

0.007

BMI, time-dependent covariate

2.0

0.248

0.095

1.28

1.061.55

0.009

Smoking, yes vs no

Risk factors for SDH

Age, y

8.3

Sex, female vs male

0.022

0.052

1.02

0.921.13

0.673

0.099

0.101

1.10

0.911.35

0.327
0.124

Heart rate, bpm

11.3

0.069

0.045

1.07

0.981.17

Total cholesterol, mg/dL

40.8

0.004

0.047

1.00

0.921.10

0.930

Blood glucose, mg/dL

18.5

0.079

0.060

0.92

0.821.04

0.190

0.129

0.100

1.14

0.941.38

0.195

Smoking, yes vs no
BMI, baseline

3.6

0.049

0.046

1.05

0.961.15

0.280

BMI, time-dependent covariate

1.9

0.654

0.057

1.92

1.722.15

0.0001

8.3

0.596

0.047

1.82

1.651.99

0.0001

Risk factors for ISH

Age, y
Sex, female vs male

0.333

0.096

1.40

1.161.68

0.0005

Heart rate, bpm

11.7

0.050

0.044

1.05

0.961.15

0.259

Total cholesterol, mg/dL

41.0

0.0003

0.045

1.00

0.911.09

0.994

Blood glucose, mg/dL

20.7

0.011

0.044

1.01

0.931.10

0.806

0.068

0.094

1.07

0.891.29

0.470

BMI, baseline

3.9

0.0005

0.047

1.00

0.911.10

0.991

BMI, time-dependent covariate

1.9

0.143

0.051

1.15

1.041.28

0.005

Smoking, yes vs no

Censored for those receiving hypertension medication and for those sustaining myocardial infarction, cerebral
vascular accident, or congestive heart failure. Adjusted for baseline blood pressure groups. BMI, baseline indicates
BMI average from biennial examinations 3 and 4; BMI, time-dependent covariate, BMI change from baseline to
biennial examination to where person developed hypertension end point and subtracting baseline BMI.
* coefficients per 1-SD increment in predictor variable.

Additional Analyses

methods were substituted for censoring. In contrast, there was

a notable increase in the HR for new-onset ISH from 1.69 to
3.79 (95% CI, 2.81 to 5.09) after substitution of the inclusion
method for censoring and an increase in the HR to 3.83 (95%
CI, 2.64 to 5.55) after substitution of the exclusion method for
censoring.

When the new-onset BP category was based on 1 rather than

2 consecutive biennial examinations, the results were essentially unchanged (data not shown).
To estimate the potential bias of censoring subjects at the
time of starting antihypertensive therapy or on sustaining a
cardiovascular complication, HRs for developing IDH, SDH,
and ISH were recalculated (1) after inclusion of subjects who
started therapy and/or events subsequent to baseline and (2)
after excluding all subjects from baseline who subsequently
started therapy and/or had events. The overall results of the
study for new-onset IDH and SDH were essentially unchanged, or there was a modest strengthening of HRs across
all BP categories when either the inclusion or exclusion

The major findings of this study were that normal and

high-normal BP had the highest HRs for new onset of IDH
and ISH, whereas IDH had by far the highest HR for
new-onset SDH over a 10-year follow-up period. The majority (59%) of those who developed ISH did not have antecedent diastolic hypertension; indeed, their average maximum
DBP before developing ISH was 81 mm Hg. Only 18% of
those who developed new-onset ISH had a previous DBP of
95 mm Hg or higher. Baseline BMI was a predictor of IDH,
and an increase in BMI during follow-up was a predictor of
IDH, SDH, and ISH. Other predictors of hypertensive sub-

23% had a maximum DBP of 90 to 94 mm Hg (average

maximum DBP of 91.6 mm Hg), and 18% had a maximum
DBP of 95 mm Hg or higher (average maximum DBP of
99.4 mm Hg).

Discussion

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1126

Circulation

March 8, 2005

types were young age and male sex for IDH and old age and
female sex for ISH.
Note that what was previously called normal and highnormal BP in the Sixth Joint Report of the National Committee on Detection, Evaluation, and Treatment of High Blood
Pressure9 (JNC-VI) has now been renamed prehypertension
in the JNC 71 report to indicate a likelihood of increased
cardiovascular risk. We have chosen to report our data using
these former JNC-VI categories to examine any differences in
risk of developing hypertensive subtypes between these
categories.

Hemodynamic Mechanisms
The frequent progression from prehypertension to IDH in
young adults is consistent with underlying increased peripheral resistance.13 Brachial DBP and SBP rise with
increases in peripheral resistance, but the rise in peripheral
SBP, unlike DBP, is partially attenuated by the reduction
in peripheral amplification that occurs with the development of hypertension in young adult men and to a lesser
extent in young women.13,14 There are 2 lines of evidence
supporting this concept. Wilkinson and colleagues,15 using
pulse-wave analysis with applanation tonometry, showed
that a rise in peripheral DBP was accompanied by an
attenuated rise in peripheral SBP as a result of decreased
peripheral amplification in subjects 50 years old but not
in those 50 years old. Similarly, Millasseau and colleagues16 showed that carotid-femoral pulse-wave velocity, an indicator of aortic stiffness, was more closely
correlated with peripheral DBP than SBP in subjects 50
years old; this was not found in those 50 years old.
In older people, ISH results from increased elastic artery
stiffness, which increases pulse-wave velocity and wave
reflection amplitude.13 In the present study, alteration in
hemodynamics, in the absence of direct measurements, can
be inferred from longitudinal changes in BP variables. Because the majority of persons who developed new-onset ISH
had no previous diastolic hypertension, we infer that largeartery stiffness and not vascular resistance was the predominant mechanism for the rise in SBP.3,17 In contrast, a
minority of persons with new-onset ISH had antecedent
diastolic hypertension. This small subset of individuals may
have developed ISH from large-artery stiffness superimposed
on antecedent high vascular resistance, consistent with socalled burned-out diastolic hypertension.18

Significance of IDH
The results of the present study indicate that there is a
significantly increased likelihood of IDH developing in persons with antecedent prehypertension. Furthermore, participants with IDH at baseline were 23 times as likely to develop
SDH as those with optimal blood pressure, and 82.5% of
persons with baseline IDH developed new-onset SDH during
the ensuing 10 years of follow-up. IDH was characterized as
occurring in overweight or obese younger men, who in turn
had a high risk for the future development of SDH. These
findings, therefore, question the validity of earlier studies that
concluded that IDH was artifactual6 or was without increased
cardiovascular risk.2,19 22 The present study did not examine

cardiovascular outcomes, so we can only hypothesize that

IDH is associated with increased risk for clinical events.

Overweight and Obesity as Predisposing Factors

to Hypertensive Subtypes
Strong evidence23 implicates weight gain and obesity as
prime factors in the future development of diastolic hypertension. Indeed, both baseline BMI and subsequent weight
gain were strong determinants of new-onset IDH and SDH in
the present study. Surprisingly, BMI at baseline was not a
predictor of ISH; however, an increase in BMI during
follow-up was a significant but weak predictor. The lack of
association of baseline BMI with the incidence of ISH in our
study is supportive of a cross-sectional Mexican survey,24
which failed to show a significant association of excess body
weight with ISH.

Strengths and Limitations of the Study

Because of the narrow diagnostic thresholds that define and
separate nonhypertensive status and various hypertensive
subtypes from each other, there is the probability of random
variation of BP measurements from one biennial examination
to the next, and hence, the possibility of misclassification of
baseline and follow-up BP categories. To minimize this
problem, we defined our 6 baseline BP categories on the basis
of BP recorded at biennial examinations 3 and 4 and by the
average of examinations 3 and 4; these criteria were used to
remove persons at baseline with the specific hypertensive
subtype outcome variable. Similarly, we required that the
new-onset hypertension be present at 2 consecutive or the
average of 2 consecutive examinations during follow-up.
These requirements may have resulted in a survival bias
because the presence of 2 consecutive examinations required
patient survival and attendance at both visits; however,
because the results from the use of 2 consecutive examinations for the development of new-onset outcome variables
were ostensibly the same as or even stronger than noted with
a single examination, this potential bias does not appear to be
important.
Furthermore, we favored censoring persons rather than
including them in the study after they had started antihypertensive therapy during follow-up. Substitution of the inclusion method for censoring resulted in a greater likelihood of
SDH converting to ISH, because with treatment, DBP usually
decreased to 90 mm Hg, whereas SBP often remained
140 mm Hg. We also favored censoring persons rather than
excluding them from the entire study if they were started on
antihypertensive therapy during follow-up. Substitution of the
exclusion method for censoring also resulted in a greater
likelihood of SDH converting to ISH. This may have occurred because the exclusion of many subjects with severely
elevated DBP who began therapy resulted in a larger percentage of subjects with mildly elevated DBP that would more
easily transition to ISH over the 10-year follow-up period.
We believe that censoring is the least problematic and the
most conservative of the 3 approaches, in that it preserves the
natural history of age-related BP changes until the initiation
of therapy or onset of cardiovascular events: In this way,
selection bias is minimized. Finally, because the subjects of

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Franklin et al
the original Framingham sample were largely middle-class
and white, our findings may not be generalizable to other
ethnic groups.

Perspective
Given the propensity for increased BMI and weight gain in
the development of new-onset of IDH and the high probability of IDH to transition to SDH, it is likely that IDH is not a
benign condition. With the predicted aging of the US population over the next 20 years, the number of elderly persons
with ISH should continue to grow5 unless there is a dramatic
improvement in primary prevention. The majority of individuals with new-onset of ISH arise from those with normal or
high-normal BP. Our findings support the close monitoring of
persons who are currently prehypertensive and the use of
lifestyle measures to prevent the progression from prehypertension to diastolic and/or systolic hypertension.

Acknowledgments
The Framingham Heart Study is funded by National Institutes of
Health contract NO1-HC-25195.

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Predictors of New-Onset Diastolic and Systolic Hypertension: The Framingham Heart

Study
Stanley S. Franklin, Jose R. Pio, Nathan D. Wong, Martin G. Larson, Eric P. Leip,
Ramachandran S. Vasan and Daniel Levy
Circulation. 2005;111:1121-1127; originally published online February 21, 2005;
doi: 10.1161/01.CIR.0000157159.39889.EC
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 2005 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539

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