Medical Hypotheses 142 (2020) 109780

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

Mindfulness with paced breathing reduces blood pressure T

a b,⁎ b b
Jacqueline Brenner , Suzanne LeBlang , Michelle Lizotte-Waniewski , Barbara Schmidt ,
Patricio S. Espinosab,c, David L. DeMetsd, Andrew Newberge, Charles H. Hennekensb
a
Accelerated Premedical-Medical Program BS/MD at Penn State and Sidney Kimmel Medical College at Thomas Jefferson University, United States
b
Charles E. Schmidt College of Medicine, Florida Atlantic University, United States
c
Marcus Neurosciences Institute, Boca Raton Regional Hospital and Baptist Health South Florida, United States
d
Department of Biostatistics and Informatics, University of Wisconsin, School of Medicine & Public Health, United States
e
Marcus Institute for Integrative Health, Thomas Jefferson University, United States

ARTICLE INFO ABSTRACT

Keywords: Elevated blood pressure (BP) is a major avoidable cause of premature morbidity and mortality in the United
Mindfulness States (US) and worldwide, due primarily to increased risks of stroke as well as myocardial infarction. While
Paced breathing there are therapeutic lifestyle changes and adjunctive pharmacologic medications of proven benefit, recent in-
Blood pressure terest has increasingly focused on Complementary and Alternative Medicine, in particular, Mind-Body
Interventions. With respect to BP, it is tempting to speculate that mindfulness with paced breathing will have
beneficial effects in the short run that may translate into lowered risks of stroke in the long run. Paced breathing
is deep diaphragmatic breathing with typical rates equal to or less than 5–7 breaths per minute compared with
the usual rate of 12–14. One plausible mechanism of benefit is that paced breathing stimulates the para-
sympathetic nervous system which alters neuronal function in specific areas of the brain and reduces stress
chemicals. The hypothesis that mindfulness with paced slow breathing reduces BP could be directly tested in
randomized trials designed a priori to do so. Subsequently, a finding that mindfulness with paced breathing
reduces BP would also lead to direct tests in randomized trials of reductions of carotid atherosclerosis and, if so, a
larger scale trial to test whether there is a direct impact of mindfulness with paced breathing on reducing the
risks of stroke and MI. If rigorous testing of this medical hypothesis led to positive results this would have large
and important clinical and policy implications in the US and worldwide.

Introduction/Background Despite these sobering statistics, in the US and most developed

Cardiovascular disease (CVD), principally myocardial infarction
(MI) and stroke, is the leading cause of premature deaths in the United
States (US) and is rapidly becoming so worldwide [1].
CVD accounts for over 800,000 deaths in the US each year, and
more than 17 million worldwide. In the US, CVD accounts for over 40%
of total mortality with MI accounting for 25% and stroke 16.5% of all
deaths. Further, worldwide, stroke accounts for 11.0% of total deaths.
In addition, in the US stroke alone ranks 5th in all-cause mortality
killing nearly 133,000 people annually [2]. For example, sudden car-
diac death is responsible for about 1 in 7 total US deaths and is the first
symptomatic event in at least 25% of cases [3]. Finally, in 76% of pa-
tients who experience a first stroke, the initial presenting symptom is
the stroke itself. The estimated annual cost of MI in the US is ap-
proximately $11.5 billion and that of stroke approximately $18 billion,
due, in large part, to the costs of disability [4].
countries, there had been consistent declines in mortality from MI and
stroke over the past several decades beginning in about 1960 until
about 2016. Although the initial declines in MI and stroke were attri-
butable mainly to primary prevention, more recent decreases in mor-
tality were due mainly to more aggressive diagnoses and treatment [5].
From 2014 to 2017, life expectancy significantly decreased by
0.3 years. In 2018 there was a 0.1 year increase in US life expectancy
due, largely, to lower death rates from cancer, heart disease, respiratory
diseases and unintentional injuries. Thus, at present, the average US life
expectancy is 78 years and 8 months (81.2 years in women and
76.2 years in men) [6].
As a consequence, there are increasing challenges for clinicians to
aggressively implement a multifactorial approach to risk reduction with
therapeutic lifestyle changes (TLCs) and adjunctive drug therapies of
proven benefit in the primary prevention of stroke and MI [1,7]. Blood
pressure (BP) is the most important major and modifiable risk factor for

⁎
Corresponding author at: Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road BC-71, Boca Raton, FL 33431, USA.
E-mail address: sleblang31@gmail.com (S. LeBlang).

https://doi.org/10.1016/j.mehy.2020.109780
Received 22 December 2019; Received in revised form 24 March 2020; Accepted 21 April 2020
0306-9877/ © 2020 Elsevier Ltd. All rights reserved.
J. Brenner, et al.
reducing risks of stroke and MI as well as mortality from CVD and
deaths from all causes. More recently, there has been increasing interest
in the role of heart rate variability (HRV) and its potential effects on
CVD as well as all-cause mortality [8].
In many primary prevention subjects, adoption of TLCs could mi-
tigate the need for adjunctive drug therapies of proven benefit.
Nonetheless this strategy is difficult to achieve or maintain, and may be
insufficient [1]. Fortunately, even for patients who prefer prescription
of pills to proscription of harmful lifestyles, these drug therapies will
still have net benefits. Specifically, in randomized trials and their meta
analyses, pharmacologic therapies reduce BP by about 3–5 mm of
mercury (mm Hg) systolic and 2–3 mm Hg diastolic. These reductions
over several years lead to 42% reductions in stroke and about 17%
reductions in MI [9–11]. Postulated mechanisms include improvements
in baroreflex dysfunction, oxidative stress, vascular remodelling and
inflammation [12]. For example, inflammation from chronic conditions
such as elevated BP is likely to lead to carotid atherosclerosis, a major
risk factor for stroke as well as MI [13]. The adoption into clinical
practice and maintenance of TLCs and adjunctive drug therapies to
treat elevated BP will continue to reduce both the incidence of, and
mortality from, stroke, MI and other major clinical manifestations of
CVD in the US and worldwide [1].
The Hypothesis/theory
Mindfulness with paced breathing decreases BP. Mindfulness is
defined as a mental state achieved by focusing awareness on the present
moment, while calmly acknowledging and accepting one's feelings,
thoughts, and bodily sensations [14]. At present, however, there are
various types of mindfulness practiced, many without standardization
of protocols and some, but not all, include paced breathing. While de-
finitions vary, paced breathing has been defined as deep diaphragmatic
breathing with a rate of 5–7 breaths per minute compared with the
usual rate of 12–14 [15–17]. A possible mechanism is that paced
breathing via pulmonary stretch receptors stimulates the vagus nerve
and the parasympathetic nervous system to reduce stress chemicals in
the brain and facilitate a vascular relaxation response. [16,17]. It has
also been suggested that slow respiratory rates (RRs) affect vagal tone
enteroreceptors and mechanoreceptors in the nasal vault which signals
the olfactory bulb and portions of the frontal cortex to decrease in-
flammation [15]. The inspiration/expiration,(I/E) rate may also play a
role in the parasympathetic response as a lower ratio had a positive
effect on HRV only with slow but not fast RRs [18]. In addition, HRV
across low RRs was decreased by parasympathetic blockade with no
change following sympathetic blockade when both were compared with
placebo [19]. Further, in a meta-analysis of 191 patients from 9 un-
controlled neuroimaging studies, which is useful to formulate, but not
test hypotheses, HRV was correlated with activity of the ventromedial
prefrontal cortex and parasympathetic nervous system [20]. Finally,
additional support for the medical hypothesis that mindfulness with
paced breathing reduces BP derives from two recent reports [21,22].
One suggested that diaphragmatic breathing alone decreases stress
[21]. The second suggested that paced breathing, when synchronized
with rhythmic muscle contraction, leads to more resilient activation of
the parasympathetic response than either alternating contractions or
breathing alone [22]. Both these observations are compatible with the
hypothesis that mind body interactions (MBIs) reduce stress [21,22].
Based on an incomplete but intriguing totality of evidence, it is
plausible to hypothesize that mindfulness, especially when practiced
with paced breathing, reduces BP.
Evaluation of the hypothesis
With respect to lowering BP and prevention of hypertension, nu-
merous TLCs have been evaluated in randomized trials. Specifically,
Phase I of the Trials of Hypertension Prevention (TOHP I) was designed
2
Medical Hypotheses 142 (2020) 109780
to test the short-term feasibility and efficacy of seven non-
pharmacological interventions in persons with high normal BP. These
included the lifestyle interventions of weight loss, sodium reduction,
and stress management, and the nutritional supplement interventions of
calcium, magnesium, and potassium and fish oil [23]. The two inter-
ventions that produced statistically significant reductions in blood
pressure were weight loss and sodium reduction. Weight loss produced
a reduction of 2–3 mm Hg systolic BP and sodium reduction produced a
1 mm Hg decrease [24]. To test the efficacy of weight loss and/ or
sodium reduction in decreasing BP as well as the overall incidence of
hypertension, TOHP II recruited 2,382 moderately overweight men and
women with a high-normal level of diastolic BP in a randomized 2x2
factorial design during a 3–4-year follow-up period. The trial demon-
strated statistically significant and clinically important effects of weight
loss and/or sodium reduction on the development of hypertension [25].
The hypothesis that mindfulness with paced breathing decreases BP
can also be tested directly in a randomized trial of adequate statistical
power. In such a trial eligible and willing subjects would be assigned at
random to mindfulness with paced breathing or mindfulness without
paced breathing. In this trial, the primary outcome would be BP re-
duction, which has clear clinical relevance and HRV, a secondary
endpoint of potential clinical relevance.
In addition, at present, neuroimaging provides a powerful tool to
analyze the structure and function of the brain by noninvasive techni-
ques such as computed tomography and magnetic resonance imaging.
Thus, a neuroimaging sub-study would provide a direct test of whether
mindfulness with paced breathing increases blood flow to the frontal
lobes. This hypothesis derives from the fact that paced breathing sti-
mulates the parasympathetic nervous system which alters neuronal
function in specific areas of the brain and reduces stress chemicals
[20,26].
If such a trial were to show positive short-term results, this would
lead to a medium-term goal to conduct a randomized trial of mind-
fulness with paced breathing that assesses various biomarkers which
might be surrogates for future risk of stroke. For example, isometric
yoga increased vagal tone and was associated with statistically sig-
nificant decreases in blood biomarkers of inflammation [27]. It is also
possible to address other precise, but also more expensive surrogates of
stroke, such as inhibition of progression of carotid atherosclerosis as
measured by carotid ultrasound. If the medium-term goal is achieved it
would then be logical to propose a large-scale, long-term randomized
trial of sufficient size and duration to test the hypothesis of whether
mindfulness with paced breathing decreases risk of stroke [28].
An adequate test of the hypothesis that mindfulness with paced
breathing reduces BP requires a sample size of about 400 to achieve
90% power to detect the same magnitude of effects seen in TOHP 1.
Empirical data
Complementary and Alternative Medicine (CAM) is a common
phrase applied to health care practices that traditionally have not been
part of conventional western medicine.
In a case series, which is useful to formulate but not test hypotheses
[28,29] individuals who practiced slow and regular breathing had
lower BPs [30]. Two observational case-control studies, which can test
moderate to large effects, [28,29] contribute empirical data to the
formulation of this medical hypothesis. In one, long-term meditators
had lower respiratory rates when compared to non-meditators [31]. In
another, those who practiced controlled breathing slower than 6
breaths per minute had lower BP than subjects who sat quietly [32].
Thus, slow respiration, perhaps through engagement of an extensive
range of parasympathetic processes in the body, may affect BP as well
as cardiac rhythms, and metabolism in both the brain and periphery
[33]. In addition, HRV [34] and pulse pressure, defined as the differ-
ence between systolic and diastolic BP, are direct markers of para-
sympathetic output. It is also important to note that the effects of
J. Brenner, et al.
respiration on parasympathetic indices of HRV when recorded under
resting state conditions are minimal at best, and resting state HRV is
recorded best under conditions of spontaneous breathing [20,35].
With respect to perhaps the most clinically relevant outcome of BP,
some, but not all trials and their meta analyses of CAM and MBIs, such
as yoga and meditation, suggest possible beneficial effects on BP
[20,26,36–42]. In a randomized trial of 12 weeks duration, a yoga
program was associated with significant decreases in 24-hour ambula-
tory BP [26]. In a review which included several randomized trials,
yogic breath regulations decreased BP [37]. In one study, increased
parasympathetic activity was seen in the slow but not fast breathers
which resulted in lowering the blood pressure [32]. In a subsequent
investigation, controlled breathing but not the exercise portion of yoga
contributed to the decreased BP [38]. Another author reported a sig-
nificant decrease in BP with stepwise slower paced breathing [43].
Further, administration of buscopan, an anticholinergic leading to
parasympathetic blockade, led to no change on BP in healthy volunteers
who performed slow Bhastrika Pranayamic breathing whereas there
was an improvement in blood pressure with the same breathing tech-
nique without buscopan [39].
Paced breathing has been associated with increased blood flow to
the frontal lobe, in particular the prefrontal cortex and anterior cin-
gulate gyrus [20,26]. In addition, in an uncontrolled case series of 293
patients followed for 3.7 years, which is useful to formulate but not test
hypotheses, amygdalar activity was correlated with systemic in-
flammation including arterial inflammation and CVD events [40]. All
these observations are compatible with effects of paced breathing on
the response to stress and sympathetic tone. Possible mechanisms of
benefit include the downregulation of gene expressions of inflammatory
markers such as nuclear factor kappa B and conserved transcriptional
response to adversity molecular patterns [41].
It is also plausible that such activities reduce sympathetic activity,
improve endothelial function and produce beneficial effects on BP and
HRV, possibly mediated through the release of nitric oxide [44].
Consequences of the hypothesis and discussion
The hypothesis that mindfulness with paced breathing will reduce
BP is promising but unproven. Plausible mechanisms for benefit include
sustained effects on the parasympathetic nervous system. If so, CAM
and MBI will represent a safe, effective, and easily affordable means to
reduce BP in the short run. Subsequently, a finding that mindfulness
with paced breathing reduces BP would also lead to direct tests in
randomized trials of reductions of carotid atherosclerosis and, if so, a
larger scale trial to test whether there is a direct impact of mindfulness
with paced breathing on reducing the risks of stroke and MI. All of these
issues have potentially large and important clinical and policy im-
plications in the US and worldwide. It is also possible, however, that, to
paraphrase Thomas Huxley, this beautiful hypothesis will be slain by
ugly facts [45].
Conflicting interests
Ms. Brenner, Dr. LeBlang , Dr. Lizotte-Waniewski, Dr. Espinosa and
Dr. Newberg report no disclosures. Ms. Schmidt discloses that she re-
ceives royalities for authorship of The Practice: Simple tools for
managing stress, finding inner peace, and uncovering happiness.
Professor DeMets reports that that he serves as an independent scientist
in an advisory role to the National Institutes of Health, the US Food and
Drug Administration and the pharmaceutical and medical device in-
dustry on the design, monitoring and analysis of randomized trials; to
investigators and sponsors as Member of Data Monitoring Committees
for Abbvie, AstraZeneca, Amgen, Actelion, Boehringer Ingelheim,
DalCor, GlaxoSmithKline, Merck, Sanofi, and Teva; and receives roy-
alties for authorship or editorship of 3 textbooks and owns no stock in
any pharmaceutical or device company. Professor Hennekens reports
3
Medical Hypotheses 142 (2020) 109780
that he serves as an independent scientist in an advisory role to in-
vestigators and sponsors as Chair or Member of Data and Safety
Monitoring Boards for Amgen British Heart Foundation, Cadila,
Canadian Institutes of Health Research, DalCor, Regeneron, and the
Wellcome Foundation; to UpToDate and the US Food and Drug
Administration; receives royalties for authorship or editorship of 3
textbooks and as co-inventor on patents for inflammatory markers and
cardiovascular disease that are held by Brigham and Women’s Hospital;
has an investment management relationship with the West-Bacon
Group within SunTrust Investment Services, which has discretionary
investment authority and does not own any common or preferred stock
in any pharmaceutical or device company.
Acknowledgment
We are indebted to Heather Johnson, MD, FACC and Anton Borja,
DO for advice and help.
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