Blood Pressure and Risk of Secondary Cardiovascular Events in Women : The Women's

Antioxidant Cardiovascular Study (WACS)

Peter J. Mason, JoAnn E. Manson, Howard D. Sesso, Christine M. Albert, Marilyn J. Chown,
Nancy R. Cook, Philip Greenland, Paul M Ridker and Robert J. Glynn
Circulation. 2004;109:1623-1629; originally published online March 15, 2004;
doi: 10.1161/01.CIR.0000124488.06377.77
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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Blood Pressure and Risk of Secondary Cardiovascular

Events in Women
The Womens Antioxidant Cardiovascular Study (WACS)
Peter J. Mason, MD, MPH; JoAnn E. Manson, MD, DRPH; Howard D. Sesso, ScD, MPH;
Christine M. Albert, MD, MPH; Marilyn J. Chown, BSN, MPH; Nancy R. Cook, ScD;
Philip Greenland, MD; Paul M Ridker, MD, MPH; Robert J. Glynn, ScD
BackgroundIn apparently healthy people, the relation between blood pressure and risk of subsequent cardiovascular
disease (CVD) is linear. In persons with CVD, the relation is uncertain.
Methods and ResultsWe conducted a prospective study of 5218 older women with CVD who reported their blood
pressure at baseline in the Womens Antioxidant Cardiovascular Study (WACS), an ongoing double-blind, placebocontrolled secondary prevention trial of the benefits and risks of antioxidant vitamins, folic acid, vitamin B6, and vitamin
B12 among women with CVD or 3 coronary risk factors. A total of 661 confirmed CVD events (nonfatal myocardial
infarction, nonfatal stroke, coronary artery bypass graft procedure, percutaneous coronary angioplasty, or CVD death)
occurred during a median follow-up of 6.5 years. After controlling for age, randomized treatment assignment,
antihypertensive medication use, and coronary risk factors, we found that systolic blood pressure (SBP) was a strong
predictor of CVD events and that the relation between SBP and CVD risk was positive, continuous, and linear (P for
linear trend0.001). For each 10-mm Hg increment in SBP, there was a 9% (95% CI 4% to 15%) increase in risk of
secondary CVD events. Diastolic blood pressure, mean arterial pressure, and pulse pressure were weaker predictors of
CVD risk in this cohort, and joint consideration of SBP and diastolic blood pressure found that only SBP significantly
predicted risk. Use of antihypertensive medication did not modify the relationship of SBP with CVD events.
ConclusionsIn this population of women with CVD, we observed a strong, continuous, and linear association between
SBP and risk of secondary CVD events. SBP was the blood pressure measure most strongly related to CVD risk.
(Circulation. 2004;109:1623-1629.)
Key Words: hypertension cardiovascular diseases prevention women

ypertension is a strong independent risk factor for the

development of cardiovascular disease (CVD). In primary prevention, the relationship between blood pressure
(BP) and cardiovascular risk appears to be positive, graded,
and continuous.1,2 Current guidelines in primary and secondary prevention reflect these findings.35 Most of the evidence
in support of BP treatment guidelines comes from primary
prevention trials6,7 and observational studies in patients without CVD,8 11 although recent trials show benefit of antihypertensive therapy in patients with preexisting CVD.12,13
In secondary prevention, the relationship between BP
and CVD events is less certain. Although the argument for
a linear relation is strong, it is based primarily on data in
primary prevention clinical trials involving a restricted
range of BP values and extrapolations that assume the

validity of the linear logistic model. Nonlinear relations

have been reported14 17 but not widely accepted.6,7 Previous work also suggests that joint consideration of systolic
BP (SBP) and diastolic BP (DBP), as well as consideration
of nonlinear relationships with CVD risk, may improve
prediction.18 20 Despite the apparent uncertainties, the
traditional view that the relationship between BP and CVD
risk is linear generally prevails in clinical practice.3,5
Whether this assumption is correct with respect to secondary prevention remains unproven.
The objective of this analysis was to examine the relationship between BP and secondary cardiovascular events in a
population of older women with CVD. We systematically
tested for both linear and nonlinear relationships between
various measures of BP and CVD risk.

Received June 21, 2001; de novo received October 16, 2003; revision received January 5, 2004; accepted January 14, 2004.
From the Division of Preventive Medicine, Department of Medicine, Brigham and Womens Hospital, Harvard Medical School (P.J.M., J.E.M., H.D.S.,
C.M.A., M.J.C., N.R.C., P.G., P.M.R., R.J.G.), Boston, Mass, and the Department of Preventive Medicine, Northwestern University Medical School
(P.G.), Chicago, Ill.
Correspondence to Robert J. Glynn, ScD, Brigham and Womens Hospital, Division of Preventive Medicine, 900 Commonwealth Ave E, Boston, MA
02215-1204. E-mail rglynn@rics.bwh.harvard.edu
2004 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org

DOI: 10.1161/01.CIR.0000124488.06377.77

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Methods
Study Population
The Womens Antioxidant Cardiovascular Study (WACS) is an
ongoing randomized, double-blinded, placebo-controlled secondary
prevention trial of the benefits and risks of antioxidant vitamins, folic
acid, vitamin B6, and vitamin B12 that is being conducted among US
female health professionals 40 years and older with known CVD or
3 coronary risk factors.21 CVD was defined as a self-reported
history of myocardial infarction (MI), angina pectoris, coronary
revascularization, stroke, transient cerebral ischemia, carotid endarterectomy, or peripheral artery surgery on the baseline questionnaire.
Primary exclusion criteria for enrollment were history of cancer
(except for nonmelanoma skin cancer), active liver disease or
cirrhosis, chronic kidney failure, current use of warfarin or other
anticoagulant, or unwillingness to comply with study medications or
to withhold use of out-of-study vitamin supplements.
WACS randomized 8171 women between April 1995 and October
1996. For the purposes of the present analysis, we excluded women
with 3 coronary risk factors but without known CVD (n2933)
and those who did not provide complete baseline BP information
(n20), which yielded a study population of 5218 women.

Assessment of BP
Self-reported BP measurements were obtained from prerandomization questionnaires. Participants reported SBP in 1 of 9 categories:
110, 110 to 119, 120 to 129, 130 to 139, 140 to 149, 150 to 159,
160 to 169, 170 to 179, and 180 mm Hg. DBP was reported in 1
of 7 categories: 65, 65 to 74, 75 to 84, 85 to 89, 90 to 94, 95 to 104,
and 105 mm Hg. In health professionals, self-reported BP has good
reliability, reproducibility, and construct validity.8,2224 Continuous
BP values were assigned to each participant by taking the midpoint
value for their reported BP category. Participants with SBP 110 or
180 mm Hg were assigned the values 95 or 190 mm Hg, respectively; those with DBP 65 or 105 mm Hg were assigned the
values 55 or 110 mm Hg, respectively. We calculated mean arterial
pressure (MAP; 2/3 DBP1/3 SBP) and pulse pressure (PP;
SBPDBP) using the generated values of SBP and DBP.

Assessment of Other Risk Factors

Prevalent CVD was determined from WACS prerandomization
questionnaires and categorized hierarchically: MI, stroke, revascularization procedure (PTCA, CABG, carotid endarterectomy, and
peripheral artery surgery), and symptomatic vascular disease (angina
pectoris and transient cerebral ischemia). Questionnaires also asked
about baseline characteristics (age at randomization, race, weight,
height, alcohol use, exercise frequency, menopausal status, serum
cholesterol level, and current use of BP, cholesterol, or diabetes
medications) and coronary risk factors (current tobacco use, parental
history of MI at age 65 years, history of diabetes, history of
elevated cholesterol, and history of hypertension).

End-Point Ascertainment and Confirmation

The primary outcome measure in WACS is a combined end point of
nonfatal MI, nonfatal stroke, coronary revascularization procedure
(CABG or PTCA), or CVD mortality. Participants received questionnaires every 6 months for the first year after randomization and
annually thereafter; the response rate for the most recently completed
follow-up questionnaire (48 months) was 90%, and vital status was
known for 99% of participants. On all questionnaires, participants
reported cardiovascular outcomes since completion of the preceding
questionnaire. An end-points committee reviewed all reported
events; only confirmed events are included in the present analysis.
MI was confirmed if symptoms were consistent with World Health
Organization criteria and the event was associated with elevation of
serum cardiac enzymes or diagnostic changes on ECG.25 Stroke was
confirmed if the participant experienced a new neurological deficit
that persisted longer than 24 hours. Revascularization procedures
were confirmed by review of medical records. CVD death was

confirmed if a cardiovascular mechanism was suggested from

autopsy reports, death certificates, and medical records.

Statistical Methods
Baseline variables were summarized as means and SDs (continuous
variables) or proportions (categorical variables). We used Cox
proportional hazards regression to determine the relative risk (RR)
and 95% CI of first postrandomization CVD events according to
categories of SBP and DBP. SBP category 120 to 129 mm Hg and
DBP category 75 to 84 mm Hg were defined as the reference groups
for their respective comparisons. Initial models adjusted for age and
randomized treatment assignment, and multivariate models also
included terms for body mass index, past or current tobacco use,
alcohol use, exercise frequency, history of elevated cholesterol,
diabetes, current antihypertensive medication use, prior MI, prior
stroke, and prior revascularization. Additional adjustment for parental history of MI at age 65 years, menopausal status, serum
cholesterol level, and hormone replacement therapy had little effect
on the results, and these variables were not included in the final
models.
To assess the shape of the relationship between BP and CVD risk,
we used 3 complementary approaches. For each approach, we used
likelihood ratio tests to compare the competing model with the
simpler model that assumes a linear relationship between BP and the
log hazard. First, we used the traditional test for deviation from
linearity that compares the linear model to the model that includes
indicator variables for BP categories. Second, we considered curvilinear relations by adding a quadratic term to the linear model. Third,
we used flexible spline methodology to compare models using
splines with simpler linear models.26 We constructed piecewise
linear spline models using knots at 130 and 160 mm Hg, thus
generating 3 SBP groups below 130 mm Hg (110, 110 to 119, and
120 to 129 mm Hg), 3 groups between 130 and 160 mm Hg (130 to
139, 140 to 149, and 150 to 159 mm Hg), and 3 groups above
160 mm Hg (160 to 169 mm Hg, 170 to 179, and 180 mm Hg). For
DBP, we used a single knot at 80 mm Hg. All piecewise linear spline
models included terms for both SBP and DBP. We examined
potential effect modification by age, type of CVD, and antihypertensive therapy. In models that examined interactions, joint relations
between 2 BP variables, and stratification according to antihypertensive therapy, we used collapsed categories of SBP (quintiles) and
DBP (quartiles). Tests of the proportional hazards assumption found
no evidence for violation of the assumption of a uniform relative
hazard over the duration of follow-up. Additionally, we calculated
the RR of CVD for categories of MAP and PP, respectively. Ten
subjects (3 CVD events) were excluded from the multivariate
analyses because of missing data on covariates.

Results
Baseline Characteristics
The mean age of women in the present study was 62.18.7
years. Means for SBP and DBP were 133.917.3 and
80.410.4 mm Hg, respectively (Table 1). Before randomization, 1327 women experienced an MI, 611 had a stroke,
738 had undergone a revascularization procedure, and 2542
reported angina or other symptomatic vascular disease.
Women with angina or other symptomatic vascular disease
had lower rates of self-reported hypertension, elevated cholesterol, diabetes, tobacco use, and BP-lowering or cholesterol-lowering medication use than women with prior MI,
stroke, or revascularization procedure. During 31 714 personyears of follow-up (median follow-up 6.5 years), there were
871 confirmed CVD events among 661 women: 118 CVD
deaths, 131 MIs, 138 strokes, 182 CABG procedures, and 302
PTCA procedures.

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Mason et al
TABLE 1.

Blood Pressure and Secondary Cardiovascular Risk

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Baseline Characteristics for Participants With Prevalent CVD in WACS

Age, meanSD, y
2

MI
(n1327)

Stroke
(n611)

Procedure*
(n738)

Angina or Other
Symptomatic CVD
(n2542)

63.38.5

61.38.8

63.88.1

61.38.8

62.18.7
28.66.2

Total
(n5218)

BMI, kg/m

28.86.1

28.05.9

28.05.8

28.96.3

White, %

94.1

93.8

95.8

93.1

History of hypertension, %

67.2

66.1

70.3

60.1

64.0

Antihypertensive therapy, %

55.8

56.5

60.0

49.4

53.4

93.8

Mean SBP, mm Hg

134.117.6

134.417.2

135.116.8

133.217.2

133.917.3

Mean DBP, mm Hg

80.310.8

80.99.8

80.39.7

80.410.5

80.410.4

History of high cholesterol, %

72.3

58.1

81.7

61.4

66.7

Cholesterol-lowering therapy, %

34.1

17.2

46.4

16.3

25.2

Diabetes, %

22.5

15.4

19.7

12.5

16.4

Current cigarette smoking, %

20.8

17.4

21.3

13.3

16.8

Rarely/never

71.1

66.8

63.8

65.6

66.9

Weekly

20.1

24.6

24.4

25.4

23.8

8.8

8.7

11.8

9.0

9.3

41.7

32.4

42.4

37.7

38.7

Current alcohol use, %

Daily
Parental history of MI at 65 y, %
Exercise frequency, %
120 kcal/wk

24.5

27.8

24.5

25.4

25.3

120449 kcal/wk

23.0

26.6

26.4

25.8

25.3

4501200 kcal/wk

26.6

22.5

23.3

25.1

24.9

1200 kcal/wk

25.9

23.2

25.8

23.8

24.5

Postmenopausal, %

85.1

78.7

86.7

79.0

81.6

Current HRT, %

41.7

45.0

49.3

50.7

47.6

BMI indicates body mass index; HRT, hormone-replacement therapy.

*Women reporting prior CABG, PTCA, carotid endarterectomy, or peripheral artery surgery.
Women reporting angina pectoris or transient cerebral ischemia but no prior MI, stroke, or CABG/PTCA.

SBP and CVD Risk

In the age-adjusted model (Figure 1), we found a continuous,
positive, graded relation between SBP and CVD risk (P for
linear trend 0.0001). Below the reference category of 120 to
129 mm Hg, there was a modest, nonsignificant decrease in
risk. All women reporting SBP values 130 mm Hg had a
significant increase in risk of CVD events. Risk was increased most markedly in women who reported SBP values
160 mm Hg, as follows: 160 to 169 mm HgRR 2.45,
95% CI 1.73 to 3.47; 170 to 179 mm HgRR 2.72, 95% CI
1.55 to 4.75; and 180 mm HgRR 3.83, 95% CI 2.23 to
6.48. The addition of covariates did not alter the overall
relation between SBP and CVD risk (P for linear
trend0.001), and there was a 9% (95% CI 4% to 15%)
increase in CVD risk for each 10-mm Hg increment in SBP
(Table 2). Using likelihood ratios for comparison, we did not
find evidence for nonlinear (P0.9) or curvilinear (P for
quadratic 0.3) relationships between SBP and CVD risk in
the multivariate model.
The results of the age-adjusted piecewise linear spline
model for the joint effects of SBP and DBP with CVD risk
(Figure 2) did not significantly differ from the simpler linear
model (P0.7). In fact, the overall shape of the curve
remained positive and graded, with the slopes of the 3 regions
delineated by the 2 knots not differing significantly. Impor-

tantly, the slope across the 3 lowest categories (110, 110 to

119, and 120 to 129 mm Hg) was significantly different from
zero (P0.046), consistent with a continuous relationship
between SBP and CVD risk that extends to values of SBP that
are within normal range. The addition of covariates did not
alter the overall relation between SBP and CVD risk, and
there were no significant differences between slopes in the
different regions (Figure 2). However, after controlling for
other covariates, only the third group (SBP values
160 mm Hg) had a slope that was significantly different
from zero (P0.009). When likelihood ratios were used for
comparison, the piecewise linear spline model was not
significantly better than the simpler, multivariate-adjusted
linear model (P0.4).

DBP and CVD Risk

DBP was a weaker predictor of CVD risk, as indicated by the
smaller likelihood ratio statistic (Table 2). In the age-adjusted
analysis, DBP had a significant positive linear relationship
with CVD risk (P for linear trend 0.001), and no substantial
deviation from linearity was apparent. On further control for
potential confounding variables, this trend was no longer
significant (P0.19). No J-shaped relation between DBP and
CVD risk was apparent in either age-adjusted or fully
adjusted analyses. The age-adjusted and multivariate-adjusted

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Figure 1. RR (95% CI) of CVD events according to SBP and DBP category. Referent categories are SBP (120 to 129 mm Hg) and DBP
(75 to 84 mm Hg). RR is adjusted for age, randomized treatment assignments, body mass index, tobacco use, alcohol use, exercise
frequency, diabetes, history of elevated cholesterol, antihypertensive therapy, prior MI, prior stroke, and prior revascularization.

piecewise linear models for DBP and CVD risk generated a

similar-shaped relationship between DBP and CVD risk
compared with the simpler linear models (Figure 2).

SBP, DBP, and CVD Risk

The association between SBP and CVD risk was not appreciably altered in models that considered SBP and DBP
simultaneously (Table 2). When likelihood ratios were used
for comparison, the addition of DBP did not improve the
model that already contained SBP (P0.5). For DBP, the
inclusion of SBP in the model attenuated an already modest
effect and significantly improved the overall model
(P0.004). We also found no significant interaction between
linear SBP and linear DBP (P0.8).

MAP, PP, and CVD Risk

Both MAP and PP had significant positive linear relationships with risk of subsequent CVD events in the present study
(Table 2). However, on the basis of likelihood ratio tests,
neither variable was as strong a predictor of CVD risk as
SBP, and neither variable added significantly to a model that
included SBP. Using MAP values between 95 and
100 mm Hg as the reference group, we found a modest
increase in CVD risk associated with the highest MAP
category (106 mm Hg); the age-adjusted and multivariateadjusted RRs were 1.46 (95% CI 1.18 to 1.80) and 1.20 (95%
CI 0.96 to 1.49), respectively. Using PP values between 46 to
54 mm Hg as the reference group, we found a modest

increase in CVD risk for women in the highest PP category

(60 mm Hg); the age-adjusted and multivariate-adjusted
RRs were 1.25 (95% CI 1.04 to 1.51) and 1.09 (95% CI 0.90
to 1.32), respectively. We also found no evidence for deviations from linearity in the relationships of MAP and PP with
CVD risk.

Subgroup Analysis
In subgroup analyses that adjusted for multiple covariates, we
found no evidence for interactions between BP and age
(P0.7), type of CVD at entry (P0.24), or use of antihypertensive therapy (P0.32).

Discussion
BP is considered an important modifiable risk factor in both
primary and secondary CVD prevention, and this is reflected
in current clinical statements. Yet the shape of the relationship between BP and CVD risk is not certain and may depend
on age, presence of underlying cardiovascular disease, length
of follow-up, and antihypertensive treatment.2729 The prospective data from the present study demonstrate that SBP is
a strong independent predictor of CVD events among middleaged and older women with known CVD. The relation
between SBP and CVD risk was positive, graded, and
continuous in both age-adjusted and multivariate-adjusted
models. In the multivariate model, significant elevations in
risk (RR 1.28, 95% CI 1.00 to 1.64) were noted among
women with high-normal BP (130 to 139 mm Hg) relative to

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TABLE 2. Age and Multivariate Adjusted RR (95% CI) of CVD Events According to BP
Category (SBP, DBP, MAP, and PP)
Variable/Tests

SBP Only

DBP Only

Both SBP and DBP

Age-adjusted*

1.17 (1.121.22)

1.19 (1.131.26)

Multivariate

1.09 (1.041.15)

1.10 (1.041.17)

382.77 (17 df )

382.97 (18 df )

SBP (per 10 mm Hg)

2 Log likelihood
DBP (per 10 mm Hg)
Age-adjusted

1.17 (1.091.26)

0.98 (0.881.09)

1.06 (0.971.16)

0.98 (0.881.08)

MAP Only

373.63 (17 df )

382.97 (18 df )

Age-adjusted

1.22 (1.141.29)

Multivariate

1.10 (1.021.18)

377.43 (17 df )

1.18 (1.121.23)

1.10 (1.031.15)

Multivariate
2 Log likelihood

PP Only

MAP (per 10 mm Hg)

2 Log likelihood
PP (per 10 mm Hg)
Age-adjusted
Multivariate
2 Log likelihood

380.72 (17 df )

*Adjusted for age and randomized treatment assignment.

Adjusted for age, randomized treatment assignments, body mass index, tobacco use, alcohol use, exercise
frequency, diabetes, history of elevated cholesterol, prior MI, prior stroke, and prior revascularization.
The joint model considered linear SBP and DBP terms simultaneously in addition to age and other coronary risk
factors.

those with normal levels (120 to 129 mm Hg). DBP, MAP,

and PP were weaker predictors of CVD risk, and there was no
evidence of a J-shaped relationship for BP in either treated
(antihypertensive therapy) or untreated women. We did not
find evidence to support a nonlinear relation between SBP
and risk or evidence that joint consideration of both SBP and
DBP improved evaluation of CVD risk.
There is growing evidence that SBP is an important
independent risk factor for CVD morbidity and mortality in
both primary and secondary prevention.28 31 Prospective
observational studies have been important in assessing risk
across the full range of BP values and in heterogeneous
populations but have focused primarily on the relation between BP and CVD mortality.1,11,16 18 The findings of the
present study add to these prior results by demonstrating that
elevations of SBP increase the risk of both CVD morbidity
and mortality among women with CVD. That SBP was the
strongest predictor of CVD risk in this cohort of middle-aged
and elderly women is consistent with previous reports and
may reflect age-dependent changes in arterial stiffness.27,28
Unlike reports from the Framingham Heart Study, among
subjects with previous heart disease, we did not find an
association between low BP and adverse risk.14,16 DAgostino
et al16 reported a U-shaped relation between DBP and
biennial CVD death rate and a similar but nonsignificant
relation for SBP. More recently, Kannel et al14 reported a
U-shaped relation between BP (DBP and SBP) and biennial
CVD death among elderly men and women with heart
disease. The differences compared with the present results
might be explained in part by the slightly older and more

heterogeneous Framingham cohort having a larger representation of patients with more severe noncardiac comorbidities and thus a larger proportion of patients with an association between ill health (causing low BP) and mortality
(reverse causality). Furthermore, the use of an outcome
defined by short-term follow-up (biennial CVD death rate)
may have increased the impact of this interaction on the
observed association between BP and CVD mortality.
As demonstrated previously,17,27,29 the length of follow-up
is critically important in determining the observed relationship between BP and mortality. In men (aged 45 to 57 years)
with heart disease screened for the Multiple Risk Factor
Intervention Trial, there was a J-shaped relation between SBP
and CVD mortality during the first 2 years of follow-up but
a linear relation during 16-year follow-up.29 Similarly, Glynn
et al27 reported that within an elderly population-based
cohort, there was a continuous relation between BP and
cardiovascular mortality after exclusion of deaths from shortterm follow-up (3 years) but a J-shaped relation when these
events were included. We found no evidence for a different
relationship of SBP with CVD risk in early (first 3 years)
versus later follow-up. Although some have argued that the
increased risk of secondary events is caused by decreased
coronary perfusion in the setting of significant coronary
stenosis, it seems more likely that the association is explained
by the effect of noncardiac premorbid conditions on lowering
the systemic BP. Regardless, J-shaped relations demonstrated
from observational data need to be interpreted with caution
because they may not have implications for antihypertensive
therapy.

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Figure 2. Multivariate adjusted log hazard (95% CI) for joint effects of SBP and DBP, as piecewise linear splines, with CVD risk. Adjustment was for age, randomized treatment assignments, body mass index, tobacco use, alcohol use, exercise frequency, diabetes, history of elevated cholesterol, prior MI, prior stroke, and prior revascularization.

Our finding that CVD risk increases with borderline

elevations in SBP is consistent with previous findings in
primary prevention.1,8,27 This finding is also consistent with
recommendations from the Seventh Report of the Joint
National Committee on Prevention, Detection, and Treatment
of High Blood Pressure that call for initiating antihypertensive therapy in patients with diabetes or chronic kidney
disease with SBP 130 or DBP 80 mm Hg.3 Although
observational, our findings suggest that among women with
preexisting CVD, even borderline elevations in SBP are
associated with increased risk of future CVD events.
The present study is one of the first to examine prospectively the relationship between BP and the risk of secondary
CVD events exclusively in women. The prospective design
and relatively large sample size allowed for a thorough
examination of these associations. However, there are several
limitations to our study worth noting. First, the use of
self-reported BP values is subject to misclassification. Previous reports from female health professionals have demonstrated good reliability and validity of self-reported BP.21,23
However, decreased precision in the reported DBP might
explain, in part, the weak and primarily positive relation

observed between DBP and CVD risk and the weaker risk
prediction from PP. Although the same limitation applies to
SBP, it had a powerful and compelling relation with CVD
risk. Second, we were unable to account for the form or dose
of cardiac medications taken at baseline. Thus, we cannot
comment on the potential interaction between specific medications and BP as it impacts the risk of secondary CVD
events. Third, our cohort primarily consisted of white female
health professionals, and thus the results might not fully apply
to women with different ethnic, socioeconomic, or clinical
characteristics.
In summary, the present analysis demonstrates that SBP is
a strong predictor of secondary CVD events in women. These
data suggest that there is a significant increase in CVD risk,
regardless of antihypertensive treatment status, associated
with higher SBP. The present data do not substantiate a
J-shaped relationship between BP and CVD risk or the
importance of joint relations between DBP and SBP with
CVD risk. Although further clinical investigation is needed to
explore the potential benefit of lowering BP below normal
values, our data suggest that women with CVD and borderline elevations in SBP are at increased risk of future events
and might benefit from a lower targeted BP.

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Acknowledgments
This study was supported by grants from the National Heart, Lung,
and Blood Institute (HL07575 and HL46959), Bristol-Myers Squibb
(Drs Sesso and Glynn), and the Donald W. Reynolds Foundation (Dr
Ridker). The authors would like to acknowledge the invaluable
contributions of the entire staff of WACS, under the leadership of
Elaine Zaharris, Jean MacFadyen, Ellie Danielson, Claudia Chae,
Shamikhah Curry, Margarette Haubourg, Felicia Jackson, Tony
Laurinaitis, Philomena Quinn, Harriet Samuelson, and Marty Van
Denburgh. We are also indebted to the 8171 dedicated and committed participants of WACS.

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