week 8- Cardiac markers & Thyroid Flashcards
• What are the novel cardiac biomarkers?
o Lp (a)
o Homocysteine
o hsCRP
• what is Lp(a)?
o Independent risk factor for CHD
o = “LDL like” Lp + glycoprotien (a) (Apo(a) structurally like plasminogen, w/o fibinolytic activity)
o role in initiation, progression and possible rupture of atheromatous plaque
o Competes w plasminogen particle and inhibits thrombolytic activity
o inhibits NOS
• what are risks of elevated Lp(a)?
o ↑ incidence CHD < 50 or > 70
o Mid-age F, >30 mg/dL assoc w 2x risk CHD
o W ↑ LDL-C →risk of angina
o Assoc w development of first MI in men
• What can increase Lp(a) levels?
o ↑ production (liver) in nephrotic syndrome
o ↓ clearance in dialysis pts
• What are indications of getting Lp(a) measured?
o premature atherosclerosis or FHx
o ↑ LDL & other risk factors
o Not recommended for first line screening
• What are normal and critical Lp(a) levels? Caveat?
o Optimal: < 20 mg/dl o Borderline High Risk: 20 – 30 o High Risk: 31 – 50 o Very High Risk: > 50 o But half of all MIs occur in ppl w normal plasma lipid levels → atherosclerosis mb an inflammatory dz → so we have additional CAD risk factor biomarkers
• Why is hsCRP used as a CVD biomarker?
o Inflammation is a risk factor of CVD →cytokines in blood, assoc w risk
o = “acute phase reactant”, ↑ w inflammation from any cause
o predictive value of hsCRP is significantly higher than total cholesterol, HDL, LDL, Lp(a), and homocysteine
o = best marker dt long half life and stability
o tx inflammation → ↓CRP, representing ↓ cardiovascular risk.
o Detectable to 0.01 mg/dL (vs regular CRP)
• What may CRP levels indicate?
o > 1.5 mg/dl (RR: 0-3) = acute inflammatory response
o >10 often dt bacterial infx
• What is the role of CRP in atherogenesis?
o Unknown causative role
o present in the atherosclerotic lesion, may actively contribute to progression and/or instability of atherosclerotic plaque.
• What is homocysteine?
o Intermediary amino acid in methionine → cysteine
o Mod ↑ in 5-7% pop
o independent risk factor for development of atherosclerotic vascular disease/CVD and venous thrombosis (but less important than classic factors)
o Can result from genetic defects, drugs, vitamin deficiencies, smoking
• How is homocysteine directly involved in vascular injury?
o Cytotoxic effect on endothelial cells →damage arterial wall →lipids accumulate →plaque
o Produces ROS → LDL oxidation
o Smooth muscle hypertrophy
• Who should be screened for homocysteine? How? How are hi levels treated?
o Screening recommended w premature CVD (or unexplained DVT) and absence of other risk factors
o Use plasma from lavender tube (EDTA)
o Tx: folate, B6, B12 supplements (required in homocysteine metabolism)
• What are normal and critical homocysteine levels?
o Normal: 4 –17 umol/L o Desirable: < 10 o borderline hi: 12-15 o mod: 16-30 o high: 31-100 o very high: > 100
• What are inherited and acquired causes of ↑ homocysteine?
o I: Cystathione b-synthase def, MTHFR def or defect (in at least 43% pop), Methionine synthase defect, B12 transport defect, B12 coenzyme synthesis defect
o A: B6 B12 or folate def, Chronic dz, CRF, Hypothyroidism, Psoriasis, Malignancies, ALL, Anticonvulsants, methotrexate
• What are tests for determining cardiac damage?
o CK: Total Creatine Kinase o CK-MB: Isoenzyme of CK, myocardial-bound o cTnT: Cardiac Troponin T o cTnI: Cardiac Troponin I o Myoglobin o AST, LDH
• What are cardiac markers?
o Located in myocardium
o Released in cardiac injury: MI, Non-Q-wave infarction, Unstable angina, Others (trauma, cardiac surgery, myocarditis etc)
o measured in blood
• what info can cardiac markers provide?
o Rule in/out acute MI
o Confirm old MI (several days)
o Monitor success of thrombolytic tx
o Risks stratification of unstable angina (if healthy, done by assess of cardiac risk factors, not markers)
• What determines the rate at which cardiac markers are released?
o Size and subcellular distribution
• What happens in MI that causes release of cardiac markers?
o Coronary artery occlusion →myocardial ischemia →anoxia →ATP pump fails, leak ions, eg K, PO4
o →lack of collateral blood flow → metabolites accumulate, leak, eg lactate, Ado
o →reversible damage → membrane damage, leak myocardial markers (enzymes, proteins)
o →irreversible damage, cell death, necrosis
• What are the average detection, peak, and disappearance times of cardiac markers after MI?
o Myoglobin: 1-4 h, 6-7 h, 24 h o CK-MB mass: 3-12 h, 12-18 h, 2-3 d o Total CK: 4-8 h, 12-30 h, 3-4 d o cTnT: 4-12 h, 12-48 h, 5-15 d o cTnI: 4-12 h, 12-24 h, 5-7 d
• what is creatine kinase (total CK)? Normal ranges?
o Enzyme, catalyzes ATP + creatine → ADP + phosphocreatine
o Isoenzymes in heart muscle, skeletal muscle, brain
o ↑ within 4-6 hs of acute MI, peak 18 hrs
o Returns to normal in 2-3 days
o M: 38-175 U/L
o F: 26-140
• What can cause ↑ CK?
o MI o Progressive MD o Dermatomyositis & polymyositis o Muscle trauma: Rhabdomyolysis or Myocarditis o Acute cerebrovascular dz, Brain trauma o Surgery
• What are the CK isoenzyme tests that can ↑ specificity? Normal ranges?
o CK-BB: brain, 0%
o CK-MB: heart, st skeletal muscle, 0-6% (this one used for possible MI)
o CK-MM: skeletal & cardiac muscle, 94-100%
• When does CK-MB increase?
o 4-6 hrs post-MI, peak 12-24 hrs, normalize 24-48 hrs
o Also ↑ in: Myocardial ischemia, Muscular dystrophy, Muscle trauma, Myocarditis
