Dyslipidemias Flashcards
Calculating LDL (why and formula?)
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
CVD Risk factors (and how to estimate risk)
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
Frequency to check cholesterol?
> 20 yo –> lipid panel every 5 years
Goals for LDL-C
0-1 risks: 160
>2 risks: 130 (10 year risk 20%): 100 (or 70 now favored)
Determining Cause of High LDL
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)
High LDL
Familial Hypercholesterolemia
1/500, AD, half don’t have LDL-receptor, other half have defective LDL-receptor
Elevated LDL leads to premature death (
High LDL
Decreased LDL clearance
diets high in sat or trans fats, hypothyroidism, nephrotic syndrome, cyclosporin
High Triglycerides (normal level/poss causes)
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)
High Triglycerides
Increased VLDL production
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)
High Triglycerides
Decreased TG-rich Lipoprotein Catabolism
(Primary/Secondary)
Primary: LPL or C2 defic, familial dysbetalipoproteinemia
Secondary: to DM, EtoH, renal failure
Increased Non-HDL
VLDL, IGL, LDL (all apoB-100 containing lipoproteins)
Better predictor of VD than LDL alone
Increased Non-HDL
Familial dysbetalipoproteinemia
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
Low HDL (labs/assoc/mutations/acquired)
Increased Lipoprotein (a)
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)
What is seen in elite athletes and in insulin resistance?
Fat droplets (high TGs) in muscle
Statin benefit groups (4)
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]
Statin (mech)
inhibits HMG CoA, which reduces production of LDL AND incr LDL receptor expression (so increases LDL clearance)
Statin (6% rule/order of potency)
For each dose doubling, LDL falls 6% (use to weigh benefits and side effects)
Risuvastatin>atorvastatin>simvastatin
Statin side effects
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
Other cholesterol reducing tx
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]
Triglyceride Reducing Drugs
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)
Lipid types and CVD risk
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
PCSK9 inhibitor antibodies
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
MTP inhib with Lomitapide
acts on liver and intestine, and apoB-48 secretion
ADR: BAD, steatorrhea
