15 - Cardiac and Lipid Profile

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15 Cardiac and Lipid Profile

Cardiac Profile

Myocardial Ischemia Most often caused by atherosclerosis Inflammation of the coronary arteries Thrombosis Coronary vasospasm

Three patterns of Ischemic Heart Disease: 1. Chronic ischemic heart disease 2. Angina pectoris (stable & unstable) 3. Acute myocardial infarction

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

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

Cardiac Function Tests: ECG & Cardiac Imaging

ECG 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

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 Muscle

Cardiac Muscle

Brain

0 trace BB 94% MM

0 trace BB 1% MB 99% MM

0% BB 20% MB 80% MM

97% BB 3% MB 0%MM

B


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) x 100 Total CK (U/L)

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

Skeletal Muscle Damage = increased serum CK-MB with RI 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 C-

reactive 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


Current Cardiac Marker Characteristics & Clinical Utility Marker Tissue Source Physiologic Function Diagnostic Window Clinical Utility Creatine Kinase (CK) Total Activity

Skeletal muscle Cardiac muscle Skeletal muscle

Rephosphorylation of ADP, forming ATP in muscle contraction

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

Limited diagnostic value since it is increased in various disease states. CK isoenzyme analysis is more useful for diagnosis

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

Mass assay of CK-MB isoenzyme, the current gold standard for early diagnosis of AMI

CK-MB Isoforms and Isoforms ratio

Same as above Same as above Rise: 2-6 hr Peak: 6-12 hr Normal: 24-36 hr

Early marker of AMI, more specific than myoglobin

Myoglobin Cardiac muscle Skeletal muscle

Oxygen binding protein

Rise: 2-3 hr Peak: 6-9 hr Normal: 24-36 hr

Non-specific early marker to rule in/rule out AMI

CK-MB Isoforms and Isoforms ratio

Same as above Same as above Rise: 2-6 hr Peak: 6-12 hr Normal: 24-36 hr

Early marker of AMI, more specific than myoglobin

Cardiac Troponin T (cTnT)

Cardiac muscle; regenerating skeletal muscle

Same as above Rise: 4-8 hr Peak: 14-18 hr Normal: >14 days

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.

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.

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%).

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.

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 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.


HDL 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 Coefficient of Variation Total Cholesterol 5.0% Triglycerides 17.8% LDL-cholesterol 7.8% HDL-cholesterol 7.1% ApoA-1 7.1% ApoB 6.4%

Hyperlipoproteinemia

Type Lipoprotein Pattern I Extremely elevated TG due to chylomicrons IIa Elevated LDL IIb Elevated LDL and VLDL III Elevated cholesterol; presence of b-VLDL; VLDL-

C/plasma TG ratio >0.3 IV Elevated VLDL V 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 ml of plasma in a test tube is allowed to stand inside a refrigerator at 4o C undisturbed overnight.

2. Chylomicrons accumulate as a floating cream layer. 3. 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


Lipid Interpretation for Coronary Heart Disease

Risk Factors for CHD Positive Risk Factors:

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

menopause. - Family history of premature CHD ( /JPEG2000ColorImageDict > /AntiAliasGrayImages false /CropGrayImages true /GrayImageMinResolution 300 /GrayImageMinResolutionPolicy /OK /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 300 /GrayImageDepth -1 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict > /GrayImageDict > /JPEG2000GrayACSImageDict > /JPEG2000GrayImageDict > /AntiAliasMonoImages false /CropMonoImages true /MonoImageMinResolution 1200 /MonoImageMinResolutionPolicy /OK /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 1200 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict > /AllowPSXObjects false /CheckCompliance [ /None ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile () /PDFXOutputConditionIdentifier () /PDFXOutputCondition () /PDFXRegistryName () /PDFXTrapped /False

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15 - Cardiac and Lipid Profile

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