Hyperlipidemia Flashcards

Question

What is the pathogenesis of atherosclerosis?

Answer 1

-Develops in response to altered endothelial integrity or injury. (usually resulting from HTN) Injury can be from mechanical forces, or nonmechanical agents (exp. homocysteine, CO) -Monocytes adhere to vessel surface & become macrophages. -Macrophages highly oxidize LDL and then take up the LDL creating foam cells -Oxidized LDL is dangerous Oxidation of LDL may be cytotoxic all cell types within vessel wall able to oxidize Oxidized LDL induces expression of adhesive cell-surface proteins (exp. VCAM)- these allow other stuff to accumulate -Lipid accumulates in SMC, macrophages, and extracellular matrix -Ultimately get build up of SMC, macrophages, fibrous tissue and lipid to form plaque. -Platelets adhere to site of injury and secrete growth factors -HDL promotes “reverse cholesterol transport”

Answer 2

Preventing the development of atherosclerosis and cardiovascular disease

Answer 3

Prevent the progression of cardiovascular disease and recurrence of cardiovascular events

Answer 4

Decrease morbidity and mortality | Achieve target goals for each lipid

Answer 5

Cholesterol reduction decreases progression, increases regression, & decreases formation of new lesions. Cholesterol reduction decreases CV events, revascularization, and mortality Cholesterol reduction in some instances decreases all cause mortality

Answer 6

``` LDL-C ( mg/dL) < 100 Optimal 100-129 Above, near optimal 130-159 Borderline High 160-189 High ≥190 Very high ```

Answer 7

HDL-C (mg/dL)- want it between 40-60 | 60 High

Answer 8

TC (mg/dL) < 200 Desirable 200-239 Borderline High ≥240 High

Answer 9

``` Triglycerides (mg/dL) < 150 Normal 150-199 Borderline high 200-499 High ≥ 500 Very high ```

Answer 10

Low Risk (0-1risk Factors): LDL < 160mg/dL

Answer 11

Moderate-High Risk: LDL < 130mg/dL | Optional: LDL < 100mg/dL for patients with 10-20% 10 year risk

Answer 12

``` DM:LDL < 100 mg/dL Optional: LDL < 150 mg/dL HDL: > 40 mg/dL for males > 50 mg/dL for females ```

Answer 13

Cigarette smoking Hypertension: BP ≥140/90 mm Hg or on antihypertensive medication Low HDL-C: <65 years Age male ≥45 years female ≥55 years *HDL-C ≥60 mg/dL is a negative risk factor and negates one other risk factor.

Answer 14

- Myocardial infarction, unstable or stable angina, post-CABG, s/p angioplasty or other PCI - Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) - Diabetes - Multiple risk factors that confer a 10-year risk for CHD >20%

Answer 15

``` Age Total cholesterol HDL cholesterol SBP Smoking status ```

Answer 16

Diet, exercise, and weight reduction | LDL>160mg/dL + 1 risk factor = drug candidate

Answer 17

After baseline labs – reevaluate after 4-8 weeks and then after changes Fasting Lipid Panel every 1-2 years

Answer 18

- Decrease synthesis VLDL and LDL - Enhance VLDL clearance - Enhance LDL catabolism - Decrease cholesterol absorption - Elevate HDL - Or some combination of action

Answer 19

- Inhibits mobilization of FFA’s from adipose tissue => results in decreased VLDL synthesis by the liver - Lowers TG (20-50%), LDL (5-25%) and increases HDL (15-30%) - Reduces major coronary events and possibly mortality

Answer 20

Mixed hyperlipoproteinemias Adjunct to increase HDL (most effective agent) Adjunct to decrease TG

Answer 21

Vasodilation => flushing, itching & HA Slow realease niacin doesn’t cause as much flushing but it doesn’t work as well, But you can also have them take it with an ASA will avoid these side effects. GI => N, dyspepsia, activation of PUD Hyperuricemia Worsen glucose tolerance- therefore a problem in DM patients and there might be better choices. Hepatotoxicity => LFTs > 3X normal More severe cases = fatigue, nausea, anorexia Dose dependent and more common with SR products Baseline LFTs and monitor q6-8 weeks x 1 year

Answer 22

Glucose, uric acid at baseline and dose threshold LFTs (AST/ALT) Baseline monthly until dose stable for SR Q 3 months for first year on SR niacin Check once at dose threshold for IR and ER (4-8 weeks) For all forms check LFTs Q 6 months

Answer 23

Relative: DM, gout, peptic ulcer Absolute: Liver disease

Answer 24

- Hypotension with BP lowering drugs - Diabetic meds may need adjusting secondary to hyperglycemia - Increased risk of hepatotoxicity with HMG-CoA reductase inhibitors (statins)

Answer 25

Gemfibrozil (Lopid) Clofibrate (Atromid-S) Fenofibrate (Tricor)

Answer 26

MOA: inhibits lipolysis and increases lipoprotein lipase; decreasing serum VLDL and increasing HDL Effects on lipoproteins: Decreases TGs by 30-50% and increases HDL by 10-20%; may increase LDL (increase in LDL is not something we could like to see) Reduce major coronary events; inconclusive data regarding increase CV, non-CV, & total mortality In several trials the decrease in CHD deaths were offset by increased mortality secondary to gallstones and pancreatitis

Answer 27

Approved indication = lowering of TG in patients with hypertriglyceridemia Also used for combined increased cholesterol and TG (in combination)

Answer 28

-Most common – GI (decrease with time) -Myopathy – sx: muscle soreness pain Increased risk if on statin Baseline CPK => 10X normal d/c Decreased renal function = increases risk -Hepatoxicity -Neutropenia -Gallstones and pancreatitis Avoid in high risk groups – women, Native Americans, obese patients.

Answer 29

Cholestyramine (Questran) | Colestipol (Colestid)

Answer 30

Bile acid binding resins By inhibiting enterohepatic recycling of bile acids and salts, the liver is stimulated to convert stored cholesterol to bile acids Forms insoluble complex Increases expression of LDL receptors and LDL uptake in peripheral circulation Reduces total cholesterol and LDL in a dose-dependent manner 15-30% reduction in LDL; 15-18% with colesevelam; increase HDL 3-10%; and increase TGs 0-12% (this is the problem so need to make sure pt doesn’t already have problems with TG) Reduce major coronary events and CHD deaths

Answer 31

Primarily GI Constipation, bloating, gas, nausea Avoid in patients with diverticulosis, swallowing difficulties, GI motility disorders ↑ TGs

Answer 32

warfarin, thyroid, digoxin | Separate all meds by at least 2 hrs, if you have taken it wait 4 hours to take it.

Answer 33

Absolute: Biliary obstruction, fasting TGs > 500mg/dL Relative: fasting TGs > 200 mg/dL

Answer 34

``` Lovastatin (Mevacor), Pravastatin (Pravachol), Fluvastatin (Lescol), Simvastatin (Zocor), Rosuvistatin (Crestor), Atorvastatin (Lipitor) ```

Answer 35

Competitively inhibit the rate-limiting enzyme (HMG-CoA Reductase) necessary for cholesterol synthesis results in an increase in hepatic LDL receptors Decreased cholesterol concentration within cell Low intracellular cholesterol stimulates synthesis of LDL receptors and LDL clearance from peripheral circulation Low intracellular cholesterol decreases secretion of VLDL

Answer 36

Decreases LDL 20-60% Decreases TGs 10-30% Increases HDL 5-10%

Answer 37

Major coronary events and stroke CV-related and total mortality Coronary procedures (PCI/CABG)

Answer 38

Stabilize atherosclerotic plaques Enhance vascular nitric oxide production Attenuate inflammation due to vascular injury Decrease oxidative stress

Answer 39

Modulate glomerular mesangial and interstitial inflammatory processes

Answer 40

Improve insulin sensitivity (beneficial in type II DM)

Answer 41

Inhibit bone resorption

Answer 42

Efficacy greatest if given with dinner or at bedtime to coincide with peak cholesterol biosynthesis (due to peaking cholesterol in the middle of the night)

Answer 43

Few side effects, excellent patient acceptance Most common = HA, myalgias, GI (dyspesia) Hepatotoxicity = LFTs > 3X normal Check LFTs every 4-6 weeks for 1 year Alcohol and prior liver disease increase risk Myopathy = muscle aches, soreness, weakness and CPK > 10X normal Increased levels = increased risk Doses should not exceed those required to attain ATP III goals Risks are associated with the higher levels.

Answer 44

-Drug interactions: (few) -Cyp450 3A4 Inhibitors: Cyclosporine, grapefruit juice, macrolides, triazole antifungals, fluoroquinolones, SSRIs, diltiazem, verapamil, amiodarone, omeprazole, protease inhibitors -Pravastatin, Fluvastatin (2C9) and Rosuvastatin (2C9 minor) not metabolized by 3A4 -Lovastatin increases warfarin effects -Drugs that cause myopathy Gemfibrozil and niacin

Answer 45

AST/ALT before and 12 weeks after initiation of statin or after dosage increase then periodically (every 6 months), CK at baseline and if symptoms

Answer 46

Liver and renal disease | Contraindicated in pregnancy

Answer 47

HMG-CoA reductase inhibitors (statins)

Answer 48

Increased risk of myopathy and hepatotoxicity | Monitor LFT’s baseline, Q 6-12 weeks x 6 months then periodically

Answer 49

Cholesterol absorption inhibitor - Inhibits absorption of cholesterol at the brush border of SI->decreased delivery of cholesterol to liver - Decreased total cholesterol, LDL-C and TG; increased HDL-C - Decreases LDL-C by 15-20%, TGs by 5-10% and increases HDL by 4-9% in monotherapy and as add-on - No data on CV morbidity or mortality - No effect on blood levels of fat soluble vitamins

Answer 50

May increase risk of AST/ALT elevation when used in combination with statins ADRs: HA, GI, arthralgia, sinusitis

Answer 51

Should only be used when other therapies are not working

Answer 52

- Decrease CVD risk by ~ 35% from epidemiologic studies - Decrease LDL 15-20%, Increase HDL 5-20%, -Increase TG’s 10-25%, - Decrease Lp (a) 20-30%

Answer 53

- WHI and HERS study demonstrated no benefit on CV risk and increased risk of breast CA - ACC/AHA recommends that estrogen/progesterone not be initiated or continued to prevent CAD in postmenopausal women.

Answer 54

- Effective at lowering TG’s (25-30%); can increase LDL (5-10%) esp at higher doses (> 3 gm/day), minimal effects on HDL - MOA: Not understood, one possible mechanism is increased plasma lipoprotein lipase activity. - Supplementation demonstrated to decrease CHD events (MI, death, nonfatal stroke)- in trials

Answer 55

- Decrease TG’s by 45% (baseline TGs > 500 mg/dL) - Side Effects: Higher doses (> 3 gm/day) can effect bleeding time and may impair insulin secretion, GI (nausea, diarrhea, taste disturbance)

Answer 56

Good (↓ LDL 10-15%)

Answer 57

Probably good (↓ TC 5-15%)

Answer 58

Not so good (↓ TC 5-8%) | Made patients leak out fatty stuff from butt

Answer 59

Has activity against HMG Co-A reductase | ↓ LDL 20 - 25%

Answer 60

--Moderate alcohol consumption is associated with lower mortality Most evidence with red wine --Moderate consumption (< 2 drinks/day; 20 gm/day alcohol) associated with: ~ 12% increase in HDL-C decreased LDL oxidation decreased platelet aggregation --Higher consumption associated with increased mortality Increased BP, arrhythmia, TG, stroke, and MI

Answer 61

Based on goal LDL and % reduction required Initiate therapeutic lifestyle changes Smoking cessation Diet, including plant stanols/sterols, fish oils, & fiber Weight reduction, physical activity

Answer 62

If LDL-C > 20% above goal or patient is high or moderately high risk, statins should be the initial drug choice

Answer 63

If LDL-C < 20% above goal, then a statin, niacin, ezetimibe, or BAR are good choices

Answer 64

IF TGs > 500, then initiate TG lowering therapy (fibrate or niacin) to reduce risk of pancreatitis

Answer 65

When initiating drug therapy for patients at very high risk, high risk, or moderately high risk the intensity of therapy should be such to achieve a 30 – 40% LDL reduction

Answer 66

Repeat fasting lipid profile in 4 – 6 weeks If not at goal, intensify statin dose OR Add ezetimibe, BAR (bile acid resin), or niacin

Answer 67

Once LDL goal achieved, assess TGs and HDL If TG > 200 mg/dL, achieve non-HDL-C (TC – HDL-C) goal (LDL goal + 30 mg/dL) Intensify therapy with LDL-lowering drug OR Add niacin or fibrate If TG < 200 mg/dL, HDL < 40 mg/dL, & CHD or equivalent, consider fibrate or niacin

Answer 68

Low HDL-C: <40 mg/dL (no specific goal defined for raising HDL-C)

Answer 69

- All persons with low HDL-C: achieve LDL-C goal; then ↓ weight, ↑ physical activity (if metabolic syndrome is present) - Those with TG 200–499 mg/dL: achieve non–HDL-C goal* as secondary priority - Those with TG <200 mg/dL: consider drugs for raising HDL-C (fibrates, niacin)

Answer 70

LDL-C ≥190 mg/dL usually traced to genetic forms of hypercholesterolemia

Answer 71

- Early detection in young adults through cholesterol screening to prevent premature CHD - Family cholesterol testing to identify affected relatives - Combination drug therapy usually required to achieve target LDL-C levels

Answer 72

Borderline high 150–199 | ↓ weight, ↑ physical activity

Answer 73

High 200-499 | ↓ weight, ↑ physical activity, consider drug treatment to reach non–HDL-C goal-‡

Answer 74

Very High > 500 | Very low-fat diet, ↓ weight, ↑ physical activity, nicotinic acid or fibrate

Answer 75

- -Primary target of therapy: identification of LDL-C; goal for persons with diabetes: <100 mg/dL - -Therapeutic options: - -LDL-C 100–129 mg/dL: increase intensity of TLC; add drug to modify atherogenic dyslipidemia (fibrate or nicotinic acid); intensify risk factor control - -LDL-C ≥130 mg/dL: simultaneously initiate TLC and LDL-C–lowering drugs - -TG ≥200 mg/dL: non–HDL-C* becomes secondary target

Answer 76

Increased TG Decreased HDL LDL concentrations do not significantly differ from concentrations in non-DM patients However, DM LDL is predominately small, dense LDL