Clin. Cardiol. 30 (Suppl.
I), I-4–I-9 (2007)
The Pathophysiology of Chronic Ischemic Heart Disease
Carl J. Pepine, M.D., MACC, Wilmer W. Nichols, PH.D.
Division of Cardiovascular Medicine, Gainesville, FL 32610-0277, USA
Summary
With our success in management of acute coronary
syndromes (ACS), aging population and epidemics of
diabetes and obesity, the management of patients with
chronic coronary artery disease is becoming an increas-
ing important part of clinical practice. Although the rates
of death and myocardial infarction (MI) in this group of
patients are not high as a group, a subgroup has very high
risk but many have poor quality of life related to limiting
angina. The purpose of this article is to review the patho-
physiology of the chronic angina syndrome to provide
an improved understanding of the basis for the compre-
hensive management required to yield patient benefits.
Where possible, targets for novel therapeutic approaches
are highlighted.
Key words: atherothrombosis, atheroma, cardiac
ischemia, coronary perfusion, energics, ischemic precon-
ditioning, NSTEMI, STEMI, susceptible myocardium,
unstable angina pectoris, vascular remodeling
Clin. Cardiol. 2007; 30 (Suppl. I): I-4–I-9.
 2007 Wiley Periodicals, Inc.
Introduction
Over the last three decades, considerable advances
have been made in understanding the pathophysi-
ology of ischemic heart disease (IHD), but these
advances have focused on the ACS (e.g., ST-elevation
Address for reprints:
Carl J. Pepine, M.D., MACC
Chief, Cardiovascular Medicine, Gainesville,
FL 32610-0277, USA
e-mail: pepincj@medicine.ufl.edu
Published online in Wiley InterScience
(www.interscience.wiley.com).
DOI:10.1002/clc.20048
 2007 Wiley Periodicals, Inc.
myocardial infarction [STEMI], non-STEMI [NSTEMI],
or unstable angina pectoris [UAP]) and percutaneous
revascularization.1 In our opinion, understanding the
pathophysiology of the chronic coronary syndrome
(CCS) has lagged. This deficit has contributed to the
fact that, until this year, no new treatments for CCS
had been approved for several decades. Recently, new
insights into the mechanisms underlying CCS have led
to the emergence of new anti-ischemic treatments with
novel mechanisms of action.
The purpose of this communication is to critically
review the pathophysiology of chronic IHD. Where pos-
sible, suggestions are provided for new targets that could
lead to novel approaches to management of the growing
number of patients with CCS.
Myocardial Oxygen Supply–demand Balance
General Considerations
Cardiac ischemia results from an imbalance between
myocardial oxygen supply and demand. In this review,
cardiac ischemia is taken as myocellular hypoxia or the
condition resulting when oxygen supplied to a region
of heart muscle is insufficient to meet its needs. The
clinical phenotype accompanying cardiac ischemia has
traditionally been subdivided into the ACS and CCS. A
sudden reduction in coronary flow and hence, myocardial
oxygen supply, is usually the mechanism of ACS. Here,
recent plaque injury (e.g., rupture, erosion, hemorrhage),
often superimposed on thrombosis and/or microem-
bolism, endothelial dysfunction and heightened smooth
muscle reactivity abruptly reduce coronary blood flow
and lead to acute ischemic myocyte injury.1 By contrast,
an abrupt increase in myocardial oxygen demand, in the
setting of limited ability to increase myocardial oxygen
supply, is usually the mechanism of ischemia in the CCS.
Disorders of coagulation, endothelial and/or smooth mus-
cle cell (SMC) function, as well as the myocardium also
play a role.2
But it is the myocardial consequences of the oxygen
supply–demand imbalance that are of central impor-
tance as they determine the clinical outcome in any
 C. J. Pepine and W. W. Nichols: Pathophysiology of chronic IHD
↑ O2 Demand ↓ Myocyte pO2,
↓ ATP and pH
• Heart rate ↑ Glucose oxidation
• Arterial stiffness Ca2+ overload
• Preload ↑Na
• Contractility
• Wall tension
Myocardial dysfunction
(↓ systolic function/
↑ diastolic stiffness)
Sympathetic activation
Electrical instability
Arteriolar dysfunction
Myocardial edema
“Myocardial ischemia begets more ischemia”
FIG. 1 Factors Important in Chronic IHD.
given patient. In patients with CCS, the episode of
ischemia is transient (e.g., reversible) and without evi-
dence of myocyte injury. If the ischemic episode results
in myocyte injury or myonecrosis or the pattern, sever-
ity or inciting factors for ischemia change abruptly, an
ACS has evolved. When this occurs, as stated above, it is
usually related to recent plaque injury. Life-threatening
arrhythmias may occur with either acute or CCS but are
more frequent after reperfusion in ACS (Figure 1).
Specific Considerations
Conditions Transiently Increasing Myocardial Oxygen
Demand: In CCS, cardiac ischemia is usually the result
of an increase in one or more determinants of myocar-
dial oxygen demand. These include increases in heart
rate (HR), left ventricular (LV) loading [afterload (e.g.,
systolic wall stress, arterial stiffness, systolic blood pres-
sure [SBP], etc.) or preload (e.g., diastolic wall stress,
end diastolic pressure and volume, and wall thickness)]
and/or contractility that are necessitated by increases in
physical and/or emotional activity levels. Also impor-
tant in increasing or amplifying the ischemic episode
is the augmentation in these determinants of oxygen
demand that occurs during the actual ischemic episode.
The exact mechanism responsible for this secondary rise
in oxygen demand is not completely known. This sec-
ondary increase occurs in both painful and asymptomatic
ischemic episodes and with painful episodes, it appears
before the actual perception of pain. So while pain/chest
discomfort and related symptoms increase determinants
of oxygen demand, this is not the only mechanism
involved. This secondary increase in myocardial oxy-
gen demand increases the magnitude and/or prolongs the
duration of a given ischemic episode, and therefore has
the potential to worsen the myocardial consequences of
a given ischemic episode.
Suppressing the ability to increase HR, afterload,
preload and/or contractility provides targets for tradi-
tional anti-ischemic treatments like nitrates (BP), beta-
blockers (HR, BP and contractility), and calcium antag-
onists (BP and contractility with all calcium antagonists
plus HR with the nondihydropyridines).
I-5
Fixed O2 Supply
•Negative remodeling
•Flow limiting stenosis
•Endothelial dys/impaired dilation
•Microvascular dysfunction
• Decreased aortic diastolic
pressure (amplitude and duration)
Conditions Limiting Increases in Myocardial Oxygen
Supply: Limitation to increases in myocardial oxygen
supply may result from either coronary vascular or
nonvascular conditions. Among vascular conditions lim-
iting increases in oxygen supply is a reduced ceiling
in myocardial blood flow due to flow-limiting obstruc-
tion(s) with inadequate collateral circulation. Flow-
limiting coronary obstruction(s) may occur at the epicar-
dial (e.g., conduit) vessel level and the microvessel level.
The obstruction may be “dynamic” (e.g., altered smooth
muscle reactivity, shedding of platelet microaggregates,
etc.) or “relatively fixed” (e.g., atheroma, thrombus
and/or embolus). But in most CCS cases components
of both dynamic and fixed obstruction are present. The
ultimate importance of these factors, in terms of limiting
coronary blood flow, is governed by the size of the vessel
lumen available for blood flow. The size of the vascu-
lar lumen or microvessels is determined by the process
termed vascular remodeling (see below).
Coronary Reactivity: Conduit Vessel vs. Microcircu-
lation Dysfunction: Altered coronary reactivity (e.g.,
impaired dilation from endothelial dysfunction, height-
ened smooth muscle activation like spasm, etc.) at both
macro and microvascular levels may contribute to limit
blood flow. Periodic embolization of platelet microag-
gregates from roughened plaque surfaces may also limit
flow at the microvessel level. Accumulating evidence
implicates coronary microcirculation dysfunction in IHD.
This includes: wide variability in effort tolerance over
time; large scatter between stenosis severity and coronary
flow reserve; reduced flow responses in regions perfused
by nonstenotic vessels; wide variability in flow after suc-
cessful stenting; the ∼25% of biomarker-positive ACS
cases with no flow-limiting large vessel stenosis; and
necropsy evidence for microvascular embolization.3
Dilation of coronary resistance arterioles (e.g., nico-
randil and fasudil) represents a potential therapeutic tar-
get for CCS under current investigation.
Disorders of Coronary Endothelium: Risk conditions
(increased SBP, low-density lipoprotein [LDL], obe-
sity, diabetes, aging, etc.) increase oxidant stress within
endothelial cells to impair nitric oxide production, release
and/or activity.4 Resulting endothelial injury unfavorably
Clinical Cardiology DOI:10.1002/clc
I-6 Clin. Cardiol. Vol. 30 (Suppl. I), February 2007
alters all endothelial-mediated activities (e.g., impairs
smooth muscle relaxation, stimulates smooth muscle
growth, disrupts the anticoagulant surface, impairs fibri-
nolysis, etc.) and this is termed endothelial dysfunction.
When this persists it can lead to intimal thickening with
atheroma formation.
Disorders of Vascular Smooth Muscle: Heightened
vascular SMC activity and/or impaired relaxation, either
secondary to endothelial dysfunction or directly due to
SMC dysfunction, occurs in both conduit and resis-
tance vessels (e.g., limited flow reserve). In many
patient groups (e.g., hypertensives, diabetics, elderly,
postmenopausal women, hypercholesterolemics, etc.),
disorders at the resistance vessel (e.g., endothelial and
SMC dysfunction) level may predominate to result in
ischemia and/or amplify ischemia due to other mecha-
nisms (e.g., atheroma obstruction).
Atherothrombosis: Stable vs Vulnerable Plaque:
Atheroma formation, with or without thrombus, accounts
for plaque volume increases with the potential to limit
increases in coronary flow. While vulnerable plaques
(e.g., prone to ruptures, erosions or intraplaque hemor-
rhages with thrombus formation) are considered mech-
anisms of ACS, the pathophysiologic mechanism(s)
responsible for the evolution of CCS are not entirely
clear. But multivessel flow-limiting obstructions are
observed in the majority with CCS with a highly vari-
able degree of lumen compromise (minimum lumen area
and area stenosis). Continuing oxidant stress, interacting
with vascular smooth muscle and inflammatory cells as
well as matrix changes results in “vascular remodeling”,
which determines the size of vessel lumen available for
blood flow with any given lesion.
Vascular Remodeling: Conduit coronary artery lumen
size, the cross-sectional area available for blood flow,
is of fundamental importance in the pathophysiology of
IHD. The process describing the relationship between
changes in atheroma volume, and lumen and external
vessel size is termed vascular remodeling that can be
positive or negative.5 – 7 Continuing oxidant stress, inter-
acting with vascular smooth muscle and inflammatory
cells, as well as matrix changes, results in “vascu-
lar remodeling”, which determines the size of vessel
lumen available for blood flow with any given lesion.5
Recently, differences in vascular remodeling related to
estrogen receptor alpha expression have implicated vari-
ation in SMC phenotype in some of the gender-related
differences in coronary artery disease.8 These SMCs are
directly responsible for extracellular matrix production
and assure the integrity of the artery wall. They may be
decreased, apoptotic, or dysfunctional in terms of synthe-
sis and repair of extracellular matrix, which is destroyed
in vulnerable plaque by macrophages.
Positive (or Compensatory) Remodeling: Coronary
lumen size is usually maintained as atheroma volume
increases by positive or compensatory remodeling (e.g.,
atherosclerotic mass remains external to the lumen).
Plaque deposition (atheroma volume) occurs principally
within the vascular wall, with compensatory enlargement
of the elastic external membrane (positive remodeling)
permitting the external vessel to enlarge to maintain
lumen size.1,7 Compensatory vessel enlargement occurs
more often and to a greater degree in ACS than in
those with CCS.9 In ACS, vulnerable plaque is a more
important pathophysiologic factor than is the degree of
stenosis, whereas in CCS, the degree of stenosis seems
to be a more important factor. Hence loss of positive
remodeling seems to be a central feature in CCS.
Negative (or Loss of Compensatory) Remodeling:
When the compensatory process becomes exhausted, the
atheroma volume begins to compromise the coronary
artery lumen so the cross-sectional area available for
blood flow decreases. As this progresses, the ceiling for
flow increases in response to increasing oxygen demand
and becomes lowered. Eventually, either as a result of
continued increases in atheroma volume or exhaustion
of compensatory enlargement, or more likely both pro-
cesses, the lumen begins to narrow. Luminal narrowing
of ∼70% may limit the ceiling for increases in blood
flow in response to increases in demand, and results in
ischemia. Vessel shrinkage occurs in most patients with
a CCS and a few patients with an ACS presentation.5,9
Furthermore, vessel wall compliance appears greater in
patients with CCS, indicating a relation between vascular
distensibility and positive vessel remodeling.
Although trigger mechanisms for different forms of
remodeling in response to plaque accumulation are
incompletely understood, alterations in flow dynamics
and, in particular, shear stress at the endothelial cell
surface, likely play a role in the vessel response. As
the ability of the vessel to distend is dependent on
intact endothelial function, vessel compliance may influ-
ence the remodeling pattern. Preliminary data show
that eccentric plaques have better remodeling capability,
which may result from better distensibility and preserved
endothelial and vascular smooth muscle function of a
portion of the vessel circumference. Whether these fac-
tors (e.g., remodeling ability, vessel compliance, plaque
topography, etc.) influence the clinical presentation is
unknown. Evidence for a relationship between arterial
remodeling and increased vulnerability to plaque rupture
is accumulating.
Vulnerability to plaque rupture has traditionally been
associated with a decrease in collagen and SMC com-
ponents, especially in the shoulder region with abun-
dant inflammatory cells. Conversely, lack, or exhaustion,
of positive remodeling may signal plaque stability of
chronic stable ischemic syndrome.
Nonvascular: Nonvascular conditions contributing to
ischemia may involve hydraulic conditions determining
coronary blood flow and extravascular compression of
microvessels may result from myocardial hypertrophy or
infiltration (e.g., amyloid, myxedema, granuloma, tumor
cells, etc.).2
Clinical Cardiology DOI:10.1002/clc
 C. J. Pepine and W. W. Nichols: Pathophysiology of chronic IHD
Reduced Diastolic Pressure-time: Oxygen extraction
from blood perfusing myocardium is very high; there-
fore, an increase in myocardial oxygen supply can only
be met by an increase in coronary blood flow. Since
most (∼80%) myocardial blood flow occurs in diastole,
central aortic diastolic pressure amplitude and duration
of diastole are the principal nonvascular determinants of
coronary perfusion. Traditionally, primary concern for
myocardial ischemia is directed toward investigation for
conduit coronary artery obstruction with far less concern
for other factors that may limit coronary blood flow.
But minor changes in diastolic duration may have as
much effect on coronary flow as a severe conduit vessel
stenosis.10
Central Arterial Stiffness: Central arterial stiffness is
increased in atherosclerosis and is an independent pre-
dictor of adverse coronary events.11,12 As central arte-
rial stiffness and wave reflection amplitude increase,
systolic aortic pressure rises, pulse pressure widens,
and myocardial systolic wall stress and oxygen demand
increase while diastolic (e.g., coronary perfusion) pres-
sure decreases.13 Such changes in ventricular/vascular
coupling unbalance the supply/demand ratio and pro-
mote myocardial ischemia and angina. With normal coro-
nary blood vessels, however, blood flow is maintained
over a wide range of perfusion pressures by autoreg-
ulation (e.g., as perfusion pressure declines, vasodi-
lation maintains blood flow).14 Also, in the presence
of hypertrophy of the left ventricle (LV) and other
conditions associated with increased myocardial oxy-
gen demand (e.g., tachycardia), coronary blood flow
increases to meet the demand. But when the LV ejects
into a stiff or noncompliant aorta, systolic pressure and
hence myocardial oxygen demand increase while dias-
tolic pressure decreases but coronary flow increases in
response to increased demand as contractile function is
maintained.15 – 17 But increased aortic stiffness decreases
coronary flow reserve and during increased myocardial
contractility endocardial flow becomes impaired with
subendocardial ischemia.16 These undesirable alterations
are enhanced with a high-grade coronary stenosis or dur-
ing reductions in diastolic BP.18 In stable angina patients
there is an inverse relationship between central aortic
stiffness and coronary flow.19
Other Considerations
Blood
Since the level of hemoglobin is critically important
relative to myocardial oxygen delivery, anemia wors-
ens the consequences of any supply–demand imbal-
ance (e.g., heightened coagulation, platelet activation-
aggregation and adhesion, etc.). Additionally, the level
of hemoglobin has an important independent predictive
value for adverse outcomes in ACS and CCS. A minimal
I-7
reduction in hemoglobin, associated with an increase in
risk (∼20% increase/Gm/dl), is relatively small indicat-
ing that low hemoglobin is likely a marker for other pro-
cesses that influence the course of IHD patients beyond
the lower oxygen carrying capacity.20 This may be linked
to a defect in the supply and function of vascular pre-
cursor cells, which are critically important for repair of
vascular injury over time. Atherosclerosis risk condi-
tions, including aging, limit these circulating precursor
cells. These concepts have stimulated interest in the use
of various growth factors and methods to enhance these
precursor cells as possible therapy for ACS or CCS.
Atherosclerosis risk conditions or other alterations
(e.g., hypercoagulable states) may result in suscepti-
ble blood, a concept put forward to describe blood of
individuals that is prone to thrombosis.2 Blood mark-
ers reflecting hypercoagulability include fibrinogen, DD-
dimer, and factor V Leiden; increased platelet activa-
tion/aggregation (e.g., gene polymorphisms of platelet
glycoproteins IIb/IIIa, Ia/IIa, and Ib/IX); increased coag-
ulation (e.g., clotting factors V, VII, and VIII; von
Willebrand factor; and factor XIII); decreased anti-
coagulation (e.g., proteins S and C, thrombomodulin,
and antithrombin III); decreased endogenous fibrinoly-
sis (e.g., reduced tissue plasminogen activator, increased
type 1 plasminogen activator inhibitor (PAI-1), certain
PAI-1 polymorphisms) and prothrombin mutation (e.g.,
G20210A). Other thrombogenic factors include anticar-
diolipin antibodies, thrombocytosis, sickle cell disease,
polycythemia, diabetes mellitus, hypercholesterolemia,
and hyperhomocysteinemia. Increased viscosity can con-
tribute to hypercoagulability as well as to ischemia.
Transient hypercoagulability is also a consideration with
many traditional risk conditions (e.g., smoking, dehy-
dration, infection, adrenergic surge, cocaine, estrogen
replacement, postprandial state, etc.). Patients with these
conditions may present with ACS, but heightened platelet
activation, adhesion and intracoronary thrombi also may
contribute to limit coronary flow in CCS.21
Myocardium
Susceptible Myocardium: The outcome of a given
ischemic period may be worse in certain individuals with
myocardial disorders and this concept may be termed
susceptible myocardium. Susceptible myocardium is
defined here as myocardium altered so that the patient is
susceptible for near term adverse events (e.g., myocar-
dial injury, infarction, heart failure or arrhythmias). Sus-
ceptible myocardium may be associated with numer-
ous conditions. They include conditions resulting in
altered myocardial function or structure (e.g., ischemia,
scarring, hypertrophy, infiltration, inflammation); altered
sympathetic nervous system activity (e.g., hyperactivity,
impaired reactivity); valvular heart disease (e.g., severe
Clinical Cardiology DOI:10.1002/clc
I-8 Clin. Cardiol. Vol. 30 (Suppl. I), February 2007
LV outflow obstruction as in aortic stenosis or hyper-
trophic cardiomyopathy); some electrophysiologic disor-
ders such as prolonged QT syndromes; commotio cordis
and some others. Several of these conditions may coex-
ist in a given patient. The transient swelling with ion
shifts that accompany ischemia may result in suscep-
tible myocardium. In the latter case, this swelling may
form part of a positive feedback loop whereby “ischemia
begets more ischemia” (Figure 1).
Warm-up Effect and Ischemic Preconditioning: Tran-
sient ischemia triggers both myocardial stunning
(reversible contractile dysfunction despite return of per-
fusion) and ischemic preconditioning (protection against
infarction caused by subsequent coronary occlusion).22
In patients with angina, contractile function may remain
depressed after exercise-induced ischemia (e.g., stun-
ning). Such patients may also develop less evidence of
ischemia during sequential exercise testing (e.g., “warm-
up” phenomenon). The degree of stunning and protection
after exercise is proportional to the severity of dysfunc-
tion during stressful stimuli. So, ischemic precondition-
ing may be considered a negative susceptibility factor.
All preconditioning stimuli may not use the same sig-
naling pathways, so development of tolerance to cardio-
protection by one stimulus may still permit protection
by intervention employing different signaling pathways.
Understanding processes responsible for the warm-up
effect may provide novel therapeutic approaches for CCS
patients.
Energics: Providing adequate energy for the function-
ing of the myocardium is critically important. Myocytes
derive most of their energy via fatty acid metabolism
but this metabolic pathway requires more oxygen than
the glucose pathway to yield the same amount of energy
(ATP). Theoretically, limiting fatty acid oxidation should
promote a shift toward the more oxygen-efficient glucose
pathway. Thus, in a limited flow state (e.g., coronary
stenosis) such a metabolic shift should permit myocytes
to at least maintain energy production. Thus a shift to the
glucose pathway may be considered a negative suscep-
tibility factor. Although this is an attractive therapeutic
target in patients with CCS, it has been difficult to prove
that clinically useful anti-ischemic or antianginal agents
act via this mechanism.
Ion Flux in Ischemia: During severe myocardial
ischemia [K+]e, [Ca2+ ]e and [H+ ]e increase, [Na+ ]e
increases transiently and extracellular osmolality of
ischemic muscle increases as H2 O-shifts from the extra-
cellular to intracellular space. Shrinkage of the extracel-
lular space due to the H2 O-shift and decrease of pHe
increase [Ca2+ ]e contribute to Ca2+ overload during
ischemia. This may cause compression of the vascular
space, that has the potential to further limit O2 supply.
The increase of [K+ ]e is mainly caused by the release of
K+ from the intracellular space. Changes of [K+ ]e and
[K+ ]i cause a decrease of membrane potential to a range
in which slow response potentials and re-entry excita-
tions can occur. The increase of [K+ ]e is a major factor
causing early postischemic arrhythmias.
Late Na+ Current Inhibition: Myocardial ischemia is
associated with ↑ Na+ entry into cardiac cells. Increased
Na+ activates the Na+ /Ca2+ exchanger, causing efflux
of Na+ and influx of Ca2+ . Increased Ca2+ (Ca2+
overload) may cause electrical and mechanical dysfunc-
tion. Increased late INa is an important contributor to
Na+ -dependent Ca2+ overload. If the late Na+ cur-
rent is an important contributor to myocardial ischemia
through Ca2+ overload, then inhibition of this current
(e.g., with ranolazine) would have the potential to blunt
some of the adverse effects of ischemia (e.g., increased
LV end diastolic pressure, reduced developed pressure,
and decreased recovery of ventricular function). The
late Na+ current is conducted by selected channels that
appear critically important in these adverse effects of
ischemia. These channels remain closed and nonconduct-
ing throughout the plateau phase of the action potential.
However, a small proportion of channels either do not
close or they close and then reopen. These channels
allow a sustained current of Na+ to enter. This current is
referred to as the late Na+ current to distinguish it from
the peak current.
Accumulation of Na+ secondary to enhanced late INa
leads to activation of the reverse mode of the Na+ /Ca2+
exchanger, with subsequent efflux of excess Na+ and
influx of Ca2+ so eventually Ca2+ overload of myocytes
results. It is proposed that Na+ -related Ca2+ overload
mediates a vicious cycle of ischemia begetting more
ischemia. Ca2+ overload may result in increased LV dias-
tolic tension. As a result, myocardial O2 consumption
increases and intramural microvessels are compressed,
causing increased O2 demand and decreased O2 supply,
respectively. Positive feedback during ischemia increases
the imbalance between myocardial oxygen supply and
demand. Experimental data suggest that late INa block-
ade blunts postischemic contractile abnormalities and
this could also provide benefit in ischemia. So manip-
ulation of the late INa could also influence myocardial
susceptibility.
Symptoms
Angina pectoris is the classical clinical manifestation
of the chronic ischemic syndromes, but our understand-
ing of the mechanistic details of this disabling symptom
complex remains incomplete almost three centuries after
its description. Estimates indicate that at lease 16 million
Americans have chronic IHD as recurrent angina pec-
toris, but it is also recognized that most of the patients
that we are now seeing are different from those investi-
gated several decades ago before the advent of contem-
porary medical and revascularization. A brief literature
search yields many terms to describe these CCS patients.
But it is unknown if the pathophysiology is the same
Clinical Cardiology DOI:10.1002/clc
 C. J. Pepine and W. W. Nichols: Pathophysiology of chronic IHD
or different in these groups. We also now that most
ischemic episodes are not accompanied by recognizable
symptoms. These unrecognized episodes may be atypical
or completely silent yet portend an impaired prognosis.
So, estimates on the magnitude of this problem represent
only a small fraction of the total burden of chronic IHD
in America. Among chronically symptomatic patients,
symptoms occur late in the cascade of events that char-
acterize the process called myocardial ischemia. These
events include biochemical alterations, impaired ven-
tricular muscle relaxation (e.g., diastolic dysfunction),
increased resistance to ventricular filling, and elevated
ventricular filling pressure, impaired contraction (e.g.,
systolic dysfunction), and electrocardiographic changes
(principally involving the ST segment). Approximately,
one-half of patients with stable or unstable angina also
have asymptomatic episodes.
Summary and Conclusions
The material reviewed is important to better under-
standing of the complexities of chronic ischemic syn-
dromes and provide direction for new management
strategies.
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