15 Cardiac and Lipid Profile

Cardiac Profile

Cardiac Function Tests: ECG & Cardiac Imaging

Myocardial Ischemia

Most often caused by atherosclerosis

Inflammation of the coronary arteries

Thrombosis

Coronary vasospasm

ECG

Three patterns of Ischemic Heart Disease:

1.
Chronic ischemic heart disease
2.
Angina pectoris (stable & unstable)
Acute myocardial infarction
3.
WHO Diagnosis of Acute Myocardial Infarction (AMI)
Presence of two of the three ff. 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

Non-invasive, records electrical impulses

Useful in arrhythmia assessment
Relatively specific for diagnosis of AMI
Diagnostic sensitivity is 50% on initial presentation of
chest pain

Cardiac Imaging Techniques Scintigraphy

Monitor myocardial uptake of Technetium

99m pyrophosphate to detect infarcted

areas from 18-24 hrs after infarction

Sensitivity
84% for transmural (Q wave) infarctions
32% for nontransmural (non Q wave) infarctions
Cardiac Enzyme Studies
Patient Preparation:

No special preparation is required

Avoid excessive physical activity prior to CK total,

CK isoenzymes & myoglobin testing
Specimen Collection:

Serum is the specimen of choice

Heparinized plasma is acceptable

Venous whole blood for rapid Cardiac Troponin T

method

Dissection of the left anterior descending

artery showing blood clot (thrombosis)

Close-up view of the thrombosed L.A.D. artery

Total obstruction of the coronary artery as

seen in myocardial infarction

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, and at 12 hours
Creatine Kinase

A cytoplasmic and mitochondrial enzyme

Catalyzes reversible phosphorylation of creatine by

ATP for striated muscle cell contraction
Skeletal muscle has 5-10x the amount present in

cardiac muscle

Increased in various diseases

Measurement of isoenzyme more useful for diagnosis

of AMI
CK Isoenzymes

Two subunits: M Muscle

B Brain

Three isoenzymes: CK-BB (CK-1)

CK-MB (CK-2)
CK-MM (CK-3)
Number is based on relative electrophoretic mobility

with the most anodal fraction as number 1

Relative Proportion of CK Isoenzymes in Normal Serum and
Major Tissue Sources
Serum
Skeletal
Cardiac
Brain
Muscle
Muscle
0 trace BB 0% BB
97% BB
0 trace BB
<6% MB
1% MB
20% MB
3% MB
>94% MM
99% MM
80% MM 0%MM

rainwater@mymelody.com || 1st semester, AY 2011-2012

CK-MB Isoenzyme

Measured by MASS assay methods, the current gold

standard biochemical marker for AMI
Interpret with caution as overlap between cardiac

and skeletal muscle tissue values occur

Relative Index (RI)

CK-MB mass concentration to total CK activity

A tool to evaluate increased total CK activity

Not to be used if total CK is normal or CK-MB mass <

10ug/L
RI (%) = CK-MB (ug/L)
Total CK (U/L)

100

Cardiac Muscle Damage =

increased serum CK-MB with RI >6% of total CK
Skeletal Muscle Damage =
increased serum CK-MB with RI <6% of total CK

CK Isoforms (Isoenzyme Subtypes)

Produced in the blood stream in a time dependent

manner by sequential and irreversible cleavage of
lysine residues from CK-M subunit by lysine
carboxypeptidase

2 isoforms of CK-MB, 3 isoforms of CK-MM

CK-MB2: CK-MB1 is 1.0 normally, increased in AMI

Sensitivity of the ratio is second only to myoglobin in

detecting early AMI
Troponin

Troponin protein complex is located on the thin

filament of striated muscle (both cardiac & skeletal)
Regulation of calcium mediated muscle contraction
via its interaction with actin and myosin
Consist of 3 subunit proteins:
T (TnT) Tropomyosin binding subunit
I (TnI)
Myosin ATPase inhibiting subunit
C (TnC) Calcium binding subunit
(lacks cardiac specificity)

Cardiac Troponin T & Cardiac Troponin I

Serial measurements used in the diagnosis of AMI

Highly specific for myocardial damage

Initial rise as early as 3 hours after AMI

TnI remains elevated up to 5-9 days, TnT up to 14

days

Increased levels may predict poor outcome in

unstable angina
Myoglobin (Mb)

Cytoplasmic oxygen binding heme protein present in

striated muscle cells

Rapidly released to the circulation after muscle injury

A sensitive marker in the absence of concomitant

skeletal muscle trauma or renal failure

Specimens collected serially every 1-2 hours during

the first 2-10 hours after infarction

Levels that double within 1-2 hours are highly

suggestive of AMI

Aspartate Aminotransferase (AST)

Used to be called Serum Glutamate Oxaloacetate

Transaminase (SGOT)
Elevated to 4-10x the upper limit of normal in AMI

nd

Elevation within 12 hours of infarction, peak by 2

th
day & return to normal by 5 day

Secondary rise may reflect extension/recurrence of MI

Not routinely used for the diagnosis of AMI due to its

distribution in many tissues and lack of myocardialspecific isoenzyme
Lactate Dehydrogenase (LD)

Catalyzes the reversible oxidation of lactate to

pyruvate with the oxidation of NADH to NAD

Highest values (2-40 fold elevations) in megaloblastic

anemia, extensive carcinomatosis, severe shock, and
hypoxia

Moderate elevation (2-4 fold) in myocardial infarction,

pulmonary infarction, granulocytic or acute leukemia,
Hodgkins disease, hemolytic anemia, infectious
mononucleosis & progressive muscular dystrophy
Slight elevation in hepatitis, obstructive jaundice and

cirrhosis
Relative Percentage of LD Isoenzymes in Various Tissue
Tissue
LD1
LD2
LD3
LD4
LD5
Serum
25
35
20
15
5
Heart
45
40
10
5
0
Red Cells
40
35
15
10
0
Renal Cortex
35
30
25
20
0
Lung
10
15
40
30
5
Skeletal Muscle
0
0
10
30
60
Liver
0
5
10
15
70
LD Isoenzyme
In cardiac muscle, LD1/LD2 ratio is generally 0.5-0.75

In AMI, elevation of LD consists largely of LD1 and LD2,

the ratio often reverses

LD1/LD2 ratio > 1 (flipped pattern) in AMI, assumed

within 12-24 hours

LD1 resists denaturation at 65C for 30 minutes while

other 4 isoenzymes are destroyed
C-Reactive Protein

Atherosclerosis is an inflammatory disease and Creactive protein (CRP) is an acute-phase reactant that
is thought to be stimulated into hepatic production
by the release of circulating inflammatory mediators.
CRP reflects the extent of ischemia, necrosis,and

atherosclerosis; reflects the amount of circulating

proinflammatory cytokines.

Combined CRP levels and lipoprotein assessment

have additive usefulness in the evaluation of
apparently healthy people.
Future Thrusts

Serum amyloid A is an acute-phase reactant protein

and a marker for plaque rupture and inflammation.

D-dimer, an indirect marker of thrombin generation,

may be useful for diagnostic purposes in ACS.
Fibrinogen, von Willebrand factor antigen, and

fibronopeptide A appear to have utility in risk

stratification.

Plasma homocysteine concentration, a risk marker for

vascular disease, may predict late events

Median 2.5 years

rainwater@mymelody.com || 1st semester, AY 2011-2012

Current Cardiac Marker Characteristics & Clinical Utility

Marker
Tissue Source
Physiologic Function
Creatine
Skeletal muscle
Rephosphorylation of
Kinase (CK)
Cardiac muscle
ADP, forming ATP in
Total Activity
Skeletal muscle
muscle contraction

Diagnostic Window
Rise: 6-8 hr
Peak: 24-36 hr
Normal: 3-4 days

CK-MB
Isoenzyme,
Mass

Cardiac muscle
Skeletal muscle to a
much lesser extent

Same as above

Rise: 4-6 hr
Peak: 12-24 hr
Normal: >48 hr

CK-MB
Isoforms and
Isoforms ratio
Myoglobin

Same as above

Same as above

Cardiac muscle
Skeletal muscle

Oxygen binding
protein

Same as above

Same as above

Cardiac muscle;
regenerating
skeletal muscle

Same as above

Rise: 2-6 hr
Peak: 6-12 hr
Normal: 24-36 hr
Rise: 2-3 hr
Peak: 6-9 hr
Normal: 24-36 hr
Rise: 2-6 hr
Peak: 6-12 hr
Normal: 24-36 hr
Rise: 4-8 hr
Peak: 14-18 hr
Normal: >14 days

CK-MB
Isoforms and
Isoforms ratio
Cardiac
Troponin T
(cTnT)

Clinical Utility
Limited diagnostic value since it is
increased in various disease states.
CK isoenzyme analysis is more useful for
diagnosis
Mass assay of
CK-MB isoenzyme, the current gold
standard for early diagnosis of AMI
Early marker of AMI, more specific than
myoglobin
Non-specific early marker to rule in/rule
out AMI
Early marker of AMI, more specific than
myoglobin
As above for cTnI

Lipids and Lipoproteins

Lipids

A group of water-insoluble substances that are

extractable by nonpolar (fat) solvents, such as alcohol
and ether.
Include: fatty acids, neutral fats, waxes and steroids.
Compound lipids: glycolipids, lipoproteins, and
phospholipids.
Main groups: cholesterol and esters, glycerol esters
(TG), fatty acids, phospholipids.

Cholesterol

A sterol that is turned into bile acids and steroid

hormones and is a key constituent of cell membranes.
Largely endogenous and synthesized in liver.

Diet influences blood levels by 10 to 20%.

30 to 60% of cholesterol in diet is absorbed mixed

with conjugated bile acids, phospholipids, fatty acids,
and monoacylglycerides.
Triglycerides

Most abundant dietary fat and compose 95% of all fat

stored in adipose tissue.

Prime function: furnish energy for the cell.

In the intestines, in the presence of lipases and bile

acids are hydrolyzed into fatty acids, glycerol and
monoglycerides.

After absorption, are reconstituted into chylomicrons.

Unlike cholesterol, diet greatly affects levels.

Lipoproteins

Lipid-protein complexes in which lipids (which are

hydrophobic) are transported in the blood.

Lipoprotein particles consist of a spherical

hydrophobic core of TG or cholesterol esters
surrounded by an amphophilic mono-layer of
phospholipids, cholesterol, and apolipoproteins.

Chylomicrons
Large particles produced by the intestines that are very

rich in triglycerides (90%) of dietary origin, poor in

cholesterol and phospholipids, and low in protein (1%).

VLDL

Very-low-density lipoproteins.
Like chylomicrons, are triglyceride-rich (50%), can
float and make plasma turbid.
Unlike chylomicrons, are endogenous (liver).
Contains cholesterol and phospholipids (40%), and
protein (10%).
Action of Lpl gives rise to IDL.

LDL

Lipoprotein Metabolism

Exogenous metabolism: from dietary fat to

chylomicrons to glycerol, free fatty acids, and
monoglycerides.

Endogenous metabolism: from chylomicron remnant

to the liver to synthesis of VLDL, IDL, LDL, HDL.

Less dense than water due to high lipid to protein

ratio and floats.
Cause of milky plasma.
Due to action of lipoprotein lipase, becomes
triglyceride-poor: remnant.

Low-density lipoproteins
Make up 50% of total lipoproteins.
Even when in high concentration, does not cause
turbidity of plasma.
Esterified cholesterol makes up 50% of mass.
Subfraction: small particles with lower
cholesterol/apoB ratio that are seen in
dyslipoproteinemia associated with CAD.

rainwater@mymelody.com || 1st semester, AY 2011-2012

HDL

Hyperlipoproteinemia

High-density lipoproteins
Contain 50% protein, mostly apoA-I and II.
Subclasses: HDL2 and HDL3.
Low levels of apoA-I related to Coronary Artery
Disease.

Apolipoproteins
The hydrophilic components of lipoproteins (Lipids must be in
water soluble micellar structures for transport in plasma.)
Grouped by function:

ApoA: major protein of HDL;

ApoA-I activates LCAT, which esterifies
cholesterol in plasma.

ApoB: major protein (95%) of LDL.

ApoC: major protein of VLDL. ApoC-II activates

lipoprotein lipase.

ApoD and ApoE

Patient Preparation

Cholesterol:
Nonfasting acceptable for screening

12-14 hr fast for diagnosis

HDL / LDL Cholesterol: 12 hr or more fasting

Triglycerides: 12 hr or more fasting

Apolipoproteins: 12 hr or more fasting

General Lab Precautions
Interference in laboratory testing will occur in
specimens that are:

Lipemic

Turbid
Hemolyzed

Icteric
Do not use lubricated test tube stoppers for
triglyceride test as free glycerol can increase value
(correct with sample blank).
Physiologic Variation*
Component

Total Cholesterol

Triglycerides

LDL-cholesterol
HDL-cholesterol

ApoA-1

ApoB

Coefficient of Variation
5.0%
17.8%
7.8%
7.1%
7.1%
6.4%

Type
I
IIa
IIb
III
IV
V

Lipoprotein Pattern
Extremely elevated TG due to chylomicrons
Elevated LDL
Elevated LDL and VLDL
Elevated cholesterol; presence of b-VLDL; VLDLC/plasma TG ratio >0.3
Elevated VLDL
Elevated VLDL with chylomicrons

Fredrickson Classification*
Type
Refrigerator Test
Electrophoresis
I
+, clear plasma
Normal
IIa
-, clear plasma
High b band
IIb
-, cloudy plasma
High b & pre-b
III
, cloudy plasma
Broad b band
IV
-, cloudy plasma
High a-2 band
V
+, cloudy plasma
High a-2 band

original method of classifying lipid-related

diseases that enabled correlation of clinical
disease syndromes to laboratory assessment.
Standing Plasma Test

1.
2.
3.

2 ml of plasma in a test tube is allowed to stand inside

o
a refrigerator at 4 C undisturbed overnight.
Chylomicrons accumulate as a floating cream layer.
Turbid plasma contains excessive VLDL.

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 HDL

Lp (a) Lipoprotein Excess

Diagnosing Hypertriglyceridemia

rainwater@mymelody.com || 1st semester, AY 2011-2012

Lipid Interpretation for Coronary Heart Disease

Risk Factors for CHD

Positive Risk Factors:

Hypertension or on anti-HPN medication

Low HDL-cholesterol

Diabetes mellitus

Age: Male >45 yr; Female >55 yr or premature

menopause.
Family history of premature CHD (<55 yr for
father and <65 yr for mother)
Current cigarette smoking

Negative Risk Factors:

High LDL-cholesterol: >60 mg/dl

Adults: Cholesterol and HDL*

Total Cholesterol:
Desirable level
Borderline High
High
HDL-Cholesterol

Low

<200 mg/dl
200-239 mg/dl
>240 mg/dl
<35 mg/dl

Children of Hypercholesterolemics
T Chol
Category
(mg/dl)
Acceptable
<170
Borderline
170-199
High
>200

LDL-C
(mg/dl)
<110
110-129
>130

rainwater@mymelody.com || 1st semester, AY 2011-2012