Chapter 27 - Dyslipidemia Flashcards
Primary (familial) hypercholesterolemias (FH)
Genetic defects that cause severe cholesterol elevations.
Heterozygous familial hypercholesterolemia (HeFH) and Homozygous familial hypercholesterolemia (HoFH).
Familial dyslipidemias are categorized by the Fredrickson classification.
SECONDARY(OR ACQUIRED)
poor diet and lack of physical activity –> central adiposity.
Medical conditions that cause dyslipidemia include hypothyroidism and diabetes.
very high risk and must be treated: LDL > 190 and TG > 500 mg/dL
Friedewald equation:
Lipid panels (i.e.,TC,HDL,TG) are taken after 9- 12hour fast.
Non-HDL and apoB do not require fasting for accurate assessment. If not fasting, the TG level can be falsely elevated, which can cause an incorrect LDLcalculation.
LDL = TC - HDL - (TG/5)
not used when the TGs are > 400 mg/dL.
Drug that inc LDL + TG
Immunosuppressants (cyclosporine and tacrolimus)
Atypical antipsychotics
steroids
Effavirenz
Diuretics
Protease inhibitors
(Imm A Ste Eff Di Pro)
Drugs that inc LDL
fish oil (Except Vascepa)
Drugs that inc TG
Propofol
IV lipids emulsions
bile acid sequestrants (5%)
Conditions that inc LDL/ TG …
obesity
smoking
alcoholism
diabetes
hypothyroidism
nephrotic syndrome
liver/ kidney disease
poor diet
pregnancy
pcos
non HDL
non HDL = TC - HDL
desirable < 130 mg/dl
LDL levels
desirable: <100 mg/dl
high: >= 190
HDL
desirable:
men: >= 40 mg/dl
women: >= 50 mg/dl
TG
desirable: < 150
very high: >= 500 (Severe hypertriglyceridemia)
Calculating ASCVD risk Input
■ Gender, age (20 - 79 years) and race
■ TC and HDL
■ Systolic blood pressure & whether antihypertensive treatment is used
■ The presence of diabetes and smoking status
(9)
when should the ASCVD risk assessment be repeated in those with a low 10 yr risk
This risk assessment should be repeated every 4 - 6 years in those found to be at a low 10-year risk (<7.5%).
Risk score is not needed for patients with:
and why
- clinical ASCVD,
- diabetes or
- LDL >= 190 mg/dL
as all patients in these groups should be started on a statin.
If a risk-based treatment decision is still uncertain after a quantitative risk assessment
Additional risk-enhancing factors should be considered to assist with decision making.
Risk-enhancing factors:
- very high LDL,
- family history of premature ASCVD,
- metabolic syndrome,
- chronic kidney disease,
- history of preeclampsia or premature menopause,
- chronic inflammatory disorders,
- high CRP,
- high coronary artery calcium score (CAC)
- abnormal ankle brachial index.
What does CAC indicates?
The CAC measurement is helpful in deciding if statins should be initiated in those with 10-year ASCVD risk of
7.5 - 19.9%.
A CAC score >= 100 Agatston units indicates statins should be initiated.
What is an ASCVD event?
CVA, TIA, ACS, MI, angina, CAD, PAD
Lifestyle modification
- Diet to maintain a healthy weight (BMI18.5 - 24.9 kg/m 2)
- Rich in vegetables, fruits, whole grains and high-fiber foods, such as in plant-based and Mediterranean diets.
- Fish with high-fat content (rich in omega-3 fatty acids).
- Limit saturated fat, trans fat (partially hydrogenated) & cholesterol by choosing lean meats, non-meat alternatives & low-fat dairy products.
- Aim for 5 - 6%of calories from saturated fat.
- Limit added sugars & salt
- Limit smoking and alcohol
- Aerobic physical activity 3 - 4 times per week,
lasting 40 minutes/session (decreases LDL3 - 6 mg/dL)
NATURAL PRODUCTS that can lower LDL
- Red yeast rice (contains naturally occurring HMG-CoAreductase inhibitors in low amounts.)
- Fibrous foods
What organ damage can many cholesterol lowering drugs cause? Explain.
- Drugs: niacin, fibrates, potentially statins and ezetimibe
- Cause: Liver damage
- Do not use if the AST or ALTis > 3 times the upper limit of normal.
- Statins: nonsignificant inc in liver enzymes but LFTs should still be monitored.
MOA of Statins
inhibits the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which prevents the conversion of HMG-CoA to mevalonate.
rate- limiting step in cholesterol synthesis.
What statin intensity should be used for Secondary Prevention of ASCVD
high intensity
except: (Give mod)
- not a candidate for high-intensity or
- patient > 75 years with LDL 70-189 mg!dL
primary elevation of LDL >= 190 mg/dl
give high int statin
Diabetes + Age 40 - 75 years + LDL between 70 -189 mg/dl
Regardless of 10-year ASCVD risk –> Mod
Multiple ASCVD risk factors –> High
Age 40-75 years + LDL between 70-189 mg/dl
10-yr ASCVD risk >= 20% –> High
10-yr ASCVD risk 7.5-19.9% + risk-enhancing factor –> Mod
high intensity statins
Atorvastatin: 40 - 80 mg (Lipitor)
Rosuvastatin: 20 - 40 mg (Crestor)
Mod intensity statins
Pitavastatin: 2 - 4 mg
Rosuvasttain: 5 - 10 mg
Atorvastatin: 10 - 20 mg
Simvastatin: 20 - 40 mg
Lovastatin: 40 mg
Pravastatin: 40 - 80 mg
Fluvastatin: 40 BID or 80 XL mg
Low intensity statins
Pitavastatin: 1 mg
Simvasttain: 10 mg
Pravastatin: 10 - 20 mg
Lovastatin: 20 mg
Fluvastatin: 20 - 40
Muscle Damage from Statins
- symmetrical pain
- within 6 weeks
- Rhabdomyolysis: muscle symptoms with very high CPK {>10,000) + muscle protein in the urine (myoglobinuria), which can lead to acute renal failure
What could provide relief for mild sx of muscle SE from statins?
Coenzyme Q 10
How can you reduce the risk of myalgia?
- Avoid drug interactions, including OTC products.
- Do not use simvastatin 80 mg/day.
- Do not use gemfibrozil + statin.
How can you manage myalgias?
- Hold statin, check CPK, check other possible causes.
- After 2-4 weeks: re-challenge with same statin at same or lower dose.
- Most patients who did not tolerate a statin will tolerate it when re-challenged, or will tolerate a different statin.
- If myalgias return, discontinue statin.
- Once muscle symptoms resolve, use a low dose of a different statin; gradually inc dose.
atorvastatin
Lipitor
GF is a 58 year old male who presents to his primary care manager for his annual checkup. His past medical history is significant for hypertension, allergic rhinitis, and GERD. He currently takes diltiazem 240mg daily, hctz 25mg daily, loratadine 10mg daily, and omeprazole 20mg daily. Based on GF’s lipid profile and current CV risk, the decision is made to start statin therapy, specifically simvastatin. Which of the following is true regarding dosing of simvastatin with GF’s current medication regimen?
A. The dose of simvastatin should not exceed 40mg daily.
B. The dose of simvastatin should not exceed 20mg daily.
C. The dose of simvastatin should not exceed 10mg daily.
D. The dose of simvastatin should not exceed 5mg daily.
Answer with rationale:
The correct answer is C. Close attention is required when administering simvastatin with certain medications due to the potential for decreased simvastatin metabolism and increased risk of toxicity due to CYP 3A4 inhibition. Additionally, grapefruit juice due to its potent CYP 3A4 inhibition should be avoided with simvastatin therapy. There are some medications such as itraconazole or clarithromycin (common with H. pylori regimens) that are contraindicated with simvastatin. Answer C is correct as this patient is receiving dilitiazem which necessitates a dose maximum of 10mg daily. The other medications on GF’s profile do not require adjustment of simvastatin making the other answers incorrect.
Fluvastatin
Lescol
Lescol XL
Lovastatin
Altoprev
Mevacor
Pitavastatin
Livalo
Zypitamag
Pravastatin
Pravachol
Rosuvastatin
Crestor
Ezallor
Sprinkle
Simvastatin
Zocor
FloLipid
What are some contraindications of statin therapy
Do not use in pregnancy, breastfeeding
Do not use strong CYP3A4 inhibitors with simvastatin and lovastatin
Do not use with liver disease, including any unexplained inc LFTs
Do not use cyclosporine with pitavastatin
what are some warnings for statin therapy?
Muscle damage
Diabetes: inc AlC/FBG; benefit of statin outweighs risk
Inc Hepatotoxicity, with inc LFTs(rare),
immune-mediated necrotizing myopathy (IMNM) (rare)
Rosuvastatin: proteinuria, hematuria - usually transient
Atorvastatin: hemorrhagic stroke (if recent stroke or TIAs); benefit of statin outweighs risk
What increases the risk of muscle damage with statin (Warning)
Muscle damage:
- Myopathy/rhabdomyolysis with inc CPK ± acute renal failure,
- Higher risk with higher dose (e.g.. simvastatin 80 mg),
- advanced age (~ 65 years),
- niacin,
- fibrates (e.g.,gemfibrozil),
- CYP3A4 inhibitors,
- hypothyroidism (uncontrolled),
- renal impairment
What should you monitor baseline/routine with statin therapy?
Lipid panel (TC, LDL, HDL, TGs) 4-12 weeks after starting treatment and then every 3-12 months (usually annually), LFTs
What should you monitor with statin therapy if pt is symptomatic?
- Myalgia/myopathy: check CPK
- Little/no urine: check SCr/BUN for acute renal failure due to rhabdomyolysis
- Abdominal pain or jaundice: check LFTs for possible hepatotoxicity
When can you take:
Crestor, Lipitor, Livalo, Lesco/XL, Pravachol, and FloLipid?
Can take Crestor,Lipitor, Livalo, Lesco/XL and Pravachol at any time of day
FloLipid is taken on an empty stomach
What should you do:
For CrCI < 30 ml/min
For eGFR < 60 ml/min
For CrCI < 30 ml/min, use lower starting doses of lovastatin, simvastatin and rosuvastatin
For eGFR < 60 ml/min, use lower starting dose of pitavastatin
Rosuvastatin exposures are — times — in — patients - consider —.
Rosuvastatin exposures are 2 times higher in Asian patients - consider 5 mg starting dose
What are the lipid effects of statin?
Dec LDL ~20-55%
Inc HDL ~5-15%
Dec TG ~10-30%
High intensity: dec >= 50% LDL;
Mod intensity: dec 30 - 49 % LDL;
High intensity: dec < 30 %