Intern Emerg Med
DOI 10.1007/s11739-016-1527-2
IM - ORIGINAL
Risk factors for silent myocardial ischemia in patients
with well-controlled essential hypertension
Domenico Rendina1,2 • Renato Ippolito1 • Gianpaolo De Filippo1,3 •
Riccardo Muscariello1 • Daniela De Palma1 • Silvana De Bonis2,4 •
Michele Schiano di Cola1 • Domenico Benvenuto2 • Maurizio Galderisi5
Pasquale Strazzullo1 • Ferruccio Galletti1
Received: 4 April 2016 / Accepted: 18 August 2016
Ó SIMI 2016
Abstract Silent myocardial ischemia (SMI) is frequently
observed in patients with essential hypertension (EH). The
major risk factor for SMI is uncontrolled blood pressure
(BP), but SMI is also observed in patients with well-con-
trolled BP. To evaluate the prevalence of SMI and the
factors associated with SMI in EH patients with well-
controlled BP. The medical records of 859 EH patients who
underwent simultaneous 24-h ambulatory blood pressure
monitoring (ABPM) and 24-h ambulatory electrocardio-
gram recording (AECG) were retrospectively evaluated.
Each SMI episode was characterized by: (a) ST segment
depression C0.5 mm; (b) duration of ST segment depres-
sion [60 s; and (c) reversibility of the ST segment
depression. Overall 126 EH patients (14.7 %) had at least
one episode of SMI. The SMI events were more frequent
among patients with poorly controlled compared to those
with well-controlled BP [86/479 (17.95 %) vs. 40/380
(10.52 %), p \ 0.01]. Among EH patients with well-
Electronic supplementary material The online version of this
article (doi:10.1007/s11739-016-1527-2) contains supplementary
material, which is available to authorized users.
& Domenico Rendina
domenico.rendina@unina.it
1
Department of Clinical Medicine and Surgery, Federico II
University, Via Pansini 5, 80131 Naples, Italy
2
Spinelli Hospital, Belvedere Marittimo, Cosenza, Italy
3
Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre,
Unité Diabète-Hypertension-Nutrition de l’Adolescent,
Le Kremlin-Bicêtre, France
4
Cardiology Unit, Ferrari Hospital, Castrovillari, Cosenza,
Italy
5
Department of Advanced Clinical Sciences, Federico II
University, Naples, Italy
•
controlled BP, current and past smoking as well as the
presence of an additional metabolic syndrome (MetS)
constitutive element (obesity, impaired fasting glucose
level or dyslipidemia) were significantly associated with
the occurrence of SMI. In all EH patients with well-con-
trolled BP and AECG evidence of SMI, there were one or
more coronary artery stenotic lesions greater than 50 %
found at coronary angiography. In EH patients who are
current smokers, or have one or more additional compo-
nents of a MetS there is markedly reduced benefit associ-
ated with good BP control with regard to the occurrence of
myocardial ischemia: in this patient category, an AECG
may help detect this condition.
Keywords Asymptomatic coronary artery disease
Blood
pressure control
24-h ambulatory blood pressure
monitoring
24-h ambulatory electrocardiogram
Introduction
Silent myocardial ischemia (SMI) is defined as the objec-
tive evidence of myocardial ischemia in the absence of
clinical manifestations [1]. This phenomenon is related to
the combination of an increasing demand for oxygen and
an altered supply of it secondary to abnormal microvas-
cular or endothelial responses [1–4]. In the Framingham
study, the SMI prevalence in adult men and women is
approximately 10 % based on an exercise electrocardio-
gram (ECG), and as much as 25 % based on a 24-h
ambulatory electrocardiogram (AECG) [5, 6]. In patients
with coronary artery disease (CAD), the SMI prevalence
during AECG monitoring ranges from 50 to 80 % in dif-
ferent studies [7, 8], the main factors triggering ischemia
being a high systolic blood pressure (SBP) and an elevated
123

heart rate [9]. In patients with hypertension, the prevalence
of SMI varies from 15 to 80 % in different studies [10–14],
the major risk factor for SMI being poor blood pressure
(BP) control. SMI is also observed in patients with well-
controlled BP [10, 15], however, to our knowledge, no
study has assessed the factors associated with SMI occur-
rence and its clinical significance in patients with well-
controlled essential hypertension (EH). To this end, we
examined the medical records of a large consecutive series
of patients hospitalized at the Spinelli Hospital (Belvedere
Marittimo, Italy). The Spinelli Hospital is a primary care
center mainly focused on internal medicine, and has been
involved in a non-profit epidemiological research project in
collaboration with the Department of Clinical Medicine
and Surgery of the Federico II University (Naples, Italy)
aiming at the evaluation of metabolic syndrome (MetS) co-
morbidities in elderly patients [16, 17].
Patients and methods
Study population
From all the medical records of the Caucasian individuals
hospitalized at the Spinelli Hospital from January 1st 2005
to December 31st 2008, we selected those of in-patients
discharged with a diagnosis of EH (Additional Table 1) in
whom (1) the EH diagnostic evaluation and clinical man-
agement had been performed according to current pub-
lished guidelines at the time of clinical evaluation [18–20]
and (2) both an AECG and an 24-h ambulatory blood
pressure monitoring (ABPM) had been performed
simultaneously.
Exclusion criteria
Predefined exclusion criteria were: (a) personal history of
CAD or pacemaker or cardioverter defibrillator implanta-
tion; (b) modification of the current antihypertensive drug
therapy in the last 30 days; (c) secondary hypertension
[18–20]; (d) clinical or subclinical thyroid dysfunction
[16]; (e) ECG evidence of pre-excitation syndrome, atrial
fibrillation, atrioventricular block, non-specific ST-T
changes or left ventricular (LV) hypertrophy [21–23];
(f) abnormal LV global systolic function, LV regional
dyssynergy, valvular heart disease of medium or severe
grade, pericarditis, or primary cardiomyopathies at 2D
echocardiography [24]; (g) serum levels of troponin
I [ 0.03 lg/L [25] or serum electrolyte abnormalities at in-
hospital admission [26]; (h) estimated glomerular filtration
rate \60 mL/min/1.73 m2 [16]; (i) major debilitating
physical illnesses; (j) pregnancy; (k) incomplete data
collection.
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Intern Emerg Med
All the clinical procedures were conducted in accor-
dance with the Declaration of Helsinki. The study protocol
has been approved by the Federico II University Hospital
Ethical Committee.
Patients’ medical evaluation
BP was measured on at least 2 days during hospitalization
with the patient seated, and the average of the last two
measurements was used for the analysis. According to
current guidelines [27], hypertension was considered well-
controlled if BP was \140/85 and \140/90 mmHg in
patients with or without diabetes mellitus, respectively. All
the selected patients had a 12-lead ECG, a transthoracic
echocardiogram and an ABPM performed to estimate their
global cardiovascular risk, and to evaluate the appropri-
ateness and effectiveness of ongoing antihypertensive
therapy. The ABPM was performed with a Spacelabs
recorder type 90207 (Spacelabs Healthcare Inc., Issaquah,
USA). The instrument was programmed to provide a BP
measurement every 15 min from 07:00 to 23:00 and every
30 min from 23:00 to 07:00. Only the ABPM records with
at least 70 % reliable daytime and nighttime BP mea-
surements were considered for the analysis. The following
ABPM parameters were recorded: (a) 24-h mean SBP and
DBP, (b) daytime mean SBP and DBP, (c) nighttime mean
SBP and DBP, and (d) awakening mean SBP and DBP. The
pulse pressure (PP), mean arterial pressure (MAP), and
double product (DP) were calculated as described else-
where [28, 29]. The ABPM records were independently
reviewed by four operators (RI, MSdC, RM, and DDP),
who were not aware of the AECG data. In case of dis-
crepancies, a discussion with another author was planned,
if necessary.
AECG
The AECG monitoring was prompted by one or more of
the symptoms/clinical signs reported in Additional Table 2
[30]. The AECGs were performed with a Syneflash digital
recorder (Ela Medical, Le Plessis-Robinson, France). The
digital analysis was performed using a Medical SyneTec
scanner (software 2.00, release 2, Ela Medical, Le Plessis-
Robinson, France). The system acquisition frequency and
the sensitivity threshold were 200 Hz and 10 mV, respec-
tively. Modified V5 and V1 leads were obtained (CM5 and
CM1). Only AECGs with at least 20 h of reliable records
were considered for the study. The diagnosis of SMI was
limited to the following conditions: (a) at least 0.5 mm ST
segment depression; (b) duration of ST segment depression
[60 s; and (c) reversibility of ST segment depression.
Using these criteria, the AECG is the method of choice for
SMI detection with a specificity [95 % [3, 31, 32].
Intern Emerg Med
Repeated episodes of SMI must be separated by an interval
of at least 1 min, during which the ST segment returns to
baseline. The baseline ST level was defined as the pre-
dominant ST level throughout the registration. The AECG
records were independently analyzed by DR, SDB, and
DB, who were not aware of the ABPM data. In case of
discrepancies, a discussion with another author was plan-
ned, if necessary. Nevertheless, for both the ABPM and the
AECG evaluation, there was no case of discrepancy
between observers.
All the biochemical and anthropometric parameters
were evaluated as previously described [16, 17].
The diagnosis of MetS was performed according to
published guidelines, adapted to Caucasian subjects [33].
Additional heart tests
According to the protocols of Spinelli Hospital, a
Treadmill Stress Test (TST), performed and analyzed
according to standardized criteria [34], has been proposed
to each EH patient with AECG evidence of SMI. In
patients unable to perform or to complete the TST and in
those with positive TST, a coronary angiography was
performed. The two-dimensional Quantitative Coronary
Algorithm was used for CAD evaluation and classifica-
tion [35].
Statistical analysis
The statistical analyses were performed using the SPSS
(Statistical Package for Social Science) software version 15
(SPSS Inc., Chicago, IL). The results were expressed as
mean ± standard deviation for continuous variables and as
absolute (percentage) values for discrete variables.
Contingency tables and Chi-square tests were used for
univariate analyses. Analysis of variance (with Bonferroni
correction for multiple comparisons) was used to test for
between-group differences in parametric variables. Linear
regression and Pearson’s correlation were used to test the
strength of possible associations between any two vari-
ables. Logistic regression analysis was used to evaluate the
association of a given variable with SMI occurrence
accounting for potential confounders. A value of p \ 0.05
was accepted as significant.
Results
After considering the exclusion criteria, the clinical records
of 859 EH patients were selected and examined: 380 had
well-controlled BP, whereas 479 had poorly controlled BP
(Table 1). The patients with well-controlled BP had a
lower BMI and a lower prevalence of three MetS
constitutive traits other than high BP (high waist circum-
ference, low serum HDL-cholesterol or high serum
triglycerides) than those with poor BP control. The ABPM
parameters were all lower in the patients with good BP
control than in those with poorly controlled EH. There was
no significant difference in the prevalence of the use of any
class of antihypertensive drugs between the two patient
groups (Additional Table 3).
SMI occurrence
Overall, 235 episodes of SMI were recorded. As expected
[36–38], a higher frequency of events was seen in the early
morning. One-hundred-twenty six EH patients (14.7 %)
showed at least one episode of SMI: forty of these (32.7 %)
had good BP control. EH patients with good BP control
showed a significantly lower risk of SMI occurrence
compared to patients with poor BP control [40/380,
10.52 % vs. 86/479, 17.95 %, p = 0.003, odds ratio (OR)
0.59, 95 % confidence intervals (CI) 0.41–0.83]. In addi-
tion, a lower average number of SMI events was detected
among well-controlled patients compared with those with
poor BP control (1.4 ± 0.4 vs. 2.1 ± 0.7, p = 0.02). As
shown in Fig. 1, at any hour of the day there are a lower
number of SMI events in patients in good BP control than
in poorly controlled patients.
SMI in patients with well-controlled EH
The clinical characteristics of patients with well-controlled
hypertension, classified according to the occurrence or
absence of at least one SMI event during AECG (SMI
group and no-SMI group, respectively), are shown in
Table 2. ABPM and AECG parameters are not different
between the two groups (Additional Table 4). There is a
higher prevalence of current and past smokers as well as of
patients with at least one additional MetS constitutive trait
(other than high BP) in the SMI group compared with the
no-SMI group (p \ 0.02 in all cases). These results were
confirmed at multivariable analysis. In particular, current
and past smokers have a higher probability of SMI
occurrence compared to those who have never smoked.
This difference remains after adjustment for age, BMI,
gender, biochemical and ABPM parameters, and occur-
rence of an additional constitutive MetS trait (OR 2.06,
95 % CI 1.64–2.48; and OR 1.97, 95 % CI 1.37–2.46 for
current and past smokers, respectively). Patients with an
additional constitutive MetS trait also have a higher prob-
ability of SMI occurrence compared to those without
additional MetS traits, even after adjustment for age, BMI,
gender, biochemical and ABPM parameters, and smoking
habits (OR 2.01, 95 % CI 1.65–2.37). No difference is
observed in the prevalence of the use of any class of
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 Intern Emerg Med

Table 1 Clinical characteristics

Good blood pressure control p
of patients with essential
hypertension according to blood Yes No
pressure control
Number (%) 380 (44.23) 479 (55.76)
Age (years) 66.9 ± 11.4 68.3 ± 9.0 0.69
Male (n; %):female (n; %) 178; 46.84:202; 53.16 203; 42.37:276; 57.62 0.21
Body mass index (kg/m2) 25.8 ± 3.7 27.5 ± 3.2 0.02
Serum creatinine (lmol/L) 83.2 ± 16.7 83.8 ± 16.5 0.71
Serum sodium (mmol/L) 140.0 ± 1.9 139.9 ± 2.3 0.79
Serum potassium (mmol/L) 4.1 ± 0.3 4.1 ± 0.3 0.31
Serum chloride (mmol/L) 99.1 ± 2.1 98.7 ± 3.3 0.53
Serum calcium (mmol/L) 2.39 ± 0.01 2.40 ± 0.02 0.39
Serum phosphate (mmol/L) 1.11 ± 0.14 1.11 ± 0.15 0.34
24 h systolic BP (mmHg) 117.6 ± 7.9 133.9 ± 11.9 \0.01
24 h diastolic BP (mmHg) 70.5 ± 5.2 82.8 ± 7.9 \0.01
Daytime systolic BP (mmHg) 119.9 ± 8.9 135.3 ± 12.1 \0.01
Daytime diastolic BP (mmHg) 72.1 ± 6.1 84.0 ± 8.7 \0.01
Nighttime systolic BP (mmHg) 106.9 ± 7. 5 130.5 ± 14.3 \0.01
Nighttime diastolic BP (mmHg) 63.6 ± 4.9 77.1 ± 8.2 \0.01
Awakening systolic BP (mmHg) 125.8 ± 10.7 135.8 ± 15.9 \0.01
Awakening diastolic BP (mmHg) 75.3 ± 8.4 88.0 ± 9.8 \0.01
24-h heart rate (bpm) 69.5 ± 7.4 69.9 ± 8.8 0.88
Daytime heart rate (bpm) 72.1 ± 7.9 72.2 ± 9.5 0.97
Nighttime heart rate (bpm) 64.0 ± 7.7 64.4 ± 8.9 0.67
Current smoker (n; %) 115; 30.3 177; 36.9 0.08
Past smoker (n; %) 46; 12.1 61; 12.7
Never smoker (n; %) 219; 57.6 241; 50.3
High waist circumference (n; %) 114; 30.0 189; 39.5 \0.01
Abnormal glucose metabolism (n; %) 41; 10.8 73; 15.2 0.07
Low serum HDL-cholesterol (n; %) 65; 17.1 121; 25.3 \0.01
High serum triglycerides (n; %) 57; 15.0 102; 21.3 0.02
SMI (n; %) 40; 10.5 86; 17.9 \0.01
Data are expressed as mean ± standard deviation and as number (percentage) for continuous and discrete
variables, respectively. BP blood pressure, Bpm beats per minute, HDL high density lipoprotein, SMI silent
myocardial ischemia. BP control was defined good if all BP measurements obtained during the hospital-
ization were\140/85 and\140/90 mmHg in patients with and without diabetes mellitus, respectively [27].
Waist circumference, glucose metabolism, and levels of HDL-cholesterol and triglycerides were evaluated
according to criteria of the American Heart Association/National Heart, Lung, and Blood Institute for
diagnosis of metabolic syndrome in Caucasian subjects: High waist circumference = waist circumference
C102 cm in men and C88 cm in women; Abnormal glucose metabolism = fasting serum glucose
C5.6 mmol/L or drug treatment for elevated blood glucose; High serum triglycerides = serum triglycerides
[1.7 mmol/L or current drug treatment for hypertriglyceridemia; Low serum HDL-cholesterol = HDL-
cholesterol \1.03 mmol/L in men and \1.3 mmol/L in women or drug treatment for low HDL-cholesterol
[33]

antihypertensive drugs between the SMI and no-SMI
groups (d.n.s).
Among EH patients with good BP control, 151
(39.73 %) were never smokers and had no additional MetS
traits, 68 (17.89 %) were never smokers but had one or
more additional MetS traits, 56 (14.73 %) were current or
past smokers without additional MetS traits and 105
(27.63 %) were current or past smokers and also had
additional MetS traits. As reported in Fig. 2a, only 3
(1.99 %) well-controlled EH patients in the first category
(never smokers without additional MetS traits) suffered a
SMI event. In the remaining three categories, the preva-
lence of SMI was much higher (13.23, 16.07 and 18.09 %,
respectively, for never smokers with at least one additional
MetS traits, smokers without additional MetS traits, and
smokers with at least one additional MetS traits). As

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three categories of well-controlled EH patients have a SMI

Fig. 1 24 h distribution of SMI events in EH patients with good or
poor BP control. The figure shows the total number of SMI events
occurred at each hour of the day and their distribution in patients with
good and poor BP control. BP control was defined good if all BP
measurements obtained during the hospitalization were \140/
90 mmHg (\140/85 mmHg in patients with diabetes mellitus). SMI
silent myocardial ischemia, EH essential hypertension, BP blood
pressure
reported in Fig. 2b, only well-controlled EH patients, never
smokers, and with no additional MetS traits have a lower
SMI risk compared to poorly controlled EH patients (OR
0.11, 95 % CI 0.04–0.35). On the contrary, the remaining
risk not different from that of poorly controlled EH
patients.
As abrupt and significant changes in BP and heart rate
(HR) may induce SMI (1), we compared the values of SBP,
DBP, HR, and some derived indices (i.e., PP, MAP, and
DP) recorded in each patient immediately before a SMI
event with the respective values recorded in the no-SMI
group at the same hour of the day. As reported in Fig. 3, in
each case and for each parameter, the values recorded
immediately before the SMI event fall within two standard
deviations (SD) above or below the mean value recorded in
the no-SMI group at the same hour of the day. For SBP and
DBP, in eight patients, both the values recorded immedi-
ately before the SMI event are higher than the mean plus 1
SD of the no-SMI group. In one patient in the SMI group
this is true only for SBP. For the HR, in 15 patients, the HR
values recorded immediately before the SMI event are
between 1 and 2 SD of the HR value recorded in the no-
SMI group. Regarding the derived indices, the values
recorded immediately before a SMI event falls within one
SD above or below the respective mean values recorded in
the no-SMI group at the same hour of the day in the large
majority of cases (for 37/40, 36/40, and 35/40 for PP,
MAP, and DP, respectively).

Table 2 Clinical characteristics

Patients with good blood pressure control p
of patients with essential
hypertension and good blood With SMI Without SMI
pressure control classified
according to the occurrence of Number (%) 40 (10.5) 340 (89.5)
silent myocardial ischemia Age (years) 68.4 ± 12.7 66.7 ± 11.4 0.47
during 24-h ambulatory
Male (n; %):female (n; %) 23; 57.5:17; 42.5 155; 45.6:185; 54.4 0.18
electrocardiogram
Body mass index (kg/m2) 26.6 ± 4.0 25.7 ± 3.8 0.37
Serum creatinine (lmol/L) 82.2 ± 19.4 83.3 ± 16.7 0.57
Serum sodium (mmol/L) 139.7 ± 2.1 140.0 ± 1.9 0.72
Serum potassium (mmol/L) 4.2 ± 0.5 4.1 ± 0.3 0.36
Serum chloride (mmol/L) 98.2 ± 2.4 99.2 ± 2.2 0.84
Serum calcium (mmol/L) 2.35 ± 0.12 2.39 ± 0.09 0.31
Serum phosphate (mmol/L) 1.08 ± 0.17 1.11 ± 0.13 0.64
Current smoker (n; %) 20; 50 95; 27.9 0.01
Past smoker (n; %) 8; 20 38; 11.2
Never smoker (n; %) 12; 30 207; 60.9
High waist circumference (n; %) 17; 42.5 97; 28.5 0.10
Abnormal glucose metabolism (n; %) 8; 20 33; 9.7 0.06
Low HDL-cholesterol (n; %) 11; 27.5 54; 15.9 0.08
High triglycerides (n; %) 10; 25 47; 13.8 0.10
One additional MetS trait (n; %) 28; 70 145; 42.6 \0.01
Data are expressed as mean ± standard deviation and as number (percentage) for continuous and discrete
variables, respectively. Blood pressure (BP) control was defined good if all BP measurements obtained
during the hospitalization were \140/85 and \140/90 mmHg in patients with and without diabetes mel-
litus, respectively [27]. Waist circumference, glucose metabolism, and levels of HDL-cholesterol and
triglycerides were evaluated according to published criteria [33]. Bpm beats per minute, HDL high density
lipoprotein, SMI silent myocardial ischemia

123

Fig. 2 Prevalence (a) and relative risk (b) of SMI in EH patient with
good BP control compared to EH patients without good BP control.
EH patients with good BP control have been classified into four
categories according to smoking habits (smokers vs. no smokers) and
the occurrence of at least one additional MetS trait other than
hypertension (patients with or without at least one additional MetS
trait). The four categories of EH patients with good BP control were
compared to patients with poor BP control. MetS – Smoke - = EH
patient without additional MetS trait never smoker. MetS ? Smoke -
= EH patient with at least one additional MetS trait never smoker.
MetS – Smoke ? = EH patient without additional MetS trait smoker.
MetS ? Smoke ? = EH patient with at least one additional MetS trait
smoker. SMI silent myocardial ischemia, EH essential hypertension,
BP blood pressure
Only 21 of 40 patients with well-controlled EH and
AECG evidence of SMI were able to complete a standard
TST: in all these cases, the test was positive for inducible
myocardial ischemia. Thus, all 40 patients with well-con-
trolled EH and AECG evidence of SMI underwent coro-
nary angiography, which showed in all cases the
occurrence of a stenosis [50 % in at least one coronary
artery: in 18 patients the stenosis was [75 %. Twelve
patients were treated with percutaneous coronary angio-
plasty and six underwent coronary artery bypass surgery.
Discussion
Main study findings
Previous observations indicate poor BP control as a major
risk factor for SMI in hypertensive patients [7–14, 39]. In
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Intern Emerg Med
Fig. 3 SBP, DBP, HR, PP, MAP, and DP values recorded in each EH
patient with good BP control before SMI events. The SBP, DBP, HR,
PP, MAP, and DP values recorded before each SMI event in each EH
patient with good BP control were compared with the respective
values recorded in EH patients with good BP control and without SMI
at the same hour of the day and expressed as mean values ± SD. SD
standard deviation, SMI silent myocardial ischemia, SBP systolic
blood pressure, DBP diastolic blood pressure, HR heart rate, PP pulse
pressure, MAP mean arterial pressure, DP double product. PP, MAP,
and DP values were calculated as described elsewhere [28, 29]
addition, the global cardiometabolic risk profile in patients
with hypertension disease (GOOD) survey shows that BP
control is significantly worse in hypertensive patients with
MetS, in particular in those with visceral obesity and
dyslipidemia, than in patients with EH only [40]. The
results of our study are consistent with these notions but we
also find that a percentage of EH patients with well-con-
trolled BP (10.5 %) have one or more SMI episodes at
AECG. The factors significantly associated with SMI
occurrence in this category of patients are: previous or
current smoking and the presence of one or more MetS
constitutive trait(s): the coexistence of these factors
markedly or completely blunts the benefit derived from
good BP control. The SMI episodes observed in our study
show a circadian variation with clustering around morning
awakening. This circadian distribution is very similar to
that already described in EH patients [10] and in patients
with CAD [41], and mimic the circadian variations of
myocardial infarction and sudden cardiac death [42]. A
similar rhythm has also been found in several physiological
processes, which could trigger the onset of cardiovascular
events. The blood fibrinolytic activity is lower in the early
morning hours whereas platelet aggregation and circulating
levels of epinephrine, norepinephrine, cortisol, and renin
are higher [43]. An increased alpha-sympathetic vasocon-
strictor activity has also been described at morning awak-
ening in a number of CV conditions including EH [44]. On
the other hand, thanks to the simultaneous BP and ECG
recording, we can reasonably exclude that abrupt and sig-
nificant changes in BP and in HR come before SMI
Intern Emerg Med

occurrence in the large majority of patients. However, with false-positive ST segment responses to TST [48]. It is
regard to the possible SMI triggering mechanism in desirable in the future to use newer technologies for con-
patients with well-controlled BP, it should be noted that tinuous monitoring, such as measurement of intramyocar-
although heart rate, pulse pressure, blood pressure, and dial pH, temperature, and other local metabolic parameters
double product registered just before the ischemic episode [49], which can ensure better diagnostic performances.
fall within a respective mean ± 1 SD, the large majority of
these values are higher respect to the mean (Fig. 3).
Clinical relevance
Accordingly, it could be one of the triggering SMI mech-
anisms. These associations are observed in patients with no
Our novel findings of a high prevalence of SMI in well-
known personal history of CAD and no clinical evidence of
controlled hypertensive patients and its association with
myocardial ischemia. We also show that, in all patients
smoking and MetS biochemical traits are highly relevant
with well-controlled BP having SMI at AECG, coronary
on clinical and epidemiological grounds given the very
angiography shows one or more stenotic lesions greater
high prevalence of hypertension in the elderly population
than 50 %, requiring percutaneous coronary angioplasty or
and its major role in causing cardiovascular disability and
coronary artery bypass surgery in a substantial proportion
death. The adopted exclusion criteria allow us to consider
of patients.
the coronary stenosis as the cause of observed ST-T
changes. The availability of a practical test for detection of
Study strengths and limitations
SMI in hypertensive patients is most important given that
at least two-thirds of ischemic ST-depression episodes in
While most previous clinical studies focusing on hyper-
these patients occur in the absence of cardiac symptoms
tension and SMI involve patients attending third level
[1–4]. Several studies have demonstrated the ability of
Hypertension Centers [10, 39, 45–47], the present obser-
AECG to detect SMI in various patient categories
vations were made in a general medicine hospital setting:
[2, 3, 10, 31, 32, 39, 45–47, 50], nevertheless, to our
thus our study results refer to a larger target population.
knowledge, no one has focused on the possible role of
Other strengths of our study are: (1) the a priori inclusion
AECG in detecting SMI in hypertensive patients with well-
of all individuals hospitalized over the selected observation
controlled BP.
period; (2) the extensive patient clinical evaluation that
Notwithstanding the limitation given by the retrospec-
allows the exclusion from the analysis of all individuals
tive nature of our study results, we believe that they
with clinical features susceptible to bias our statistical
strongly suggest the opportunity for an additional diag-
analysis; (3) the exclusion of patients with overt clinical
nostic evaluation such as AECG or an ECG stress test in
evidence of myocardial ischemia as indicated by altered
the clinical management of patients with well-controlled
troponin levels or suggestive echocardiographic findings at
EH who are or have been smokers or have one or more
hospitalization; (4) the careful standardization of the bio-
constitutive MetS biochemical traits (i.e., obesity or car-
chemical and cardiological investigation methods applied
bohydrate or lipid metabolic disorders) in addition to high
(the Spinelli Hospital having been awarded the UNI EN
BP, as recently proposed for diabetic patients [51, 52]. The
ISO 9001:2000 quality certificate for provision of diag-
study results also identify a possible cause of the residual
nostic and therapeutic healthcare services); (5) the simul-
risk in a subset of treated EH patients with good BP control
taneous recording of ABPM and AECG.
[53, 54].
This study has some limitations. The study participants
had an elevated mean age and a high prevalence of car-
diovascular risk factors: as a consequence, our findings can
Conclusions
be generalized only to a population of elderly hypertensive
patients at high cardiovascular risk. It is also a retrospec-
SMI is highly prevalent in EH patients with well-controlled
tive study, and thus a causal relationship between MetS
BP and is most often associated with current or previous
constitutive trait or smoking and SMI occurrence cannot be
smoking or with MetS constitutive traits: these results
conclusively established. Despite the fact that an AECG
suggest the usefulness of adding AECG or an ECG stress
and standard TST are the most readily available and fre-
test to the routine evaluation of this category of patients to
quently used tests to identify SMI in clinical practice, they
improve our assessment of the global cardiovascular risk.
have some structural limitations. In particular, AECG may
be difficult to interpret because of a large number of arti- Acknowledgments The authors are grateful to the owners and the
facts [30]. A wide variety of miscellaneous situations, medical director of the Spinelli Hospital who granted the free use of
including electrolyte abnormalities, drug use, and repolar- the facilities and services required to conduct the study. This study
was supported by unrestricted grants from Stroder/Società Italiana
ization abnormalities on the rest ECG, are associated with

123

dell’Osteoporosi del Metabolismo Minerale e delle Malattie dello
Scheletro (to DR) and Società Italiana Medicina Interna (to RI).
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Statement of human and animal rights All the clinical procedures
were conducted in accordance with the Declaration of Helsinki on
human experimentation. The study protocol has been approved by the
Federico II University Hospital Ethical Committee.
Informed consent Informed consent was obtained from all individ-
ual participants included in the study.
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