DYSLIPIDEMIA

WINTANA TEKLEHAIMANOT

4TH YEAR PHARMACY STUDENT

FLORIDA A & M UNIVERSITY

DISEASE STATE PRESENTATION

OBJECTIVE

• Define dsylipidemia with its risk factors, prevalence and pathophysiology

• Describe the elements of diagnosis and the various non- pharmacological and pharmacological treatment options

• Compare and contrast primary literature based on guideline recommendation

• Discuss the clinical pearls and pharmacists role in managing patients with dyslipidemia

KEY TO ABBREVIATIONS

Total Cholesterol (TC)

Low Density Lipoproteins (LDL)

High Density Lipoproteins (HDL)

Very Low Density Lipoproteins (VLDL)

Triglycerides (TG)

DEFINITION• Abnormalities of plasma lipoproteins in our body

responsible for transporting major lipids:

• LDL • HDL• Chylomicrons (TG)• VLDL

• Elevation of TC ,LDL,TG, and low HDL or in some combination

• Result in a predisposition to arterial diseases such as:

• Coronary • Cerebrovascular• Peripheral Vascular

CLASSIFICATION

• Phenotype caterogy: I; Ila; IIb; III; IV; V

• Clinically:

• Isolated hypercholesterolemia: mostly due to LDL elevation

• Mixed or combined dyslipidemia: elevations of TC or LDL, and TG

• Isolated hypertriglyceridemia: elevation in TG only

• Low HDL-cholesterol: either isolated or in association with hypercholesterolemia or hypertriglyceridemia

PREVALENCE• Direct relationship between LDL levels and new onset of

CHD and recurrent coronary invents:

• Framingham Heart Study• Multiple Risk Factor Intervention Trial (MRFIT)• Lipid Research Clinics (LRC) trial

• About 46.8% American adults over age 20 are at borderline high risk with TC >200mg/dL

• More than half are unaware• Only one-third are receiving treatment• Less than 20% have achieved their LDL goal

PREVALENCE

• Major risk factor for mortality:

• Coronary Heart Disease (70%deaths) • Ischemic heart disease (50% deaths) • Preexisting CHD or prior MI (5-7 times increased risk)

• Leading cause of death for both men and women of all races and ethnicities

• Incidence is higher in industrialized countries• LDL is a significant predictor of mortality and mobidity• Strong correlation between BMI and incidence of

hypercholesterolemia

ETIOLOGY• Primary

• Single or multiple gene mutations• Children and young adults• Small percentages

• Secondary

• Most adults cases• Sedentary lifestyle• Certain disease states• Alcohol dependence• Certain medication use

PATHOPHYSIOLOGY

Atherosclerosis begins with injury to the endothelial cells that line the artery walls

• LDL enters intima through intact endothelium (influx > eliminating capacity and formation of LDL extracellular pool)

• Intimal LDL is oxidized into pro-inflammatory lipids• Oxidized LDL causes adhesion and entry of monocytes

and T lymphocytes across endothelium• Monocytes differentiate into macrophages and then

consume large amounts of LDL, transforming into foam cells

• Foam cells release growth factors (cytokines) that encourage atherosclerosis

RISK FACTORS• Additive effects to developing CV disease with:

• Diabetes• Hypothyroidism• Excess body weight (BMI >25 kg/m2)• Cholestatic liver disease• Cigarette smoking• Low HDL• Hypertension• Electrocardiogram abnormalities• Hyperhomocystinemia• Autoimmune phenomena• Nephrotic syndrome• Use of certain medication

COMPLICATIONS

• Myocardial Infaction

• Ischemic cardiomyopathy

• Sudden death

• Stroke

• Erectile dysfunction

• Peripheral vascular disease

• Acute limb ischemia

TESTS

Lipid Profile

• Total cholesterol (TC) >200 mg/dL;• LDL-cholesterol >100 mg/dL; • Non-HDL-cholesterol >130 mg/dL; • HDL-cholesterol <40 mg/dL for men; <50 mg/dL

for women• Triglycerides >150 mg/dL

TSH levels

• 0.3 - 3.04 mIU/L

DIAGNOSTIC CRITERIA

RISK STRATIFICATION

FRAMINGHAM RISK SCORE

TREATMENT APPROACH

NON-PHARMACOLOGICAL TREATMENT

• Dietary reduction total and saturated fat

• Weight loss in overweight patients

• Aerobic exercise

• Addition of plant stanols/sterols to the diet

• Dietary Recommendation:• Total fat intake 25% and 35% • Saturated fat <7% • Trans fat intake <1% of total daily calories• Cholesterol intake from food <300 mg/day• Increasing fish oil intake w/ omega-3 fatty acids

may help lower TG levels

PHARMACOLOGICAL TREATMENT

Drug MOA Adverse effects/Contraindication Drug interactions/Monitor

Reductase Inhibitors (Statins) ↓ LDL ↑ HDL↓ TG’sRefer to next slide

Increase LDL catabolism Inhibit LDL synthesis Also have roperties of breaking down existing plaques

↑ Liver enzymesMyalgia & rhabdomyolysisCI: active liver diease, high EtOH consupmtion, pregnancy

P450 metabolism (3A4 inh)Fibric acids = myopathiesErythromycin = ↑ myositisWarfarin = ↑ warfarin levelsM: LFT: 0,3,6,12 months→annually ; CKP

Bile Acid-Binding ResinsCholestyramine & Colestipol↓ LDL 10-20%↑ HDL 0-2%↑ TG’s 0-5%

Increase LDL catabolismDecrease cholesterol absorptionAlso adjunct

Constipation, nausea, fecal impaction, boating

CI: biliary obstruction, dysbetalipoproteinemia,TG > 500mg/dL

Binds to:Digoxin; Thyroxin, Warfarin, Take resins 2 hrs  before or after other medsMix→juice/milk/water/applesauce (metamucil)M: LFT's,TGs

Fibric Acid DerivativesGemfibrozil, Fenofibrate↓ LDL 10%↑ HDL 10-25%↓ TG’s 40-50%

Increase VLDL clearanceDecrease VLDL synthesisAlso an adjunct

Abdominal pain, rash myopathy, rhabdomyalysis CI: Severe hepatic & renal disease

Statins = myopathiesBile acid-binding resins – separate doses by 2 hrs. M: CBC,Scr (↓ dose if ↑ Scr),Glucose, LFT's , CKP

Niacin↓ LDL 10-15%↑ HDL 10%↓ TG’s 20-80%

Decrease LDL and VLDL synthesis

Flushing, pruruitus (pretreat w/ ASA), hepatotoxic; GERD, glucose intolance, hyperuricemia

CI: severe peptic ulcer Dx, chronic liver Dx,overt diabetes & severe goutM: LFT's, glucose, uric acid

Ezetimibe↓ LDL 17%↑ HDL 1.3%↓ TG’s 6%

Inhibits absorption of  cholesterol at the small intestine brush borderAlso an adjunct/booster for statins

Diarrhea, abdominal painArthralgia; Back painFatigueCI: Hepatic

Fibrates = gall bladder disease, myopathyM: LFT's

Statin Daily Adult Dose Providing Similar Average LDL-lowering (%)a,1-10

Atorvastatin (Lipitor) --- --- 10 mg (35-39%) 20 mg (43%) 40 mg (50%) 80 mg (55-60%)

Atorvastatin/ezetimibe(Liptruzet)

--- --- --- --- 10/10 mg (53%) to 20/10 mg (54%)

40/10 mg (56%) to 80/10 mg (61%)

Fluvastatin (Lescol, Lescol XL)b

20 mg (22%)

40 mg (25%)

80 mg (35% [as XL product])

--- --- ---

Lovastatin (Mevacor)c

10 mg (21%)

20 mg (24-27%)

40 mg (30-31%) to 80 mg (40-42% [as 40 mg BID])

80 mg (40-42% [as 40 mg BID])

--- ---

Pitavastatin (Livalo)d --- 1 mg (31-32%) 2 mg (36-39%) 4 mg (41-45%) --- ---

Pravastatin (Pravachol)e

10 mg (22%)

20 mg (32%)

40 mg (34%) to 80 mg (37%) 

80 mg (37%)

--- ---

Rosuvastatin (Crestor)f,g

--- --- --- 5 mg (45%) 10 mg (46-52%) to 20 mg (47-55%)

20 mg (47-55%) to40 mg (55-63%)

Simvastatin (Zocor)h

5 mg(26%)

5 mg (26%) to 10 mg (30%)

20 mg (38%)

40 mg (29-41%)

80 mg (36-47%)

---

Simvastatin/ezetimibe (Vytorin)i

--- --- --- 10 mg/10 mg (45%)

20 mg/10 mg (52%) to 40 mg/10 mg (55%)

40 mg/10 mg (55%) to 80 mg/10 mg (60%)

NEW CONTROVERSIAL STUDY • Use of Omega 3 fatty acid for hypertriglyceridemia due to increased risk

of prostate cancer

• Title: • Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT

Trial

• Background: • Based on previous study, Prostate Cancer Prevention Trial (PCPT) claims

high concentration of serum phospholipid long-chain ω-3 fatty acids are associated with large increase in the risk of high-grade prostate cancer

• Method: • Case-cohort design nested within SELECT

• Result:• Higher total long-chain ω-3 PUFA were associated with increased risks of

total, low-, and high-grade cancer. Compared with men in the lowest quartile of total long-chain ω-3 PUFA, men in the highest quartile had 44% (95% CI= 8%- 93%), 71% (95% CI= 0%- 194%), and 43% (95% CI= 9%- 88%) increased risk for low-grade, high-grade and total cancer, respectively.

• Conclusion:• This study does not prove fish oil supplementation to increase prostate

cancer risk, however more investigation would be beneficial

CLINIAL PEARLS

• Statins are once-daily dosing, unless otherwise specified.

• Statins in severe renal impairment should be used in caution of doses over 40 mg daily

• Statins if CrCl <30 mL/min should be used in caution of doses over 20 mg daily

• Monitor for drug interactions when using antihyperlipidemia drugs

• Combination therapy for non-therapeutic patients may be beneficial, however, must monitor for side effects

• Lifestyle modification is the best approach to treating dyslipidemia

PHARMACISTS ROLE

REFERENCE