16 - Dyslipidemia Flashcards
Describe the “lipid profile”
- Variability in cholesterol test = 7-11%; cholesterol changes < 7% w/ a statin dose increase
- “Healthy” values:
- Total cholesterol < 5.2 mmol/L
- LDL < 3.4 mmol/L
- HDL > 1 (men) > 1.3 (women)
- TG < 1.7 mmol/L
- No longer recommended to fast for tests
What is the role of LDL, HDL, and triglycerides?
- High levels of LDL promotes buildup of plaque in the artery walls
- HDL helps carry LDL-cholesterol away from artery walls
- Triglycerides are a type of fat found in the blood; high levels associated w/ excess weight, excess alcohol consumption & diabetes (don’t know if they play a role in cardiac disease)
Hyperlipidemia is an independent risk factor for:
- Coronary heart disease (angina, MI)
- Cerebrovascular disease (ischemic stroke)
- Peripheral artery disease
Modifiable risk factors for CVD
- Diet, exercise
- Smoking
- Stress
- Hypertension, dyslipidemia
- BMI > 27
- Sedentary lifestyle
- Excessive alcohol intake
Non-modifiable risk factors for CVD
- Genetics (family history of premature CHD, < 55 if male, < 65 if female; familial hypercholesterolemia, very high cholesterol regardless of diet, very rare)
- Gender (male)
- Age
- Chronic kidney disease
- Ethnicity
Why should we do a risk assessment for dyslipidemia?
- Identify px most likely to benefit from pharmacotherapy
- Reassure low risk individuals w/o any treatable risk factors & a healthy lifestyle that they are doing well
- Advise individuals w/ treatable risk factors or unhealthy behaviours to address these factors
- Engage px in tx decisions & increase adherence to therapy
Advantages to ASCVD over Framingham
- Broader population
- Narrower outcomes (easier to translate)
- Results based on study that looked at chance of dying from a heart attack, chance of having a stroke, & chance of having a non-fatal heart attack
Causes of dyslipidemia
- Genetics (ex: familial hypercholesterolemia)
- Conditions (type 2 DM, CKD, hypothyroidism, nephrotic syndrome, cholestatic liver disease)
- Lifestyle (saturated fats increase lipids; refined carbs & simple sugars increase TG; smoking decreases HDL; aerobic exercise increases HDL; moderate EtOH increases HDL)
- Drugs => drug-induced hypercholesterolemia (progestins, thiazide diuretics, anabolic steroids, beta blockers, isotretinoin)
- Thiazide diuretics increase TC & LDL 5-10%, and TG 5-15%
- Beta blockers increase TG 15-50%, less w/ selective BB; also decrease HDL 5-20% but still decrease CVD events & mortality
3 things that can positively affect lipid profile & decrease risk of CV events
- Physical activity
- Diet (Mediterranean decreases CVD mortality)
- Can improve Framingham by 30% (but only if pt can commit to this diet for the next 10 years)
- Stop smoking
Relative risk reduction w/ a statin
25-30% reduction in CV events (MI, stroke, CHD death)
What should be considered when determining which statin to use?
- Efficacy & harm = consider them all the same
- Drug interactions = simvastatin & lovastatin > atorvastatin > pravastatin & rosuvastatin
- Cost = similar (all available generic)
- Dose = w/ some exceptions, generally start at equivalent of 10 mg atorvastatin (40 mg lovastatin & pravastatin; 20 mg simvastatin; 5 mg rosuvastatin)
What is the target for statin therapy?
- Guidelines say primary target < 2 mmol/L or >/ 50% decrease in LDL-C (if started as high risk, Framingham >/ 20%)
- Trials didn’t target LDL, nor did they increase or decrease meds to meet targets, nor did they compare one LDL target to another
- Summary = don’t target specific lipid levels & don’t repeat lipid level testing for a pt on a statin (no data that changing dose changes relative 10-year CVD risk)
General side effects of statins
- Muscle pain (myalgia)
- Upper GI (diarrhea, nausea, dyspepsia), sleep disturbances ~ 5-10%
- New onset type 2 DM (very rare, don’t mention to pt)
Effect of statins on aminotransferases
- > 3x ULN occurs in < 2-3% of px on statins (NNH = 250)
- Liver failure RARE (less than 2/million px/year)
- Get a baseline; no follow-up necessary unless concerning sx (ex: dark urine, upper abdominal pain, N/V, yellowing of skin or eyes, general itchiness, pale stools)
Describe statin associated muscle complaints
- Usually starts in larger muscles
- Diffuse (not unilateral)
- Onset about 1-12 months of therapy (or after dose increase/addition of interacting drug)
- Myalgia = no significant increase in creatinine kinase
- In practice, 5-10% of statin treated px report muscle complaints
Difference between myositis and rhabdomyolysis
- Myositis = myalgia + CK levels 2-10x ULN; may be caused by strenuous exercise
- Rhabdomyolysis = severe, progressive muscle aches w/ CK > 3-10x ULN & marked sCr elevation or myoglobinuria
What should be done if a pt is on a statin and has new unexplained muscle sx?
Ask about other sx and have CK checked
The amount of effort spent persevering w/ statin therapy in subjects w/ AEs should be directly related to ____
The level of CV risk for the individual pt
Management of myalgia
- Hold statin for 1-2 weeks (or until sx resolve) and re-challenge
- Can use different statin and/or dose reduction OR reassess risk vs. benefit of restarting statin (is the pt high or low risk of CVD, is it primary or secondary prevention)
Management of myositis
- If CK > 2-4x ULN but < 10x ULN – D/C statin & follow until sx resolve or CK returns to normal
- Consider precipitating factors (thyroid, exercise, drug interactions)
- Reassess risk vs. benefit of restarting statin
- Change statin and/or reduce dose & titrate up slowly
Management of rhabdomyolysis
- Stop statin + hospitalization for supportive tx
- May later rechallenge w/ low dose of different statin (once sx resolved, can take months to years)
When should you retest lipids if a pt is not on a statin?
2016 CCS dyslipidemia guidelines = CV risk assessment should be completed every 5 years for men & women aged 40-75 y/o or whenever a px expected risk status changes
Should statins be used in the elderly?
- Statins should never be started for primary prevention in px > 75 y/o
- Px > 75 y/o shouldn’t even have their lipids checked
Which px are considered “high risk”?
- Framingham score >/ 20%
- Clinical vascular disease
- Abdominal aortic aneurysm
- Diabetes & age >/ 40 y/o or > 15 years duration & age >/ 30 years or microvascular disease
- Chronic kidney disease
- High risk hypertension
Should statins be used post-MI and in px w/ CAD?
- For px w/ CAD, statins have RRR of CHD event or death of ~25% & ARR of mortality of ~3% (statins considered secondary prevention at this point)
- High dose (80 mg vs. 10-20 mg atorvastatin equivalent) gave additional 10% RRR (1% ARR) in CHD events or death over 2.5 years
What is the effect of adding ezetimibe to statin therapy?
- IMPROVE-IT study looked at over 18,000 post-MI px
- Intervention was simva 40 mg + ezetimibe VS. simva 40 mg alone x 7 years
- Results = adding ezetimibe decreased LDL by 15-20%; RRR=6% for CV events, ARR=1.8% for CV death, MI, or stroke
- No big differences in safety
What are PCSK-9 inhibitors and what is their effect on lipids?
- Monoclonal antibodies that inhibit proprotein convertase subtilisenkexin type 9
- In RCTs, lowered LDL by 50-70%
Are PCSK-9 inhibitors used in practice?
- Evolocumab + statin vs. statin alone x 2.2 years decreased LDL by extra 50% (FOURIER trial)
- Reduced CV events from 5.1% of patients/year to 4.5%
- However, didn’t reduce deaths
- Little is known about long-term safety
What are some other agents that lower triglycerides?
- Niacin – decrease TG by 20-35% (AIMHIGH study was stopped b/c no decrease in CVD risk)
- Fibrates – decrease TG by 20-50% (multiple meta-analyses concluded can decrease non-fatal MI by ~10%, but no difference in overall CVD)
- Omega-3 fatty acids – decrease TG by 25-30% (multiple meta-analyses show no benefit in any CV outcome)
What are the effects of TG on pancreatitis?
- High TG are risk factor for pancreatitis
- JAMA meta-analysis concluded that statins decrease pancreatitis (NNT = 1200 at 5 years); fibrates increase pancreatitis (NNH = 935 a 5 years)
