Diseases Of Lipid Metabolism

Question 1

Lipid profile testing

Answer 1

. Blood collected after 12 hr fast

Question 2

Total cholesterol diserable, borderline, and high numbers

Answer 2

. Desirable: <200
. Border: 200-239
. High: > 240

Question 3

TAG desirable, borderline, high, and very high levels

Answer 3

. Normal: <150
. Border: 150-199
. High: 200-499
. Very high >500

Question 4

HDL low level and high level

Answer 4

. Low: <40

. High: >60

Question 5

LDL normal, near normal, borderline high, high, and very high values

Answer 5

. Normal: <100
. Near normal: 100-129
. Borderline high: 130-159
. High: 160-189
. Very high: >190

Question 6

Friedewald equation

Answer 6

. LDL = TC - HDL- (TG/5)

. Only valid w/ patient fasting and if lipids are reported in mg/dL units and TG< 400

Question 7

Specialized tests that may be included w/ lipid profile

Answer 7

. Direct LDL 
. VLDL
. non-HDL
. Apo levels 
. APo E genotyping
. lipoprotein a (LAL-like lipoprotein particle)
. Lipoprotein particle size
. Lipoprotein electrophoresis

Question 8

Primary lipid disorders

Answer 8

. Uncommon
. Suspected if: physical manifestations of hyperlipidemia, early athlerosclerotic heart disease, family history, extremely high blood lipid levels

Question 9

Familial combined hyperlipidemia

Answer 9

. Most common hyperlipidemia (1% pop.)
. Mild-moderate in severity
. Hepatic overproduction of VLDL and possibly limits VLDL clearance from blood
. May be due to overproduction of apo B-100
. Mild-moderate elevation of TAGs and/or cholesterol
. Diagnosis challenging

Question 10

Familial hypercholesterolemia

Answer 10

. Mutation in gene coding for LDL receptor or genes for apo B-100 and PCSK-9
. Could effect LDLR synthesis, transport to cell surface, B 100 binding, endocytosis, or recycling
. LDL not cleared from blood and severe hypercholestermia ensues
. Autosomal dominant w/ gene-dosage effect (heterozygous has symptoms but not as severe as homozygous
. Treat w/ statins, lifestyle, or plasma spheres is to remove cholesterol from blood

Question 11

Tangier disease

Answer 11

. Autosomal
. Mutation in gene coding for ABCA1 cholesterol transporter
. Accumulation of cholesterol in various organs and tissues (tonsils common)
. Low blood HDL
. Early atherosclerotic disease common

Question 12

Sitosterolemia

Answer 12

. Abnormal accumulation of plant sterols and mildly elevated cholesterol in blood
. Gene mutation in ABCG5/8 or NPC1L1

Question 13

Abetalipoproteinemia

Answer 13

. Autosomal recessive condition assoc. w/ mutation in gene coding for microsomal triglyceride transfer protein (MTP)

Question 14

Apolipoprotein C-II and familial hyperchylomicronemia deficiencies

Answer 14

. Assoc. w/ severe hypertriglyceremia
. Mutation in genes coding for lipoprotein lipase or apo C-II
. Symptoms in childhood: colic, abdominal pain, failure to thrive
. Symptoms as adult: pancreatitis, heart disease from hyperlipidemia

Question 15

Secondary lipid disorders

Answer 15

. Acquired
. Common causes: DM, pregnancy, hypothyroidism, kidney/liver disease, excess alcohol, meds
. Treatment: treat underlying cause

Question 16

Multifactorial lipid disorders

Answer 16

. Polygenic hypercholesterolemia (nonfamilial)
. Most common cause of hypercholesterolemia
. Genetic susceptibility from multiple genes interacts w/ environmental factors to produce mild-moderate hypercholesterolemia
. Inc. risk for heart disease

Question 17

Mathematical relationship btw dietary intakes of fats and serum cholesterol

Answer 17

. Change in cholesterol = 2.32(change in sat. Fat) + 0.32(change in monounsat. Fat) - 1.46(change in polyunsat. Fat) + 0.065(change in dietary chol) + 0.83

Question 18

T/F trans-fat has effect on serum total cholesterol

Answer 18

T, inc. risk for heart disease

Question 19

Groups of patients that should be treated w/ statin

Answer 19

. Patients w/ pre-existing atherosclerotic cardiovascular disease
. Pts w/ LDL over 190
. 40-75 y/o w/ LDL 70-189 and 10-yr risk for atherosclerotic cardiovascular disease (ACVD) event over 7.5%
. 40-75 y/o w/ diabetes and LDL 70-189

Question 20

Guidelines don’t recommend statin therapy for these groups of patients:

Answer 20

. Pts over 75 (unless pre-existing ACVD present)
. Pts doing dialysis
. Pts w/ certain types of heart failure

Question 21

Controversy over guidelines

Answer 21

. Risk calculator overestimates risk for CVD

. Unnecessarily prescribing statins

Question 22

Metabolic syndrome

Answer 22

. Concurrent presence of multiple lipid and non-lipid risk factors for CHD in patient
. Presence of risk factors inc. risk for CHD at any LDL level
. Management focuses on reduction of underlying causes and treatment of lipid and non-lipid risk factors (anti-hypertensives)

Question 23

Metabolic syndrome diagnosis

Answer 23

. 3 of the following: 
. Abdominal obesity (waste over 40 in men, 35 in women)
. TAGs over 150
. low HDL (Under 40 men, Uber 50 women)
. Bp over 130/85
. Fasting blood glucose over 110

Question 24

Lomitapide

Answer 24

MTTP inhibitor lowers hepatic VLDL synthesis

. Used for familial hypercholesterolemia

Question 25

Mipomersen

Answer 25

. Antisense oligonucleotide lowers hepatic B-100 synthesis

. Used to treat familial hypercholesterolemia

Question 26

Infant presentation of abetalipoproteinemia

Answer 26

. Failure to thrive
. Diarrhea
. Neurologic symptoms
. Fat soluble vitamin deficiency (ADEK)

Question 27

Most important type of dietary fat in cholesterol serum levels

Answer 27

. Saturated fat