A 53-year-old man presents with recurrent chest pain that has gotten progressively worse over the last several weeks.

He says that approximately a year ago the pain would occasionally occur when he was mowing his yard but now the pain sometimes occurs while he is sitting in a chair at night reading a book.

The pain which is localized over the sternum lasts much longer now than it did a few months ago.

What type of disease does this individual have at present?

Myocardial IschaemiaAn imbalance between the supply of oxygen

and the myocardial demand resulting in myocardial ischaemia.

Most occurs because of atherosclerotic plaque within one or more coronary arteries.

Limits normal rise in coronary blood flow in response to increase in myocardial oxygen demand

Oxygen Carrying CapacityThe oxygen carrying capacity relates to the

content of hemoglobin and systemic oxygenation

When atherosclerotic disease is present, the artery lumen is narrowed and vasodilatation is impaired

Coronary blood flow cannot increase in the face of increased demands and ischemia may result

This causes myocardial cells to switch from aerobic to anaerobic metabolism, with a progressive impairment of metabolic, mechanical, and electrical functions.

Angina pectoris is the most common clinical manifestation of myocardial ischemia. It is caused by chemical and mechanical stimulation of sensory afferent nerve endings in the coronary vessels and myocardium.

During ischemia, ATP is degraded to adenosine, which, thay diffuses to the extracellular space, causing arteriolar dilation and anginal pain.

Adenosine as a pain messenger: Adenosine induces angina mainly by stimulating the A1 receptors in cardiac afferent nerve endings.

The coronary blood flow may be reduced by a mechanical obstruction due to- atheroma- thrombosis- spasm- embolus- coronary ostial stenosis- coronary arteritis

There can be reduction in the flow of oxygenated blood due to :-

- Anaemia- Carboxyhaemoglobinaemia- HypotensionIncreased demand for oxygen occurs in:-- increase cardiac output (e.g. thyrotoxicosis)- myocardial hypertrophy (e.g.hypertension or aortic stenosis)

AnginaWhen ischemia results it is frequently

accompanied by chest discomfort: Angina Pectoris

Angina is a symptom not a diseasechest discomfort associated with abnormal myocardial function in the absence of myocardial necrosis

May develop sudden increase in frequency and duration of ischemic episodes occurring at lower workloads than previously or even at rest

In the majority of patients with angina, development of myocardial ischemia results from a combination of fixed and vasospastic stenosis

WHO Diagnosis of Acute Myocardial Infarction (AMI):

Presence of two of the three criteria:1. History of characteristic chest pain2. Electrocardiographic changes (pathologic Q waves, ST segment and T wave changes)3. Typical pattern of serum cardiac enzyme

rise, peak and return to reference range

Risk factors

Risk factorsFamily HistorySmokingHypertensionDiabetes MellitusHypercholesterolaemiaLack of exercise

What are the investigations you advice for him?

a. ECG b. serum cardiac enzymes 

c. Lipid profiled. chest x-ray e. coronary angiogram 

Ischaemic heart disease

Laboratory Investigations- Specimen Collection:

Serum is the specimen of choice

Heparinized plasma is acceptable

Venous whole blood for rapid Cardiac Troponin T.

- Collection Time: Serial specimens collected at appropriate

time intervals

Serial measurements are most useful

Samples are drawn on admission

at 2-4 hours

at 6-8 hours

at 12 hours

Lipid Disease PatternsHigh cholesterol with High LDL-CHigh Triglycerides with Normal CholesterolHigh Cholesterol and High Triglycerides with

or without Low HDL-CLow Total Cholesterol with Low or Normal

HDLIsolated Low HDLIsolated High LDLLp (a) Lipoprotein Excess

200-500 mg/dl >500 mg/dl< 200 mg/dl

Diet andretest inone year

Evaluate for risk factors:

AlcoholismDiabetes MellitusGlycogen Storage

DiseaseHypertensionHyperuricemiaHypothyroidism

MedicationsOral contraceptives

PancreatitisPregnancy

Renal disorder

No riskfactors+ Risk factor or+ Family history

Diet anddrugsDiet

Male > 160 mg/dl Female > 135 mg/dl

Lipid Interpretation for Coronary Heart Disease

Lipids normalT Chol <200 mg/dlLDL <130 mg/dlHDL >45 mg/dl

Lipids normalT Chol <200 mg/dlLDL <130 mg/dlHDL >45 mg/dl

Repeat after 5 yrsRepeat after 5 yrs

Lipids abnormalT Chol 200-239 mg/dlLDL 130-159 mg/dlHDL 35-45 mg/dl

Lipids abnormalT Chol 200-239 mg/dlLDL 130-159 mg/dlHDL 35-45 mg/dl

Lipids abnormalT Chol >240 mg/dlLDL >160 mg/dlHDL <35 mg/dl

Lipids abnormalT Chol >240 mg/dlLDL >160 mg/dlHDL <35 mg/dl

RISK FACTORSCerebrovascular diseaseCigarettes >10/dayDiabetes mellitusFH of CHD/vascular diseaseHypertensionMaleOcclusive peripheral vascular diseaseOverweight >30%

RISK FACTORSCerebrovascular diseaseCigarettes >10/dayDiabetes mellitusFH of CHD/vascular diseaseHypertensionMaleOcclusive peripheral vascular diseaseOverweight >30%

Diet and/orDrugs

Diet and/orDrugs

DietRetest in 1 yr

0-1 risk factorNo coronary HD0-1 risk factorNo coronary HD

2 or morerisk factors2 or morerisk factors

Plasma cardiac markers of post- myocardial infarction.

CK = creatine kinase AST = aspartate transaminase LDH = lactate dehydrogenaseMYOGLOBINTRPONIN

MYOGLOBIN low-molecular-weight heam-containing

protein found in both skeletal and cardiac muscle.

Typical rise occurs within 2-4 hours after the onset of acute myocardial infarction. This is useful for the early diagnosis of acute myocardial infarction, as this rise is generally earlier than used cardiac markers.

myoglobin is not cardiac specific, better used in conjunction with other markers.

Creatine kinase and CK-MB Creatine kinase acts as a regulator of high-energy

phosphate production and utilization within contractile tissues.

Cytoplasmic CK is a dimer, composed of M and/or B subunits, which associate forming CK-MM, CK-MB and CK-BB isoenzymes

Cytosolic CK regenerate ATP from ADP, using PCr. There are two mitochondrial creatine kinase

isoenzymes, Mitochondrial creatine kinase is directly involved

in formation of phospho-creatine (PCr) from mitochondrial ATP,

CKCK-MM is the main isoenzyme found in

striated muscleCK-MB is found mainly in cardiac muscle

Trace amounts of CK-MB are found in skeletal muscle.

CK-BB is the predominant isoenzyme found in brain, colon, ileum, stomach and urinary bladder.

CKMost of the CK released after a myocardial

infarction is, in fact, the MM isoenzyme CK-MM.

A raised plasma total CK activity, due to entirely CK-MM, may follow recent intramuscular injection, exercise or surgery (NON SPECIFIC)

limited prognostic value

CK CK-MB also exists as two isoforms, namely

CK-MB1 and CK-MB2. CK-MB2 is predominantly released from

the myocardium. CK-MB that is routinely assayed reflects the

sum of the two isoforms. Normally CK-MB1 predominates in plasma,

but after an acute myocardial infarction this is reversed.

CK- MM has longer half life than MB.

CK Plasma enzyme activity is raised in about 95

% of cases of myocardial infarction and are sometimes very high.

second rise of plasma enzyme → extension of the damage

A prolonged rise in plasma CK →may suggest a cardiac ventricular aneurysm .

plasma enzyme activity does not usually rise significantly after episode of angina pectoris without infarction.

An increase in CK-MB in the plasma may not be seen until 4-8 h after the onset of chest pain.

When the diagnosis is not obvious, an elevated CK-MB or an increase in CK-MB of more than 15% over a 4-h period, even if both values are within the reference range, are suggestive of myocardial infarction.

The detection of a trend by serial measurements, may provide more information than single measurements.

ASTHepatic congestion due to right-sided heart

dys function may contribute to the rise of plasma AST activity

If there is primary hepatic dysfunction, plasma AST rises whereas LDH1 activity usually remains normal.

The sequence of changes in plasma AST activity in MI are similar to those of CK .

AST and LDHAST and LDH measurements are rarely of

practical value in the management of patients with suspected myocardial infarction.

Exceptionally, when a patient with chest pain presents late, measurement of LDH may be helpful as this enzyme remains elevated in the plasma for several days following myocardial infarction.

CARDIAC TROPONIN Cardiac troponins have been recommended as

the biochemical cardiac marker of choice. Troponins are muscle-regulator/ proteins

present in skeletal and cardiac muscle. Three troponins (TnC), (Tnl) and (TnT). Tn I and TnT appear in the plasma 48 hours

after symptoms of acuteMI, and are best measured 12 hours after the start of chest pain useful in the late presentation of chest pain.

An increased Tnl or TnT concentration is a sensitive marker of occult myocardial damage.

CARDIAC TROPONINAn increased Tnl or TnT concentration is a

sensitive marker of occult myocardial damage even in non-ischaemic conditions.

Troponin T may be elevated in patients with chronic renal failure and thus may not be so cardiac-specific

They are therefore not early markers of acute myocardial infarction, but they do stay elevated for about 7-10 days in plasma, which makes them useful in the late presentation of chest pain

CARDIAC TROPONIN

The 3 components of Troponin complex :

1. Troponin C = Ca++ binding.2. Troponin I = Actinomyosin ATPase inhibiting

element. * It binds actin inhibiting its binding to myosin * It is encoded by 3 different genes, giving rise to 3 isoforms. - Slow Skeletal Muscle - Fast - Cardiac Cardiac Muscle

* It is released within 4 hrs of the onset of ischemic Symptoms of myocardial infarction. So, it is used as a marker of myocardial infarction. peaks 14-24hrs and remains elevated for 3-5

days.

3. Troponin T = Tropomyosin binding element Its level increases within 6 hours of myocardial

infarction. Peaks at 72 hrs remains elevated 7-10 days.

2 Isoforms in the heart TnT1+ TnT2 are used as cardiac markers.

Troponin complex consist of 3 components

actintroponin

tropomyosinmyosin binding site

Ca2+Ca2+

Ca2+

Ca2+

the calcium ions bind to the troponin and changes its shape

Ca2+Ca2+

Ca2+

Ca2+

the troponin displaces the tropomyosin and exposes the myosin binding sites

Ca2+Ca2+

Ca2+

Ca2+

the bulbous heads of the myosin attach to the binding sites on the actin filaments

Ca2+ Ca2+

Ca2+

the myosin heads change position to achieve a lower energy state and slide the actin filaments past the stationary myosin

Ca2+ Ca2+

Ca2+APi PiPi

APi PiPi

APi PiPi

ATP binds to the bulbous heads and causes it to become detached

Ca2+ Ca2+

Ca2+

APi Pi

Pi

APi Pi

Pi

APi Pi

Pi

hydrolysis of ATP provides the energy to “re-cock” the heads

Ca2+ Ca2+Ca2+

APi Pi

Pi

APi Pi

Pi

APi Pi

Pi

calcium ions are re-absorbed back into the T system

APi Pi

Pi

APi Pi

Pi

APi Pi

Pi

the troponin reverts to its normal shape and the tropomyosin move back to block the myosin binding sites

Ischaemia-modified albuminA new marker, ischaemia-modified albumin,

is raised in the presence of myocardial ischaemia and may be used in the future in conjunction with conventional cardiac markers.

Increased coronary artery disease risk is least correlated with the following EXCEPT:a. elevated total cholesterol levels b. elevated LDL levels c. elevated HDL levels d. elevated Lipoprotein (a) levels e. elevated triglyceride levels 

Increased coronary artery disease risk is least correlated with the following EXCEPT:a. elevated total cholesterol levels b. elevated LDL levels c. elevated HDL levels d. elevated Lipoprotein (a) levels e. elevated triglyceride levels 

Which cardiac enzyme would you expect to rise within the next 3 to 8 hours :

a.Creatine kinase (CK)b.Lactic dehydrogenase (LDH)c.LDH - 1d.LDH – 2

Which cardiac enzyme would you expect to rise within the next 3 to 8 hours :

a.Creatine kinase (CK)b.Lactic dehydrogenase (LDH)c.LDH - 1d.LDH – 2

The laboratory tests that would confirm  a diagnosis of myocardial infarction include:

a.LDH, CK-MB and ASTb.Serum calcium, and APPTc.Sedimentation rate, and ALTd.Paul-Bunnell and serum potassium

The laboratory tests that would confirm  a diagnosis of myocardial infarction include:

a.LDH, CK-MB and ASTb.Serum calcium, and APPTc.Sedimentation rate, and ALTd.Paul-Bunnell and serum potassium

  Elevation of which of the following serum enzyme markers would be most useful in diagnosing a myocardial infarction in a patient who comes to your office 3 days after an episode of severe and prolonged substernal chest pain? 

a. LDH isoenzymes b. CK.MB c. TroponinI d. myoglobin 

 

  Elevation of which of the following serum enzyme markers would be most useful in diagnosing a myocardial infarction in a patient who comes to your office 3 days after an episode of severe and prolonged substernal chest pain? 

a. LDH isoenzymes b. CK.MB c. TroponinI d. myoglobin 

 

When cardiovascular disease is a concern, reduction of the saturated fat in the diet and substitutes made of polyunsaturted fat is desired. When teaching the client about this diet the one should instruct the patient to avoid : 

a.Fishb.Corn oil c.Whole milkd.Soft margarine

When cardiovascular disease is a concern, reduction of the saturated fat in the diet and substitutes made of polyunsaturted fat is desired. When teaching the client about this diet the one should instruct the patient to avoid : 

a.Fishb.Corn oil c.Whole milkd.Soft margarine

Which protein inhibits the interaction of actin and myosin? 

a. troponin C b. troponin T c. troponin I d. tropomysin

Which protein inhibits the interaction of actin and myosin? 

a. troponin C b. troponin T c. troponin I d. tropomyosin

myocardial infarctionMany patients with myocardial infarction

have a typical history of crushing central chest pain, perhaps radiating to the arm or jaw, associated with typical ECG changes. myocardial infarction can, however, present atypically, or even be clinically silent, particularly in the elderly

Troponin I and TnT appear in the plasma 4-8 hours after symptoms of acute myocardial infarction, and are best measured 12 hours after the start of chest pain.

They are therefore not early markers of acute myocardial infarction, but they do stay elevated for about 7-10 days in plasma, which makes them useful in the late presentation of chest pain