Dyslipidemia
Describe the LDL impact of doubling the dose of a statin.
Doubling dose of statin = decrease LDL by another 6%
Manage AST/ALT elevations with statins, niacin, and fibrates.
All cause liver damage- d/c drug if AST (10-40 units/L) or ALT (10-40 units/L) is 3 times ULN • Statins: check at baseline and then if symptoms are clinically indicated • Fibrates: check at baseline and periodically through therapy [LFT are dose-related] • Niacin: check at baseline; every 6 to 12 weeks for the first year and then every 6 months
Determine the presence or absence of health consequences of chronic dyslipidemia.
Elevated LDLs are a major contributing factor to atherosclerosis and coronary heart disease. It can manifest as angina, myocardial infarction, arrhythmias, stroke, peripheral arterial disease, and aortic aneurysm.
Identify dose limitations when using statins with interacting medications.
If using Simvastatin with Amlodipine, do not use more than 20 mg of Simvastatin
Treatment for Adults ≥21 Years of Age with Clinical ASCVD, on Statin for Secondary Prevention WITHOUT Comorbidities.
o Maximize statin therapy and lifestyle modifications o Then consider Ezetimibe first. o Then consider PCSK9 inhibitor (as add on or replacing Ezetimibe)
Treatment for Adults Aged 40 to 75 Years Without ASCVD, but with Diabetes and LDL-C 70 to 189 mg/dL, on Statin for Primary Prevention
o Maximize statin therapy and lifestyle modifications o Then consider Ezetimibe first. o You may use BAS if Ezetimibe intolerant and TG <300 mg/dL
Treatment for Adults Aged 40 to 75 Years Without Clinical ASCVD or Diabetes, with LDL-C 70 to 189 mg/dL and an Estimated 10-Year Risk for ASCVD of ≥7.5%, on Statin for Primary Prevention
o Maximize statin therapy and lifestyle modifications o Then consider Ezetimibe first. o You may use BAS if Ezetimibe intolerant and TG <300 mg/dL
Treatment for Adults ≥21 Years of Age with Clinical ASCVD, on Statin for Secondary Prevention WITH Comorbidities.
o Maximize statin therapy and lifestyle modifications o Then consider Ezetimibe or PCSK9 inhibitor first depending on reduction needed - <25% = Ezetimibe, >25% = PCSK9 inhibitor o Then add the other agent
Treatment for Adults ≥21 Years of Age with LDL-Cholesterol ≥190 mg/dL (Not Due to Secondary Modifiable Causes) on Statin for Primary Prevention
o Maximize statin therapy and lifestyle modifications o Then consider Ezetimibe or PCSK9 inhibitor first depending on reduction needed - <25% = Ezetimibe, >25% = PCSK9 inhibitor o Then add the other agent
Define and differentiate (avoid discussing diagnosis): ASCVD, clinical ASCVD, and CAD.
• ASCVD: arteriosclerotic cardiovascular disease usually caused by heart attack or stroke by a build-up of plaque over time • Clinical ASCVD: includes acute coronary syndromes, or a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease of atherosclerotic origin • CAD: impedance/blockage of 1(+) arteries that supply blood to the heart caused by atherosclerosis
Discuss the impact of physical activity on hypertriglyceridemia.
• Aerobic activity enhances lipid oxidation, facilitating the hydrolysis and utilization of triglycerides in skeletal muscle. • It is recommended that 60 minutes of daily aerobic exercise eliminates the rise in triglyceride rich lipoproteins that is caused by a high CHO diet • "Overall, exercise is most effective in lowering triglycerides (eg. 20% to 30%) when baseline levels are elevated (>150 mg/dL), activity is moderate to intensive, and total caloric intake is reduced"
Traditional risk factors for ASCVD calculation:
• Age, sex, race, total cholesterol, HDL, SBP, treatment of high blood pressure, diabetes, and smoking status. • These are the most pertinent in assessing ASCVD risk.
Recognize common strong CYP inhibitors and strong CYP inducers in order to recognize when significant drug interactions may occur.
• CYP inhibitors o Gemfibrozil o Ketoconazole o Nefazodone o Ritonavir o Grapefruit juice o Diltiazem/Verapamil • CYP inducers: o Rifampin o Phenytoin o Phenobarbital o Nafcillin
Identify drug-drug interactions that should be avoided with lipid lowering therapies.
• CYP3A4: o Atorvastatin (substrate) o Lovastatin (substrate) o Pravastatin (substrate) o Simvastatin (substrate) o Fluvastatin (substrate) • CYP2C9: o Simvastatin (substrate) o Rosuvastatin (substrate) o Fluvastatin (substrate)
Exogenous cholesterol transport
• Chylomicrons o responsible for transporting the triglycerides and cholesterol that we have absorbed in our diet and delivering it to body tissues o During circulation, lipoprotein lipases (LPLs) hydrolyze fatty acid chains on the TGs on the chylomicron - the result is free fatty acids that can be used by tissues for energy or stored in adipose tissue; after this happens, the chylomicron is referred to as a "chylomicron remnant" • Chylomicron Remnants o The chylomicron remnant returns to the liver and binds to LDL receptors o Hepatic cells take in the remnant and repackages its remaining TGs and cholesterol for delivery in VLDLs
Given a patient case, counsel the patient using lay terms, on the benefits of lipid lowering therapy.
• Counsel patient about how too much cholesterol in your system, can put you at a greater risk for heart disease, cause buildup of plaque in artery walls, and raise your risk for a heart attack. • Lipid lowering therapy can Increase survival benefit for primary prevention (patients without clinical ASCVD) and secondary prevention (with clinical ASCVD) • Contact HCP right away if you are passing brown or dark-colored urine, pale stools, feel more tired, eye discoloration. These may be signs of liver damage.
Reduce the risk of ADRs from niacin products through appropriate product selection, dose titration, and counseling practices
• Dose Titration: o Start at low dose and titrate to higher doses over a period of weeks as tolerated. • Counseling: o avoid fatty meals to decrease GI effects o avoid hot beverages and alcohol to reduce flushing o may take niacin with food, or pre-medicate with aspirin 325 mg 30 min before to alleviate flushing symptoms
When given a patient scenario, assess current lifestyle efforts and develop lifestyle plans in order to reduce ASCVD risk according to the 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk.
• Eating Habits o DASH Diet: - Eat vegetables, fruits, whole grains. This includes low-fat dairy products, poultry, fish, legumes, non-tropical vegetable oils, and nuts. - Limit intake of sweets, sugar-sweetened beverages, and red meats. o Aim for a diet regimen that achieves 5%-6% of calories from saturated fat o Reduce percent of calories from saturated fat o Reduce percent of calories from trans fat • Physical Activity o Engage in aerobic activity 3-4 sessions per week, lasting about 40 min per session o Involve moderate to vigorous-intensity physical activity
Drugs that cause Hypertriglyceridemia (↑ TGs):
• Estrogens • Thiazides • Glucocorticoids • Beta blockers • Protease Inhibitors • Atypical Aps • Anabolic Steroids
Additional risk factors that can influence ASCVD risk:
• Family history of premature CVD o Specifically, if the history is a first degree relative (mother, father, sibling) the risk increases o *Men <55 y/o* o *Women <65 y/o* • Levels of high sensitivity C-reactive protein (hs-CRP) o May be useful in driving statin therapy in patients with intermediate risk • Levels of Coronary Artery Calcium (CAC) o Associated with evaluating risk for developing coronary heart disease specifically • Ankle Brachial Index score o Useful in more individualized classification of CHD risk severity in men and women. If >/= to 2 in high-risk men, down-classify their risk score. If >/= to 2 in low-risk women, up-classify their score.
Compare and contrast the various medications used to treat hypertriglyceridemia and describe their impact on triglyceride reduction.
• Fibrate = 30-50% TG reduction • Omega-3 = 20-50% TG reduction • Immediate-release niacin = 20-50% TG reduction • Extended-release niacin = 10-30% TG reduction • Statins = 10-30% TG reduction • Ezetimibe = 5-10% TG reduction • If patient had CKD, AVOID Fenofibrate • If patient had gout, AVOID Niacin • If patient was pregnant, AVOID Fibrates
Which Non-Statin Therapy to add:
• For all for the 4 Statin Benefit Groups consider ezetimibe first • For the first 2 Statin Benefit Groups, you may then consider PCSK9 inhibitor (as add on or replacing ezetimibe). The 2 statin groups are: o Adults ≥21 Years of Age with Clinical ASCVD, on Statin for Secondary Prevention o Adults ≥21 Years of Age with LDL-Cholesterol ≥190 mg/dL (Not Due to Secondary Modifiable Causes) on Statin for Primary Prevention • BAS can be used if patient is ezetimibe intolerant or triglycerides <300 mg/dL o used in last 2 statin groups
When given a patient scenario, establish the primary lipoprotein target per 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease in Adults.
• Generally, LDL ≥50% reduction is the goal o For 1st statin group, you may consider LDL <70 mg/dL or non-HDL <100 mg/dL o For other statin group, consider LDL <100 mg/dL or non-HDL <130 mg/dL • If TG are >500 mg/dL, TG become the primary goal.
Recognize which common or severe ADRs are dose related (increase risk with increased dose)
• Hepatotoxicity (increase serum transaminase enzyme levels-ALT/AST] • Myositis (severe myopathy) • Flushing (titrate first, then d/c if needed)
Categorize statins by LDL lowering intensity.
• High Intensity: o Atorvastatin (40)-80 mg o Rosuvastatin 20 (40) mg • Moderate Intensity: o Atorvastatin 10 (20) mg o Rosuvastatin (5) 10 mg o Simvastatin 20-40 mg o Pravastatin 40 (80) mg • Low Intensity: o Simvastatin 10 mg o Pravastatin 10-20 mg o Lovastatin 20 mg o Fluvastatin 20-40 mg
Identify differences in ADRs among individual resins and among niacin products (IR, Niaspan, and SR).
• IR = greatest risk of developing flushing • SR = greatest risk of developing hepatotoxicity • ER = reduced risk of flushing
When is Non-Statin Therapy Used:
• If patient does not have ≥50% LDL-C on maximally tolerated statin therapy: o Address statin adherence o Intensify lifestyle (may consider phytosterols) o Increase to high-intensity statin if not already taking o Evaluate for statin intolerance if unable to tolerate moderate-intensity statin - Consider referral to lipid specialist if statin intolerant o Control other risk factors • If patient still does not have ≥50% LDL-C reduction on maximally tolerated statin therapy, you can then add non-statin therapy.
ASCVD risk in Layman's Terms (for patient):
• If the patient has a 10-year risk of 12%: Of 100 patients with the same risk factors as you, 12 of these patients will have a heart attack, stroke, or die from a heart-related event in the next 10 years. • If the patient has a lifetime risk of 12%: Of 100 patients with the same risk factors as you, 12 of them would develop some form of cardiovascular disease (CVD) or plaque buildup in the heart, brain or blood vessels within the next 30 years or over your lifetime.
Endogenous cholesterol transport
• In the liver, extra glucose can be converted to Acetyl-CoA. Acetyl-CoA can be converted through biosynthesis to cholesterol in a long pathway in which HMG-CoA reductase is the rate-limiting step. Also, Acetyl-CoA can be converted to fatty acids through another pathway • VLDL o Main role: transport fatty acids to tissues o The cholesterol and TGs from both the chylomicron remnants and biosynthesis pathway are packaged in VLDLs o VLDLs are released from the liver to travel to tissues; in the tissues, LPLs hydrolyze the TG fatty acid chains into free fatty acids o This causes the VLDL to become an IDL. o Through hepatic lipases, IDLs are converted to LDLs • LDL o Main role: transport cholesterol to tissues o Contains the greatest % of cholesterol compared to other lipoproteins o LDLs circulate and deliver cholesterol to cells; cholesterol is used to maintain cell membrane integrity and is the starting material for hormones in the body o After delivering cholesterol to tissues, LDLs return to the liver and bind at LDL receptors which then undergo endocytosis o Inside hepatic cells, LDLs are either recycled or excreted through bile • HDL o Main role: clear excess cholesterol from periphery o After it picks up cholesterol from the periphery, it returns to the liver o On hepatocytes, HDL binds to scavenger receptors and undergoes endocytosis o The HDL and its contents are then either recycled or excreted
Compare and contrast pros and cons for the following methods of starting statin therapy: typical starting dose or intensity-based dosing.
• Intensity-based dosing: o Pro = Achieving therapeutic outcomes o Con = increased risk for ADRs • Typical starting dose: o Pro = decreased risk for ADRs o Con = sub-therapeutic outcomes
Manage complaints of mild, moderate or severe muscle pain or fatigue with statins.
• Most often occur within 6 weeks of starting treatment and can occur after years of treatment and including myalgias, weakness, stiffness/cramps. • Pain is symmetrical • Do not use simvastatin 80 mg/day or gemfibrozil with statin • Manage myalgia o Hold statin if intolerable check possible causes and CK levels o 2-4 weeks: re-challenge with same statin or decrease dose • Most patients who do not tolerate a statin will tolerate it when re-challenged, or will tolerate a different statin • If myalgias return when the original statin is reinitiated, d/c original statin. o Once symptoms resolve, use a low dose of a different stain, then gradually increase
Describe the most common clinical presentations of dyslipidemia. (It is not important to memorize the various phenotypic / genetic classifications of dyslipidemia.)
• Most patients are asymptomatic for years • Symptomatic patients may report: o Symptoms of cardiovascular diseases - Chest pain - Palpitations - Sweating without exertion - SOB without exertion o Abdominal pain • Other physical signs o Arcus cornae - opaque ring on the outer edge of iris o Xanthomas - large foam cells under the skin o Xanthelasma - lipid yellow plaques on eyelids o Pts with ↑ TGs (> 1000 mg/dl) - acute pancreatitis - severe abdominal tenderness/pain, fever, N/V - hepatosplenomegaly - abdominal tenderness/pain, fever, N/V o Peripheral neuropathy o High BP o BMI > 30 kg/m2 o Waist size > 35 inches and > 40 inches in women and men, respectively
Differentiate myopathy and rhabdomyolysis.
• Myopathy- general term for disease of the muscles, muscle weakness +/ increase in CPK o Myalgia: specifically -muscle pain, soreness, tenderness, stiffness o Myositis: muscle inflammation o Rhabdomyolysis: extreme myopathy- muscle symptoms + very high CK >10,000 + muscle protein in urine (myoglobinuria), which can lead to acute renal failure -brown or dark urine
Secondary Causes of Dyslipidemia: Diseases
• Nephrotic Syndrome • AIDS • Chronic Renal Failure • Chronic Liver Disease • Biliary Obstruction • Acute Hepatitis
Differentiate between OTC and prescription niacin products regarding their risk of ADRs.
• Niacin also called Nicotinic acid or vitamin B3 o Doses for cholesterol are much higher than doses found in multivitamin products • IR = most efficacious- major flushing, chills, pruritus, GI upset, low hepatoxicity • SR = mild flushing, severe hepatotoxicity and GI upset • ER = more tolerable- mild flushing, mild hepatotoxicity
Drugs that cause ↓ HDL:
• Non-ISA beta blockers • Progestins • Anabolic Steroids • Loops diuretics
Compare and contrast available OTC omega 3 fatty acid supplements and prescription omega 3 fatty acids for amount of active ingredient per capsule (EPA/DHA content) and pill burden for triglyceride lowering (avoid charting all available OTC products).
• Omega-3-Acid Ethyl Esters (Lovaza): o 465 mg eicosatetraenoic acid (EPA) and 375 mg docosahexaenoic acid (DHA) • Icosapent ethyl (Vascepa): o ≥ 96% EPA and NO DHA • Omega-3-carboxylic acids (Epanova): o The 1-gram capsule is composed of: 850 mg polyunsaturated fatty acid - Multiple omega-3 fatty acids - Mainly EPA and DHA • The combination of EPA and DHA have been shown to greatly reduce triglycerides. • The use of EPA only (as in Vascepa) still significantly reduces triglycerides but does not cause as much of an increase in LDL-C as Lovaza.
Compare and contrast prescription omega 3 fatty acids regarding their impact on TG and LDL.
• Omega-3-Acid Ethyl Esters (Lovaza): o TG: ↓ by 14% to 30% o LDL: ↑ • Icosapent ethyl (Vascepa): o TG: ↓ 27% o LDL: -- • Omega-3-carboxylic acids (Epanova): o TG: ↓ o LDL: ↑
Define (avoid discussing diagnosis): PAD, CVA, TIA, revascularization, MI.
• PAD: peripheral artery disease which narrowing of arteries reduce blood flow • CVA: cerebral vascular accident also known as stroke which brain cells suddenly die due to lack of oxygen because of blockage or rupture of an artery in the brain • TIA: transient ischemia attack is similar to a stroke but doesn't cause permanent damage; mini-stroke • Revascularization: restoration of blood flow by bypass or graft • MI: myocardial infarction is a heart attack due to sudden lack of blood circulating
Given a patient case, select the most appropriate course of action for managing ASCVD risk and/or triglyceride lowering in the following special patient populations • Patients > 75 years of age: • Pregnant patients: • Patients with renal impairment:
• Patients > 75 years of age o Evidence supports the continuation of statins beyond 75 years of age in persons who are already taking and tolerating these drugs. • Pregnant patients o Women who are taking statins should discontinue the medication (except for BAS) immediately if the patient is already pregnant - at least 1 month and preferably 3 months before attempted conception o Pregnant patients on BAS should be monitored for vitamin K deficiency. o Statin and ezetimibe therapy should be restarted after completion of breastfeeding. • Patients with renal impairment o Fenofibrate is contraindicated
Describe the role in therapy, if any, of various dietary supplements (plant stanols/sterols and red yeast rice) used to reduce LDL and ASCVD risk.
• Plant stanols/sterols: o Effective at lowering LDL o Structurally similar to cholesterol so they can replace cholesterol from the body by consuming through certain foods like margarine, yogurt, etc. o Ultimately, reduce amount of cholesterol absorption from the gut • Red yeast rice: o Ingredients in red yeast rice have traces of Hmg-CoA reductase inhibitor activity which can cause drug interaction with statins. [don't want duplicate therapy]
Differentiate the terms primary and secondary prevention as they relate to ASCVD risk reduction and lipid lowering trials.
• Primary Prevention = patient is at risk for clinical ASCVD but has not had an event. • Secondary Prevention = patient has Clinical ASCVD and is on a statin to prevent another event.
Drugs that cause Hypercholesterolemia (↑ LDLs):
• Progestins • Thiazides • Glucocorticoids • Beta blockers • Protease Inhibitors • Atypical APs • Anabolic steroids
Recognize ADRs that necessitate discontinuation of each class.
• Rhabdomyolysis and/or CK >10 • LFT >3 x ULN • TG > 400 • eGFR <30 mL/min/1.73m2
Discuss how often ASCVD risk factors and a 10-year ASCVD risk score should be assessed.
• Starting at age 40 until age 79, a patient can be assessed for 10-year ASCVD Risk. o The patient should be assessed *every four to six years.* • Before age 40, patients can only be assessed for lifetime risk, and this can start as early as age 20. o The patient should be assessed *every four to six years*
Given a patient case, counsel the patient on each newly prescribed lipid lowering therapy.
• Statins: o Contact PCP - if you have muscle weakness, tenderness, aching, cramping, stiffness, pain, fever or feel more tired than muscle s/s of muscle damage - passing brown or dark-colored urine, pale stools, feel more tired, eye discoloration s/s of liver damage o Take statins in evening due to cholesterol synthesis being highest • Ezetimibe: o Contact PCP - if you have muscle weakness, tenderness, aching, cramping, stiffness, pain, fever or feel more tired than muscle s/s of muscle damage - passing brown or dark-colored urine, pale stools, feel more tired, eye discoloration s/s of liver damage - take medication once daily, with or without food • PCSK9 Inhibitors: o Medication can cause allergic reactions so seek care right away if you develop rash, redness, severe itching, swollen face or trouble breathing o Store in refrigerator • BAS: o Separate the dose of this medication from multivitamins, due to decreased absorption of vitamins A, D, E, K, folate and iron - May need to take a multivitamin o Medication can cause constipation so may want to initiate a stool softener based on recommendation • Fibrates: o Contact PCP - Muscle aches - Abdominal pain, nausea, vomiting s/s of inflammation of the gallbladder or pancreas • Fish Oils: o No side effects caused usually, but can cause stomach upset, burping or abnormal sense of taste (Lovaza) or joint pain (Vascepa) • Niacin: o Contact PCP - passing brown or dark-colored urine, pale stools, feel more tired, eye discoloration s/s of liver damage o Flushing (warm, redness, itching of the skin) is common side effect with consistent use - can take Aspirin or ibuprofen 30-60 minutes before the dose to help decrease flushing o If you have diabetes, check BS levels when starting this medication due to chance of mild increase
Given a patient case, assess the need for and order the required and optional baseline monitoring parameters for efficacy and safety of each therapeutic agent / class.
• Statins: o Efficacy: LDL reduction based on intensity o Safety: s/s myalgia, rhabdomyolysis, glucose levels • Ezetimibe: o Efficacy: LDL and TG reduction o Safety: myopathies (esp with statins), GI upset • PCSK9 Inhibitors: o Efficacy: LDL reduction o Safety: LDL reduction, injection site reaction, s/s infections • BAS: o Efficacy: 15-30% LDL reduction, up to 50% when combined with statin o Safety: vitamins, fasting lipid panel in 4-6 weeks, d/c if TG >400 • Fibrates: o Efficacy: f/u in 3 months for TG improvement o Safety: d/c if LFT >3 ULN, renal function, beware of gallstones, d/c if LFT >3 ULN o • Fish Oils: o Efficacy: TG reduction o Safety: LFT, LDL, bleeding time, rash, taste alterations, fish allergies, Afib/flutter • Niacin: o Efficacy: f/u 4 weeks after initiation and dose changes o Safety: d/c if LFT >3 ULN, uric acid, glucose, myopathy, increase risk for heart events
Compare and contrast routes of elimination and the requirement for dosage adjustments for starting and maximum doses in special populations (renal or hepatic impairment, elderly). • Statins: • Ezetimibe: • PCSK9 Inhibitors: • BAS: • Fibrates: • Fish Oils: • Niacin:
• Statins: o Elimination = Feces o Dosing Adjustment = - Renal: some have no adjustment, some half the dose - Hepatic: contraindicated in pts with hepatic impairment/liver disease - Elderly: not recommended due to increase CK (marker for MI) and risk of myopathy - Pregnancy: contraindicated • Ezetimibe: o Elimination = Renal o Dosing Adjustment = - Hepatic: contraindicated in pts with hepatic impairment/liver disease - Pregnancy: should be avoided • PCSK9 Inhibitors: o Elimination = Hepatic o Dosing Adjustment = None • BAS: o Elimination = Feces (stays in GI) o Dosing Adjustment = None • Fibrates: o Elimination = Renal - Renal: Fenofibrate is contraindicated o Dosing Adjustment = None • Fish Oils: o Elimination = o Dosing Adjustment = None • Niacin: o Elimination = Renal o Dosing Adjustment = None
Compare and contrast the mechanisms of action of the various lipid lowering therapies in order to understand which lipids they alter. • Statins: • Ezetimibe: • PCSK9 Inhibitors: • BAS: • Fibrates: • Fish Oils: • Niacin:
• Statins: o Inhibit LDL synthesis o Enhanced LDL catabolism mediated by LDL-R • Ezetimibe: inhibits the absorption of cholesterol from the small intestine, specifically via inhibition of Niemann-Pick C1-Like1 (NPC1L1) sterol transporter • PCSK9 Inhibitors: prevent the degradation function of PCSK9 on LDL receptors and promote the uptake and clearance of cholesterol (via LDL) in the liver • BAS: bind with bile acids in the intestine, preventing their reabsorption and producing insoluble complex, which is excreted in the feces • Fibrates: ↑VLDL clearance; ↓VLDL synthesis • Fish Oils: Not completely understood - proposed mechanisms: o ↑lipoprotein lipase activity o ↑ removal of triglycerides o ↓ production of triglyceride rich VLDL • Niacin: ↓ hepatic synthesis of VLDL, which leads to a ↓ in the synthesis of LDL
Compare and contrast the effects (↑, ↓, or ↔) and extent of the effects (% reduction/increase for starting and maximum doses) of the individual agents within each class on LDL, TG, and HDL. • Statins: • Ezetimibe: • PCSK9 Inhibitors: • BAS: • Fibrates: • Fish Oils: • Niacin:
• Statins: ↓ LDL, ↑ HDL, ↓ TG • Ezetimibe: ↓ LDL, ↑ HDL, ↓ TG • PCSK9 Inhibitors: ↓ LDL (>25%), ↑ HDL 8%, ↓ TG 10-17% • BAS: ↓ LDL by 15-21%, ↑ HDL by 3-9%, ↑ TG by 2-16% • Fibrates: ↓ LDL, ↑ HDL, ↓ TG • Fish Oils: ↑ LDL 5% to 10%, ↑ HDL 1% to 3%, ↓ TG 25% to 30% • Niacin: ↓ LDL 15%, ↑ HDL 25%, ↓ TG 30%
Determine if a patient is a candidate for 10 year and lifetime risk calculation.
• The 10-year Hard ASCVD Risk Calculation should be used on non-Hispanic Whites and non-Hispanic African Americans aged 40-79, • Lifetime risk should be calculated on patients 20-59. • It is possible to assess risk in patients outside of this age range, but significant evidence is lacking to support risk calculation in these populations. • It should be used on patients that have not had a CV event or patients that have a family history of hypercholesterolemia.
ASCVD risk in Professional Terms (for provider):
• The Hard ASCVD Risk score is a measure of a patient's likelihood to experience a non-fatal Myocardial Infarction, a fatal or non-fatal stroke, or develop Coronary Heart Disease over the next 10 years, and pharmacological therapy can be initiated according to the guidelines as needed. • The Lifetime ASCVD Risk score is a measure of a patient's likelihood to experience a non-fatal Myocardial Infarction, a fatal or non-fatal stroke, or develop coronary heart disease over the next 30 years and should not be used as a means for selecting pharmacological therapy. It should be used as a means to motivate lifestyle changes in younger individuals.
Compare this to the recommendation in the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease in Adults.
• The data provides no single threshold of triglyceride level above which pancreatitis may occur, but the statement describes increased risk arbitrarily by levels exceeding 1000 mg/L • "Data suggests that statin or fibrate monotherapy may be beneficial in patients with high triglyceride levels (>204 mg/dL), low HDL-C (<34 mg/dL), or both." • "Utilizing triglyceride-lowering medications to prevent pancreatitis in those with triglyceride levels 500 mg/dL is reasonable in addition to intensive therapeutic lifestyle change." • The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease in Adults recommend evaluating and treat laboratory abnormalities including triglycerides >/=500 mg/dL. o "Fenofibrate may be considered concomitantly with a low- or moderate- intensity statin only if the benefits from ASCVD risk reduction or triglyceride lowering when triglycerides are >/=500 mg/dL are judged to outweigh the potential risk for adverse effects." o "If EPA and/or DHA are used for the management of severe hypertriglyceridemia, defined as triglycerides >/=500 mg/dL, it is reasonable to evaluate the patient for gastrointestinal disturbances, skin changes, and bleeding. "
Recognize the presence or absence of evidence (eg, cardiovascular event data) for various therapies as discussed in DiPiro and ACC/AHA guidelines.
• The following therapies have evidence for decreased CV events o Statins o Ezetimibe o PCSK9 inhibitors o BAS
Describe the process of atherosclerotic plaque formation.
• The process of plaque formation starts with damage to the endothelial wall on the inner wall of an artery. It is referred to as an inflammatory condition. • LDLs begin to collect on the damaged endothelium and extracellular matrix under the endothelium. • Once in the artery wall, LDLs are oxidized. This promotes monocytes to the area which transform into macrophages. • Macrophages phagocytize the oxidized LDLs. Due to the elevated LDLs, macrophage become "fat laden". • At this point, the macrophage dies and becomes a foam cell; it begins to release cytokines that recruit more monocytes. • The inflammatory response causes more endothelial cells to become damaged; this proliferates and leads to more deposition of LDLs. • The underlying smooth muscle layer begins to secrete a fibrous cap to cover the plaque of foam cells. Also, the smooth muscle begins to deposit calcium into the plaque. • Over time, this narrows the artery and restricts the flow of blood; the calcium deposits harden the arteries.
Discuss dietary management of hypertriglyceridemia and its effects on triglyceride lowering.
• Triglyceride lowering within the range of 20-50% can be shown with practices including: weight loss, reducing simple CHO at the expense of increasing dietary fiber, eliminated processed trans-fat, restricting fructose and SFA, implementing Mediterranean-style diet, and consuming marine-derived omega 3 PUFA • Dietary practices or factors that are associated with higher triglyceride levels include: excess body weight (especially visceral adiposity), simple CHOs, including added sugars and fructose, and alcohol.
Recognize nonpharmacologic causes of secondary dyslipidemia.
• Weight gain • Saturated or trans fats • Very low-fat diets • High carb intake • Malnutrition • Smoking • Altered Metabolism: o Obesity o Hypothyroidism o Pregnancy o Diabetes (poorly controlled)
Explain when treating triglycerides should be the primary target.
• When TG > 500 mg/dL • These patients have risk of pancreatitis