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Definition :
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Definition Hyperlipidemia, hyperlipoproteinemia or
dyslipidemia is the presence of raised or abnormal levels of
lipids and/or lipoproteins in the blood
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Lipids are insoluble in aqueous solution.
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Lipids (fatty molecules) are transported in a protein capsule,
and the density of the lipids and type of protein determines
the fate of the particle and its influence on metabolism.
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Lipid and lipoprotein abnormalities are extremely common in
the general population, and are regarded as a highly
modifiable risk factor for cardiovascular disease due to the
influence of cholesterol, one of the most clinically relevant
lipid substances, on atherosclerosis.
Pathobiology of Atherosclerosis
When excess cholesterol deposits on cells
and on the inside walls of blood vessels
it forms an atherosclerotic plaque
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The first step of atherosclerosis is
injury to the endothelium which results
in atherosclerotic lesion formation
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When the plaque ruptures, blood clots
form which lead to decreased blood
flow, resulting in cardiovascular events
Complications of Hyperlipidemia
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Macrovascular complications:
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Unstable Angina (chest pain)
Myocardial Infarction (heart attack)
Ischemic Cerebrovascular Disease (stroke)
Coronary Artery Disease (heart disease)
Microvascular complications:
 Retinopathy (vision loss)
 Nephropathy (kidney disease)
 Neuropathy (loss of sensation in the feet and
legs)
Risk Factors for Hyperlipidemia
Obesity
 Type 2 diabetes mellitus
 Advanced age Hypothyroidism
 Obstructive liver disease
 Genetics
 Drug induced:
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(e.g. glucocorticoids, thiazide diuretics, beta blockers, protease
inhibitors, sirolimus, cyclosporine, progestins and alcohol)
Treatment Goals :
 Reduce total cholesterol and LDL (bad)
cholesterol
 Prevent the formation of atherosclerotic
plaques and stop the progression of
established plaques
 Prevent heart disease
 Prevent morbidity and mortality
Non-Pharmacological Treatment :
1.
Lipid lowering therapy should be started with lifestyle
modification for at least 12 weeks
2.
Increase physical activity
3.
Weight reduction
4.
Diet modification:
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Total fat 25-35% of total calories
Saturated fat <7% of total calories
Polyunsaturated fat up to 10% total calories
Monounsaturated fat up to 20% total calories
Carbohydrates 50-60% total calories
Fiber 20-30 g/ day total calories
Protein 15% total calories
Cholesterol <200 mg/day
Pharmacological Treatment :
Pharmacological Treatment If non-pharmacological treatment is not successful, a
lipid-lowering drug should be started, especially in high risk populations
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1st step:
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Initiate LDL-lowering drug therapy .
○ Start with statins, bile acid sequestrants, or nicotinic acid.
○ Evaluate after 6 weeks .
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2nd step:
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If goal was not reached, intensive lipid-lowering treatment should be started .
○ Increase dose of statins .
○ Bile acid sequestrants or nicotinic acid should be added.
○ Evaluate after 6 weeks .
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3rd step:
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If goal is not reached, intensive lipid lowering should be continued or individual should be
referred to a lipid specialist .
○ If goal was reached, other lipid risk factors should be treated .
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4th step:
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Monitor response and compliance.
Pharmacological Treatment
Pharmacological Treatment
1. Statins (HMG CoA Reductase Inhibitors)
○ Atorvastatin (Lipitor® )
○ Simvastatin (Zocor®)
○ Lovastatin (Mevacor®): extended release
○ Pravastatin (Pravachol®)
○ Fluvastatin (Lescol®)
○ Lescol XL: 80 mg tablets .
○ Rosuvastatin (Crestor®): tablets
Statins (HMG CoA Reductase Inhibitors)
Effectiveness of statins:
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Reduce LDL cholesterol by 18-55%
Decrease TG by 7-30%
Raise HDL cholesterol by 5-15%
Statins are the most effective in lowering LDL
cholesterol
Statins are the most effective in patient who
has low HDL and high LDL
Statins (HMG CoA Reductase Inhibitors)
Mechanism of action:
Statins inhibit HMG-CoA reductase
(enzyme involved in cholesterol
synthesis) thus decreasing mevalonic
acid production and stimulating LDL
breakdown.
Statins (HMG CoA Reductase Inhibitors)
Side effects:
 Muscle break down (rhabdomyolysis)
 Increased liver enzymes
 leading to renal failure
 Fatigue, mild stomach disturbances,
headache, or rash
Statins (HMG CoA Reductase Inhibitors)
Avoid use in:
 Active or chronic liver disease and pregnancy
Use with caution with:
 Concomitant use of cyclosporine, macrolide
antibiotics, antifungal agents. For example:
Itraconazole, ketoconazole, erythromycin,
clarithromycin, cyclosporine, nefazodone, HIV
antiretrovirals
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When statins are used with fibric acids and niacin,
appropriate caution should be taken because of
increasing incidence of muscle breakdown
Statins (HMG CoA Reductase Inhibitors)
Drug- food interaction:
 Grapefruit juice increases concentration of statins
 Pravastatin, rosuvastatin & fluvastatin concentrations
are not affected by grapefruit juice.
Monitoring:
 Muscle soreness, tenderness, or pain.
 Liver function tests : baseline, 4-6 weeks after
starting therapy, and then annually.
 Muscle enzyme levels when individual has muscle
pain
Pharmacological Treatment:
2. Bile Acid Sequestrants
Mechanism of action:
Bile acid sequestrants bind to bile acids in the
intestine, thus inhibits uptake of intestinal bile
salts into the blood and increases the fecal loss
of bile salt-bound LDL
Bile Acid Sequestrants:
1) Cholestyramine (Questran®):
Usual dose: 4 g by mouth 1-2 times a day with meal
to a maximum of 24 g per day.
2) Colesevelam (Welchol®):
Usual dose: 3 tablets by mouth twice daily with
meals or 6 tablets once daily with a meal.
3) Colestipol (Colestid®)
Usual dose:
○ Granules: 5-30 g by mouth daily given once or 2-4 times a
day with meal
○ Tablets: 2-16 g by mouth daily.
Bile Acid Sequestrants:
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Effectiveness:
○ Reduces LDL cholesterol by 15-30%
○ Increases HDL cholesterol by 3-5%
○ Increases TG.
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Drug interaction:
○ Decreased absorption of fat soluble Vitamins:
A, D, E, K, C and folic acid
○ Decreased absorption of other drugs:
tetracycline, thiazide diuretics, aspirin,
phenobarbital, pravastatin, digoxin
Bile Acid Sequestrants:
Side effects:
Stomach upset, constipation accompanied by heart burn,
nausea, and bloating
Avoid use in:
 A disease called dysbetalipoproteinemia
 Triglycerides >400 mg/dL
Use caution if:
 Triglycerides >200 mg/dL.
 Colesevalam is much better tolerated than cholestyramine
or colestipol
 Statins and other drugs should be taken 1-2 hours before
and 4-5 hours after bile acid sequestrants
Pharmacological Treatment:
3) Nicotinic Acid:
Mechanism of action:
Nicotinic acid decreases the clearance of ApoA1
to increase HDL; it inhibits the synthesis of
VLDL
Effectiveness:
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Decreases LDL cholesterol by 5-25 %
Increases HDL cholesterol by 15-35%
Decreases TG by 20-50%
Nicotinic acid is the most potent drug that
increases HDL cholesterol
Nicotinic Acid:
Side effects:
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Flushing (taking aspirin or ibuprofen can reduce symptoms)
Increases blood glucose due to impaired insulin sensitivity
Gout
Liver toxicity associates with sustained release form (Niaspan)
Upper stomach distress and muscle weaknes
Avoid use in:
○ Chronic liver disease
○ Severe gout
Use with caution in:
○ Type 2 diabetes (high dose)
○ Gout
○ Peptic ulcer disease
Pharmacological Treatment:
4) Fibric Acids :
Mechanism of action:
Fibric acid up-regulates fatty acid transport protein and fatty acid
oxidation; thus it reduces the formation of VLDL, increases
formation of HDL, and enhances the breakdown of TG
Agents:
○ Gemfibrozil (Lopid®)
○ Fenofibrate (Tricor®)
Fibric Acids:
Effectiveness:
○ Reduces LDL cholesterol by 20-50% with normal TG
○ Increases LDL cholesterol with high TG
○ Reduces TG by 20-50%
○ Increases HDL cholesterol by 10-20%
○ Fibric acids are very effective in lowering TG and
preventing pancreatitis
○ Fibric acids reduce VLDL, but fibric acids might
increase LDL and total cholesterol
Fibric Acids:
Side effects:
 Dyspepsia, gallstones, muscle ache, rash
 Unexplained non-coronary heart disease deaths
 Weakness, tiredness, elevations in muscle enzyme
Avoid use in:
 Severe renal disease
 Severe hepatic disease
Drug interaction:
 Fibric acids bind to albumin and increase the effect
of anticoagulants
Pharmacological Treatment:
5) Ezetimibe (Zetia)
Mechanism of action:
Inhibits absorption of cholesterol in the small intestine; thus it
decreases the delivery of cholesterol to the liver and increases
the clearance of cholesterol from the blood
Side effects:
chest pain, dizziness, diarrhea, abdominal pain
Drug interaction:
 Bile acid sequestrants decrease ezetimibe concentrations
○ Ezetimibe should be spaced 2 hours before or 4 hours
after bile acid sequestrants administration
 Fibric acids increase ezetimibe concentrations