neutrophil to lymphocyte ratio
TRANSCRIPT
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CHAPTER - I
INTRODUCTION
Myocardial Infarction is a common condition and frequently encountered in
emergency departments. The Patients are normally assessed by diagnostic flow
charts including clinical and electrocardiographic data, as well as myocardial
necrosis markers i.e. CK-MB (creatine phosphokinase) (Zazula, A D et al 2008).
Coronary heart disease is associated with the multifactorial condition
atherosclerosis. (I.J.Kullo 2010). Atherogenesis is an active inflammatory process
triggered by endothelial injury. (S. Anwaruddin et al 2007). Since it is an
inflammatory disease, some inflammatory markers have been proposed /
suggested for evaluation of cardiovascular risk. (LI Dong-bao et al 2009). Recent
data suggests that some specific subtypes of leukocytes and Neutrophil /
Lymphocyte (N/L) ratio have higher predictive value in assessing the
cardiovascular risk (LI Dong–bao, et al, 2009).. In patients prescribed angioplasty
N/L ratio is independent predictor of long term mortality (Duffy BK, et al, 2006).
Neutrophil / Lymphocyte (N/L) ratio act as a better acceptable marker for acute
coronary syndrome; such possibility is based on two distinctive mechanisms. (G.
Ndrepepa et al 2009). Undoubtedly Neutrophilia would reflect systemic
inflammatory status and as a consequence of high cardiovascular risk and
lymphopenia would reflect the acute stress presented by MI. (G. Ndrepepa et al
2009). Recent studies have demonstrated that evaluation of white blood cell
(WBC) count during acute myocardial infarction is associated with reduced
epicardial blood flow in myocardial reperfusion and adverse outcome. (Coller B.
S, 2005). Chatzizisis Y et al in 2007 have suggested that Atherosclerosis is
characterized by intimal lesions called atheromas that protrude into vessel
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lumen .Besides mechanically obstructing blood flow, atherosclerotic plaques can
rupture, leading to catastrophic vessel thrombosis (Marijn C et al 2007). Because
coronary artery disease is an important manifestation of MI, epidemiologic data
related to atherosclerosis mortality typically reflect deaths caused by Myocardial
Infarction (Braunwald E et al 2008). Inflammatory cells and pathways contribute
to the initiation, progression, and complications of atherosclerotic lesions leading
to MI (Alain T 2006). Although normal vessels do not bind inflammatory cells,
early in atherogenesis, dysfunctional arterial endothelial cells express adhesion
molecules that encourage leukocyte adhesion; ICAM-2 in particular, binds
neutrophils (Bjorn P et al 2008 & Abigail W et al 2009). After these cells adhere
to the endothelium, they migrate into the intima under the influence of locally
produced Chemokines. (Alain T 2006). Most myocardial infarcts are transmural,
in which the ischemic necrosis involves the full or nearly full thickness of the
ventricular wall in the distribution of a single coronary artery (Woo KM 2009). In
contrast, a subendocardial (nontransmural) infarct constitutes an area of
ischemic necrosis limited to the inner one third to one half of the ventricular wall.
(Woo KM 2009). Owing to the characteristic electrocardiograph changes resulting
from myocardial ischemia / necrosis in various distributions, transmural infarcts
are often referred to as “ST elevation infarcts” and subendocardial infarcts are
known as “non-ST elevation infarcts.” (Goodcare S et al 2009). The overall total
mortality within the first year is about 30% (Beaglehole R et al 2007). Thereafter
there is 3% to 4% mortality among survivors with each passing year as per data
available in literature (Gaziano TA 2005).
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OBJECTIVES
1. To estimate the Neutrophil / Lymphocyte ratio in patients of Myocardial
Infarction.
2. To evaluate the association between Neutrophil / Lymphocyte ratio and
different risk factors.
3 To define a tool for determination of early action in cases with possible
risk of morbidity and mortality after the index event.
4
CHAPTER -II
REVIEW OF LITERATURE
1. Demography
The human heart is a remarkably efficient, durable, and reliable pump that
propels over 6000 liters of blood through the body daily and beats more than 40
million times a year, thereby providing the tissues with a steady supply of vital
nutrients and facilitating the excretion of waste products. As might be anticipated,
cardiac dysfunction can be associated with devastating physiologic
consequences. Cardiovascular disease is the number one cause of death
worldwide, with about 80% of the burden occurring in developing countries.
(Gaziano, TA. 2005., Beaglehole, R. et al, 2007). In the United States, heart
disease accounts for nearly 40% of all postnatal deaths, totaling about 750,000
individuals annually; this is nearly 1.5 times the number of deaths caused by all
forms of cancer combined. It is estimated that one third of Americans have one
or more types of cardiovascular disease. Moreover, 32% of heart disease deaths
are “premature,” occurring in individuals younger than age 75 (Heart Association
statistics Committee, 2007). If all major forms of cardiovascular disease were
eliminated, life expectancy would increase by 7 years.
2. Cardiac Structure and Specializations
Heart weight varies with body height and weight; it normally averages
approximately 250 to 300 gm in females and 300 to 350 gm in males, or roughly
0.4% to 0.5% of body weight. The usual thickness of the free wall of the right
ventricle is 0.3 to 0.5 cm, and that of the left ventricle 1.3 to 1.5 cm. Increases in
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cardiac size and weight accompany many forms of heart disease. Greater heart
weight or ventricular thickness indicates hypertrophy, and an enlarged chamber
size implies dilation. An increase in cardiac weight or size or both (resulting from
hypertrophy and/or dilation) is termed cardiomegaly.
The efficient pumping of blood by the heart to the entire body requires the
normal function of each of its key components, the myocardium, valves,
conduction system, and coronary arterial circulation.
2.1 Blood Supply
To meet their energy needs, cardiac myocytes rely almost exclusively on
oxidative phosphorylation, which is manifest by the abundant mitochondria that
are found in these cells.[5] Oxydative phosphorylation requires oxygen, making
cardiac myocytes extremely vulnerable to ischemia. A constant supply of
oxygenated blood is thus essential for cardiac function. Most of the myocardium
depends on nutrients and oxygen delivered via the coronary arteries, which arise
immediately distal to the aortic valve, initially running along the external surface
of the heart (epicardial coronary arteries) and then penetrating the myocardium
(intramural arteries). These small penetrating arteries yield arterioles and,
ultimately, provide a rich network of capillaries enveloping individual cardiac
muscle cells.
The three major epicardial coronary arteries are
(1) The left anterior descending (LAD)
(2) The left circumflex (LCX) arteries, Both arising from branches of the left
(main) coronary artery,
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(3) The right coronary artery. Branches of the LAD are called “diagonal” and
“septal perforators,” and those of the LCX are “obtuse marginals.”
Most coronary arterial blood flow to the myocardium occurs during ventricular
diastole, when the microcirculation is not compressed by cardiac contraction.
2.2 Ischemic Heart Disease
Ischemic heart disease (IHD) is the leading cause of death worldwide for
both men and women (7 million per year). IHD is the generic designation for a
group of pathophysiologically related syndromes resulting from myocardial
ischemia—an imbalance between the supply (perfusion) and demand of the
heart for oxygenated blood. Ischemia brings not only an insufficiency of oxygen,
but also reduces the availability of nutrients and the removal of metabolites For
this reason, ischemia is generally less well tolerated by the heart than pure
hypoxia, such as may be seen with severe anemia, cyanotic heart disease, or
advanced lung disease.
In more than 90% of cases, the cause of myocardial ischemia is reduced
blood flow due to obstructive atherosclerotic lesions in the coronary arteries.
Thus, IHD is often termed coronary artery disease (CAD) or coronary heart
disease. In most cases there is a long period (up to decades) of silent, slow
progression of coronary lesions before symptoms appear. Thus, the syndromes
of IHD are only the late manifestations of coronary atherosclerosis that may have
started during childhood or adolescence.
In addition to coronary atherosclerosis, myocardial ischemia may be
caused by coronary emboli, blockage of small myocardial blood vessels, and
lowered systemic blood pressure (e.g., shock). Moreover, in the setting of
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coronary arterial obstruction, ischemia can be aggravated by an increase in
cardiac energy demand (e.g., as occurs with myocardial hypertrophy or
increased heart rate [tachycardia]), by diminished availability of blood or oxygen
due to shock, or by hypoxemia. Some conditions have several deleterious
effects; for example, tachycardia increases oxygen demand (because of more
contractions per unit time) and decreases supply (by decreasing the relative time
spent in diastole, when cardiac perfusion occurs).
3. Pathogenesis
The dominant cause of the IHD syndromes is insufficient coronary
perfusion relative to myocardial demand, due to chronic, progressive
atherosclerotic narrowing of the epi-cardial coronary arteries, and variable
degrees of superimposed acute plaque change, thrombosis, and vasospasm.
3.1 Chronic Atherosclerosis.
More than 90% of patients with IHD have atherosclerosis of one or more
of the epicardial coronary arteries. The clinical manifestations of coronary
atherosclerosis are generally due to progressive narrowing of the lumen leading
to stenosis (“fixed” obstructions) or to acute plaque disruption with thrombosis,
both of which compromise blood flow. A fixed lesion obstructing 75% or greater
of the lumen is generally required to cause symptomatic ischemia precipitated by
exercise (most often manifested as chest pain, known as angina); with this
degree of obstruction, compensatory coronary arterial vasodilation is no longer
sufficient to meet even moderate increases in myocardial demand. Obstruction of
90% of the lumen can lead to inadequate coronary blood flow even at rest. The
progressive myocardial ischemia induced by slowly developing occlusions may
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stimulate the formation of collateral vessels over time, which can protect against
myocardial ischemia and infarction and mitigate the effects of high-grade
stenosis (Regieli, JJ. et al, 2007).
Although only a single major coronary epicardial trunk may be affected,
two or all three—the left anterior descending (LAD), the left circumflex (LCX), and
the right coronary artery (RCA)—are often involved by atherosclerosis. Clinically
significant stenosing plaques may be located anywhere within these vessels but
tend to predominate within the first several centimeters of the LAD and LCX and
along the entire length of the RCA. Sometimes the major secondary epicardial
branches are also involved (i.e., diagonal branches of the LAD, obtuse marginal
branches of the LCX, or posterior descending branch of the RCA), but
atherosclerosis of the intramural (penetrating) branches is rare.
3.2 Acute Plaque Change
The risk of an individual developing clinically important IHD depends in
part on the number, distribution, structure, and degree of obstruction of
atheromatous plaques. However, the varied clinical manifestations of IHD cannot
be explained by the anatomic disease burden alone. This is particularly true for
the so-called acute coronary syndromes, unstable angina, acute MI, and sudden
death. The acute coronary syndromes are typically initiated by an unpredictable
and abrupt conversion of a stable atherosclerotic plaque to an unstable and
potentially life-threatening atherothrombotic lesion through rupture, superficial
erosion, ulceration, fissuring, or deep hemorrhage. In most instances, the plaque
change causes the formation of a superimposed thrombus that partially or
completely occludes the affected artery (Fuster, V, et al, 2007, Falk, E, et al,
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2005). These acute events are often associated with intralesional inflammation,
which mediates the initiation, progression, and acute complications of
atherosclerosis.
3.3 Consequences of Myocardial Ischemia.
In each syndrome the critical consequence is downstream myocardial
ischemia. Stable angina results from increases in myocardial oxygen demand
that outstrip the ability of stenosed coronary arteries to increase oxygen delivery;
it is usually not associated with plaque disruption. Unstable angina is caused by
plaque rupture complicated by partially occlusive thrombosis and
vasoconstriction, which lead to severe but transient reductions in coronary blood
flow. In some cases, microinfarcts can occur distal to disrupted plaques due to
thromboemboli. In MI, acute plaque change induces total thrombotic occlusion
and the subsequent death of heart muscle. Finally, sudden cardiac death
frequently involves an atherosclerotic lesion in which a disrupted plaque causes
regional myocardial ischemia that induces a fatal ventricular arrhythmia.
4. Myocardial Infarction (MI)
MI, also known as “heart attack,” is the death of cardiac muscle due to
prolonged severe ischemia. It is by far the most important form of IHD. About 1.5
million individuals in the United States suffer an MI annually.
4.1 Incidence and Risk Factors.
MI can occur at virtually any age, but its frequency rises progressively with
increasing age and when predispositions to atherosclerosis are present. Nearly
10% of myocardial infarcts occur in people under age 40, and 45% occur in
people under age 65. Blacks and whites are equally affected. Throughout life,
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men are at significantly greater risk than women (Mendelsohn ME, et al, 2005)
Indeed, except for those having some predisposing atherogenic condition,
women are protected against MI and other heart diseases during the
reproductive years. However, the decrease of estrogen following menopause is
associated with rapid development of CAD, and IHD is the most common cause
of death in elderly women. Postmenopausal hormonal replacement therapy is not
currently felt to protect against atherosclerosis and IHD (Wenger NK, et al 2004).
4.2 Coronary Arterial Occlusion.
In the typical case of MI, the following sequence of events is considered
most likely
The initial event is a sudden change in an atheromatous plaque,
which may consist of intraplaque hemorrhage, erosion or ulceration, or
rupture or fissuring.
When exposed to subendothelial collagen and necrotic plaque
contents, platelets adhere, become activated, release their granule
contents, and aggregate to form microthrombi.
Vasospasm is stimulated by mediators released from platelets.
Tissue factor activates the coagulation pathway, adding to the bulk
of the thrombus.
Frequently within minutes, the thrombus evolves to completely occlude the
lumen of the vessel.
Compelling evidence for this sequence has been obtained from
(1) Autopsy studies of patients dying of acute MI.
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(2) Angiographic studies demonstrating a high frequency of thrombotic occlusion
early after MI.
(3) The high success rates of coronary revascularization (i.e., thrombolysis,
angioplasty, stent placement, and surgery) following MI and
(4) The demonstration of residual disrupted atherosclerotic lesions by
angiography after thrombolysis. Coronary angiography performed within 4 hours
of the onset of an MI shows a thrombosed coronary artery in almost 90% of
cases. However, when angiography is delayed until 12 to 24 hours after onset,
occlusion is seen only about 60% of the time, suggesting that some occlusions
resolve due to fibrinolysis, relaxation of spasm, or both.
4.3 Myocardial Response.
Coronary arterial obstruction compromises the blood supply to a region of
myocardium, causing ischemia, myocardial dysfunction, and potentially myocyte
death. The anatomic region supplied by that artery is referred to as the area at
risk. The outcome depends predominantly on the severity and duration of flow
deprivation.
The early biochemical consequence of myocardial ischemia is the
cessation of aerobic metabolism within seconds, leading to inadequate
production of high-energy phosphates (e.g., creatine phosphate and adenosine
triphosphate) and accumulation of potentially noxious metabolites (such as lactic
acid) Because of the exquisite dependence of myocardial function on oxygen,
severe ischemia induces loss of contractility within 60 seconds. This cessation of
function can precipitate acute heart failure long before myocardial cell death.
Ultrastructural changes (including myofibrillar relaxation, glycogen depletion, cell
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and mitochondrial swelling) also develop within a few minutes of the onset of
ischemia. Nevertheless, these early changes are potentially reversible. As
demonstrated both experimentally and in clinical studies, only severe ischemia
lasting 20 to 30 minutes or longer leads to irreversible damage (necrosis) of
cardiac myocytes. Ultrastructural evidence of irreversible myocyte injury (primary
structural defects in the sarcolemmal membrane) develops only after prolonged,
severe myocardial ischemia (such as occurs when blood flow is 10% or less of
normal).
A key feature that marks the early phases of myocyte necrosis is the
disruption of the integrity of the sarcolemmal membrane, which allows
intracellular macromolecules to leak out of cells into the cardiac interstitium and
ultimately into the microvasculature and lymphatics in the region of the infarct.
Tests that measure the levels of myocardial proteins in the blood are important in
the diagnosis and management of MI. With prolonged severe ischemia, injury to
the microvasculature then follows.
In most cases of acute MI, permanent damage to the heart occurs when
the perfusion of the myocardium is severely reduced for an extended interval
(usually at least 2 to 4 hours), This delay in the onset of permanent myocardial
injury provides the rationale for rapid diagnosis in acute MI—to permit early
coronary intervention, the purpose of which is to establish reperfusion and
salvage as much “at risk” myocardium as possible.
Ischemia is most pronounced in the subendocardium; thus, irreversible
injury of ischemic myocytes occurs first in the subendocardial zone. With more
extended ischemia, a wave front of cell death moves through the myocardium to
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involve progressively more of the transmural thickness and breadth of the
ischemic zone. The precise location, size, and specific morphologic features of
an acute MI depend on:
Necrosis is usually complete within 6 hours of the onset of severe
myocardial ischemia. However, in instances where the coronary arterial collateral
system, stimulated by chronic is-chemia, is better developed and thereby more
effective, the progression of necrosis may follow a more protracted course
(possibly over 12 hours or longer).
Knowledge of the areas of myocardium perfused by the three major
coronary arteries helps correlate sites of vascular obstruction with regions of
myocardial infarction. Typically, the left anterior descending branch of the left
coronary artery (LAD) supplies most of the apex of the heart (distal end of the
ventricles), the anterior wall of the left ventricle, and the anterior two thirds of the
ventricular septum. By convention, the coronary artery (either the right coronary
artery [RCA] or the left circumflex artery [LCX] that perfuses the posterior third of
the septum is called “dominant” (even though the LAD and LCX collectively
perfuse the majority of the left ventricular myocardium). In a right dominant
circulation, present in approximately four fifths of individuals, the LCX generally
perfuses only the lateral wall of the left ventricle, and the RCA supplies the entire
right ventricular free wall, the posterobasal wall of the left ventricle, and the
posterior third of the ventricular septum. Thus, occlusions of the RCA (as well as
the left coronary artery) can cause left ventricular damage. The right and left
coronary arteries function as end arteries, although anatomically most hearts
have numerous intercoronary anastomoses (connections called the collateral
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circulation). Little blood courses through the collateral circulation in the normal
heart. However, when one artery is severely narrowed, blood flows via collaterals
from the high- to the low-pressure system, and causes the channels to enlarge.
Thus, progressive dilation and growth of collaterals, stimulated by ischemia, may
play a role in providing blood flow to areas of the myocardium otherwise deprived
of adequate perfusion.
4.4 Transmural versus Sub-endocardial Infarction.
The distribution of myocardial necrosis correlates with the location and
cause of the decreased perfusion. Most myocardial infarcts are transmural, in
which the ischemic necrosis involves the full or nearly full thickness of the
ventricular wall in the distribution of a single coronary artery. This pattern of
infarction is usually associated with a combination of chronic coronary
atherosclerosis, acute plaque change, and superimposed thrombosis. In
contrast, a subendocardial (nontransmural) infarct constitutes an area of
ischemic necrosis limited to the inner one third to one half of the ventricular wall.
As the subendocardial zone is normally the least perfused region of myocardium,
this area is most vulnerable to any reduction in coronary flow. A subendocardial
infarct can occur as a result of a plaque disruption followed by a coronary
thrombus that becomes lysed before myocardial necrosis extends across the full
thickness of the wall; in this case the infarct will be limited to the distribution of
the coronary artery that suffered plaque change. However, subendocardial
infarcts can also result from prolonged, severe reduction in systemic blood
pressure, as in shock superimposed on chronic, otherwise noncritical, coronary
stenoses. In the subendocardial infarcts that occur as a result of global
hypotension, myocardial damage is usually circumferential, rather than being
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limited to the distribution of a single major coronary artery. Owing to the
characteristic electrocardiograph changes resulting from myocardial
ischemia/necrosis in various distributions, transmural infarcts are often referred
to as “ST elevation infarcts” and subendocardial infarcts are known as “non-ST
elevation infarcts.”
Biochemical abnormalities may also persist for a period of days to several
weeks in myocytes that are rescued from ischemia by reperfusion. These are
thought to underlie a phenomenon referred to as stunned myocardium, a state of
reversible cardiac failure that usually recovers after several days (Kloner RA, et
al, 2001). Reperfusion also frequently induces arrhythmias. Myocardium that is
subjected to chronic, sublethal ischemia may also enter into a state of lowered
metabolism and function that is referred to as hibernation (Heush G, et al, 2005)
The function of hibernating myocardium may be restored by revascularization
(e.g., by CABG surgery, angioplasty, or stenting). Paradoxically, repetitive short-
lived transient severe ischemia may protect the myocardium against infarction (a
phenomenon known as preconditioning) by mechanisms that are not understood
(Eisen A, et al, 2004).
5. Clinical Features.
MI is diagnosed by clinical symptoms, laboratory tests for the presence of
myocardial proteins in the plasma, and characteristic electrocardiographic
changes. Patients with MI often present with a rapid, weak pulse and profuse
sweating (diaphoresis). Dyspnea due to impaired contractility of the ischemic
myocardium and the resultant pulmonary congestion and edema is common.
However, in about 10% to 15% of patients the onset is entirely asymptomatic and
the disease is discovered only by electrocardiographic changes or laboratory
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tests that show evidence of myocardial damage. Such “silent” MIs are particularly
common in elderly patients and in the setting of diabetes mellitus.
The laboratory evaluation of MI is based on measuring the blood levels of
proteins that leak out of fatally injured myocytes; these molecules include
myoglobin, cardiac troponins T and I, the MB fraction of creatine kinase (CK-MB),
lactate dehydrogenase, and many others (Jaffe AS, et al, 2004). The diagnosis of
myocardial injury is established when blood levels of these cardiac biomarkers
are increased in the clinical setting of acute ischemia. The rate of appearance of
these markers in the peripheral circulation depends on several factors, including
their intracellular location and molecular weight, the blood flow and lymphatic
drainage in the area of the infarct, and the rate of elimination of the marker from
the blood.
The most sensitive and specific biomarkers of myocardial damage are
cardiac-specific proteins, particularly Troponins I and T (proteins that regulate
calcium-mediated contraction of cardiac and skeletal muscle). Troponins I and T
are not normally detectable in the circulation. Following an MI, levels of both
begin to rise at 2 to 4 hours and peak at 48 hours. Formerly the “gold standard,”
cardiac creatine kinase remains useful. Creatine kinase, an enzyme that is
present in brain, myocardium, and skeletal muscle, is a dimer composed of two
isoforms designated “M” and “B.” MM homodimers are found predominantly in
cardiac and skeletal muscle; BB homodimers in brain, lung, and many other
tissues; and MB heterodimers principally in cardiac muscle, with lesser amounts
also being found in skeletal muscle. As a result, the MB form of creatine kinase
(CK-MB) is sensitive but not specific, since it is also elevated when skeletal
muscle is injured. CK-MB begins to rise within 2 to 4 hours of the onset of MI,
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peaks at about 24 hours, and returns to normal within approximately 72 hours.
Although the diagnostic sensitivities of cardiac troponin and CK-MB
measurements are similar in the early stages of MI, elevated troponin levels
persist for approximately 7 to 10 days after acute MI, well after CK-MB levels
have returned to normal. Troponin and CK-MB levels peak earlier in patients
whose hearts are successfully reperfused, because proteins are washed out of
the necrotic tissue more rapidly. An unchanged level of CK-MB and troponin over
a period of 2 days essentially excludes the diagnosis of MI.
6. Consequences and Complications of MI.
Long-term prognosis after MI depends on many factors, the most
important of which are the quality of residual left ventricular function and the
extent of vascular obstructions in vessels that perfuse the viable myocardium.
The overall total mortality within the first year is about 30%. Thereafter there is
3% to 4% mortality among survivors with each passing year. Infarct prevention
through control of risk factors in individuals who have never experienced MI
(primary prevention) and prevention of reinfarction in those who have recovered
from an acute MI (secondary prevention) are important strategies that have
received much attention and achieved considerable success.
6.1 Acute coronary syndrome (ACS)
Acute coronary syndrome (ACS) is usually one of three diseases that
involved the coronary arteries: ST elevation myocardial infarction (30%), non ST
elevation myocardial infarction (25%), or unstable angina (38%) (Torres, M. et al.
2007).
6.2 Signs and symptoms
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The cardinal sign of decreased blood flow to the heart is chest pain
experienced as tightness around the chest and radiating to the left arm and the
left angle of the jaw. This may be associated with diaphoresis (sweating), nausea
and vomiting, as well as shortness of breath. In many cases, the sensation is
"atypical", with pain experienced in different ways or even being completely
absent (which is more likely in female patients and those with diabetes). Some
may report palpitations, anxiety or a sense of impending doom and a feeling of
being acutely ill. The description of the chest discomfort as a pressure has little
utility in aiding a diagnosis as it is not specific for ACS (Woo, KM, et al, 2009).
6.3 Biomarkers for diagnosis
The aim of diagnostic markers is to identify patients with ACS even when
there is no evidence of heart muscle damage.
• Ischemia-Modified Albumin (IMA) - In cases of Ischemia - Albumin undergoes a
conformational change and loses its ability to bind transitional metals (copper or
cobalt). IMA can be used to assess the proportion of modified albumin in
ischemia. Its use is limited to ruling out ischemia rather than a diagnostic test for
the occurrence of ischemia.
Glycogen Phosphorylase Isoenzyme BB-(GPBB) is an early marker of
cardiac ischemia and is one of three isoenzyme of Glycogen Phosphorylase.
Troponin is a late cardiac marker of ACS Biomarkers for Risk
Stratification.
19
Natriuretic Peptide - Both B-type Natriuretic peptide (BNP) and N-terminal
Pro BNP can be applied to predict the risk of death and heart failure following
ACS.
Myeloperoxidase (MPO) - The levels of circulating MPO, a leukocyte
enzyme, elevate early after ACS and can be used as an early marker for the
condition.
Myeloperoxidase (MPO) is a well-known enzyme, mainly released by
activated neutrophils, characterized by powerful pro-oxidative and
proinflammatory properties. Recently, myeloperoxidase has been proposed as a
useful risk marker and diagnostic tool in acute coronary syndromes and in
patients admitted to emergency room for chest pain.
7. Pathophysiological Role of Myeloperoxidase in Ischemic Heart Disease
Oxidative stress and inflammation play important roles in the
pathogenesis of destabilization of coronary artery disease (CAD) leading to acute
coronary syndromes (ACS). Infiltrating macrophages and neutrophils participate
in the transformation of stable coronary artery plaques to unstable lesions
(Takahiko, N, et al. 2002, Sugiyama, S. et al. 2001).
Recently, there has been a renewed interest in MPO, a proinflammatory
enzyme that is abundant in ruptured plaque (Mulane, K.M, et al. 1985) and can
be measured in peripheral blood.
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MPO is a hemoprotein that is stored in azurophilic granules of
polymorphonuclear neutrophils. MPO catalyzes the conversion of chloride and
hydrogen peroxide to hypochlorite and is secreted during inflammatory condition.
It has been implicated in the oxidation of lipids contained within LDL cholesterol.
In addition, MPO consumes endothelial-derived NO, thereby reducing NO
bioavailability and impairing its vasodilating and anti-inflammatory properties.
Major evidence for MPO as enzymatic catalyst for oxidative modification of
lipoproteins in the artery wall has been suggested in a number of studies
performed with low-density lipoprotein (Holvoet, P. et al 1998).
In contrast to low-density lipoprotein, plasma levels of high-density
lipoprotein (HDL)-cholesterol and apoAI, the major apolipoprotein of HDL,
inversely correlate with the risk of developing coronary artery disease. There is
now strong evidence that HDL is a selective in vivo target for MPO-catalyzed
oxidation, which may represent a specific molecular mechanism for converting
the cardioprotective lipoprotein into a dysfunctional form, raising the possibility
that the enzyme represents a potential therapeutic target for preventing vascular
disease in humans (Saffitz JE, et al, 2006). (Shao, B, et al. 2006) showed that
atorvastatin reduced serum MPO and CRP concentrations in patients with ACS.
MPO activity can be measured in blood and tissues by spectrophotometric
assays using hydrogen peroxide and odianisidine dihydrochloride as substrates.
In addition, MPO content can be measured in neutrophils as an index of
degranulation with the Coulter counter and flow cytometry and circulating MPO
by ELISA.
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There is extensive evidence to support a pathogenic role for both local and
systemic inflammation in acute coronary syndromes. There is also evidence that
increased concentrations of inflammatory markers at presentation can identify
patients at high risk of future ischemic events, suggesting that the intensity of the
inflammatory response influences clinical outcome in acute coronary syndromes.
More recent data suggest that the inflammatory process is sustained long after
the clinical event has resolved and that this ongoing inflammation is associated
with an increase in subsequent ischemic events.
However, some important questions relating to inflammation in acute
coronary syndromes remain unanswered. Firstly, it remains to be elucidated
whether the inflammatory process observed is a precursor or a consequence of
coronary plaque rupture; the emerging data suggest that the inflammatory
process is indeed a precursor of the clinical event.
22
CHAPTER – III
MATERIAL AND METHODS
1. Setting
Coronary Care Units (CCU) of Isra University Hospital, Dewan Mushtaq
Civil Hospital Hyderabad and Red Crescent Chest Pain Unit Latifabad,
Hyderabad.
1.1 Study Design:
Cross – sectional
1.2 Sample Size:
140 Subjects were divided into three groups:
1) Non Cardiac Group: Comprising of 42 individuals having non cardiac chest
pain and a normal electrocardiogram (ECG) and CKMB.
2) AMI with ST-segment Elevation (STE) Group: Comprising 58 patients with
Myocardial infarction having STE on electrocardiogram.
3) AMI with Non-ST Segment Elevation (NSTE) Group: Comprising 40 patients
of myocardial infarction having NSTE on the electrocardiogram.
1.3 Inclusion Criteria:
All the patients of either gender having ages over 35 years, presenting at
emergency department / CCU with AMI.
1.4 Exclusion Criteria:
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Patients with age under 35 years.
Patients with a history of trauma, surgery and infectious diseases in the 30
days prior to admission.
Patients with neoplasia
Patients on prolonged immune-suppressors therapy (Corticoids & NSAIDs
included).
1.5 Sample Collection
[
l Blood was collected by veinipuncture from the antecubital fossa in
disposable 3.0 cc syringes under aseptic conditions and preserved in EDTA
bottles from every patient admitted with complaints of severe chest pain in
said hospital locations.
l The collected sample bottles were marked with patients name and DOA
along with the record number from their files.
l A Proforma was duly filled by this researcher when each patient was
stabilized after explaining to them the purpose. The same was explained to their
relatives at the time of admission and before the blood was drawn.
l The TLC and other cardiac markers were determined by automatic analyzers
in the clinical laboratories of the said CP & CC Us.
l Slides were prepared for manual DLC and stained with Leishmann’s stain
using the Standard protocols.
l The findings were interpreted and correlated with the patient’s clinical
condition and Proforma.
24
PROTOCOL FOR LEISHMANN'S STAIN PREPARATION:
l Add 15 Gms Leishmann's powder (Eosinate of Methylene blue) in 100%
methanol. (Use after 24hrs.)
PHOSPHATE BUFFER (Sorensen)
l STOCK A: (0.2M sodium di-hydrogen orthophosphate [mw 156].
To prepare dissolve 3.12g in 100ml distilled water.
l STOCK B: (0.2M di-sodium hydrogen orthophosphate [mw 142].
To prepare dissolve 2.83g in 100ml distilled water.
l FOR PH 6.8: add 25.5ml of Stock A to 24.5ml of Stock B and make up to
100ml with distilled water.
1.6 Method of Staining:
Put slides on a rack and cover with 1-2 ml of Prepared Leishmann's stain
for 20 seconds.
Add 2ml of pH6.8 buffer and tip the rack up and down to mix the solutions,
stain for 7 minutes.
Rinse quickly in distilled water then treat with pH6.8 buffer for 2 minutes.
Rinse quickly in distilled water, shake off the excess and carefully air dry at
room temperature.
Mount on the observation platform of a light microscope and observe using a
10x eye piece and (Cedar Wood) oil immersion objective lens: (100 x) to increase
the magnification 1000 times.
1.7 Observations.
25
NEUTROPHILS - dark purple nuclei, pale pink cytoplasm, reddish-lilac
small granules.
EOSINOPHILS - blue nuclei, pale pink cytoplasm, red to orange-red large
granules.
LYMPHOCYTES - dark purple to deep bluish purple nuclei, sky blue
cytoplasm.
BASOPHILS - purple to dark blue nucleus, dark purple, almost black large
granules.
MONOCYTES – Light to dark pink cytoplasm with color less cytoplasm and
occasional deep pink large granule.
STATISTICS
DATA ANALYSIS
The data collected through duly filled Proforma was computerized and the
variables were analyzed by using SPSS version 16.
A p - value of ? 0.05 was considered to be significant.
Mean & SD were calculated.
T-test was applied to continuous variables.
Chi-square test was applied to categorical variables.
The N/L Ratio was subjected to the following parameters as well
Sensitivity
Specificity
Positive predictive value
26
Negative predictive value
Odds Ratio
27
CHAPTER-IV
RESULT
The study was conducted on 140 individuals, between the age group of 35
years to 85 years. 140 individuals divided in to 05 groups that ranges 10 year in
each groups Tab: IV-01.
Gender distribution was also recorded in each group that is shown in table
#I V-01.
The highest ratio of the individuals were recorded between the age of 45-
55 years with significant p value<0.05.
All the groups of individuals were analyzed in three categories i.e. non
cardiac cases, AMI-with STE & AMI with NSTE.
The neutrophil count was recorded in all three categories for all
individuals. Study results show the neutrophil count to be within normal range in
non cardiac cases however it showed a marked increased in AMI with STE
Fig.IV-1.
Similarly lymphocyte count was also recorded in all three categories for all
140 individuals. The lymphocyte count was significantly raised in non-cardiac
cases but it was found to be significantly decreased in AMI with STE as
compared to with AMI with NSTE, Fig. IV-02.
The total leukocyte count was also recorded in all 140 individuals. It was
found to be gradually increased from non cardiac cases to AMI with STE.
28
In AMI with NSTE it was also increased but not as much as in AMI with
STE. Fig.IV-03.
In graph # the results of N/L ratio are shown that reveals that neutrophil /
lymphocyte ratio is significantly increased in AMI with STE (p< 0.01) Fig.IV-04.
The analytical output of this study shows that odds ratio is significantly
increased for N/L ratio (5.67). This is highly significant.
Furthermore, sensitivity and specificity analysis results revealed that N/L
ratio is about (94.83%) sensitive and 95.21% specific for the objective to be
recorded for the study. In view of the results of sensitivity and specificity, positive
predictive value and negative predictive values were also estimated, that has
shown a significant calculation. Odds for neutrophils, lymphocytes and
leukocytes was also analyzed Tab.IV-02.
In non-cardiac cases CKMB was found normal i.e. 92.9% individuals
having normal CKMB count while 7.1% having increased.
In AMI, NSTE it was raised in 62.5% individuals while it was not done in
37.5% individuals. In AMI with STE, CKMB was found significantly increased in
all the individuals of this group Tab.IV-03.
In non cardiac cases Trop.T was negative in all individuals of this group
while in AMI with NSTE it was raised in 42.5% of individuals and 57.5% of
individuals it was not done. In AMI with STE it was increased in 66.5% of
individual while in 34.5% of individuals it was not checked. The results were
significant Tab.IV-04.
29
Table IV-01. Distribution of Cases by Age & Gender
(n=140)AGE GROUPS
(YEARS35-45
46-55
56-65
66-75
76-85
Male101535158Female81320124Total1218285527
30
Table IV-02. Comprehensive Analytical Out Put
ANALY T IC AL OU T PU T
O d d s R a tio
S en sit iv ity(% )
S p ec ific ity (% )
P o sit iv eP red ic t iv e
V a lu e(% )
N eg a tiv e P red ic t iv e
V a lu e (% )
N /L R a tio 5 .6 7 9 4.83 9 5.21 9 3.89 9 1.72
N eu tro p h ils 3 .8 4
L y m p h o cy tes 0 .7 6
L eu cocy tes 2 .3 7
ANALY T IC AL OU T PU T
O d d s R a tio
S en sit iv ity(% )
S p ec ific ity (% )
P o sit iv eP red ic t iv e
V a lu e(% )
N eg a tiv e P red ic t iv e
V a lu e (% )
N /L R a tio 5 .6 7 9 4.83 9 5.21 9 3.89 9 1.72
N eu tro p h ils 3 .8 4
L y m p h o cy tes 0 .7 6
L eu cocy tes 2 .3 7
Table # 02
31
32
Table IV-03. Risk Factors Association with N/L Ratio
Risk Factors Associa tion With N/L Ratio
BMI Dia be tes Me llitus Sm oking Hypertension
Norm a l Yes No Yes No Yes No Yes No
N /L R atio
NIL NIL
Fam ily History of CAD
Over W e ight
Unde r W e ight
Non cardia c che st pa in
(42 = n)
2.38 (n=% )
80.95(n=% )
16.66(n=% )
100(n=% )
11.90 (n=% )
88.09(n=% )
21.42 (n=% )
78.57(n=% )
100(n=% )
(1.5 - 3) (1.5 – 2.5) (1.5 – 2.5) (1.5 - 3) (1.5 - 3) (1.5 - 3) (1.5 – 2.5) (1.5 – 3.9) (1.5 - 3) (1.5 – 2.5) (1.5 – 2.5)
AMINSTE
(40 = n)
30.00 (n=% )
45.00(n=% )
25.00(n=% )
50.00(n=% )
50.00(n=% )
35.00 (n=% )
65.00(n=% )
52.50 (n=% )
47.50(n=% )
77.50(n=% )
22.50(n=% )
(2.5 – 3.5) (2.5 – 3.5) (2.5 – 3.5) (2.5 – 3.5) (2.5 – 3.5) (2.5 – 3.5) (2.5 – 3.5) (2.5 – 4.0) (2.5 – 3.5) (2.5 – 3.5) (2.5 – 3.5)
AMISTE
(58 = n)
44.82 (n=% )
46.55(n=% )
8.62(n=% )
55.17(n=% )
44.82(n=% )
41.37 (n=% )
58.62(n=% )
56.89 (n=% )
43.10(n=% )
81.03(n=% )
18.96(n=% )
(3.5 – 5.5)P < 0.01
(3.5 – 4.5)p < 0.05
(3.5 – 4.5)p < 0.05
(4.5 – 6.5)P < 0.01
(3.5 – 4.5)p < 0.05
(5.5 – 6.5)P < 0.01
(3.5 – 4.5)p < 0.05
(5.5 – 6.5)P < 0.01
(3.5 – 4.5)p < 0.05
(4.5 – 5.5)P < 0.01
(3.5 – 4.5)p < 0.05
Table # 03
33
Table IV-04. ECG Changes
NC AMI-STE NSTE-AMI Total
42 58 40 140
34
35
Table IV-05. Percentage of sample with regard to BMI
36
Table IV-06. Gender Distribution (n=140)
37
Table IV-07. Percentage of sample size with / without DM
38
Table IV-08. Percentage of patients with prevalence of Smoking
Y e s N o
N C 11 .9 0 8 8 .1 0
A M I-N S T E 3 5 6 5
A M I-S T E 4 1 .3 7 5 8 .6 3
Y e s N o
N C 11 .9 0 8 8 .1 0
A M I-N S T E 3 5 6 5
A M I-S T E 4 1 .3 7 5 8 .6 3
H yp e r te n s io n (% )
Y e s N o
N C N il 1 0 0
A M I
N S T E7 7 .5 2 2 .5
A M I S T E 8 1 .0 4 1 8 .9 6
H yp e r te n s io n (% )
Y e s N o
N C N il 1 0 0
A M I
N S T E7 7 .5 2 2 .5
A M I S T E 8 1 .0 4 1 8 .9 6
Table # 08: Smoking
Table # 09: HTN
39
Table IV-09. Percentage of cases with / without Hypertension
Y e s N o
N C 11 .9 0 8 8 .1 0
A M I-N S T E 3 5 6 5
A M I-S T E 4 1 .3 7 5 8 .6 3
Y e s N o
N C 11 .9 0 8 8 .1 0
A M I-N S T E 3 5 6 5
A M I-S T E 4 1 .3 7 5 8 .6 3
H yp e r te n s io n (% )
Y e s N o
N C N il 1 0 0
A M I
N S T E7 7 .5 2 2 .5
A M I S T E 8 1 .0 4 1 8 .9 6
H yp e r te n s io n (% )
Y e s N o
N C N il 1 0 0
A M I
N S T E7 7 .5 2 2 .5
A M I S T E 8 1 .0 4 1 8 .9 6
Table # 08: Smoking
Table # 09: HTN
40
Table IV-10. Association of major risk factors with MI.
N C A M I-N S T E A M I-S T E P value
G end erM ale - 64 .28
F em ale – 35.71M ale – 65
F em ale – 35M ale 65 .5 1
F em ale – 34.48--
B M I (% ) 16 .6 50 46 .55 < 0 .05
D M (% ) N il 50 44 .82 < 0 .05
S m oking (% ) 11 .90 35 41 .37 < 0 .05
F am ily (% ) 21 .42 65 72 .41 < 0 .01
H T N (% ) N il 77 .5 81 .03 < 0 .01
C K -M B N il 625 50 < 0 .05
N C A M I-N S T E A M I-S T E P value
G end erM ale - 64 .28
F em ale – 35.71M ale – 65
F em ale – 35M ale 65 .5 1
F em ale – 34.48--
B M I (% ) 16 .6 50 46 .55 < 0 .05
D M (% ) N il 50 44 .82 < 0 .05
S m oking (% ) 11 .90 35 41 .37 < 0 .05
F am ily (% ) 21 .42 65 72 .41 < 0 .01
H T N (% ) N il 77 .5 81 .03 < 0 .01
C K -M B N il 625 50 < 0 .05
Table # 10
41
Table IV-11. CKMB Cross tabulation
42
Case * CKM B Crosstabulation
CKMB Total
Raised Norm al Not done
Case NC Count 3 39 0 42
% within C ase 7.1% 92.9% .0% 100.0%
% within CKMB 5.3% 100.0% .0% 30.0%
AMI-N STE Count 25 0 15 40
% within C ase 62.5% .0% 37.5% 100.0%
% within CKMB 43.9% .0% 34.1% 28.6%
AMI-STE Count 29 0 29 58
% within C ase 50.0% .0% 50.0% 100.0%
% within CKMB 50.9% .0% 65.9% 41.4%
Total Count 57 39 44 140
% within C ase 40.7% 27.9% 31.4% 100.0%
% within CKMB 100.0% 100.0% 100.0% 100.0%
Case * CKM B Crosstabulation
CKMB Total
Raised Norm al Not done
Case NC Count 3 39 0 42
% within C ase 7.1% 92.9% .0% 100.0%
% within CKMB 5.3% 100.0% .0% 30.0%
AMI-N STE Count 25 0 15 40
% within C ase 62.5% .0% 37.5% 100.0%
% within CKMB 43.9% .0% 34.1% 28.6%
AMI-STE Count 29 0 29 58
% within C ase 50.0% .0% 50.0% 100.0%
% within CKMB 50.9% .0% 65.9% 41.4%
Total Count 57 39 44 140
% within C ase 40.7% 27.9% 31.4% 100.0%
% within CKMB 100.0% 100.0% 100.0% 100.0%
Table # 11
43
44
Table IV-12. Trop t Cross tabulation
Case * Trop t Crosstabulation
Trop t Tota l
P os itive N egative N ot done
C ase N C C ount 0 42 0 42
% w ithin Case .0% 100.0% .0% 100.0%
% w ithin Trop t .0% 100.0% .0% 30.0%
A M I-N S TE C ount 17 0 23 40
% w ithin Case 42.5% .0% 57.5% 100.0%
% w ithin Trop t 30.9% .0% 53.5% 28.6%
A M I-S TE C ount 38 0 20 58
% w ithin Case 65.5% .0% 34.5% 100.0%
% w ithin Trop t 69.1% .0% 46.5% 41.4%
Tota l C ount 55 42 43 140
% w ithin Case 39.3% 30.0% 30.7% 100.0%
% w ithin Trop t 100.0% 100.0% 100.0% 100.0%
Case * Trop t Crosstabulation
Trop t Tota l
P os itive N egative N ot done
C ase N C C ount 0 42 0 42
% w ithin Case .0% 100.0% .0% 100.0%
% w ithin Trop t .0% 100.0% .0% 30.0%
A M I-N S TE C ount 17 0 23 40
% w ithin Case 42.5% .0% 57.5% 100.0%
% w ithin Trop t 30.9% .0% 53.5% 28.6%
A M I-S TE C ount 38 0 20 58
% w ithin Case 65.5% .0% 34.5% 100.0%
% w ithin Trop t 69.1% .0% 46.5% 41.4%
Tota l C ount 55 42 43 140
% w ithin Case 39.3% 30.0% 30.7% 100.0%
% w ithin Trop t 100.0% 100.0% 100.0% 100.0%
Table # 12
45
46
Graph IV-01. Absolute Neutrophils Count of Cases Neutrophils Count of Cases
02 0 0 04 0 0 06 0 0 08 0 0 0
1 0 0 0 01 2 0 0 01 4 0 0 01 6 0 0 01 8 0 0 0
n o n ca rd ia cp a in
AMI NST E AMIST E
p < 0.05
Ne
utr
op
hils
co
un
t
Fig. # 01
C ases C ases C ases
n=140
47
Graph IV-02. Absolute Lymphocytes Count of Cases
0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
2 5 0 0
3 0 0 0
3 5 0 0
4 0 0 0
n o n ca rd ia cp a in
AMI NST E AMIST E
p value 0.05
Ly
mp
ho
cy
tes
co
un
t
Lymphocytes Count of Cases
C ases C ases C ases
n=140
Fig. # 02
48
Graph IV-03. Total Leukocytes of Count of Cases
0
5000
10000
15000
20000
25000
non cardiacpain
AMI NSTE AMISTE
p value < 0.04
Le
uk
oc
yte
s c
ou
nt
Total Leukocytes Count of CasesFig # 03
C ases C ases C ases
n=140
49
Graph IV-04. Neutrophil/Lymphocyte Ratio
Neutrophil/Lymphocyte Ratio
0
2
4
6
8
10
12
14
16
non cardiac pain AMI NSTE AMISTE
p v alue < 0.001
N/L
ra
tio
Fig # 04
___________
50
CHAPTER-VI
DISCUSSION
It has been long known that Acute Myocardial Infarction is followed by
Neutrophilia, the early appearance of Neutrophils in the infarct zone with heavy
infiltration by 1-3 days, followed by infarct healing and replacement fibrosis as
can be seen in the researches done by (Faxon DP et al 2002; Tanya N et al in
2009 and Adelaide M et al 2008)
Neutrophilia also might indicate maladaptive processes: circulating
leukocyte-platelet aggregates appear in acute coronary syndromes and might
facilitate vascular plugging and infarct extension. (Núñez J et al 2008).
The neutrophils can make plaque disruption by releasing Myeloperoxidase
(MPO) contained in the auzerophillic granules which catalyzes the reaction
between a halide and hydrogen per oxide, while the reperfusion injury occurring
spontaneously or after therapy have been postulated to be leukocyte mediated
(Valentina L et al 2009).
The basic theme of my research is that Leukocytosis is associated with
poor prognosis and vaso-occlusive events in patient, the experimental data
suggest a direct role for leukocytes in micro vascular obstruction and (Di Stefano
R et al 2009) hold the same view
The only way to test whether leukocytes contribute directly to poor
outcome in ischemic cardiovascular disease is to assess the effect of N/L ratio
which is the mainstay of my study and has amply demonstrated that total
51
leukocyte counts, differential leukocyte counts along with N/L ratio (neutrophil /
lymphocytes ratio) are probably the only prognostic tools for the prediction of an
increased risk of morbidity and mortality in patients with Myocardial Infarction
This view was also proposed by (Barry S.C. et al 2005).
With purpose to assess whether the N/L ratio was directly associated with
MI, the study was correlated with gradual increase in N/L ratio obtained from non
cardiac chest pain patients to MI with ST segment Elevation patients.
Odds ratio was also calculated for neutrophil, lymphocyte, total leukocytes
and N/L ratio with significant results. (Table # 9).
My research showed the PPV (positive predictive value) (Table # 09) of
N/L Ratio in patients with MI which is in agreement with work done by (Matteo M
et al 2006; Lee C et al 2001 & Haim M et al 2004).
I have also discovered that Neutrophilia is an independent risk marker for
increased morbidity after an initial cardiovascular event which is totally consistent
with the work done by (Grau AJ et al 2004).
The present study has shown an independent and strong association
between N/L ratio in patients of ST segment Elevation and Non ST segment
Elevation myocardial infarction (Table# 08), Which view was put forward by Das
U. N in 2008.
My research also discovered that a very high incidence of TLC & N/L Ratio
was visible in patients with MI and these results are consistent with the studies
done by (Wheeler et al in 2004 and Papa A et al 2009), who reported that
52
increased Neutrophil counts predicts greater risk for increased morbidity and
mortality after MI than other leukocyte subtypes. (Figures 2 & 4)
Afiune et al in 2006 said that monocyte are to be associated with the
highest risk of coronary artery disease; However I strongly disagree with this
view and have shown that the N/L ratio with a high TLC works as a better
prognostic tool for MI than any other isolated subtypes of leukocytes. (Table#01)
In my research a highly significant correlation of N/L Ratio and CK-MB
level has been observed (p value <0.001) between the STE-MI & NSTE-MI
(Table# 08). On this point I am in agreement with the findings of Fox S et al, in
whose study in 2010, the peak Neutrophil count recorded during the immediate
post infarct period showed a significant correlation with maximum CK-MB levels
along with a role of increased N/L Ratio in expansion of infarct and development
of subsequent cardiac failure. This view is also shared with (Di Stefano R et al
2009).
In consideration that atherosclerotic lesion contains macrophage infiltrates
and lymphocytes in its sub-endothelial layer as suggested by Zazula et al in
2008; I postulate that the increased Neutrophilia is a result of the increased
endothelial released cytokines viz. G-CSF for the stability of the different plaque
components and the same is postulated in the study done by (Li Dong–Bao et al
in 2009).
However in this study it has been observed that myocardial infarction with
ST Elevation presented with a drastic decrease in lymphocyte counts as
compared to MI with Non ST Elevation which finding is consistent with the study
of (Poludasu S et al 2009).
53
(SHEN Xu-hua et al 2010) stated that there is no significant relations
between the increased CK-MB with N/L ratio but in contrast my work has shown
that there is high statistical significance (p value < 0.05) in correlation between
increased CK-MB levels and N/L ratio (Table# 08).
Results from other prospective studies (Roy D et al 2006, Ommen SR, et
al 1997 & He R et al 2009) have described that absolute and relative lymphocyte
concentrations are significantly lower in patients with cardiac events and my
study is totally consistent with these views.
In my research, I have correlated the various high risk factors (Table# 08)
with Non ST segment Elevation and ST segment Elevation myocardial infarction
and shows a very high degree of Sensitivity; Specificity; NPV (Negative predictive
value) and PPV (Positive predictive value) as seen in Tables# 01 & 09. This
correlation has never been done before.
54
CHAPTER-VII
CONCLUSION
From the results of my study, it can safely be concluded that N/L ratio is
increased dramatically along with a high TLC in ST segment Elevation MI and a
moderate increase of the same is seen in Non ST segment Elevation MI as
compared to non cardiac pain subjects, and is highly sensitive, specific, with a
very high PPV.
My Research clearly states that, the N/L ratio is of strong prognostic value
for predicting an increased risk of morbidity and mortality in patients who have
already suffered a Myocardial Infarction whether a STE-MI or a NSTE-MI.
In this light, it can be positively concluded that N/L ratio can be used as
preliminary prognostic tool for increased risk of morbidity and mortality after the
initial Myocardial infarction whether STE-MI or NSTE-MI.
55
CHAPTER-VIII
SUGGESTIONS
Since this was a cross sectional study it is strongly urged that a
Prospective Cohort study starting from the Index event with a minimum 18
months follow up may be undertaken to properly assess the importance of N/L
Ratio on the morbidity and mortality in the population of Pakistan.
56
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