REVIEW

Women, Hypertension, and the Systolic Blood

Pressure Intervention Trial
Nanette K. Wenger, MD,a Keith C. Ferdinand, MD,b C. Noel Bairey Merz, MD,c Mary Norine Walsh, MD,d
Martha Gulati, MD, MS,e Carl J. Pepine, MD,f for the American College of Cardiology Cardiovascular
Disease in Women Committee
a
Department of Cardiology, Emory University School of Medicine Atlanta, Ga; bTulane University Heart and Vascular Institute, Tulane
University School of Medicine, New Orleans, La; cDepartment of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, Calif; dSt. Vincent
Heart Center, Indianapolis, Ind; eDivision of Cardiology, University of Arizona-Phoenix; fDivision of Cardiovascular Medicine, University
of Florida, Gainesville.

ABSTRACT

Hypertension accounts for approximately 1 in 5 deaths in American women and is the major contributor to
many comorbid conditions. Although blood pressure lowering reduces cardiovascular disease outcomes,
considerable uncertainty remains on best management in women. Specifically, female blood pressure
treatment goals have not been established, particularly among older and African American and Hispanic
women, for whom hypertension prevalence, related adverse outcomes, and poor control rates are high. The
Systolic Blood Pressure Intervention Trial (SPRINT) planned to clarify optimal blood pressure management
in both sexes. Although confirming that a lower blood pressure goal is generally better, because female
enrollment and event rates were low and follow-up shortened, outcomes differences in women were not
statistically significant. Thus optimal blood pressure goals for women have not been established with the
highest evidence. This review addresses SPRINT’s significance and key remaining knowledge gaps in
optimal blood pressure management to improve women’s health.
Ó 2016 Elsevier Inc. All rights reserved.
The American Journal of Medicine (2016) 129, 1030-1036

KEYWORDS: Adverse outcomes; Blood pressure; Cardiovascular disease; Hypertension; Intervention; Level of evi-
dence; Sex-specific pathophysiology; Systolic Blood Pressure Intervention Trial; Treatment goals

Among women hypertension is a major contributor to obstructive sleep apnea).1 Furthermore, the prevalence of
cardiovascular disease morbidity and mortality, as well as hypertension in American female minority populations
many related conditions (eg, diabetes, renal disease, (African American and Hispanic) approaches 50%.2

Funding: This work was supported by contracts from the National Heart,
Lung and Blood Institutes, nos. N01-HV-68161, N01-HV-68162, N01-HV-
68163, N01-HV-68164, and RO1-HL-073412-01; grants U0164829, U01
HL649141, and U01 HL649241; grants from the Gustavus and Louis Pfeiffer
Research Foundation (Danville, New Jersey), The Women’s Guild of Cedars-
Sinai Medical Center (Los Angeles, California), The Ladies Hospital Aid
Society of Western Pennsylvania (Pittsburgh, Pennsylvania), and QMED, Inc
(Laurence Harbor, New Jersey); and by the Edythe L. Broad Endowment, the
Barbra Streisand Women’s Cardiovascular Research and Education Program,
the Linda Joy Pollin Women’s Heart Health Program, Cedars-Sinai Medical
Center (Los Angeles, California), and by the Emory Women’s Heart Center,
Emory University School of Medicine (Atlanta, Georgia).
Conflict of Interest: NKW reports consulting from Amgen, AstraZeneca,
Gilead Sciences, and Merck; and research grants from Alnylam Pharma-
ceuticals, Gilead Sciences, the National Heart, Lung and Blood Institute
(NHLBI), Pfizer, and the Society for Women’s Health Research. KCF reports
consulting from Amgen, Sanofi/Aventis, Eli Lilly, and Boehringer Ingelheim.
CNBM reports consulting revenue paid to Cedars-Sinai Medical Center from
Gilead, Medscape, and the National Institutes of Health (NIH); research
grants from NHLBI, Flight Attendant Medical Research Institute, Gilead, the
Louis B. Mayer Foundation, Erika Glazer Family Foundation, and NIH-
Clinical and Translational Science Institute; and payments for lectures from
Practice Point, Pri-Med, and Vascular Biology Working Group. CJP reports
grants from NIH/NHLBI during the development of this report; grants from
Amarin, Amgen, AstraZeneca, Baxter, Boehringer Ingleheim, Catadasis,
Cytori, Daiichi Sankyo, Esperion, Genentech, ISIS Pharmaceuticals, Neo-
stem, Sanofi/Aventis, and Unified Therapeutics; and consulting fees from
Sanofi, AstraZeneca, and Slack outside the submitted work.
Authorship: All authors had access to the data and a role in writing the
manuscript.
Requests for reprints should be addressed to Carl J. Pepine, MD,
University of Florida, 1600 SW Archer Road, P.O. Box 100277, Gaines-
ville, FL 32610-0277.
E-mail address: carl.pepine@medicine.ufl.edu

0002-9343/$ -see front matter Ó 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjmed.2016.06.022
Wenger et al Women, Hypertension, and SPRINT 1031

Hypertension accounts for approximately 1 in 5 deaths of cycling, pregnancy/perinatal period, lactation, gestational
American women3 and confers greater risk for ischemic diabetes/pre-eclampsia/eclampsia, reproductive disorders
stroke, intracranial hemorrhage, and heart failure among and their management, oral contraceptive use, menopause
women compared with men.4 Women account for the ma- and its management, vasomotor menopausal symptoms,
jority of stroke deaths in Americans; after nonfatal stroke hormone replacement therapy) have the potential to impact
they have greater disability than men.2 Thus blood pressure blood pressure and alter cardiovascular systems. Limited
should be at the top of the list of available information, inferred
factors important for women’s from studies in animals5,6 and
health. CLINICAL SIGNIFICANCE patients,7 implicates endothelial
Optimal blood pressure levels
Among women hypertension is a major dysfunction, increased aortic
for initiation of drug treatment, as contributor to cardiovascular disease stiffness,
well as treatment targets, have not renineangiotensinealdosterone
morbidity and mortality, as well as many
been established by the highest system activation, salt sensitivity,
related conditions; thus blood pressure
level of evidence for women in oxidative stress, and genetic fac-
general, and particularly for older should be at the top of the list of factors tors7 relative to the menopause.
women. The Systolic Blood Pres- important for women’s health. Female-specific physiologic
sure Intervention Trial (SPRINT)
Optimal blood pressure levels for initia- events interact with general de-
was anticipated to answer these tion of drug treatment, as well as treat- terminants of risk that include, but
questions. ment targets, have not been established are not limited to, aging, race/
The purpose of this review is to ethnicity, obesity, diabetes, low
by the highest level of evidence for
address how SPRINT informs physical activity levels, kidney
women in general, and particularly for
management of women with hy- disease, vitamin D deficiency,
pertension and summarize some older women. thyroid disease, and sympathetic
key remaining gaps in knowledge
The Systolic Blood Pressure Intervention overactivity.8-10 Among adult
of best approaches to managing Trial (SPRINT) was anticipated to answer women with hypertension, there is
hypertension in women that these questions; we address how SPRINT also a decrease in blood pressure
should be addressed to improve informs management of hypertension in control rates with aging, as well as
the health of the majority popula- across different racial/ethnic
women, and we summarize some key
tion with hypertension, that is, groups.11 Limited research has
remaining gaps in knowledge that
women. Our comments are not evaluated the interplay between
intended to diminish the impor- should be addressed to improve the female-specific and general blood
tance of the SPRINT data, which health of the majority population with pressure determinants of risk.
provide the evidence base to hypertension, that is, women.
establish that a lower blood pres-
Our comments are not intended to
sure target is better than the diminish the importance of the SPRINT WOMEN AND THE SPRINT
traditional <140/90 mm Hg. Our The SPRINT enrolled 9361 in-
data, which provide the evidence base to
intent is to call attention to some dividuals, mean age 67.9 years,
establish that a lower blood pressure
important lessons learned from with systolic blood pressure 130-
SPRINT and residual knowledge target is better than the traditional 180 mm Hg and increased cardio-
gaps. This information should <140/90 mm Hg; our intent is to call vascular disease risk. Baseline
provide direction to critical areas attention to some important lessons characteristics of enrolled women
of investigation needed to opti- learned from SPRINT and residual (3332 [35.6%]) were not included
mize cardiovascular health among knowledge gaps. in primary outcome or design/
women.
This information should provide direc- baseline publications.12,13 Subjects
were randomized to a systolic
tion to critical areas of investigation
blood pressure target of <120 mm
SEX-SPECIFIC needed to optimize cardiovascular Hg (intensive treatment) or <140
HYPERTENSION health among women. mm Hg (standard treatment).
PHYSIOLOGY Increased risk was defined as his-
Lowering blood pressure reduces tory of coronary heart disease,
cardiovascular-related risks for death and other adverse estimated glomerular filtration rate 20-59 mL/min/1.73 m2,
outcomes that contribute to poor quality of life, disability, 10-year cardiovascular disease risk 15%, or age 75 years.
and healthcare costs. However, hypertension management Patients with history of diabetes, stroke, >1 g in 24 h of
and risk reduction is a very complex issue for women proteinuria, heart failure, estimated glomerular filtration rate
because causes of their high rates of hypertension and <20 mL/min/1.73 m2, or receiving dialysis were excluded.
related adverse outcomes are unclear. During a woman’s After 3.26 years the trial was stopped owing to signifi-
lifetime many physiologic events (eg, menarche, menstrual cant benefit with the intensive treatment strategy. The
1032
primary outcome (first occurrence of nonfatal myocardial
infarction, other acute coronary syndrome, stroke, heart
failure hospitalization, or cardiovascular-related death) was
reduced by a quarter in the intensive treatment group (25%,
P <.001), with reduced all-cause mortality (27%, P ¼
.003).13 Adverse rates for hypotension, syncope, electrolyte
abnormalities, and acute kidney injury, but not for injurious
falls, were higher with intensive vs standard treatment.
Between-group differences were consistent across com-
ponents of the primary outcome and other secondary out-
comes, including all-cause death. The relative risk of
cardiovascular-related death was almost half with intensive
compared to standard treatment.
SUBGROUP ANALYSES IN WOMEN
Effects of intensive vs standard treatment on the primary
outcome and all-cause death were reported to be consistent
across the prespecified subgroups that included sex, and
there were no significant interactions between treatment
subgroups with respect to primary outcome or all-cause
death. Among women the primary outcome occurred in
only 4.6% (77 of 1684) of those assigned intensive treat-
ment vs 5.2% (175 of 3364) of those assigned standard
treatment. The hazard ratio (HR) (intensive vs standard
treatment) was 0.84, 95% confidence interval (CI) 0.62-
1.14, P for interaction .45. Subgroup analyses in general,
and interaction tests in particular, are recognized to be un-
derpowered and therefore interpreted with caution.
This issue of estimating conclusions from sex subgroup
analysis is an extremely important area relative to women’s
health because there are so many older women with hy-
pertension and they are prone to falls, fractures, and related
adverse events. Riskebenefit relationships are therefore
critical. Subgroup analyses are done to examine whether
observed treatment effects may differ by baseline charac-
teristics. When reported, such subgroup analyses can have
substantial influence on clinical practice and health policy
decision making. However, this influence may be
misleading because there is a well-documented history
regarding how subsequent studies have proved that many
subgroup findings are spurious particularly relative to
women’s health and cardiovascular trials. These include
trials of aspirin for secondary stroke prevention among
women; ticlopidine vs aspirin in prevention of recurrent
stroke, myocardial infarction, or vascular death among black
but not white subjects; and tamoxifen for breast cancer
prevention.14-19
For example, a randomized trial reported aspirin inef-
fective for secondary stroke prevention among women.15
However, a subsequent meta-analysis concluded that
aspirin was beneficial in both women and men.17 In another
randomized trial, subgroup analysis found ticlopidine su-
perior to aspirin in preventing recurrent stroke, myocardial
infarction, or vascular death among black subjects but not
among white subjects.19 A later trial with larger sample size
observed no significant difference between these antiplatelet
The American Journal of Medicine, Vol 129, No 10, October 2016
agents in preventing stroke, myocardial infarction, or
vascular death among black patients.18 Also recall that the
Early Breast Cancer Trialists’ Collaborative Group reported
that in tamoxifen trials, mortality reduction occurred only
among women aged 50 years.16 Yet later studies showed
benefits, so now tamoxifen and related selective estrogen
receptor modulators are even recommended for breast can-
cer prevention in premenopausal women at high risk.14
Thus, we believe that it is not possible to simply dismiss
the interaction between treatment group and sex on the basis
of SPRINT results. Our calculation of the point estimate for
the HR (women vs men) is 1.17 (95% CI 0.81-1.69). This is
an enormous range with clear potential that benefit for
intensive treatment is clinically less for women vs men.
Thus, among women the highest level of evidence is lacking
to support the benefit vs risks of intensive treatment.
WHAT EXPLAINS THE LACK OF EVIDENCE IN
WOMEN?
Under-enrollment of Women
Although hypertension is more prevalent in older women vs
older men, the proportion of women (approximately one-
third) enrolled in SPRINT is low (Figure 1) in contrast to
an average of 44% in other hypertension trials in the past
decade.20,21 Clearly, the lower-than-planned number of
women contributed to lack of a significant difference be-
tween female treatment groups.
Study Visit Schedule
Could the stringent visit schedule discourage participation
of elderly women? The SPRINT required monthly follow-
up visits for 3 months and every 3 months thereafter. This
schedule is similar to many prior hypertension trials that
achieved high rates of recruitment of women, so it is un-
likely that this contributed to under-enrollment of women.
Lack of Available Women
Is it possible that SPRINT eligibility criteria unfavorably
disadvantaged enrollment of women so that adequate
numbers of women simply were not available? A cross-
sectional, population-based study, using 2007-2012
National Health and Nutrition Examination Survey data,
estimated the prevalence, number, and characteristics of
Americans meeting SPRINT eligibility criteria.22 Impor-
tantly, of the estimated 113.8 million adult women, 44.7%
were aged 50 years, 18.1% met blood pressure criteria,
and 10.8% had high cardiovascular disease risk, of whom
6.5% had no exclusion criteria. Among American women
aged 50 years, 16.8 million were SPRINT eligible. Among
those with treated hypertension, 8.2 million were SPRINT
eligible (Table 3 in Bress et al).22 However, complete details
are not provided in that analysis by sex and SPRINT
eligibility criteria, so some exclusions may have reduced the
women available. Nevertheless, several million American
Wenger et al Women, Hypertension, and SPRINT
Figure 1 Under-enrollment of women in the Systolic Blood Pressure Intervention Trial
(SPRINT). Although hypertension is more prevalent in older women than in older men, the
proportion of women enrolled in SPRINT is low.
women likely would meet all eligibility criteria, so general
availability was not the limitation.
Enrollment Regions
Perhaps even more relevant is that the Veterans Affairs
(VA) system was one of the SPRINT enrollment regions.
Because older women constitute a very small percentage of
the VA population, this likely accounted for some under-
enrollment of women. Future study designs must provide
approaches to compensate for expected under-enrollment of
women from VA sites. Nevertheless, other hypertension
trials (ALLHAT and ACCORD-BP) had 47% women.
Apparently VA sites in these other hypertension trials had
less effect on total recruitment of women compared with
SPRINT.
Low Event Rate in Women
A higher percentage of hypertension-related cardiovascular
events is known to occur in women than men.2 These
include but are not limited to death, stroke, intracranial
hemorrhage, ventricular hypertrophy, diastolic dysfunction,
and age-related increased arterial stiffness.23 These
hypertension-related events also occur more frequently
among older women vs those aged <50 years. So it is
difficult to understand the low event rate observed among
SPRINT women. The lack of details in baseline character-
istics contributes to this dilemma.
More problematic is the fact that SPRINT investigators
recognized that they did not meet recruitment targets
for enrolling women (35.6% actual vs 50% planned),
1033
participants aged >75 years (28.2% actual vs 35% planned),
and those with chronic kidney disease (28.3% actual vs 46%
planned) or cardiovascular disease (20.1% actual vs 40%
planned).12 Although subgroup enrollment was monitored
during recruitment, modifications were neither in place a
priori nor developed during recruitment to ensure enroll-
ment of the number of participants planned for each sub-
group. The investigators commented that “unless event rates
are higher than expected or follow-up is extended, the lower
than expected enrollment for these subgroups may result in
diminished power to explore the primary hypothesis among
women, persons above 75 years, and persons with chronic
kidney disease.” The event rate was not higher (2.19%/year
observed for the standard goal vs 2.2% expected), and
follow-up was terminated early, so as the investigators
predicted, the power to examine the primary hypothesis in
women is limited. Yet the rate for the primary outcome in
women for both standard (5.4% vs 7.3%) and intensive
treatment (4.5% vs 5.5%) was lower in women vs men,
respectively. All-cause mortality with intensive treatment
was 2.73% vs 3.64% and with standard treatment was
3.28% vs 4.86% (women vs men, respectively). Thus lower-
risk women were enrolled compared with men. From data
published to date, the basis for this risk bias is unclear but
clearly warrants further exploration.
Early Termination of the Trial
Clearly the ethically correct approach was to consider early
trial termination when the benefit met prespecified stopping
rules. However, it should have been apparent that, owing to
under-enrollment and low event rates in women, the benefit
1034
only reached statistical significance among men. So an
approach to adequately address women would have been to
continue the trial in women. This recommendation would
have been more ethically compliant to the majority impacted
population of hypertensive women. Alternatively, such a
provision could have been planned prospectively by using
an adaptive design. These considerations would have
improved the possibility of providing additional evidence
needed to conclude that intensive treatment is indeed better
among women.
WHAT HAVE WE LEARNED ABOUT HYPERTENSION
IN WOMEN THAT MAY INFORM FUTURE TRIALS?
Perhaps the most relevant question going forward is what to
recommend for future hypertension and cardiovascular
disease trials to better ensure more appropriate representa-
tion of women and the elderly, a cohort mostly composed of
women. Inclusion criteria required SPRINT participants to
be aged 50 years; although more men have hypertension
before 60-65 years of age, hypertension prevalence
increases sharply among women older than that (Figure 2).
Younger women with hypertensive disorders of pregnancy
and systemic autoimmune disease (including, eg, collagen
vascular diseases, systemic vasculitides) -related
hypertension (which are dominated by younger women)
are not represented in this trial. Further, elderly women,
the predominant population with isolated systolic
hypertension, were similarly disadvantaged by arbitrarily
Figure 2 Prevalence of hypertension among adults aged
18 years, by sex and age: United States, 2011-2014. The
Systolic Blood Pressure Intervention Trial inclusion criteria
required participants to be aged 50 years; although more
men than women have hypertension before 60-65 years of
age, hypertension prevalence increases sharply among
women aged 60 years. 1Crude estimates are 31.3% for total,
31.0% for men, and 31.5% for women. 2Significant difference
from age group 18-39 years. 3Significant difference from age
group 40-59 years. 4Significant difference from women for
same age group. 5Significant linear trend. Note that estimates
for the “18 and over” category were age-adjusted by the direct
method to the 2000 US Census population using age groups
18-39 years, 40-59 years, and 60 years.12 From the US
Centers for Disease Control and Prevention/National Center
for Health Statistics, National Health and Nutrition Exami-
nation Survey, 2011-2014.
The American Journal of Medicine, Vol 129, No 10, October 2016
setting the upper age limit at 80 years (Figure 3). Only
28% of the SPRINT cohort were aged 75 years, and
although the specific representation of elderly women in
this subgroup is not provided, hypertension control in
women decreases dramatically with aging,24 non-white
race, and diabetes.25
QUESTIONS ABOUT BLOOD PRESSURE TARGETS
IN WOMEN WITH DYSGLYCEMIA AND STROKE
RISK
Patients with diabetes were specifically excluded from
SPRINT because it was assumed that the question about
lower blood pressure targets in this subpopulation had been
adequately addressed in ACCORD-BP. Although stroke risk
was reduced (HR 0.59, 95% CI 0.39-0.59, P ¼ .01) with the
lower blood pressure target, there were more treatment-
related adverse experiences preventing investigators from
recommending a lower blood pressure target. However, a
recent secondary ACCORD-BP analysis found that inten-
sive blood pressure treatment was beneficial.26 Specifically,
the risk of all-cause death, myocardial infarction, or stroke
was lower in groups intensively treated for blood pressure,
glycemia, or both vs combined standard blood pressure and
glycemia treatment. Stroke was significantly reduced by
intensive blood pressure treatment; most other risks were
either neutral or favored intensive treatment. Thus
ACCORD results in diabetic patients are consistent with
those of SPRINT in nondiabetic patients. However,
ACCORD also excluded individuals aged >80 years and
those with kidney disease, which is associated with high risk
and highly prevalent among older women, although the
outcome details were not provided in this recent analysis.
Although diabetic women are also highly prevalent in our
population, we have limited evidence to guide hypertension
management.
Controversy continues about interpretation of the lower
stroke risk observed in ACCORD-BP among those assigned
the lower blood pressure target. This is particularly relevant
for women, given that stroke is the third leading cause of
death for women. In general, women live longer than men,
so stroke will have a more negative impact on their lives.
After a stroke more women live alone, more reside in a
long-term healthcare facility, and they have a worse re-
covery than men. It is important to re-emphasize that each
year stroke kills twice as many women as breast cancer.27
In particular, exclusion of diabetic patients opens a
question of applicability to a large percentage of women
aged >60 years, because diabetes disproportionally affects
women, and they have substantially more cardiovascular
events than diabetic men. Hypertension is one of the most
important cardiovascular disease and all-cause mortality risk
factors among women in general and also with diabetes.28
Also essential to note is that hypertension is an important
modifiable risk factor for development of diabetes among
women. Women have higher residual lifetime diabetes risk
at all ages,29 with the highest lifetime risk among Hispanic
Wenger et al Women, Hypertension, and SPRINT 1035

Figure 3 How does the Systolic Blood Pressure Intervention Trial (SPRINT) inform hy-
pertension treatment goals for women? Younger women with hypertensive disorders of
pregnancy and systemic autoimmune disease are not represented in this trial. Further, although
elderly women are the predominant population with isolated systolic hypertension (ISH), only
28% of the entire SPRINT cohort were aged 75 years, and the upper limit was age 80 years.
CI ¼ confidence interval; CV ¼ cardiovascular; HR ¼ hazard ratio. Courtesy of Abigail
Beaird.

women at 52.5%; if diabetes is diagnosed at age 40 years,
women will lose 14.3 life-years and 22.0 quality-adjusted
life-years.
Although diabetes was an exclusion criterion in SPRINT,
the mean baseline fasting glucose was approximately 99 mg/
dL. So almost half of those enrolled had “prediabetes,”
which is associated with increased risks for adverse out-
comes. Unfortunately, glucose was not stratified by sex.
A special concern in older women and African American
women is resistant hypertension.30,31 Approximately 12%-
15% of patients with hypertension are considered resistant,
and compared with men, women have a higher prevalence
of resistant hypertension in part related to greater older-age
status and obesity, among the strongest predictors of resis-
tant hypertension.32 In the WISE cohort, resistant hyper-
tension was associated with >3-fold risk of major adverse
outcomes in women with ischemic heart disease vs
normotensive women. These adverse outcomes emerged
early in follow-up with greater all-cause mortality.33
Details from the SPRINT are incomplete relative to
resistant hypertension, but the mean number of antihyper-
tensive drugs used in those assigned intensive treatment at
study termination was three: 67% used a diuretic, 32% used
three drugs, and 24% used four or more drugs.
Several medications women often use may antagonize
antihypertensive agents and contribute to resistant hyper-
tension. Hypertension prevalence is 2- to 3-fold higher
while on oral contraceptive agents. Therefore, with resistant
hypertension, elimination of estradiol and oral contraceptive
agents should be undertaken whenever possible.34,35 Drugs
often used by women with potential to affect blood pressure
control include antidepressants, anorexic agents (phenter-
mine), thyroid replacement, corticosteroids, nonsteroidal
anti-inflammatory agents, decongestants, erythropoietin,
migraine medications, and immunosuppressants.
QUESTIONS ABOUT ANTIHYPERTENSIVE DRUG
CHOICE IN WOMEN
More detail is required regarding specific drug classes and
titrations to assess implications for women in SPRINT.
Women, especially African American, may have a 3-fold
increase in angiotensin-converting enzyme inhibitor-related
cough.36 Elderly women are the predominant population
with osteopenia and osteoporosis, and thiazide diuretics may
provide benefit regarding bone loss and hip fracture.37 Was
there a sex-related difference in fall risk and hip fracture that
may have been therapy-related? Further, no data are
1036
provided regarding menopausal hormone therapies, com-
mon omissions from medication registers when both sexes
are included in trials.
CONCLUSIONS
Our comments are not intended to diminish the importance
of the results from the SPRINT that provide the evidence
base to establish a lower blood pressure target; but despite
these ground-breaking results that will save lives and pre-
vent disabilities, this trial has knowledge gaps and critical
limitations in applicability to women. We urge investigators
to provide more details about sex-related recruitment ap-
proaches and outcomes so that we are better positioned to
fill these gaps in knowledge. Furthermore, trial design and
stopping rules should be tailored to accommodate all rele-
vant populations, specifically the population of women who
represent the majority of hypertensive and cardiovascular
disease patients.
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