Literature Update
Selected Abstracts From Recent
Publications in Cardiopulmonary
Disease Prevention and Rehabilitation
Peter H. Brubaker, PhD, and Sanjay Kalra, MD
■ A RANDOMIZED TRIAL OF
INTENSIVE VERSUS STANDARD
BLOOD-PRESSURE CONTROL
SPRINT Research Group, Wright JT Jr, Williamson JD,
Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM,
Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC,
Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK,
Ambrosius WT
N Engl J Med. 2015;373(22):2103-2116.
Background: The most appropriate targets for systolic
blood pressure to reduce cardiovascular morbidity and
mortality among persons without diabetes remain
uncertain.
Methods: We randomly assigned 9361 persons with a
systolic blood pressure of 130 mm Hg or higher and an
increased cardiovascular risk, but without diabetes, to a
systolic blood-pressure target of less than 120 mm Hg
(intensive treatment) or a target of less than 140 mm Hg
(standard treatment). The primary composite outcome was
myocardial infarction, other acute coronary syndromes,
stroke, heart failure, or death from cardiovascular causes.
Results: At 1 year, the mean systolic blood pressure
was 121.4 mm Hg in the intensive- treatment group and
136.2 mm Hg in the standard-treatment group. The inter-
vention was stopped early after a median follow-up of
3.26 years owing to a significantly lower rate of the pri-
mary composite outcome in the intensive-treatment
group than in the standard-treatment group (1.65% per
year vs. 2.19% per year; hazard ratio with intensive treat-
ment, 0.75; 95% confidence interval [CI], 0.64 to 0.89;
P<0.001). All-cause mortality was also significantly
lower in the intensive-treatment group (hazard ratio,
0.73; 95% CI, 0.60 to 0.90; P = 0.003). Rates of serious
adverse events of hypotension, syncope, electrolyte
140 / Journal of Cardiopulmonary Rehabilitation and Prevention 2016;36:140-144
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HCRv36n2_LitUpdate_LR 140
abnormalities, and acute kidney injury or failure, but not
of injurious falls, were higher in the intensive-treatment
group than in the standard-treatment group.
Conclusions: Among patients at high risk for cardio-
vascular events but without diabetes, targeting a systolic
blood pressure of less than 120 mm Hg, as compared
with less than 140 mm Hg, resulted in lower rates of fatal
and nonfatal major cardiovascular events and death from
any cause, although significantly higher rates of some
adverse events were observed in the intensive-treatment
group. (Funded by the National Institutes of Health;
ClinicalTrials.gov number, NCT01206062.)
Editor’s Comment: The debate about optimal blood
pressure target levels rages on, and the results from the
recently completed landmark Systolic Blood Pressure
Intervention Trial (SPRINT) certainly add more fuel to the
fire! The results of SPRINT, published in the New England
Journal of Medicine and discussed at the recent American
Heart Association 2015 Scientific Sessions, confirm that
in adults 50 years and older with high blood pressure,
targeting a systolic blood pressure of less than 120 mil-
limeters of mercury (mm Hg) reduced rates of cardiovas-
cular events, such as heart attack and heart failure, as
well as stroke, by 25 percent. Additionally, this target
reduced the risk of death by 27 percent—as compared to
a target systolic pressure of 140 mm Hg.
The SPRINT study, which began in the fall of 2009,
included more than 9300 participants age 50 and older,
recruited from about 100 medical centers and clinical
practices throughout the United States and Puerto Rico.
About 36 percent of participants were women, 58 per-
cent were white, 30 percent were African-American, and
DOI: 10.1097/HCR.0000000000000175
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 11 percent were Hispanic. The SPRINT study did not
include patients with diabetes, prior stroke, or polycystic
kidney disease, as other NIH trials were studying those
particular populations. Approximately 28 percent were
75 or older, and 28 percent had chronic kidney disease.
The study tested a strategy of using blood pressure medi-
cations to achieve the targeted goals of less than 120 mm Hg
(intensive treatment group) versus 140 mm Hg (standard
treatment group). The NIH stopped the blood pressure
intervention in August—a year earlier than planned—
after it became apparent that this more intensive interven-
tion was beneficial.
In the publication, investigators provided detailed data
showing that both cardiovascular deaths and overall
deaths were lower in the intensive treatment group.
Certain types of serious consequences were more com-
mon in the intensive group, including low blood pres-
sure, fainting, electrolyte abnormalities, and acute kidney
damage. However, other serious adverse events associ-
ated with lower blood pressure, such as slow heart rate
and falls with injuries, did not increase in the intensive
group. In patients with chronic kidney disease, there was
no difference in the rate of serious decline in kidney func-
tion between the two blood pressure goal groups. It was
clear from the results that the benefits of more intensive
blood pressure lowering exceeded the potential for harm,
regardless of gender or race/ethnicity.
In addition to its primary cardiovascular outcome, the
study will continue to examine kidney disease, cognitive
function, and dementia among the SPRINT participants;
however, these results are not yet available as additional
information will be collected and analyzed over the next
year. Although the study provides strong evidence that a
lower blood pressure target saves lives, patients and their
healthcare providers may want to wait to see how guide-
line groups incorporate this study and other scientific
reports into any future hypertension guidelines. In the
meantime, patients should talk to their healthcare provid-
ers to determine whether this lower goal is best for their
individual care. —PHB
■ STATIN THERAPY IS ASSOCIATED
WITH LOWER ALL-CAUSE
MORTALITY IN PATIENTS WITH
NON-OBSTRUCTIVE CORONARY
ARTERY DISEASE
Hwang IC, Jeon JY, Kim Y, Kim HM, Yoon YE, Lee SP, Kim HK,
Sohn DW, Sung J, Kim YJ
Atherosclerosis. 2015;239(2):335-342.
Objective: Non-obstructive coronary artery disease
(CAD) is a frequent clinical condition and is associated
with an increase in cardiovascular events. However,
appropriate medical therapy for this population is not
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HCRv36n2_LitUpdate_LR 141
known. We investigated the association between statin
use and risk of all-cause mortality and coronary revascu-
larization in patients with non-obstructive CAD.
Methods: From 2007 to 2011, we identified 8372
consecutive patients with non-obstructive CAD (1e49%
stenosis) documented by coronary computed tomogra-
phy angiography (CCTA) from 3 medical centers. Patients
with statins or aspirin use before CCTA, and a history of
revascularization before initial CCTA were excluded. All-
cause mortality and a composite of mortality and late
coronary revascularization (>90 days after CCTA) were
analyzed according to the use of statins.
Results: Mean age of the study population was 61.4 ±
10.9 years and 70.3% were male. Statins were prescribed
to 1983 (23.7%) patients. During 828 days of follow-up
(IQR 385e1342), 221 (2.6%) cases of all-cause mortality
and 295 (3.5%) cases of the composite endpoint were
observed. Statin therapy was associated with lower risks
of all-cause mortality (adjusted HR 0.397; 95% CI
0.262e0.602; p < 0.0001) and composite endpoint
(adjusted HR 0.430; 95% CI 0.310e0.597; p < 0.0001).
Association between statin therapy and better clinical
outcomes was regardless of age, sex, presence of hyper-
tension or diabetes, coronary artery calcium score, low-
density lipoprotein cholesterol levels, high-sensitivity
C-reactive protein levels, or glomerular ?ltration rate.
Conclusions: Statin therapy was associated with a
lower risk of all-cause mortality in patients with non-
obstructive CAD documented by CCTA, regardless of
combined clinical risk factors.
Editor’s Comment: HMG-CoA reductase inhibitors (ie,
statins) are a well-established therapy for the secondary
prevention of cardiovascular diseases as they slow the
progression, and potentially induce disease regression, of
coronary artery disease (CAD). Furthermore, the reported
benefits and indications for statins use continues to
expand into the primary prevention setting and other
conditions (dementia, bone health, etc) due to their
pleiotropic effects. However, the effects of statins on hard
endpoints (ie, morbidity and mortality), particularly in
those with non-obstructive CAD are largely unknown.
Thus, the purpose of this study, conducted in Seoul
Korea, was to examine the relationship between statin
therapy and risk for all–cause mortality and coronary
revascularization in patients with non-obstructive CAD
(ie, those with CAD lesions less than 49% stenosis) in a
cohort of patients referred for coronary computed tomog-
raphy angiography (CCTA).
Using a national database of more than 47,000
patients, these investigators identified 8,372 patients that
had CAD lesions, determined from CCTA, between
1-49%. Of these, 1,983 were using statins whereas 6,389
were not using statins. The primary outcome measure
was all-cause mortality whereas the secondary outcome
was a composite of all-cause mortality and late coronary
revascularization (>90 days after CCTA, including percu-
taneous coronary intervention and coronary artery bypass
Literature Update / 141
13/02/16 8:07 PM
 graft). The statin users were older, with more frequent
comorbidities and medications, higher baseline fasting
glucose, and hemoglobin A1c. Statin users also had unfa-
vorable lipid profiles and higher coronary artery calcium
(CAC) scores. During a median of 828 days of follow-up,
221 deaths and 295 composite endpoint were observed.
The risks of all-cause mortality and composite were sig-
nificantly lower in statin users than non-users even
though statin users higher risk. Furthermore, statin therapy
was associated with a lower risk of all-cause mortality of
age, sex, presence of diabetes or hypertension, or use of
aspirin. The benefits of statins was confirmed across sub-
group including; older age (> 65 yrs), males and females,
diabetic, hypertensive, aspirin user, CAC score (< 100),
low density lipoprotein (<100 mg/dL), high-sensitivity
C-reactive protein (< 2 mg/L), and renal disease.
Non-obstructive CAD is associated with a higher risk
of cardiovascular events and is present in ∼ 30% of
symptomatic and ∼ 16% of asymptomatic individuals yet
these patients are likely to receive less preventive treat-
ment compared to those with obstructive CAD.
Consequently, the results of this study identify and impor-
tant group of patients that would clearly benefit from the
preventive benefits of statin therapy. If the findings of this
study can be replicated in a larger more diverse popula-
tion, it will likely result in an expanded use of statin in the
primary prevention setting and further reduce CAD mor-
bidity and mortality which is still the number 1 killer of
American men and women. —PHB
■ EXECUTIVE SUMMARY: 2015
INTERNATIONAL CONSENSUS ON
CARDIOPULMONARY RESUSCITATION
AND EMERGENCY CARDIOVASCULAR
CARE SCIENCE WITH TREATMENT
RECOMMENDATIONS
Nolan JP, Hazinski MF, Aickin R, Bhanji F, Billi JE, Callaway
CW, Castren M, de Caen AR, Ferrer JM, Finn JC, Gent LM,
Griffin RE, Iverson S, Lang E, Lim SH, Maconochie IK,
Montgomery WH, Morley PT, Nadkarni VM, Neumar RW,
Nikolaou NI, Perkins GD, Perlman JM, Singletary EM, Soar J,
Travers AH, Welsford M, Wyllie J, Zideman DA
Resuscitation. 2015 Oct;95:E1-E31. doi: 10.1016/j.resus-
citation.2015.07.039.
Publication of the 2015 American Heart Association
(AHA) Guidelines Update for Cardiopulmonary
Resuscitation (CPR) and Emergency Cardiovascular Care
(ECC) marks 49 years since the first CPR guidelines were
published in 1966 by an Ad Hoc Committee on
Cardiopulmonary Resuscitation established by the
National Academy of Sciences of the National Research
Council.Since that time, periodic revisions to the
Guidelines have been published by the AHA in 1974,
1980, 1986, 1992, 2000, 2005, 2010, and now 2015.
142 / Journal of Cardiopulmonary Rehabilitation and Prevention 2016;36:140-144
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HCRv36n2_LitUpdate_LR 142
The 2010 AHA Guidelines for CPR and ECC provided a
comprehensive review of evidence-based recommenda-
tions for resuscitation, ECC, and first aid. The 2015 AHA
Guidelines Update for CPR and ECC focuses on topics
with significant new science or ongoing controversy, and
so serves as an update to the 2010 AHA Guidelines for
CPR and ECC rather than a complete revision of the
Guidelines.
The purpose of the Executive Summary is to provide
an overview of the new or revised recommendations
contained in the 2015 Guidelines Update. This document
does not contain extensive reference citations; the reader
is referred to Parts 3 through 9 for more detailed review
of the scientific evidence and the recommendations on
which they are based.
There have been several changes to the organization
of the 2015 Guidelines Update compared with 2010.
“Part 4: Systems of Care and Continuous Quality
Improvement” is an important new Part that focuses on
the integrated structures and processes that are necessary
to create systems of care for both in-hospital and out-of-
hospital resuscitation capable of measuring and improv-
ing quality and patient out- comes. This Part replaces the
“CPR Overview” Part of the 2010 Guidelines.
Another new Part of the 2015 Guidelines Update is
“Part 14: Education,” which focuses on evidence-based
recommendations to facilitate widespread, consistent,
efficient and effective implementation of the AHA
Guidelines for CPR and ECC into practice. These recom-
mendations will target resuscitation education of both lay
rescuers and healthcare providers. This Part replaces the
2010 Part titled “Education, Implementation, and Teams.”
The 2015 Guidelines Update does not include a separate
Part on adult stroke because the content would replicate
that already offered in the most recent AHA/American
Stroke Association guidelines for the management of
acute stroke.
Finally, the 2015 Guidelines Update marks the begin-
ning of a new era for the AHA Guidelines for CPR and
ECC, because the Guidelines will transition from a 5-year
cycle of periodic revisions and updates to a Web-based
format that is continuously updated. The first release of
the Web-based integrated Guidelines, now available
online at ECCguidelines.heart.org is based on the com-
prehensive 2010 Guidelines plus the 2015 Guidelines
Update. Moving forward, these Guidelines will be
updated by using a continuous evidence evaluation pro-
cess to facilitate more rapid translation of new scientific
discoveries into daily patient care.
Creation of practice guidelines is only 1 link in the
chain of knowledge translation that starts with laboratory
and clinical science and culminates in improved patient
outcomes. The AHA ECC Committee has set an impact
goal of doubling bystander CPR rates and doubling car-
diac arrest survival by 2020. Much work will be needed
across the entire spectrum of knowledge translation to
reach this important goal.
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 Editor’s Comment: It is highly recommended that all
staff involved with cardiac and pulmonary rehabilitation
programs, particularly those expected to perform life sup-
port, review these new guidelines. —PHB
■ AN OFFICIAL AMERICAN THORACIC
SOCIETY/EUROPEAN RESPIRATORY
SOCIETY POLICY STATEMENT:
ENHANCING IMPLEMENTATION, USE,
AND DELIVERY OF PULMONARY
REHABILITATION
Rochester CL, Vogiatzis I, Holland AE, Lareau SC, Marciniuk
DD, Puhan MA, Spruit MA, Masefield S, Casaburi R, Clini
EM, Crouch R, Garcia-Aymerich J, Garvey C, Goldstein RS,
Hill K, Morgan M, Nici L, Pitta F, Ries AL, Singh SJ, Troosters
T, Wijkstra PJ, Yawn BP, ZuWallack RL; on behalf of the ATS/
ERS Task Force on Policy in Pulmonary Rehabilitation
Am J Respir Crit Care Med. 2015;192:1373–1386.
Rationale: Pulmonary rehabilitation (PR) has demon-
strated physiological, symptom-reducing, psychosocial,
and health economic benefits for patients with chronic
respiratory diseases, yet it is underutilized worldwide.
Insufficient funding, resources, and reimbursement; lack of
healthcare professional, payer, and patient awareness and
knowledge; and additional patient-related barriers all con-
tribute to the gap between the knowledge of the science
and benefits of PR and the actual delivery of PR services to
suitable patients.
Objectives: The objectives of this document are to
enhance implementation, use, and delivery of pulmonary
rehabilitation to suitable individuals worldwide.
Methods: Members of the American Thoracic Society
(ATS) Pulmonary Rehabilitation Assembly and the
European Respiratory Society (ERS) Rehabilitation and
Chronic Care Group established a Task Force and writing
committee to develop a policy statement on PR. The
document was modified based on feedback from expert
peer reviewers. After cycles of review and revisions, the
statement was reviewed and formally approved by the
Board of Directors of the ATS and the Science Council
and Executive Committee of the ERS.
Main Results: This document articulates policy recom-
mendations for advancing healthcare professional, payer,
and patient awareness and knowledge of PR, increasing
patient access to PR, and ensuring quality of PR pro-
grams. It also recommends areas of future research to
establish evidence to support the development of an
updated funding and reimbursement policy regarding PR.
Conclusions: The ATS and ERS commit to undertake
actions that will improve access to and delivery of PR
services for suitable patients. They call on their members
and other health professional societies, payers, patients,
and patient advocacy groups to join in this commitment.
Editor’s Comment: Pulmonary rehabilitation has sev-
eral decades of data accrued to support its value, mainly
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HCRv36n2_LitUpdate_LR 143
in patients with chronic obstructive pulmonary disease
but to some degree in interstitial lung diseases too. The
benefits extend primarily to improvements in short term
effort tolerance and quality of life with less robust impact
on healthcare resource utilization and survival. The
majority of interventions, both exercise training and edu-
cation, are generally low in the need for technological
and other resources. Based on this one might expect high
prescription, uptake and compliance rates for such a
simple, safe and low cost intervention. The reality is pre-
dictably the opposite because, contrary to all well-meaning
expectations, exercise for exercise’s sake is biologically
unnatural; the naturally inactive lifestyle can therefore
only be “actively” overcome, and only if barriers are
aggressively removed.
This requires improving availability and access, as well
as a concerted promotion of rehabilitation amongst pro-
viders, insurers and other payers, as well as the intended
recipients of the benefits, patients. Various societies try to
do their bit and this American Thoracic Society/European
Respiratory Society statement is an important piece in that
effort. However, its appearance in journals with a reader-
ship that is already familiar with the potential benefits of
pulmonary rehabilitation is too much of “preaching to the
choir.” Its impact on insurer/payer behavior rests on pro-
viding broad-based leverage and, therefore, policy state-
ments like these need to be sent to the people whose
primary mandate is to restrict services in order to cut
costs, to patient support and other activist groups (in lay-
accessible language), and to primary care providers.
Hiding them in ivory tower journals limits their reach and
blunts their intended impact. —SK
■ EXERTIONAL DYSPNOEA AND
CORTICAL OXYGENATION IN
PATIENTS WITH COPD
Higashimoto Y, Honda N, Yamagata T, Sano A, Nishiyama O,
Sano H, Iwanaga T, Kume H, Chiba Y, Fukuda K, Tohda Y
Eur Respir J. 2015;46:1615–1624. doi: 10.1183/13993003.
00541-2015.
This study was designed to investigate the association
of perceived dyspnoea intensity with cortical oxygena-
tion and cortical activation during exercise in patients
with chronic obstructive pulmonary disease (COPD) and
exertional hypoxaemia.
Low-intensity exercise was performed at a constant
work rate by patients with COPD and exertional hypox-
aemia (n = 11) or no hypoxaemia (n = 16), and in
control participants (n = 11). Cortical oxyhaemoglobin
(oxy-Hb) and deoxyhaemoglobin (deoxy-Hb) concentra-
tions were measured by multichannel near-infrared spec-
troscopy. Increased deoxy-Hb is assumed to reflect
impaired oxygenation, whereas decreased deoxy-Hb
signifies cortical activation.
Literature Update / 143
13/02/16 8:07 PM
 Exercise decreased cortical deoxy-Hb in control and
nonhypoxaemic patients. Deoxy-Hb was increased in
hypoxaemic patients and oxygen supplementation
improved cortical oxygenation. Decreased deoxy-Hb in
the pre-motor cortex (PMA) was significantly correlated
with exertional dyspnoea in control participants and
patients with COPD without hypoxaemia. In contrast,
increased cortical deoxy-Hb concentration was
correlated with dyspnoea in patients with COPD and
hypoxaemia. With the administration of oxygen supple-
mentation, exertional dyspnoea was correlated with
decreased deoxy-Hb in the PMA of COPD patients with
hypoxaemia.
During exercise, cortical oxygenation was impaired in
patients with COPD and hypoxaemia compared with
control and nonhypoxaemic patients; this difference was
ameliorated with oxygen supplementation. Exertional
dyspnoea was related to activation of the pre-motor
cortex in COPD patients.
Editor’s Comment: Dyspnea is a common complaint
and a near universal symptom of significant chronic
obstructive pulmonary disease (COPD) but, despite its
prevalence, it remains poorly defined both in mechanism
and measurement. Its anatomical and physiological path-
ways are incompletely characterized, and its precise
determinants similarly so, to the point that even the spe-
cific areas of the brain that are involved remain incom-
pletely defined. New techniques, especial functional
magnetic resonance imaging (fMRI), and positron emis-
144 / Journal of Cardiopulmonary Rehabilitation and Prevention 2016;36:140-144
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HCRv36n2_LitUpdate_LR 144
sion tomography (PET) are helping in understanding
many of the issues involved, but the technological con-
straints of these methods limit their use, especially during
exercise.
This elegant study on patients with COPD, including
both patients who show hypoxemia during steady state
exercise and those who do not, uses multichannel near-
infrared spectroscopy (NIRS) in an attempt to define
changes in cortical blood flow. It does this by measuring
changes in both oxy-Hb and deoxy-Hb during exercise
and comparing the observations between controls and
patients with COPD with and without exercise associated
hypoxemia. Deoxy-Hb was found to be reduced with
exercise in the control and non-hypoxemic COPD groups,
and the decrease in the PMA region especially correlated
with perceived dyspnea; conversely, it increased in those
with hypoxemia, and the increase not only correlated with
dyspnea but was corrected by oxygen supplementation.
All this provides several important insights into the
likely role of cortical blood flow and the proportion of
oxy-Hb and deoxy-Hb in not only playing a role in dysp-
nea in COPD (and possibly more widely) but provides
further evidence of the focal importance of the PMA in
this key symptom. It also highlights the value of NIRS in
dynamically assessing cortical blood flow in situations
where other more established techniques cannot be used
because of their technical constraints, especially the need
for the head to be immobilized for fMRI and PET
scanning. —SK
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