Transcript Dyslipidemia

DYSLIPIDEMIA
WINTANA TEKLEHAIMANOT
4 TH 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 nonpharmacological 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
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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
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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:
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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)
Increase LDL catabolism
Inhibit LDL synthesis
Also have roperties of
breaking down existing
plaques
↑ Liver enzymes
Myalgia & rhabdomyolysis
CI: active liver diease, high
EtOH consupmtion,
pregnancy
Increase LDL catabolism
Decrease cholesterol
absorption
Also adjunct
Constipation, nausea, fecal
impaction, boating
P450 metabolism (3A4 inh)
Fibric acids = myopathies
Erythromycin = ↑ myositis
Warfarin = ↑ warfarin levels
M: LFT: 0,3,6,12
months→annually ; CKP
Binds to:
Digoxin; Thyroxin, Warfarin,
Take resins 2 hrs before or
after other meds
Mix→juice/milk/water/apple
sauce (metamucil)
M: LFT's,TGs
↓ LDL
↑ HDL
↓ TG’s
Refer to next slide
Bile Acid-Binding
Resins
Cholestyramine & Colest
ipol
↓ LDL 10-20%
↑ HDL 0-2%
↑ TG’s 0-5%
CI: biliary obstruction,
dysbetalipoproteinemia,
TG > 500mg/dL
Fibric Acid Derivatives Increase VLDL clearance
Gemfibrozil, Fenofibrate Decrease VLDL synthesis
↓ LDL 10%
Also an adjunct
Abdominal pain, rash
myopathy, rhabdomyalysis
CI: Severe hepatic & renal
disease
Statins = myopathies
Bile acid-binding resins –
separate doses by 2 hrs.
M: CBC,Scr (↓ dose if ↑
Scr),Glucose, LFT's , CKP
Niacin
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 gout
M: LFT's, glucose, uric acid
Inhibits absorption
of cholesterol at the small
intestine brush border
Also an adjunct/booster for
statins
Diarrhea, abdominal pain
Arthralgia; Back pain
Fatigue
CI: Hepatic
Fibrates = gall bladder
disease, myopathy
M: LFT's
↑ HDL 10-25%
↓ TG’s 40-50%
↓ LDL 10-15%
↑ HDL 10%
↓ TG’s 20-80%
Ezetimibe
↓ LDL 17%
↑ HDL 1.3%
↓ TG’s 6%
Statin
Daily Adult Dose Providing Similar Average LDL-lowering (%)a,1-10
Atorvastatin (Lipitor) ---
---
10 mg (35-39%)
20 mg (43%)
40 mg (50%)
Atorvastatin/ezetimi --be
(Liptruzet)
---
---
---
10/10 mg (53%) to 40/10 mg (56%)
20/10 mg (54%)
to 80/10 mg
(61%)
Fluvastatin
20 mg
(Lescol, Lescol XL)b (22%)
40 mg
(25%)
80 mg
--(35% [as XL product])
---
---
Lovastatin
(Mevacor)c
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%) to
40 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%)
---
---
---
10 mg/10 mg
(45%)
20 mg/10 mg
40 mg/10 mg
(52%) to 40 mg/10 (55%) to 80
mg (55%)
mg/10 mg (60%)
10 mg
(21%)
Simvastatin/ezetimi --be (Vytorin)i
80 mg (55-60%)
NEW CONTROVERSIAL STUDY
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Use of Omega 3 fatty acid for hypertriglyceridemia due to increased risk
of prostate cancer
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Title:
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Background:
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Case-cohort design nested within SELECT
Result:
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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:
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Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT
Trial
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:
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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