Cardiovascular Risk Factors

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Cardiovascular Risk Factors

• Laboratory Diagnosis of
• Acute Myocardial Infarction

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Major risk factors

• Heredity
• Sex (Male)
• Advancing Age
• Cigarette Smoking
• High Blood Pressure
• Obesity (Abdominal)
• Sedentary life style
• Increased blood cholesterol and other lipids

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Lipids

• Fatty acids
• Cholesterol and Cholesterol Esters
• Triglycerides
• Phospholipids
• Sphingolipids

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Fatty Acids

• Long straight-chain hydrocarbons with terminal
  carboxyl group
• Mainly exist as esters
• Even number of carbons unbranched
• May be saturated or unsaturated
• All synthesized by body except for linoleic and
  linolenic acid (essential fatty acids)

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Triglycerides

• 90 of dietary fat intake and 95 of fat stored
  in tissues
• Increased levels increased risk for
  arteriosclerosis
• Indicated in blood by creamy plasma layer

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Phospholipids

• Diglyceride esterified with phosphoric acid which
  is bound as ester to nitrogen-containing base or
  serine
• Essential components of cell membranes
• Align themselves between water phase and lipid
  phase

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Sphingolipids

• Contain sphingosine
• Also called ceramides- cerebral lipids containing
  amide group
• High percentage in brain and nerve sheaths

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Cholesterol

• Complex alcohol formed of 4 fused rings and a
  side chain
• Solid at body temperature
• Present in all tissues converted by gonads and
  adrenals into steroid hormones
• Ingested in meat, dairy products, eggs
• Major risk factor in CAD/atherosclerosis

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Classification of Lipoproteins

• Based on electrophoretic mobility
• Chylomicrons (slowest moving)
• Beta lipoproteins
• Pre-beta lipoproteins
• Alpha lipoproteins
• Based on Density (ultracentrifugation)
• Chylomicrons (lowest density
• Very low density lipoproteins (VLDL)
• Low density lipoproteins (LDL)
• High Density lipoproteins (HDL)

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Chylomicrons

• 85-95 triglycerides
• Transport dietary fat from intestines to
  adipose/muscle cells
• Creamy layer in plasma

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VLDL Lipoproteins

• 50-65 triglycerides
• Transport endogenous triglycerides to adipose
  tissue and fat

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Low Density Lipoproteins

• Transport cholesterol from the liver to the
  cells.
• LDL receptor proteins on cell membrane vital to
  uptake of cholesterol.
• When LDL receptors absent or deficient, blood
  levels rise and excess cholesterol deposited in
  arteries and other tissues
• Bad cholesterol
• LDL/HDL cholesterol good predictor of coronary
  artery disease risk

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HDL Lipoproteins

• Transport cholesterol from tissue to liver to be
  incorporated into bile salts.
• Good cholesterol
• Levels can be increased by exercise, weight loss

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Determination of LDL Chol.

• Friedewald Equation
• LDL chol Tot. chol HDL chol 1/5 Tgl
• (not valid if triglyceride level gt 400 mg/dL)
• Direct
• Immunochemical method taking advantage of fact
  that apo B-100 only apolipoprotein in LDL
  cholesterol

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Homocysteine

• May or may not be a risk factor for CAD
• Formed from methionine metabolism and rapidly
  metabolized by
• Remethylation (requires Vitamin B12 and folate)
• Transulfuration (requires Vitamin B6)
• Contributes to CAD by
• Direct toxic effect
• Interference with clotting factors
• Prevents small arteries from dilating

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C-reactive Protein

• An acute phase protein produced by liver in
  response to cytokine production
• Standard CRP tests cannot assess normal range
• hs-CRP assess levels within normal range
• CRP levels are elevated (but still within normal
  range) in persons with risk for CAD

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hs-CRP in Assessing Cardiovascular Risk

• Strong association between CRP and coronary
  events
• Association is independent of other confounding
  factors
• CRP is increased because of atherosclerotic
  progression

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Cardiac Markers

• Laboratory Diagnosis of Acute Myocardial
  Infarction

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Diagnosis of AMI dependent on

• Clinical symptoms
• Changes in EKG reading
• Increases in cardiac markers

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Cardiac Markers

• Myocardial proteins
• Differ in location within myocyte
• Released upon damage to cardiac muscle
• Cleared from serum
• Ideal marker
• Cardiac specific
• Rises soon after infarction
• Elevated over sustained period of time
• Easy to measure
• Quick turnaround time
• Measured at very low levels

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Enzymes as Cardiac Markers

• Creatine Kinase (CK or CPK)
• Aspartate Aminotransferase (AST) or Serum
  Glutamate Oxaloacetate Transaminase (SGOT)
• Lactate Dehydrogenase (LDH or LD)

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Creatine Kinase

• Creatine phosphate ADP ? creatine ADP
• Found in skeletal muscle, cardiac muscle, and
  brain
• Begins to rise 3-6 hours post MI, peaks at 24
  hours, normal in 3-4 days.
• Dimer of 2 subunits, M and B 3 isoenzymes

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Creatine Isozymes and Isoforms

• Isozymes of CPK may be electrophoretically
  separated
• CK-BB (CK-1) 2 B chains, fastest moving
• CK-MB (CK-2)
• CK-MM (CK-3)
• CK-MB isozymes exist in two forms, isoform 1 and
  isoform 2.
• CK-MB 2 is more specific for MI
• CK-MB 2/CK-MB 1 gt1.5 is sensitive indicator of MI

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AST or SGOT

• Aspartate a-ketoglutarate ? glutamate
  oxaloacetate
• Found in almost all tissues highest conc. in
  cardiac and skeletal muscle
• Rises 6-12 hours post MI, peaks at 24-48 hours,
  normal by day 4-6

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LD or LDH

• Oxidation of lactate to pyruvate by transfer of
  hydrogen from lactate to NAD
• Widely present
• 4 subunits composed of H or M chains
• LDHHHH (LD1) heart, fastest moving
• LDHHMM (LD2) heart
• LDHHMM (LD3)lung, many tissues
• LDHMMM (LD4) many tissues
• LDMMMM (LD5) skeletal muscle, liver

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• Begins to rise 24 48 hours post MI remains
  elevated for 7-10 days
• LD1/LD2 flip

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Myoglobin

• Oxygen carrying pigment of muscle
• Released into blood upon muscle damage
• Very sensitive to tissue necrosis

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• Advantages for Myoglobin as Cardiac Marker
• Appears in serum before other markers
• Conc. in dependent upon amount of damage
• Low renal threshold

• Disadvantages for Myoglobin as Cardiac Marker
• Even minor skeletal muscle damage can greatly
  increase myoglobin levels

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Cardiac Troponins

• Contractile proteins found in muscle that play
  role in actin-myosin interaction
• Complex of 3 protein subunits
• Troponin C calcium binding
• Troponin I inhibitory
• Troponin T tropomyosin-binding
• Cardiac specific troponin I and T have been
  identified (cTnI and cTnT)

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• cTnI used to assess patient with unstable angina
• cTnI may be used for risk stratification analysis
• Troponin has greater cardiac specificity than
  does myoglobin