2. Myocardial Infarction
■ Myocardial infarction or acute myocardial infarction
(AMI) is the medical term for an event commonly known
as a heart attack.
■ It happens when blood stops flowing properly to part of
the heart and the heart muscle is injured due to not enough
oxygen.
■ Usually this is because one of the coronary arteries that
supplies blood to the heart develops a blockage due to an
unstable buildup of white blood cells, cholesterol and fat.
The event is called "acute" if it is sudden and serious.
Dr.Amal Hamza
4. ■ A person having an acute myocardial infarction usually
has sudden chest pain that is felt behind the breast bone
and sometimes travels to the left arm or the left side of
the neck.
■ Additionally, the person may have shortness of breath,
sweating, nasusea, vomiting, abnormal heartbeats, and
anxiety.
■ Women experience fewer of these symptoms than men,
but usually have shortness of breath, weakness, a feeling
of indigestion, and fatigue.
Dr.Amal Hamza
5. ■ The diagnosis of myocardial infarction has been
based on WHO criteria which comprise a typical
history of chest pain, the presence of diagnostic ECG
abnormalities and a rise in biochemical markers.
■ The presence of two or more of these three has
defined the diagnosis.
■ Troponins are more sensitive biochemical markers.
Many studies have shown that troponins are released
in some patients without ECG changes of infarction.
Dr.Amal Hamza
6. ■ After myocardial infarction, a number of intracellular
proteins are released from the damaged cells.
■ The proteins of major diagnosis interest include:
■ Troponin I and troponin T.
■ Enzymes, such as creatine kinase (CK), CK-MB,
(AST), and (LDH).
■ Myoglobin
■ Ischaemia-modified albumin.
Dr.Amal Hamza
7. ■ Troponins and CK are the most widely established
biochemical indices of myocardial damage.
■ Myoglobin is also a sensitive index of myocardial
damage and it rises very rapidly after the event.
■ However, it is non-specific, since it is raised
following any form of muscle damage.
■ Ischaemia-modified albumin is a new early and
sensitive biochemical marker of myocardial
ischaemia, but is non-specific and not widely
available.
Dr.Amal Hamza
8. Time course of changes
■ After a myocardial infarction, the time-course of
plasma biochemical markers always follows the same
general pattern.
Dr.Amal Hamza
9. ■ A sample taken on admission, if elevated, will
make the required diagnosis, but if not
elevated will not rule out the diagnosis.
■ A sample taken between 6 and 12 h after the
onset of symptoms will give more reliable
results.
Dr.Amal Hamza
11. Troponin
■ Troponin is a complex of three regulatory proteins
(troponin C, troponin I, and troponin T) that is
integral to muscle contraction in skeletal and
cardiac muscel, but not smooth muscle.
■ The troponin complex is exclusively present in
straited muscle fibers and regulates the calcium
mediated interactions of actin and myosin.
■ Troponin T binds tropomyosin, troponin I is an
inhibitory protein and troponin C is responsible for
binding calcium.
Dr.Amal Hamza
12. ■ In human heart the cardiac-specific troponin T and
troponin I are largely insoluble, but 3-5% exists as a
soluble cytoplasmic pool.
■ Following cardiac myocyte necrosis, this soluble fraction
accounts for the early and rapid release of troponin into
the circulation and the slower release of the insoluble
fraction accounts for the prolonged plateau of troponin
release.
■ The existence of the cardiac-specific isoforms of these
troponins makes them the most specific of all the
biochemical markers for cardiac damage.
Dr.Amal Hamza
13. ■ Under normal circumstances there is no
cardiac troponin T or I detectable in the
circulation by currently available assays, so
any detectable rise is of significance.
■ Troponin may also be elevated in renal
failure, sever heart failure and acute
pulmonary embolism.
Dr.Amal Hamza
14. Creatine Kinase
■ There are three principal CK isoenzymes, each comprising
two polypeptide chains, either B or M these give the dimers
BB,MB and MM.
■ Skeletal muscle has a very high total CK contents, over 98%
normally comprises CK-MM and less than 2 % CK-MB,
CK-MB may rise to 5-15% in some patients with muscle
disease and also in athletes in training.
■ Cardiac muscle also has a high CK content. It comprises 70-
80% CK-MM and 20-30% CK-MB.
■ Its use has been largely overtaken by the widespread
availiability of troponin measurement.
Dr.Amal Hamza
15. ■ As a general rule, cardiac muscle is the only
tissue with more than 5% CK-MB.
■ Ck-MB is a more sensitive and specific test
for myocardial damage than total CK.
Dr.Amal Hamza
16. The Diagnosis of heart failure
■ Heart failure is a complex clinical condition which the
heart’s ability to pump is compromised by one or more of
a number of underlying conditions , commonly ischemic
heart disease, but also heart valve abnormalities.
■ The prognosis is poor if untreated, with a 2-years survival
rate.
■ The diagnosis of heart failure can be difficult especially
since the usual presenting symptoms such as
breathlessness or ankle swelling are common and can be
due to many different conditions.
Dr.Amal Hamza
18. ■ The definitive diagnosis is best made by echocardiography,
but access to this may be limited or delayed.
■ BNP (B-type natriuretic peptides) is a neurohormone
secreted by cardiac myocytes in response to volume
expansion and pressure overload, and plays a role in
circulatory homeostaisis.
■ In heart failure the level of BNP increases, enabling
differentiation of cardiac and pulmonary causes of
breathlessness.
■ It costs considerably less than echocardiography.
■ Levels rise with age, so age related cut –offs should be
used.
Dr.Amal Hamza
19. Cardiovascular Risk Factors
■ Many factors are associated with or cause increased
cardiovascular risk.
■ These can be divided into those which cannot be influenced
and those which can be influenced and reduction of which
has been demonstrated to reduce risk.
■ Those that cannot be influenced include a family history of
premature vascular disease, age and pre-exisiting vascular
disease.
■ Those whose modification has an established role include
cigarette smoking and hypertenstion, diabetes and
hyperlipidaemia, espcially hypercholesterolaemia.
Dr.Amal Hamza
20. Enzymes involved in lipid transport
■ Four enzymes related to clinical disorders need to be
described:
■ Lecithin cholesterol acyltransferase (LCAT) transfers an acyl
group (fatty acid residue) from lecithin to cholesterol. Forming a
cholesterol ester.
■ Lipoprotein lipase is attached to tissue capiliary endothellium
and splits triglycerides into glycerol and free fatty acids.Its
activity increase after a meal as a result of activation by apoC-II.
■ Hepatic lipase has an action similar to that of lipoprotein lipase
■ Mobilising lipase, present in adibose tissue cells, controls the
release of fatty acids from adipose tissue into plasma. It is
activated by catecolamines, GH and gluocorticoids and inhibited
by glucose and insulin.
Dr.Amal Hamza
21. Investigation of plasma lipid
abnormalities
■ Most laboratories measure
■ Plasma total cholesterol
■ HDL cholesterol
■ Triglycerides
■ Further tests to characterize the lipoprotein
abnormalities may be done in a few patients.
■ The investigations are mainly of value in the
investigation and management of ischaemic vascular
disease.Dr.Amal Hamza
22. Plasma total cholesterol
■ Random cholesterol can be measured to assess cardiovascular risk. The
following factors affect cholesterol levels:
■ Diet: The amount and the composition of dietary fat affect plasma
cholesterol. [polyunsaturated fatty acids lower plasma cholesterol while
saturated fatty acid tend to raise cholesterol level].
■ Dietary fiber may have a small effect in lowering plasma cholesterol.
■ Exercise: regular exercise tends to cause a rise in plasma HDL
cholesterol.
■ Age: In developed countries, plasma cholesterol rises with age.
■ Sex: in pre-menopausal women, plasma cholesterol is lower than in men
and plasma HDL-C is higher. These differences disappear after the
menopause.
■ Race
Dr.Amal Hamza
23. -
- Incidence of ischaemic heart disease is directly correlated
with cholesterol, even within the reference range.
- LDL-C is associated with an increased risk of ischaemic heart
disease while raised plasma HDL-C is associated with a
decreased risk of heart disease and have protective effect.
- Plasma TG also show variations with age and sex, but more
especially with diet.
Dr.Amal Hamza
24. Plasma LDL
■ Plasma LDL can be measured by ultracentrifugation, but
this is not a practical method for routine clinical
laboratory use.
■ The following formula can be used to calculate LDL on
fasting sample:
■ LDL-C = Total cholesterol - (HDL-C) - TG/2.2
■ Where all measurements are in mmol/L.
■ The molar ratio of TG to cholesterol VLDL is 2.2 as long
as the TG is less than 4.5mmol/L.
■ The formula is not valid if TG is greater than 4.5mmol/L.
Dr.Amal Hamza
25. ■ It is important to collect specimens for plasma lipid and
lipoprotein under the appropriate conditions:
■ The patients should have been leading a normal life (diet,
exercise) for at least the previous night.
■ Blood samples should be collected after an overnight fast
of 10-14 h.
■ Routine investigations:
■ Plasma cholesterol
■ Plasma HDL-C
■ Plasma fasting triglycerides.
Dr.Amal Hamza
26. Specialised investigations
■ A large number of specialized investigations,
including:
■ Ultracenterfugation
■ Apolipoprotein
■ Enzyme studies
■ Molecular genetic studies
Dr.Amal Hamza
27. Primary hyperlipoproteinaemias
■ The causes of hyperlipoproteinaemia are complex and different disease
mechanisms can give rise to similar lipid patterns.
Increased plasma lipid concentration may be due to:
■ Genetic factors -Environmental factors
■ A combination of the above -Other disease (secondary)
Types of hyperlipoproeinaemias
■ Primary hypercholesterolaemia
■ Familial hypertriglyceridaemia
■ Familial combined hyperlipidaemia
■ Remnant hyperlipoproteinaemia
■ Lipoprotein lipase deficiency
■ Secondary hyperlipidaemia
Dr.Amal Hamza
28. Primary
hypercholesterolaemia
■ In about 95% of patients with primary
hypercholesterolaemia, the abnormality is due to a
combination of dietary factors and a number of genetic
abnormalities in handling cholesterol.
■ In the minority of patients who have familial
hypercholesterolaemia, there is a specific genetic defect in
the production or nature of high-affinity tissue apoB100
itself, so that it is not recognized by the normal receptor.
Dr.Amal Hamza
29. Familial
hypertriglyceridaemia
■ This group of condition is associated with defects either in the
production or in the catabolism of VLDL.
■ Plasma triglycerides and VLDL are increased but, whereas
plasma cholesterol is also moderately increased, plasma HDL is
often reduced.
■ Patients have an increased risk of ischaemic heart disease.
Dr.Amal Hamza
30. Lipoprotein lipase deficiency
■ This is a rare autosomal recessive disorder causing
hypertriglyceridaemia and chylomicronaemia.
■ The incidence of ischaemic heart disease and acute pancreatitis
is increased.
■ The primary defect is deficiency of either lipoprotein lipase or its
activator, apoC-II.
■ Treatment involves restriction of normal dietary fat and
replacement by means of triglycerides containing fatty acids of
medium chain length (C8-C11); these are less prone to lead to
chylomicron formation.
Dr.Amal Hamza
31. ■ Three rare familial disease related to lipoprotein metabolism may
include:
■ Tangier disease is due to an increased rate of apoA-I catabolism.
■ Only traces of HDL are detectable in plasma and plasma LDL-C
ia also reduced.
■ Cholesterol esters accumulate in the lymph system.
■ A betalipoproteinaemia is associated with a complete absence of
apoB. Plasma cholesterol and TG are very low.
■ Hypobetalipoproteinaemia is due to decreased synthesis of
apoB. Plasma VLDL and LDL although reduced are not absent.
Dr.Amal Hamza
32. Other biochemical cardiovascular
markers
■ Very high levels of homocysteine, up to 50-fold normal,
are seen in homocystinuria, an inborn error of metabolism
due to deficiency of the enzymes cystathionine β-
synthase.
■ Patients develop ocular, skeletal and vascular problems
with increased arterial and venous thrombotic events at an
early age and a markedly increased mortality.
■ Lowering homocysteine in this group of patients has been
demonstrated to lower the risk of cardiovascular disease.
Dr.Amal Hamza
33. ■ Elevation in homocysteine levels are associated with
an increased risk of cardiovascular disease.
■ Homocysteine prove to be a marker of increased
vascular risk rather than a causative risk factor.
■ Homocysteine levels are strongly influenced both by
genttic factors and by diet. Folic acid and vitamins B6
and B12 are involved in the catabolic pathways of
homocysteine.
■ Patints with high CRP, an inflammatory marker or
hsCRP are at risk of cardiovascular disease.
Dr.Amal Hamza
34. ■ The origin of this increased CRP can be due to
endothelial inflammation in association with
atherosclerotic plaques.
■ It is possible to lower plasma LDL-C by dietary and
other lifestyle means but the most effective therapy,
usually leading to reduction of up to 30% or more is
achieved by HMG-CoA reductase inhibitors (statins).
Dr.Amal Hamza
