• what are some tests for determining risk of CAD?
o Lipid Panel: direct (Total cholesterol, HDL, TGs), Calculated (LDL, VLDL, Ttl Chol/HDL ratio)
o Lp(a): Lipoprotein (a)
o Lipoprotein electrophoresis
o Hcy: Homocysteine
o hs-CRP: Highly-sensitive C-Reactive Protein
o Fibrinogen
• What are some tests for determining cardiac damage?
o CK: Total Creatine Kinase o CK-MB: Isoenzyme of CK, myocardial-bound o cTnT: Cardiac TroponinT o cTnI: Cardiac Troponin I o AST o LDH o Myoglobin
• Facts on heart dz?
o Leading cause of death (M and F), 600,000 americans per year (1/4 deaths) = each minute
o Coronary heart dz MC (385,000 deaths)
o MI every 34 secs in US
o US $108.9 billion each year
• Compare rates of CA and CVD deaths by age:
o CA slightly higher in 40s-70s
o >75 CVD rates get much higher
• Rank the US regions with highest heart dz death rates?
o South//Midwest
o NE coast
o SW (CA and NV)
• What is the Framingham risk calculator?
o Estimate 10-yr risk of MI o For 20+, don’t have CVD or DM o Age and gender o Meds for HTN? o total cholesterol, HDL, smoker, systolic BP
• what is a lipid panel/lipoprotein profile?
o Measures blood cholesterol
o Direct: total chol, HDL, TGs
o Calculatd: LDL, VLDL, ttl chol/HDL ratio
• What are blood lipids?
o water-insoluble, extractable by nonpolar (fat) solvents (alcohol, ether)
o = fatty acids, neutral fats, waxes, steroids
o Compound lipids: glycolipids, lipoproteins, phospholipids
o Main groups: cholesterol/esters, glycerol esters (TG), FAs, PLs
• How do lipids move thru body?
o intestinal mucosa →chylomicrons → liver o Chylo (huge) release TGs and some cholesterol to muscle and adapocytes → remnants taken up by liver o VLDL, IDL, LDL, formed in liver, carries fat and cholesterol to body’s cells. o HDL (tiny) carry fat and cholesterol back to liver for excretion
• What happens when oxidized LDL gets high
o →atheroma in walls of arteries → atherosclerosis (foam cells, smooth mm, necrotic core, LDL; bw intima and endothelium)
o HDL can remove cholesterol from atheroma
o Atherogenic cholesterol = LDL, VLDL, IDL
• What is cholesterol?
o A sterol, → bile acids, steroid hormones, cell membranes
o Mostly endogenous, made in liver
o Diet influences blood levels 10-20%
o 30-60% in diet absorbed → mixed w conjugated bile acids, PLs, FAs, MGs
• What are normal and critical cholesterol levels?
o Adult: 400, look at genetic markers
• What are relative % of cholesterol constituents?
o 60-70% LDL
o 25-35% HDL
o Rest is VLDL, chylomicrons
o Day-to-day values can vary by as much as 15%, 8% in 1 day
• What can interfere w total chol measurement?
o Seasonal: higher in fall & winter than in spring & summer
o Estrogens: ↓ plasma LDL; PG ↑ all Cholesterols
o Position: Standing higher than sitting; sitting higher than recumbent by 15%
• When are ↑ total cholesterol levels seen?
o Type II familial hypercholesterolemia: faulty LDL uptake recpetors, tx resistant
o Hyperlipoproteinemia Types II and III, st IV & V
o Cholestasis; Hepatocellular dz & Biliary cirrhosis
o Nephrotic syndrome; Chronic renal failure
o Pancreatic neoplasms; Hypothyroidism (LDL); DM
o High cholesterol diet; Obesity
• When are ↓ total cholesterol levels seen?
o Severe liver dz o Myeloproliferative dzs o Hyperthyroidism o Diet: malabsorption, malnutrition, Vegan o Certain chronic anemias o Inflammation o Acute illness o COPD o Tangier Dz o 30-50% drop from baseline 1 week after acute MI
• What are triglycerides?
o Most abundant dietary fat; 95% of all fat stored in adipose
o Prime function: energy for cell
o hydrolyzed into FAs, glycerol, MGs in intestines w lipase and bile acids
o →absorption → reconstituted into chylo-microns
o Unlike cholesterol, diet greatly affects levels
• What are normal and critical TG levels?
o Desirable: < 150 mg/dl o Borderline High: 150 – 199 o High: 200 – 499 o Very High: > 500 o Must fast; if >400, need Lp electrophoresis to directly measure LDL
• What can cause increased TG levels?
o Hyperlipoproteinemia Types I, IIb, III, IV, V o Liver disease, Alcoholism o Nephrotic syndrome/ renal disease o Hypothyroidism, DM, Pancreatitis o Glycogen storage diseases o MI, Gout, High fat diet
• What can cause dereased TG levels?
o Severe illness o Malnutrition o Malabsorption o Hyperthyroidism o Hyperparathyroidism o COPD
• What can interfere w TG measurement?
o ↑: Transient after food or alcohol, prego, OCPs, acute illness colds flu, smoking, physical inactivity/obesity, drugs
o ↓: Transient decrease after exercise, drugs
• What are lipoproteins?
o Lipid-protein complexes in which lipids (hydrophobic) are transported in blood
o spherical hydrophobic core of TG or cholesterol esters surrounded by amphophilic mono-layer of PLs, cholesterol, apolipoproteins
• what are the 2 types of lipoprotein metabolism?
o Exogenous: dietary fat → chylomicrons → glycerol, FFAs, MGs
o Endogenous: chylomicron remnant → liver → VLDL, IDL, LDL, HDL
• What are chylomicrons?
o Large particles made by intestines, ↑ diet TG (90%), ↓chol, PL, ↓ protein (1%)
o Less dense than water, ↑ lipid:protein ratio, floats
o Cause of “milky” plasma
o lipoprotein lipase → ↓TG = REMNANT.
• What is HDL?
o 50% protein, mostly apoA-I and II.
o Subclasses: HDL2 and HDL3.
o ↓ apoA-I related to CAD
• What are normal and CAD/CHD risk ranges for HDL?
o Males: 35-65 mg/dl o Females: 35-80 o Dangerous risk: < 25 o High CHD risk: 26-35 o Moderate risk: 36-44 o Average risk: 45-59 o Below average: 60-74 o No risk: > 75 o > 60mg/dl is considered protective
What can cause ↑ and ↓ HDL levels?
o ↑: Regular aerobic exercise, Oral estrogen, Insulin, Genetically increased alpha-lipoprotein
o ↓: Cigarette smoking, Sedentary lifestyle, Obesity, Stress, recent illness, Tangier dz, Acute & chronic liver dz
• What are the chol/HDL ratio risks for CHD (M; F)?
o ½ avg: 3.4; 3.3
o Avg: 5.0, 4.4
o 2x avg: 10.0; 7.0
o 3x avg: 24.0; 11.0
• What is VLDL?
o Like chylomicrons, ↑ TG (50%), Chol and PLs (40%), protein (10%).
o Unlike chylomicrons, are endogenous (liver)
o → IDL via LpL
o float, turbid plasma
• How does VLDL →IDL →LDL?
o HDL passes ApoC-II & ApoE to nascent VLDL in plasma
o LpL hydrolyze VLDL TG in capillary endothelium → ↓size & ↑density =IDL
o IDL returns ApoC-II and ApoE to HDL
o HDL passes cholesteryl esters to IDL in exchange for PLs and TGs =LDL
• How is VLDL measured?
o Calc of lipid panel: VLDL = TG/5
o valid only if TG < 400 mg/dl in a fasting sample
o If >400, consider lipoprotein electrophoresis (VLDL is the pre-beta band)
• What can cause ↑ VLDL levels?
o Hyperlipoproteinemia Types IIb, IV, & V
o ↑ cholesterol diet
o DM, Hypothyroidism, Nephrotic syndrome
o Cholestasis, Pancreatitis, Multiple myeloma
o Apoprotein CII deficiency (activates LpL)
• What is LDL?
o up 50% of total lipoproteins, 50% Esterified cholesterol
o Formed in blood from VLDL
o Doesn’t cause turbidity of plasma, even if high
o deposits free cholesterol on cell surfaces or taken up by LDL receptors on cell surfaces
o carries ~75% blood’s cholesterol to body’s cells
o Excess cholesterol in cells inhibits LDL receptor synthesis (LDL stays in blood)
• How is LDL related to atherosclerosis?
o ↑ LDL is most directly assoc w CAD & atherosclerosis
o Susceptible to peroxidation
o M0 → foam cells → GFs stim smooth mm, calcification →atherosclerosis
• How is LDL measured?
o on a Lipid Panel = calculated value (Friedewald’s formula)
o LDL = (Ttl chol)-(HDL)-(TG/5) = Ttl chol-HDL-VLDL
o valid only if TG < 400 mg/dl in a fasting sample
• What are lipoprotein subfractions?
o small particles w lower cholesterol/apoB ratio
o mb from LDL or HDL
o seen in dyslipoproteinemia, assoc w CAD
• What is lipoprotein electrophoresis?
o Separates Lps by charge and MW
o highest protein content (HDL) move fastest and farthest
o used ONLY if TG >400
o Not commonly done since Lipid Panel came into use
• What are the types of hyperlipoproteinemia?
o I: Extremely ↑TG dt chylomicrons o IIa: ↑ LDL o IIb: ↑ LDL and VLDL o III: ↑ cholesterol; w B-VLDL; VLDL-C/plasma TG ratio >0.3 o IV: ↑VLDL o V: ↑ VLDL w chylomicrons
• What is the Fredrickson classification for lipid-related dzs?
o Original method to correlate labs and lipid dzs
o Type; refrigerator test; electrophoresis
o I; + clear plasma creamy top layer; Normal
o IIa; - clear plasma; High b band
o IIb; - cloudy plasma; High b & pre-b
o III; +/- (occult) cloudy plasma; b band
o IV; - cloudy plasma; High a-2 band
o V; + cloudy plasma creamy top; High a-2 band
• What is the standing plasma test?
o =refrigerator test in Fredrickson classification
o 2 ml plasma in test tube stands at 4o C overnight.
o Chylomicrons accumulate as a floating “cream” layer
o A turbid plasma contains excessive VLDL.
• What are normal and critical LDL levels?
o Optimal: 189
o Any higher → ↑ risk CAD
• What can cause ↑ and ↓ LDL levels?
o Primary ↑: Hypercholesteremia, Familial Type II Hyperlipidemia
o 2nd ↑: High cholesterol diet, DM, Hypothryoidism, Nephrotic syndrome, Chronic renal failure, Prego
o ↓: Severe illness, Hypolipoproteinemia/A-beta-lipoproteinemia (beta is LDL), Oral estrogen, Hyperthyroidism
• What are the apolipoproteins?
o hydrophilic part of lipoproteins (for micelles)
o ApoA: major protein of HDL; ApoA-I activates LCAT (esterifies cholesterol in plasma)
o ApoB: major protein (95%) of LDL.
o ApoC: major protein of VLDL. ApoC-II activates LpL
o ApoD and ApoE
• What are the 2 recommendations to check lipid panel?
o ATP of NCEP: start at 20, then every 5 years; ttl chol, LDL, HDL, TGs; fasting
o US preventative: F 45+, M 35+; total chol & HDL every 5 yrs; if ttl >200 or HDL<40 get fasting; start at 20 if FHx/risk factors
• How should patient prepare for lipid panels?
o Cholesterol: Non-fasting acceptable for screening; 12-14 hr fast for dx
o HDL/LDL Cholesterol, TGs, apo-Lp’s: 12 hr + fasting
• How is hyper-TG-emia dx? Tx?
o M > 160 mg/dL; F > 135 mg/dL
o 500: diet and drugs
• What are risk factors for hyper-TG-emia?
o Alcoholism, meds, OCPs, prego
o DM, Glycogen Storage Dz, Hypothyroidism
o Hypertension, Hyperuricemia
o Pancreatitis, Renal do
• What are risk factors for CHD?
o Cerebrovascular dz
o Cigarettes >10/day
o DM, HTN (or BP meds), Male
o Age: M >45, F >55, or premature menopause
o FHx: premature CHD, 30%
o Poor diet
o High lipids, low HDL (hi HDL >60 = NEG risk factor)
• What has the trend been in smoking and obesity?
o Since 1970s, smoking has ↓, obesity has ↑
o Is there a trade-off for dzs??
