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 Ischaemia
An 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 Capacity

The 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 - Hypotension Increased demand for oxygen occurs in:- increase cardiac output (e.g. thyrotoxicosis) - myocardial hypertrophy (e.g.hypertension or aortic stenosis)

Angina
When ischemia results it is frequently accompanied by

chest discomfort: Angina Pectoris

Angina is a symptom not a disease

chest 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 pain 2. 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 factors

Family History Smoking Hypertension Diabetes Mellitus Hypercholesterolaemia Lack of exercise

What are the investigations you advice for him?

a. ECG b. serum cardiac enzymes c. Lipid profile d. 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 Patterns

High cholesterol with High LDL-C
High Triglycerides with Normal Cholesterol High Cholesterol and High Triglycerides with

or

without Low HDL-C Low Total Cholesterol with Low or Normal HDL Isolated Low HDL Isolated High LDL Lp (a) Lipoprotein Excess

Male > 160 mg/dl < 200 mg/dl

Diet and retest in one year

Female > 135 mg/dl >500 mg/dl

200-500 mg/dl
Evaluate for risk factors:
Alcoholism Diabetes Mellitus Glycogen Storage Disease Hypertension Hyperuricemia Hypothyroidism Medications Oral contraceptives Pancreatitis Pregnancy Renal disorder

Diet

Diet and drugs

No riskfactors

+ Risk factor or + Family history

Lipid Interpretation for Coronary Heart Disease

Lipids normal T Chol <200 mg/dl LDL <130 mg/dl HDL >45 mg/dl
Repeat after 5 yrs Lipids abnormal T Chol 200-239 mg/dl LDL 130-159 mg/dl HDL 35-45 mg/dl 0-1 risk factor No coronary HD Lipids abnormal T Chol >240 mg/dl LDL >160 mg/dl HDL <35 mg/dl

2 or more risk factors

Diet Retest in 1 yr

RISK FACTORS Cerebrovascular disease Cigarettes >10/day Diabetes mellitus FH of CHD/vascular disease Hypertension Male Occlusive peripheral vascular disease Overweight >30%

Diet and/or Drugs

Plasma cardiac markers of postmyocardial infarction.

CK = creatine kinase AST = aspartate transaminase

LDH = lactate dehydrogenase

MYOGLOBIN TRPONIN

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,

CK
CK-MM is the main isoenzyme found in striated

muscle CK-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.

CK
Most 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 CKMM, 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.

AST
Hepatic 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 LDH

AST 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 TROPONIN
An increased Tnl or TnT concentration is a sensitive

marker of occult myocardial damage even in nonischaemic conditions. Troponin T may be elevated in patients with chronic renal failure and thus may not be so cardiac-specific

CARDIAC TROPONIN
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

The 3 components of Troponin complex : 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
1.

- 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

myosin binding site tropomyosin

actin

troponin

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

Pi Pi Pi A

Pi Pi Pi Ca2+ A

Ca2+

Pi Pi Pi A

Ca2+

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

Pi Pi Pi A Pi Pi Pi A Pi Pi Pi A

Ca2+

Ca2+ Ca2+

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

Pi Pi Pi A Pi Pi Pi A Pi Pi Pi A

Ca2+

Ca2+

Ca2+

calcium ions are re-absorbed back into the T system

Pi Pi Pi A Pi Pi Pi A Pi Pi Pi A

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

Ischaemia-modified albumin
A 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 - 1 d. 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 - 1 d. LDH 2

The laboratory tests that would confirm a diagnosis of myocardial infarction include:
a. LDH, CK-MB and AST b. Serum calcium, and APPT c. Sedimentation rate, and ALT d. Paul-Bunnell and serum potassium

The laboratory tests that would confirm a diagnosis of myocardial infarction include:
a. LDH, CK-MB and AST b. Serum calcium, and APPT c. Sedimentation rate, and ALT d. 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. b. c. d.

Fish Corn oil Whole milk 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. b. c. d.

Fish Corn oil Whole milk 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 infarction
Many 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