Coronary Heart Disease

Angiology
2014, Vol. 65(8) 660-666
Effect of Remote Ischemic Preconditioning ª The Author(s) 2013
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in the Elderly Patients With Coronary DOI: 10.1177/0003319713507332
ang.sagepub.com
Artery Disease With Diabetes Mellitus
Undergoing Elective Drug-Eluting
Stent Implantation

Xiaohan Xu, MD1, Yujie Zhou, MD, PhD, FACC, FHRS, FSCAI1,
Shengjie Luo, MD1,2, Weijun Zhang, MD1, Yingxin Zhao, MD1,
Miao Yu, MD1, Qian Ma, MD1, Fei Gao, MD1, Hua Shen, MD1,
and Jianwei Zhang, MD1

Abstract
There is conflicting evidence regarding the effectiveness of remote ischemic preconditioning (RIPC) in patients undergoing elective
percutaneous coronary intervention (PCI). Therefore, we prospectively enrolled elderly patients with coronary heart disease
(CHD) with diabetes mellitus (DM) undergoing elective drug-eluting stent (DES) implantation. They were randomized to receive
RIPC within 2 hours before PCI (n ¼ 102) or not (controls, n ¼ 98). Baseline clinical characteristics were similar between the 2
groups. Despite a trend toward decline, the median high-sensitivity cardiac troponin I (hscTnI) level (P ¼ .256) and the incidence
of myocardial infarction (MI) type 4a (P ¼ .106) in the RIPC group 16 hours after PCI procedure was not significantly different from
the control group. The RIPC could attenuate the release of a myocardial biomarker but failed to show a significant effect on hscTnI
level or MI type 4a incidence after PCI procedure in elderly patients with CHD having DM undergoing elective DES implantation.

Keywords
remote ischemic preconditioning, elderly, diabetes mellitus, drug-eluting stent, high sensitivity cardiac troponin I, myocardial
infarction type 4a

Introduction the potential risk of coronary microembolization have limited

Myocardial injury associated with percutaneous coronary inter-
vention (PCI) is a common complication of the procedure,
mostly presenting as an elevation of cardiac biomarkers. Desig-
nated as myocardial infarction (MI) type 4a in the third universal
definition of MI from the European Society of Cardiology/
American College of Cardiology Foundation/American Heart
Association/World Heart Federation, MI related to PCI is
defined by elevation in cardiac troponin (cTn) values >5 
99th percentile upper reference limit (high-sensitivity cTn I
[hscTnI] > 0.20 ng/mL as in the present study) in patients with
normal baseline values.1 With coronary microembolization of
plaque debris and side branch occlusion during PCI proposed
as the most likely causes,2,3 MI type 4a has been shown to be
an adverse prognostic indicator after elective PCI.4,5
Many methods have been tested to reduce myocardial injury
during PCI. Although some studies have demonstrated a cardi-
oprotective effect of ischemic preconditioning and ischemic
postconditioning against myocardial ischemia–reperfusion
injury (IRI), the involvement of the culprit coronary lesion and
their clinical application.6 However, the concept of remote
ischemic preconditioning (RIPC) emerging in recent years
has become increasingly attractive, not only because it has
been proved to be cardioprotective by some experimental and
clinical studies but also because it can be easily achieved by
transient limb ischemia with a pneumatic tourniquet. With
conflicting results regarding the effectiveness of RIPC in
patients undergoing elective PCI procedure, the impact of age
and comorbidities cannot be ignored.7
1
Department of Cardiology, An Zhen Hospital, Capital Medical University,
Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China
2
Capital Medical University School of Rehabilitation Medicine, China Rehabi-
litation Research Centre, Beijing, China
Corresponding Author:
Yujie Zhou, Department of Cardiology, An Zhen Hospital, Capital Medical
University, Beijing Institute of Heart Lung and Blood Vessel Disease, Anzhenli
Avenue, Chao Yang District, Beijing 100029, China.
Email: azyjzhou@126.com
Xu et al
This single-center, randomized, and prospective study was
designed to investigate the effect of RIPC on hscTnI levels,
MI type 4a incidence, and high-sensitivity C-reactive protein
(hsCRP) levels in elderly patients with coronary heart disease
(CHD) with diabetes mellitus (DM) undergoing elective
drug-eluting stent (DES) implantation.
Methods
Study Population and Protocol
From April 2013 to July 2013, after approval by the local research
ethics committee and individual informed consent, eligible
patients with DM aged 65 years undergoing coronary angiogra-
phy in the cardiology department of An Zhen Hospital (Beijing,
China) were recruited. The main exclusion criteria included pre-
vious use of trimatezidine, nicorandil (preconditioning-mimetic
agent), or glibenclamide (preconditioning-blocking agent),
uncontrolled DM (glycated hemoglobin, HbA1c >9%), elevated
cardiac biomarker at admission, MI within 6 months, stent
implantation or coronary artery bypass graft (CABG) surgery
within 6 months, cardiogenic shock, left ventricular ejection frac-
tion <50%, congenital or valvular heart disease requiring further
surgery, moderate or severe renal insufficiency with estimated
glomerular filtration rate (eGFR) <30 mL/min/1.73m2, ongoing
bleeding, or a history of bleeding diathesis, and expected life span
< 12 months. After a baseline evaluation and optimization of med-
ical therapy, eligible suitable patients were randomized by digital
method of randomization to receive or not receive RIPC as an
addition to the conventional treatment of CHD (eg, antiplatelet
drugs, anticoagulants, statins, and antianginal therapy) within 2
hours before angiography. Patients (102 in the RIPC group and
98 in the control group) were rescreened after coronary angiogra-
phy and DES implantation.
The DM was defined according to the American Diabetes
Association guidelines.8 All patients received medication such
as metformin, acarbose, gliquidone, gliclazide, glipizide, repa-
glinide, and/or insulin to control blood glucose within the target
range. The investigating physicians and interventionists were
kept blind from the group allocation until all the database was
completed and ready for statistical analysis.
Remote Ischemic Preconditioning and Control
Interventions
A pneumatic medical tourniquet cuff (width 5 cm; length 40
cm) was placed around the upper arm within 2 hours before
PCI, and RIPC was induced by 3 cycles of 5-minute pneumatic
medical cuff inflations to 200 mm Hg, followed by 5 minutes of
deflations to allow reperfusion. Patients in the control group
underwent PCI procedure without this process of transient
upper limb ischemia. The interventionists were kept blind of
the study allocation. Patients in both the groups were instructed
to avoid any vigorous activity that could induce angina during
the whole hospitalization. Conventional disposable medical
tourniquets were used around the wrist radial artery puncture
site for 6 hours after PCI in all the patients.
661
Percutaneous Coronary Intervention Procedure
All patients underwent complete revascularization—defined as
restoration of thrombolysis in MI (TIMI) flow grade 3 with
residual stenosis <30% to all myocardial territories—via a
radial arterial (right 195, left 5) approach with 3.5F or 4F guid-
ing catheters with interventional strategy at the discretion of the
interventionists according to current clinical guidelines. All
patients received one or more of the second-generation DES.
Loading doses of 300 mg aspirin and 300 mg clopidogrel were
given to all patients at least 6 hours prior to PCI, followed by a
maintenance dose of 100 mg aspirin and 75 mg clopidogrel
(300 mg aspirin and/or 150 mg clopidogrel if there were
aspirin resistance and/or clopidogrel resistance according to
their platelet aggregation tests). All patients were given sta-
tins (10 mg rosuvastatin or 20 mg atorvastatin) from admis-
sion. Weight-adjusted unfractionated heparin (70-100 U/kg)
was administered during the procedure and was routinely
discontinued at the end of the procedure. Glycoprotein IIb/IIIa
antagonist (tirofiban) was administered according to the judg-
ment of the interventionists.
Biochemistry Measurement
After a fasting state for more than 10 hours (baseline), venous
blood samples were taken on the first morning of admission
and again at around 16 hours after PCI procedure. The hscTnI
was measured by an automated immunoassay (UniCel DxI 800
Access AccuTnI chemiluminescence method, Beckman Coul-
ter, Fullerton, California). The 99th percentile of the hscTnI
level in a reference population of healthy volunteers (upper ref-
erence limit) was 0.04 ng/mL. As a measurement of accuracy
within the analytical range, the variation coefficient is <10%.
The analytical range was from 0.01 to 102 ng/mL with an assay
sensitivity of 0.006 ng/mL. The hsCRP was measured by a
latex-enhanced, high-sensitivity CRP immunoassay (Cobas
Integra, Roche Diagnostics GmbH, Mannheim, Germany),
with the reference range from 0 to 5 mg/L. Serum creatinine
was measured by an Olympus AU5400 biochemistry analyzer
(Pureauto S CRE-N method, Tokyo, Japan), with the normal
reference range from 59 to 104 mmol/L. The eGFR (expressed
as ml/min/1.73 m2 of body surface area) was calculated with
the modified GFR estimating equation for the Chinese popu-
lation: 175(serum creatinine in mg/dl)1.234  (age in
years)0.179 (0.79 if woman).9 Biochemical measurements
were made without knowledge of study allocation.
Angiographic and PCI-Related Characteristics
The characteristics of coronary lesions and intraoperative para-
meters of PCI procedures were recorded as well as angio-
graphic complications (artery dissection, perforation, or jailed
side branch with compromised flow) during PCI. Systolic and
diastolic blood pressures were monitored by intra-aortic pres-
sure through guiding catheter without guidewire. Heart rate
was measured by real-time electrocardiographic monitoring
at the time of stent inflation. Incidences of angina (chest pain,
662 Angiology 65(8)

Table 1. Demographic and Baseline Characteristics of Patients in the RIPC Group and the Control Group Before Angiography.

RIPC (n ¼ 102) Control (n ¼ 98) P

Demographics
Age, mean + SD 69.1 + 3.8 68.9 + 2.9 .720
Female, n (%) 34 (33.3) 30 (30.6) .680
Risk factors
BMI, mean + SD, kg/m2 24.2 + 2.2 24.5 + 1.6 .442
LDL-C, mean + SD, mmol/L 2.6 + 0.8 2.6 + 0.5 .342
HDL-C, mean + SD, mmol/L 1.1 + 0.3 1.1 + 0.3 .446
HbA1c, mean + SD 6.2 + 0.8 6.1 + 0.7 .413
Serum creatinine, mmol/L, mean + SD 77.9 + 16.8 74.4 + 17.4 .150
Smoking history, n (%) 54 (52.9) 58 (59.2) .374
Current smoker, n (%) 11 (10.8) 14 (14.3) .454
Hypertension, n (%) 63 (61.8) 64 (65.3) .603
Clinical details
LVEF, % 63.1 + 7.2 64.3 + 5.7 .217
Previous CABG, n (%) 6 (5.9) 3 (3.1) .535
Previous stent implantation, n (%) 20 (19.6) 24 (24.5) .405
Previous MI, n (%) 22 (21.6) 24 (24.5) .624
Time since the latest angina before PCI
<24 h, n (%) 23 (22.5) 21 (21.4) .848
24 h, <72 h, n (%) 17 (16.7) 19 (19.4) .617
72 h, n (%) 62 (60.8) 58 (59.2) .817
Angina CCS grade III/IVIV, n (%) 54 (52.9) 57 (58.2) .458
Medication, n (%)
b-Blockers 82 (80.4) 78 (79.6) .888
ACEI/ARB 77 (75.5) 73 (74.5) .870
Trimetazidine 32 (31.4) 34 (34.7) .618
Tirofiban 45 (44.1) 48 (49.0) .491
Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; CABG, coronary artery bypass graft;
CCS, Canadian Cardiology Society; HbA1c, glycosylated hemoglobin; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol;
LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention; RIPC, remote ischemic preconditioning.

tightness, or similar symptoms of myocardial ischemia) during
the procedure were also recorded.
Statistical Analysis
Continuous variables with normal distribution were presented as
mean + standard deviation and compared using the Student t test.
Continuous variables with abnormal distribution, such as hscTnI
before and at 16 hours after PCI procedure, were presented as
median (quartiles) and compared using the nonparametric
Mann-Whitney test. The hscTnI data were analyzed and classi-
fied by defined MI type 4a and below certain fold the value of the
upper reference limit. Categorical variables were presented as fre-
quencies and percentages. Differences in baseline characteristics
between the groups were compared with chi-square tests or
Fischer exact tests if expected cell frequencies were <5.
All statistical analyses were 2-tailed, and a value of P < .05 was
considered significant. Analysis was performed with SPSS soft-
ware version 17.0 for Windows (SPSS, Inc, Chicago, Illinois).
Results
Patient Baseline Characteristics
A total of 200 eligible patients were finally enrolled and ana-
lyzed. The RIPC was successfully administered to 102 patients
without complication. The 2 groups were well matched in
terms of demographic and baseline characteristics as well as
clinical medication at randomization (Table 1). Nearly, one-
third of the patients were female. More than half of the popu-
lation presented with hypertension.
Angiographic and PCI-Related Characteristics
All patients underwent complete revascularization without
major complications (death or urgent revascularization within
the first 24 hours). Angiographic and PCI-related characteris-
tics, including intraoperative conditions and complication inci-
dences, were all comparable between the 2 groups (Table 2).
High-Sensitivity cTn I
Baseline hscTnI level was comparable between the 2 groups at
randomization. Despite the trend toward decline, the median
hscTnI level in the RIPC group at 16 hours after PCI procedure
was not significantly different from the control group (0.29 vs
0.38 ng/mL, P ¼ .256; Table 3). The incidence of MI type 4a in
the RIPC group was also lower than the control group without
significant difference (52.0 vs 63.3%, P ¼ .106; Table 3), so
was the proportion of patients with hscTnI levels no more than
0.08, 0.12, 0.16, 0.20, 0.40, 0.60, and 0.80 ng/mL, separately.
Xu et al 663

Table 2. Angiographic and PCI-Related Characteristics of Patients in the RIPC Group and the Control Group.

RIPC (n ¼ 102) Control (n ¼ 98) P

Angiographic characteristics
Target vessel, n (%)
Left main 6 (5.9) 5 (5.1) .809
Left anterior descending 35 (34.3) 33 (33.7) .924
Left circumflex 33 (32.4) 32 (32.7) .964
Right coronary artery 37 (36.3) 34 (34.7) .815
Minor vessel 8 (7.8) 7 (7.1) .851
CTO, n (%) 24 (23.5) 29 (29.6) .331
Subtotal occlusion, n (%) 18 (17.6) 14 (14.3) .517
PCI-related characteristics
Predilation, n (%) 98 (96.1) 96 (98.0) .715
Postdilation, n (%) 92 (90.2) 91 (92.9) .500
Number of dilation, mean + SD 8.88 + 3.86 8.51 + 5.62 .587
Duration of dilation(s), mean + SD 48.52 + 16.90 50.32 + 23.50 .537
Pressure of dilation, mean + SD, mm Hg 17.69 + 2.62 17.29 + 3.05 .322
Mean number of stents, mean + SD 2.38 + 0.76 2.33 + 0.61 .567
Mean stent length, mean + SD, mm 24.5 + 3.9 24.5 + 5.4 .931
Contrast, mean + SD, mL 171.8 + 37.9 163.3 + 39.0 .121
SBP, mean + SD, mm Hg 133.8 + 4.2 134.5 + 2.8 .177
DBP, mean + SD, mm Hg 51.6 + 3.2 52.1 + 3.0 .268
Onset of angina, n (%) 55 (53.9) 46 (46.9) .323
HR, mean + SD, beats/min 70.2 + 6.5 71.5 + 7.4 .213
Complications
Dissection, n (%) 7 (6.9) 6 (6.1) .832
Jailed side branch, n (%) 5 (4.9) 6 (6.1) .705
Abbreviations: CTO, chronic total occlusion; DBP, diastolic blood pressure; HR, heart rate; PCI, percutaneous coronary intervention; RIPC, remote ischemic
preconditioning; SBP, systolic blood pressure; SD, standard deviation.

Table 3. Comparisons of Serum High-Sensitivity Cardiac Troponin I and High-Sensitivity C-Reactive Protein at Baseline and 16 hours After
Percutaneous Coronary Intervention.

RIPC (n ¼ 102) Control (n ¼ 98) P

hscTnI, median (IQR), ng/mL

Baseline 0.01 (0.00, 0.02) 0.01 (0.00, 0.03) .797
16 h after PCI 0.29 (0.13, 0.66) 0.38 (0.14, 0.70) .256
hscTnI  0.08 ng/mL, n (%) 11 (10.8) 9 (9.2) .706
hscTnI  0.12 ng/mL, n (%) 26 (25.5) 19 (19.4) .302
hscTnI  0.16 ng/mL, n (%) 38 (37.3) 30 (30.6) .322
hscTnI  0.20 ng/mL, n (%) 49 (48.0) 36 (36.7) .106
hscTnI > 0.20 ng/mL, n (%) 53 (52.0) 62 (63.3) .106
hscTnI  0.40 ng/mL, n (%) 62 (60.8) 51 (52.0) .212
hscTnI  0.60 ng/mL, n (%) 74 (72.5) 62 (63.3) .159
hscTnI  0.80 ng/mL, n (%) 90 (88.2) 83 (84.7) .464
hsCRP, median (IQR), mg/L
Baseline 1.6 (0.8, 3.0) 1.4 (0.7, 3.1) .631
16 h after PCI 6.7 (5.8, 8.2) 6.8 (5.8, 8.2) .774
eGFR, mean + SD, mL/min/1.73 m2
Baseline 99.1 + 20.6 100.8 + 28.2 .626
16 h after PCI 99.3 + 20.4 99.7 + 20.4 .873
Serum creatinine > 25% increase, n (%) 4 (3.9) 3 (3.1) .740
Abbreviations: eGFR, estimated glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein; hscTnI, high-sensitivity cardiac troponin I; IQR, interquartile
range; RIPC, remote ischemic preconditioning; PCI, percutaneous coronary intervention; SD, standard deviation.

High-Sensitivity C-Reactive Protein
Comparable at randomization between the 2 groups, the med-
ian hsCRP level 16 hours after PCI procedure was significantly
elevated in both the groups. The Mann-Whitney test showed
no significant difference in the median hsCRP level between
the 2 groups after PCI (6.7 vs 6.8 mg/L, P ¼ .774; Table 3).
664
Estimated Glomerular Filtration Rate
With comparable baseline renal function and contrast volume,
eGFR was similar between the 2 groups 16 hours after PCI
procedure as well as the proportion of patients with > 25%
increase in serum creatinine (Table 3). None of the patients
had >44.2 mmol/L increase in serum creatinine.
Discussion
We demonstrated that RIPC may attenuate the release of a
myocardial biomarker but failed to show a significant effect
on hscTnI level or MI type 4a incidence after PCI in elderly
patients with CHD having DM undergoing elective DES
implantation. This suggests that age and DM might diminish
the cardioprotective effect of RIPC.
Since the first report of ischemic preconditioning in 1986,10
several studies reported a cardioprotective effect of ischemic
preconditioning and ischemic postconditioning against myo-
cardial IRI in experimental models. However, due to the
involvement of the culprit coronary lesion and the potential
risk of coronary microembolization induced by the 2 strate-
gies,6 the clinical application is limited. After the discovery
of RIPC induced by transient limb ischemia,11 RIPC became
an attractive cardioprotective method that has been investi-
gated by experimental studies and clinical trials.12-16
As far as we could find in the literatures, there were 8 clinical
trials (2 in primary PCI and 6 in elective PCI)15-22 and 3 meta-
analyses23-25 regarding RIPC in PCI. Although the majority of
these studies showed that RIPC was associated with significant
lower biomarkers of myocardial injury in patients undergoing
PCI procedure,16-20 others reached different conclusions.15,21,24
The potential reasons for these conflicting results are as follows.
First, clinical settings in these studies vary, especially the differ-
ences in patient population and procedure. Taking cardiovascular
surgery and PCI altogether, a meta-analysis from 23 clinical trials
in patients undergoing cardiovascular interventions observed a
significant favorable effect of RIPC on incidence of periproce-
dural MIs as well as the release of troponin.23 However, in another
subanalysis of the same 4 studies in PCI, the protective trend of
RIPC failed to reach statistical significance in the overall PCI
analysis. Importantly, subanalysis of the 2 primary PCI trials
showed significant decrease in cardiac biomarkers in patients
receiving RIPC with no presence of heterogeneity, indicating that
the potential for benefit was closely related to the magnitude of
myocardial injury.24 Second, lack of a standard protocol for RIPC
may have contributed to inconsistent findings, such as the differ-
ences of RIPC intervention between studies19,21 especially the
duration and timing of RIPC. Moreover, although unilateral tran-
sient limb ischemia was used in the majority of the elective PCI
trials as well as in ours, bilateral application of ischemia may still
represent as a more powerful intervention. Therefore, nonoptimal
RIPC intervention and low-risk clinical setting were more reason-
able explanations for the negative results in some studies.15,21 The
optimal organ and algorithm of the RIPC intervention in relation
to the severity of myocardial ischemia remain indefinite and
Angiology 65(8)
require further investigation. Third, with small sample sizes in
these studies, false-negative results (type II errors) cannot be
excluded and might account for the negative results. Furthermore,
previous studies have already demonstrated that the effect of car-
dioprotection could be confounded by age, gender, comorbidities,
and drugs, all of which are relevant in patients with CHD. The
reduced efficacy of cardioprotective maneuvers with increased
age is mostly related to the changes in protein expression and cell
signaling important to IRI.26,27 Possibly due to the effect of estro-
gen, women are generally better protected than men from myo-
cardial ischemia and reperfusion.28 In real clinical practice,
many comorbidities including DM, hypertension, and hypercho-
lesterolemia could also impair cardioprotection against IRI and its
signaling. Another major confounder is that by inducing protec-
tion in themselves, many common drugs in patients with CHD, for
example, b-blockers, angiotensin-converting enzyme inhibitors
and angiotensin II receptor antagonists, statins, and antiplatelet
drugs, also impair cardioprotection, making it even more difficult
to identify a new cardioprotective strategy as better than contem-
porary state-of-the-art therapy.29
Due to small sample sizes, the currently available studies
were lack of analyses in the impact of age, comorbidities, and
drugs on the effect of RIPC, which cannot be excluded and
may partly lead to the conflicting findings. Hence, with the
background of previous studies, ours focused on the effect
of RIPC in elderly patients with CHD having DM undergoing
elective DES implantation. With comparable medication and
clinical characteristics between the 2 groups, the present
results revealed that the incident of MI type 4a in this study
population was 57.5%, basically consistent with Luo et al’s
results considering the impact of age and DM. Despite a trend
toward a protective effect, the current study failed to show a
significant reduction in myocardial injury biomarkers level
after PCI procedure. Although contradictory with the previous
conclusions, our results suggest that age and DM could dimin-
ish the protective effect of RIPC, as mentioned earlier.
Until now, the mechanism of the cardioprotective signal
transfer in RIPC from a distant organ is still ambiguous. Ani-
mal studies suggested multifactor theory including neuronal
transmission because cardioprotection evoked by RIPC was
dependent on the activity of the parasympathetic nervous sys-
tem,30,31 especially vagal preganglionic neurons32; humoral
transmission because Shimizu et al found that plasma from
humans or rabbits after RIPC could protect isolated perfused
rabbit hearts and isolated rabbit cardiomyocytes33; reduction
in myocardial inflammatory cytokine production such as
tumor necrosis factor a; activation of the adenosine
triphosphate-sensitive potassium channel7; and modification
of the human plasma proteins involved in acute phase
response signaling as well as physiological molecular and cel-
lular functions.34 A pilot experimental study carried out in
patients who underwent cardiac surgeries demonstrated that
RIPC could regulate hypoxia-inducible factor 1a levels, apop-
tosis, and inflammation in the myocardium of patients who
underwent cardiac surgeries and lead to increased concentrations
of circulating cytokines.35 However, experiment in an aging
Xu et al
diabetic rat model showed that with increased susceptibility to
IRI and impaired Akt signaling as a central role in prosurvival
intracellular pathway due to chronic Akt phosphorylation, cardi-
oprotective effect may no longer be achieved in these hearts.36
Another experiment in mouse models of type 2 DM also
revealed that DM may attenuate the cardioprotective effect of
ischemic postconditioning.37 In our study, with the degenerative
changes by compromised nerve vascular supply and impact of
DM on the peripheral and autonomic nervous systems, elderly
patients with CHD having DM may lose the sensitivity to RIPC
effect, while old age and DM increased the vulnerability to the
effect of IRI. Therefore, the effect of RIPC may have been abro-
gated by these comorbidities. The importance of preserved
neural pathways for the cardioprotective effect of RIPC in dia-
betic patients has also been reported in a recent study38 that may
partly explain the results of the present study.
According to previous studies, RIPC before elective coron-
ary angiography could prevent contrast medium-induced
acute renal injury in patients with impaired renal function.39
However, others reached different conclusion.19 The potential
reasons for our negative result about eGFR include the rela-
tively normal baseline renal function before PCI and nonopti-
mal detection timing, which should be 48 to 72 hours after
PCI procedure instead of 16 hours. Large-scale RCTs are
needed to confirm the potential effect of RIPC on renal injury
during elective PCI procedure.
For humane and economic reasons, our study lacked contin-
uous monitoring of hscTnI levels after PCI. The hscTnI com-
monly begins to rise at 2 to 4 hours after myocardial necrosis
and persists for up to 7 days with peak level at 12 to 24 hours.40
Therefore, instead of intermittent monitoring every 2 to 4
hours, we chose to test the hscTnI level at around 16 hours after
PCI procedure in this study, which was approximately in the
middle of peak release time window and probably closer to the
‘‘actual’’ peak level.
The CHD in the elderly patients with DM is often charac-
terized by multivessel disease, diffuse lesions and stenosis in
distal and small branches, which may need repeated coronary
interventions or CABG surgery. Considering the impact of
recent PCI procedure and other cardiac surgery on myocardial
injury and cardiac biomarkers, we excluded patients under-
going stent implantation or CABG surgery within 6 months.
This selection excludes some high-risk patients and weaken
how representative our study is.
Taking into account the complex situation of coronary
lesion, most patients experienced balloon dilation more than
once and ended up with more than one DES stent in each PCI
procedure, which is actually very common in real-world clini-
cal practice. However, with local preconditioning and postcon-
ditioning from predilation and postdilation of balloon, patients
in the control group might also receive some additional cardi-
oprotection. We compared the characteristics of coronary
lesions and intraoperative parameters of PCI procedures, which
were all similar between the 2 groups. Besides, the final results
of TIMI 3 grade flow could partly guarantee the consistency of
the blood supply after PCI procedure in all patients.
665
Considering that the statistical power might be insufficient,
we intend to expand the sample size and make detailed analyses
regarding the impact of DM on the effect of RIPC in the future.
The RIPC could attenuate the release of myocardial biomar-
kers. However, RIPC failed to show a significant effect on
hscTnI level or MI type 4a incidence after PCI in elderly
patients with CHD having DM undergoing elective DES
implantation. These findings suggest that age and DM might
diminish the cardioprotective effect of RIPC.
Acknowledgments
We thank the study participants and staff at Beijing An Zhen Hospital.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for
the research, authorship and/or publication of this article: This work
was supported by the National Natural Science Foundation of China
(81270285) and Beijing Health Scientific Research Projects (09-13).
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