Hyperlipidemia Flashcards
what is hyperlipidemia
Elevation of lipids (fatty substances) in the bloodstream
Can include:
-cholesterol
-cholesterol esters
-phospholipids
-triglycerides
hyperlipidemia: primary vs secondary
primary:
- familial disorder
secondary:
-ds risk factor- DM, hypothyroid, alcohol, cushings, kidney failure
-dietary risk factor
-drug induced- hormones, steroids, diuretics, beta blockers, birth control
hyperlipidemia: which gender is it more common in?
More common in MEN than women**
cholesterol sources
Produced by liver
- endogenous
we consume from meat, dairy, eggs, milk:
- exogenous
lipoproteins
Chylomicrons:
- triglycerides*, cholesterol, protein
- LARGEST
Very low density lipoproteins (VLDL)
Intermediate density lipoproteins (IDL)
Low density lipoproteins (LDL)
High density lipoproteins (HDL)
- good for you
- SMALLEST
atherosclerosis
-slow, progressive disease
-deposition of fatty substances (mainly cholesterol), fibrous tissue and calcium on the intimal lining of blood vessels (mainly arteries)
-Atherosclerosis increases risk of CAD -> MI
atherosclerosis: goal of tx + tx options
Goal: slow the progression of the disease and possibly reverse it
-lower total cholesterol and LDL
- raise HDL
Treat with diet + exercise -> drugs
lipoprotein levels
-12 hours fasting results
-focus on numbers that we like -> desirable
what we want:
TC: <200
LDL: <100
HDL: >60
BAD:
TC: >240
LDL: >160 = high; >190 super high
HDL: <40
triglyceride levels
Triglycerides:
- <150: normal
-150-199: borderline high
-200-499: high
-=> 500: very high
therapeutic lifestyle changes
-Dietary Modifications
-Weight reduction
-Exercise
-Quit smoking
-increase soluble fiber*
dietary modifications
Do lifestyle changes + diet modifications first!! (depending on LDL levels and risk factors)
Diet should be:
-Low in cholesterol (< 200 mg/day)
-Low in SATURATED fat (calories < 7% of total fat)
-Low calories
-Avoid trans fat
-avoid alcohol
-decrease wt
“good” fat (~30%)
Monounsaturated fatty acids (MUFA): ~15%
-Aka oleic acid
-found in olive oil, canola oil, safflower oil and sunflower oil
-Also found in walnuts, almonds, peanuts and sesame seeds and olives and avocados
Polyunsaturated fatty acids (PUFA):
-Linoleic acid (omega-6) – found in VEGETABLE oils (soybean, safflower, sunflower and corn)
-alpha-linoleic acid (omega-3) – found in certain FISH, marine oils, flaxseed and linseed oils
CHD major risk factors
Age
- men > 45
- women > 55
DM
Fam hx of early CHD
- male < 55
- female < 65
HTN (<40)*
smoking
Low HDL
Obesity
Sedentary lifestyle
Atherogenic diet
ASCVD risk calculator - use app
risk factors used in calculation: calculates 10 year risk
-Sex
-Age
-Race
-Total Cholesterol
-HDL
-Systolic BP
-Treated for High BP
-DM
-Smoker
SARTH STDS
Statin indication: evidence based data in the following pt populations
First line tx: LOWER LDL
-Patients with CAD with or without hyperlipidemia
-Men w/ hyperlipidemia but no known CAD
-Men and women with average total and LDL cholesterol levels and no known CAD
HMG-CoA reductase inhibitor MOA
aka statins:
1) block the rate-limiting step in cholesterol biosynthesis -> decreases intracellular cholesterol
2) decreases TOTAL cholesterol
3) stimulates LDL receptor synthesis
4) REDUCES LDL LEVELS significantly
5) Raises HDL
efficacy of statins (%) + dosing statins
- raises HDL: 3-15%
- lowers TG: 15-60%
- Reduce LDL: 20-60%
Efficacy increases with higher doses and more potent statins
START HIGH DOSE: rule of 6’s
- one shot at significantly lowering LDL
- Each doubling of dose after only produces an additional 6-7% reduction in LDL.
Ex: Pt with an LDL of 200 mg/dL needs to get to LDL goal of < 100 mg/dL. Atorvastatin will reduce LDL by 50% with the max dose of 80mg -> If start pt on lower dose (i.e 40 mg), they may not get to goal
Therapeutic benefits of statins
-Plaque stabilization
-Improvement of coronary endothelial dysfunction
-Inhibition of platelet thrombus formation
-Anti-inflammatory activity- less chance of plaque attaching and building
statins CI
-ACTIVE hepatic disease
- pregnancy (category X) + BREASTFEEDING
note: safe to use in non-alcoholic fatty liver disease + Hep C
statins ADR , precautions
Precautions: adjust dose if ADRs
ADRs:
-GI (n,v,d)
- high LFTs, hepatotoxicity
-myalgia, rhabdomyolosis (rare)
-CNS: ↓ cognitive function, memory loss -> Reversible you discontinue drug (tinnitus)
-CNS symptoms can just be from old age so maybe test hearing before starting
-small incidence of HYPERGLYCEMIA and increase HbA1C BUT benefit GREATER THAN risk in DM
monitoring parameters:
- lipid panel
- LFTs
- CPK/CK: check for rhabdo
- renal: check to see if you should adjust dose
Fetal Abnormalities with HMG-CoA Reductase Inhibitors
“PC FACTS”
Congenital anomalies:
-Polydactyly: extra fingers/toes
-Cleft lip: split in upper lip
-Fetal skeletal malformations
-A-V septal defects
-Club foot
-Trisomy 18: extra chromosome
Fetal Abnormalities:
-Spontaneous abortion*
HMG-CoA Reductase Inhibitors: patient risk Factors for myopathy
PATIENT FACTORS
-Age > 80
-Female
-Small body frame
-↓ hepatic/renal Fn
-Hypothyroidism
-Diet (grapefruit juice)
-polypharmacy
“a thin old (80+) lady that drinks a lot of grapefruit juice at the pharmacy for her hypothyroidism and renal/liver dysfunction”
HMG-CoA Reductase Inhibitors: drug risk Factors for myopathy
statins with higher Lipophilicity
-pravastatin and rosuvastatin least likely for ADRs (lower lipophilic)
- higher lipophilic = can more readily enter muscle cells
High bioavailability (F):
- more drugs enter systemic circulation -> higher risk for muscle damage
Limited protein binding:
- drugs less bond to plasma proteins = higher FREE concentration
CYP substrate:
- statins that are cytochrome P450 enzymes substrate = increased level of drug when taken with other drugs that inhibit enzymes -> higher risk
statins DDIs
Significant 3A4 inhibitors:
- grapefruit juice, amiodarone, azole antifungal, macrolides
- these will increase level of statins in blood
- DDIs in Lovastatin and simvastatin >Atorvastatin
Significant 2C9 inhibitors:
- amiodarone, cimetidine, azole antifungals, SSRIs, zafirlukast
- these will increase level of statins in blood
- fluvastatin
_______is a CYP2C9 substrate.
-Fluvastatin is a CYP2C9
substrate.
_________ and ________least likely for ADRs (lower lipophilic)
pravastatin
rosuvastatin
HMG-CoA Reductase Inhibitors: monitoring parameters
Lipid profile:
- Baseline; then 4-8 weeks after initiation of therapy then q 6-12 months
LFTs:
- Baseline, then periodically thereafter or if signs of liver disease (jaundice, RUQ pain)
CPK:
- baseline, then if pt has myalgia symptoms (rhabdo)
- renal: check to see if you should adjust dose
HMG-CoA Reductase Inhibitors: examples
atorvastatin (Lipitor)* (high dose, less DDIs)
rosuvastatin * (highest dose, least ADR with low lipophilicity)
fluvastatin: 2C9 substrate
lovastatin: 3A4 substrate
pravastatin: least ADR with low lipophilicity
simvastatin: 3A4
pitavastatin
Recommendation for treatment of clinical ASCVD:
For a pt Age ≤ 75yo AND no safety concern
High-intensity Statin tx -> lower dose if not tolerated
- if LDL over 70 with maximum dose: consider + ezetimibe
primary prevention of ASCVD: LDL > 190
HIGH intensity statins
-r/o secondary causes
- give to 21+ pts
- minimum: lower LDL by 50%
miscellaneous therapies
-Vitamin E
-Garlic
-HDL infusions
-Alternative therapies
-Dietary supplements
-artichoke extract lower LDL -> doesnt help anything else
-fish oil -> lowers triglycerides
- walnuts
- soy
-plant stanols/sterols
-fiber
