Dyslipidemias

Question 1

Calculating LDL (why and formula?)

Answer 1

LDL cholesterol closely related to CVD risk and can be treated. LDL most important to address clinically
Formula: LDL = total chol - HDL - (triglyc/5)
VLDL - Triglyc/5 (ONLY if triglyc

Question 2

CVD Risk factors (and how to estimate risk)

Answer 2

Age (male >45, female >55)
Fmaily hx of CHD
CHD in male first degree relative  Caucasian
DM
Current Smoking
HTN >140/90
Low HDL (60 is NEGATIVE RISK FACTOR
USE THE FRAMINGHAM RISK SCORE

Question 3

Frequency to check cholesterol?

Answer 3

> 20 yo –> lipid panel every 5 years

Question 4

Goals for LDL-C

Answer 4

0-1 risks: 160

>2 risks: 130 (10 year risk 20%): 100 (or 70 now favored)

Question 5

Determining Cause of High LDL

Answer 5

assess blood glucose, HbA1c, TSH, LFTs, creatinine, unrine protein, lifestyle, EtOH use

1) Increased LDL production (overproduction of VLDL by liver, ie insulin resistance, usu see incr in apo B too
2) Decreased LDL catabolism (familial hypercholesterolemia, decreased LDL clearance)

Question 6

High LDL

Familial Hypercholesterolemia

Answer 6

1/500, AD, half don’t have LDL-receptor, other half have defective LDL-receptor
Elevated LDL leads to premature death (

Question 7

High LDL

Decreased LDL clearance

Answer 7

diets high in sat or trans fats, hypothyroidism, nephrotic syndrome, cyclosporin

Question 8

High Triglycerides (normal level/poss causes)

Answer 8

nl = 1000 serum looks milky (leads to pancreatitis)
Rule out secondary causes by measuring TSH, Cr, LFTs, fasting glucose, urine protein, H&P, meds
1) increased VLDL production
2) decreased TG-rich Lipoprotein Catablosim
3) severe hypertriglyceridemia (>1000)

Question 9

High Triglycerides

Increased VLDL production

Answer 9

most commonly from insulin resistance (no appropriate insulin anti-lipolytic effect)
Drugs: protease inhibs (HIV drugs), oral estrogens, renal dz can also contribute
EtOH (promotes formation of fatty acids)

Question 10

High Triglycerides
Decreased TG-rich Lipoprotein Catabolism
(Primary/Secondary)

Answer 10

Primary: LPL or C2 defic, familial dysbetalipoproteinemia
Secondary: to DM, EtoH, renal failure

Question 11

Increased Non-HDL

Answer 11

VLDL, IGL, LDL (all apoB-100 containing lipoproteins)

Better predictor of VD than LDL alone

Question 12

Increased Non-HDL

Familial dysbetalipoproteinemia

Answer 12

AR, defect in IDL and remnant catabloism
Apo E2 ALLELLE (rather than E3 or E4)
Leads to decreased clearacne and accumulation of IDL as Apo E2 doesn’t bind hepatic receptors correctly
DIAGNX: LIPOPROTEIN ELECTROHORESIS, APO E genoptype
Sx: planar XANTHOMATA (palms/soles), premature atherosclerosis

Question 13

Low HDL (labs/assoc/mutations/acquired)

Question 14

Increased Lipoprotein (a)

Answer 14

Apo (a) apolipoprotein linked by single disulfide bridge to LDL apo B = lipoprotein (a)
Fx unknown but assoc with premature AS (esp. in women)
RESEMBLES PLASMINOGEN (promotes clotting)

Question 15

What is seen in elite athletes and in insulin resistance?

Answer 15

Fat droplets (high TGs) in muscle

Question 16

Statin benefit groups (4)

Answer 16

1) Clinical CVD [HIGH]
2) LDL >190 mg/dl [HIGH]
3) Primary prevention: DM, 40-75 yo, LDL 70-189 [MOD to HIGH]
4) Primary prevention: No DM, 40-75 yo, LDL 70-189, BUT >7.5% risk of CVD event in next 10 years [MOD]

Question 17

Statin (mech)

Answer 17

inhibits HMG CoA, which reduces production of LDL AND incr LDL receptor expression (so increases LDL clearance)

Question 18

Statin (6% rule/order of potency)

Answer 18

For each dose doubling, LDL falls 6% (use to weigh benefits and side effects)
Risuvastatin>atorvastatin>simvastatin

Question 19

Statin side effects

Answer 19

Dose related changes in AST/ALT (hepatic injury)
Myopathies (myalgies, myosities, rhabdo: SLCO1b1*5 allele)
New onset T2DM (1.1% risk incr)
Rare cognitive impairment

Question 20

Other cholesterol reducing tx

Answer 20

1) Sterol transporter inhibitor EZETIMIBE (at brush border of intestine) –> second line, as add on to statin[NO ADRs!!]
2) Plant sterols and stanol esters (not good evidence for reducing CVD)
3) Inhibit Bile Acid resorption of cholesterol [bile aid sequestrants]

Question 21

Triglyceride Reducing Drugs

Answer 21

Statins
Fibrates (PPAR agonist, liver and muscle oxidize more FA, some ADRs, Cr incr is reversible, contra: renal and hepatic pobs)
Omega-3 oils (fish oils) - modest effect
Niacin (nicotinic acid - also raises HDL, and drops LDL, MANY contraindications, ADR flushing)

Question 22

Lipid types and CVD risk

Answer 22

High LDL-C, consistently incr risk of CVD, multiple RCT evidence, Mech: biochemical modification and resultant inflammation
High triglycerides: variably increased risk of CVD, nto clear why, minimal data
Low HDL-C: variably increased risk of CVD, possibly reduced reverse cholesterol transport, minimal data

Question 23

PCSK9 inhibitor antibodies

Answer 23

Alirocumab and Evolocumab, approved by FDA in last 4 months AS ADJUNCTS TO STATINS for when additional lowering of LDL-C necessary
Maximum lowering with these drugs is better than most powerful statins
ADR: injection site rxn 5%, rare allergy, poss neurocognitive events, drug-induced antibodies

Question 24

MTP inhib with Lomitapide

Answer 24

acts on liver and intestine, and apoB-48 secretion

ADR: BAD, steatorrhea