Flashcards in Management of hyperlipidemia Deck (72):
- chylomicrons transport fats from intestinal mucosa to liver
- in the liver chylomicrons release TGs, come cholesterol and they become LDLs
- LDL then carries fat and choleseterol to body's cells
- HDLs carry fat and cholesterol back to liver for excretion
- when oxidized LDL cholesterol increases and atheroma formation occurs in walls of arteries, which causes atherosclerosis
- HDL cholesterol is able to go and remove cholesterol from atheroma
What is happening in atherosclerosis?
inflammatory factors are being released
Primary (hereditary) causes of dsylipidemia?
- familial hypercholesterolemia: codominant genetic disorder, occurs in heterozygous form, occurs in 1-500 individuals, mutation in LDL receptor, they are absent or defective, resulting in unregulated synth. of LDLS, high risk for atherosclerosis, tendon xanthomas (75% of pts), tuberous xanthomas, and xanthelasmas of eyes
- familial combined hyperlipidemia: autosomal dominant, increased secretions of VLDLs
- dysbetalipoproteinemia: affects 1-10,000, results in apo E2, a binding defective form of apoE (which usually plays important role in catabolism of chylomicron and VLDL), increasaed risk for atherosclerosis, peripheral vascular disease, tuberous xanthomas, striae palmaris (thick skin on palms and soles)
What are xanthomas?
- soft, yellow skin plaques or nodules that contain deposits of lipoproteins inside histiocytes, especially likely to be found on pt with hyperlipidemia
WHere are tuberous and tendinous xanthomas found?
achilles tendon, knees, elbows, ankles
Secondary causes of hyperlipidemia?
- contribute to most cases of dyslipidemia in adults
- most common cause in developed countries: sedentary lifestyle with excessive dietary intake of saturated fat, cholesterol, and trans fats
- uncontrolled DM II, metabolic syndrome
- liver and renal disease
- corticosteroid use
- progestin use
- anabolic steroid use
- ETOH use/abuse
What requirements must be met for metabolic syndrome?
Must meet 3 of the following criteria:
- abdominal obesity (>40 in men, >35 in women)
- high TG level (>150)
- low HDL (130/84 mm Hg
- impaired fasting glucose level > 100
Examples of monunsaturated fats, and effect on cholesterol levels?
- olive oil canola oil, cashews, almonds, avocados
- lowers LDLs and raises HDL
corn, soybean oil, fish oil
- lowers LDLs and raises HDL
- whole milk, butter, cheese, red meat, coconut milk
- raise both HDl and LDL
- process food - raises LDLs
5 major steps to ID pt at risk for hyperlipidemia?
- 1 obtain fasting lipid profile
- 2 ID if there are any CHD risk equivalents
- 3 ID if any major CHD RFs other than LDL
- 4 if pt has CHD risk equivalent, or 2 or more risk factors (other than LDL), calculate 10 yr risk of CHD
- 5 determine risk category, in order to establish the LDL goal, when to initiate therapeutic lifestyle changes, and when to consider drug therapy
Why are these steps so impt in preventing CHD?
- optimum tx of lipids helps in primary and secondary prevention of CVD
- generally hyperlipidemia is asx
- CVD is still #1 killer in US has been since 1900
- 50% of CVD dx and 15% of CVD deaths are in pts
Guidelines for hyperlipidemia?
- ATP III of national cholesterol education program- natl heart lung and blood institute NIH:
- summarized recommendations for management of high serum cholesterol
- ATP III based on epidemiologic observations that showed graded relationship b/t total cholesterol concentration and coronary risk
- recommendations summarized based on: primary prevention (absence of disease) and secondary prevention (presence of preexisting CHD)
Step 1 of guidelines: check lipid panel
- healthy adults, no RFs - every 5 years starting at 20
- obtain fasting serum lipid profile consisting of total cholesterol, LDL, HDL
What are the lipid panel goals?
- total cholesterol: 40 in men, >50 in women, >60 cardio protective
Goals for lipids?
LDL 60 high
serum TGs: 500 think pancreatitis
Step 2: ID CHD risk equivalents: these are?
- other forms of clinical atherosclerosis disease: clinical CHD, AAA, PAD, sx CAD
Guidelines for diabetes being a risk equivalent?
- men over 40 with DM II and any other risk factor or over 50 with no RFs
- women over 45 with DM II and any other CHD risk facotr or over 55 w/o risk factors
- men or women of any age who have had DM (I or II) for over 20 years if they have risk factor or more than 25 years w/o risk factor
Step 3: determine major risk factors of CVD? (other than LDL)
- HTN (BP>140/90 or antiHTN meds)
- low HDL 45 and women: > 55
Step 4: assessment of risk?
- for persons without known CHD, other forms of atherosclerotic disease or diabetes:
- count number of risk factors
- use framingham scoring for persons with >2 risk factors to determine absolute 10 year CHD risk
- first look at age, TC, HDL, systolic BP, smoking status, add up pts
Step 5: determine risk category
- CHD or CHD risk equivalent (10 year risk > 20%) -want LDL 130
- 2 or more risk factors (10 yr risk 130 initiate therapeutic lifestyle changes, drug therapy >130
- 0-1 risk factor (10 yr risk 190 drug lowering therapy
Secondary prevention recommendations (LDL goals, drug therapy)
-intensive statin therapy in pts with acute coronary sndrome recommended as initial therapy
- pts at very high risk for CHD events should be targeted for LDL below 70 (if unable to achieve by statin alone, use second agent)
- usualy risk pt with stable CHD unable to achieve LDL goal alone with statin 0 should have 2nd agent added
- if they don't tolerate a statin, they should be tx with another lipid lowering agent
Who is at very high risk for CHD events?
- est coronary heart disease +
mult major risk factors (diabetes)
severe or poorly controlled risk factors (cont. smoking)
mult risk factors of metabolic syndrome (esp TGs>200 + non HDL-C > 130 plus HDL less than 40
acute coronary syndrome
Goals for very high risk pts?
- more intesnive lipid lowering therapy
- LDL belwo 70
- sig. reduction in all cause mortality (RRR 13%), death from heart disease or related blood vessel disease (RRR 17%), and major CV events (RRR 24%) at levels less than 100 mg/dL
- most observers are in strong support of LDL below 70 in high risk pts
After categorizing what pr's RRR is now what?
- initiate therapeutic lifestyle changes alone (diet change should lower TGs)
- TLC and drug therapy: tx hyperlipidemia with drug therapy (decision based on LDL level)
Dietary and lifestyle changes will have what type of impact?
- may decrease LDL by 10%
- total fat
What are statins?
- HMG - CoA reductase inhibitors
- most heavily used class of lipid lowering drugs
- excellent agents at lowering LDL cholesterol and decreasing associated morbidity and mortality rates for primary and secondary prevention of CAD
- LDL lowering 20-60%
- can increase HDL (crestor mostly) and lower TGs
- well tolerated by most pts
List of statins?
- Rosuvastatin (crestor) most potent
- Atorvastatin (lipitor)
- simvastatin (zocor)
- simvastatin/ezetimibe combo (vytorin)
MOA of statins?
- blocks conversion of HMG-CoA to mevalonate which is rate limiting step in the production of cholesterol in the liver (first statin - mevacor: not as effective)
- leads to increase in number of LDL receptors in the liver
- larger amounts of LDL cholesterol is taken up by liver and digested, thereby decreasing amount of LDL in the blood stream
- HDl increases tend to occur, LDL receptors also involved in uptake of VLDL and IDL: leads to decrease in TGs
Why shouldnt you use statins with fibric acid derivatives?
- because increases chance of rhabdomyolysis
Main side effects of statins?
- muscle break down
- GI upset
- asx elevation in LFTs: ALT and AST(because affecting liver synth. of cholesterol)
- they should be checked at baseline, at 6-12 weeks, after starting or titrating, and q 6 months after
CIs of statins?
- pregnant women
- pt with active/chronic liver disease
- pt with unexplained elevated ALTs
- caution: in pt who consumes large amount of alcohol or hx of liver disease
What should you chekc if pt complains of myalgias (muscle pain)?
- CPK: creatinine phosphate kinase
- myalgias= pain
- myopathy = breakdown of muscle (pathologic)
If undesired SEs occur while on a statin what should happen?
- change statin and rechallenge
- when rhabdo occurs, stop statin use, begin IV fluid hydration to prevent renal failure - usually CKs > 15000 to cause ARF
What meds increase statin myopathy?
- gemfibrozil (fibrate)
- protease inhibitors
WHat should happen if liver transaminases greatly increase?
- occur in 0.5 - 2% of pts
- dose dependent, so usually reversed with lower doses
- can change statin and rechallenge, rarely progress to liver failure
- stop stain if LFTs are more than 3x baseline
- teach pts to report jaundice, malaise, fatigue, lethargy
- suspect hepatotoxicity with these and stop statin immediately
- monitor LFTs prior to statin initiatio, at 3 months, 6 months, then every year
What renal issues can occur with statins?
- proteinuria and renal failure are rare
- most specific to Rosuvastatin (crestor)
- get Cr at baseline and renal fn monitored at dose of 40 mg (high dose)
What education should you give to pt on statins?
- take statins in evening or bedtime (only exception is Atorvastatin - lipitor)
- majority of cholesterol production occurs during sleep
Difference b/t statins?
- all have an anti-inflammatory effect
- all are more potent by 10-15% with evening dose (except lipitor)
- despite same MOA, difference b/t agents including their ability to lower cholesterol
- Lipitor and Crestor have more effective ability to lower TGs
- Rosuvastatin (Crestor)
is more effective in raising HDL than atorvastatin, simvastastin, or pravastatin
Statins effects on lipids (dose dependent)
- lipitor (atorvastatin)
lower LDL 47-65%
raises HDL 2-9%
lowers TGs 20%
- crestor (rosuvastatin)
lowers LDL 39-60%
raises HDL 5-9%
lowers TGs 19- 35%
lowers LDL 30-40%
raises HDL 5-7%
lowers TGs 10-30%
Should you stop statins if liver transaminases are elevated?
- no unless reaching 3x normal, not a reason to stop the statin, only reason to watch closely
- statin SEs are often agent specif and not always class specific
- unexplained myalgias may occur w/o CK elevation, try a different statin
How common is rhabdomyolysis?
- uncommon unless CK is elevated to 10x normal, usually occurs in pts with multiple comorbidities
- don't have to check CK serially, may be helpful to get baseline CK
MOA of bile acid resins?
- decrease cholesterol absorption through exogenous pathway
- not absorbed through GI (blocked)
- these agents bind bile acids in the intestines, forming insoluble complex that is excreted in the feces
- this deceases return of cholesterol to the liver
- body responds by increasing LDL receptors on liver which in turn decreases amount of LDL cholesterol in bloodstream: this process interrupts enterohepatic recirculation of bile acids and affects enzyme systems - which can cause increase in TGs
When are bile acid resins used?
- as adjunct therapy
- safe in pregnancy and peds
- max effects are seen in approx 3 weeks
- effects are dose related
- should be taken with meals
- meds should be taken at least 1 hr before or 4 hours after bile acid resin
SEs of bile acid resins?
- use is often limited by SEs
- nausea, bloating and cramping
- increase in liver enzymes
- colesevalam is better: less likely to cause GI effects
Different effect of Bile acid resins?
- cholestyramine (Questran):
lower LDL: 15-30%
raises HDL: 3-5%
lowers TGs: 0-15%
- colestipol (colstid)
lowers LDL 12-25%
raises HDL 0-1%
Niacin effect on cholesterol?
- naturally occuring B vitamin (B3)
- can improve cholesterol levels when used at doses 100-300x recommended daily allowance as vitamin
- lowers LDL 15-25%
- raises HDL 35%
- lowers TGs 50%
- one of the most effective agents but most pts cant tolerate high doses required for efficacy (start with low dose)
- best drug to increase HDL!
MOA and contraindications of Niacin?
- MOA: uncertain, appears to decrease VLDL synthesis in liver and increase lipoprotein lipase activity
- absolute CIs: hepatic dysfxn, severe gout
- relative CIs: peptic ulcer disease, gout: can elevated uric acid levels
- diabetes: can worsen glucose control
SEs of Niacin?
increased prostaglandin activity leadint to pruritus and flushing to face and neck (dose of ASA can be taken 30-60 min before Niacin)
- Niaspan: extended release may help
- hepatotoxicity: monitor LFTs
- uric acid and gluocse increases: get baseline labds
- orthostatic hypotension
- dyspepsia, GI side effects
What is MOA of cholesterol absorption inhibitors?-
- Ezetimibe (Zetia)
- MOA: appears to act at brush border of small intestine
- inhibits absorption of cholesterol leading to decrease in delivery of intestinal cholesterol to the liver
- causes a reduction of hepatic cholesterol store and can increase in clearance of cholesterol from the blood
- Mechanism is complementary to that of statins
When are cholesterol absorption inhibitors used, efficacy?
- approved as monotherapy or in combo with statin
- lowers LDL up to 18% (mono therapy)
- lowers LDL up to 35% with a statin
CIs and SEs of cholesterol absorption inhibitors?
- CIs: if used w/ statin: have active hepatic disease, and elevated ALTs
- SEs: HA, diarrhea, abdominal pain
What are the 2 fibric acid derivatives?
- gemfibrozil (lopid): don't use with statin
- fenofibrate (Tricor, Trilipix)
- not considered a major class of lipid lowering drugs because they have minimal effect on LDL
- good for lowering TGs
- LFTs need to be monitored
MOA of fibric acids?
- principle effect of TGs lowering appears to be result from stimulation of lipoprotein lipase, which enhances the breakdown of VLDL to LDL
- may inhibit hepatic VLDL prod. and TG synthesis
- lower TGs up to 60%
- raise HDL up to 30%
- lowers LDL up to 20% ( Tricor most effective at LDL reduction)
CIs for fibric acid derivatives?
history of gallstones
severe hepatic or renal dysfunction
- Adverse effects:
myopathy chance increased if taken with statins
increases effects of warfarin
What is hypertryglyceridemia?
- borderline (150-199 mg/dL): calorie restriction and exercise
- high > 200 mg/dL: diet and meds
- pt with TGs > 500 are an increased risk of pancreatitis - pathophys not certain
- usually acquired problem of lipid metabolism
- low fat diet/ calorie restriction/ increase fiber
- limit alcohol, simple sugars, refined starches, saturated and trans fatty acids
- omega 3 fatty acid - fish oil: 2-4 g/ day recommended, higher dose can increase LDL
- pharm therapy with niacin, fibric acid derivative, lovaza, or statins
Benefit of fish oil supplementation?
- can lower serum triglyceride concentration by as much as 50% or more
- use is often limited by metabolic and GI side effects
- active omega 3 fatty acids constitute only 30-50% of many fish oil supplements
- Concerns about it increases LDL levels
Tx diabetics with hyperlipidemia?
- DM is considered CHD equivalent
- statin therapy very helpful (goal for LDL les than 100 in diabetics)
Tx elderly with hyperlipidemia?
- decision to tx should be highly individulalized
- concomitant illness limiting life span: probably not candidate for drug
- healthy elderly individual should not be denied drug therapy simple on basis of age alone
What lipid altering drug decreases LDL the most?
1. HMG CoA Reductase inhibitors (statins) 20-60%
2. bile acid sequestrants
3. nicotinic acid: 10-25%
What lipid altering drug increases HDL the most?
- Nicotinic acid (niacin)
- Fenofibrate (fibric acid)
What lipid altering drugs decrease TGs the most?
- Fibric acids:
4 groups that benefit from statin use?
- pts with clinical atherosclerotic disease
- pts with LDL greater than 190 (pt with FHx)
- pts with diabetes 40-75 yo with LDL levels 70-189 and without evidence of ASCVD
- pts without evidence of ASCVD or DM but have LDL levels of 70-189 and 10 yr ris of ASCVD > 7.5%
Primary prevention of CV disease?
- for pts free from CV disease: statin therapy recommended for LDL more than 190
- for diabetics: statin therapy for LDL more than 70
- for others statin therapy if 10 yr risk of CV disease is 7.5% or higher and LDL is greater than 70 mg/dL
Statins reduce risk of CV disease and stroke by how much?
- by about 20%
- think of statins as risk reduction meds same way as we consider aspirin
- no longer tx to a target LDL but we are tx to lower risk
- advise use of max tolerated statin dose
Stain intolerance guidelines?
- determine if true rxn
- investigate other potential causes of muscle sxs
- stop for week and if pain resolves, lower the dose
- switch to another statin at lower dose
- change regimen, every other day, 2x weekly
Targets of therapy for atherosclerosis?
- emohasis on both LDL and non HDL as targets of therapy
- VLDL promotes atherosclerosis and therefore potential targer for lipid lowering therapy
- non-HDL is sum of LDL and VLDL, represents cholesterol in all atherogenic lipoproteins
- non-HDL more accurartely reflects overall atherogenic burden esp with high TGs and has advantage of accurate testing in nonfasting setting
- primary prevention:
LDL lower than 100 or non HDL lower than 130
- near optimal goal: LDL 100-129 and non HDL: 130-159
- secondary prevention with established CVD: optimal goals: LDL less than 70 and non HDL less than 100
- doesn't define specific tx targets but emphasizes importance of optimal levels based on long term risk
Assessing risk of CVD?
- target major risk factors: HTN, DM, low HDL, and tobacco use
- max TLC emphasized and recommended for anyone with moderate or higher risk level
- cholesterol lowering therapy optional for mod risk, should be considered for moderately high risk and is indicated for high risk
- use Lloyd-Jones/Framingham algorithm
- dxs of family hypercholeseterolemia, DM with other RFs and chronic kidney disease should make individual mod high or high risk
- CRP may be useful in pts with moderate risk (high sensitivity CRP: for cardiac risk -> correlates with LDL, inflammatory marker, tell if elevated or not)