Dyslipidemias Practice Approach

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Dyslipidemias Practice Approach
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Role of Cholesterol

• Necessary component of Cell membranes
• These essential envelopes protect the cell from
  its external (extracellular) environment and help
  maintain its internal (intracellular) environment
• Precursor of steroid hormones
• Ovaries estrogen, progesterone
• Testes androgens
• Adrenals glands 50, e.g. aldosterone, cortisol
• Precursor of Bile Acids
• Bile Acids are important in digestion and
  absorption of fats.

Module 1
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Cholesterol Sources

• Knowing how the absorption and biosynthesis of
  cholesterol occur and are regulated, provides the
  key to understanding interventions to treat
  patients with hypercholesterolemia
• Generally, Cholesterol arises from one of two
  sources
• Exogenous (dietary reabsorbed bile) and
• Endogenous (synthesized by liver and extrahepatic
  tissues)

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Cholesterol Sources

• Dietary cholesterol can contribute as much as one
  third of the bodys total cholesterol. Endogenous
  synthesis accounts for the remaining two thirds.
• Although most tissues make cholesterol, most
  endogenous cholesterol is primarily synthesized
  in the liver and the small intestine. The small
  intestine is also the site of uptake of dietary
  cholesterol.)

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The Exogenous Pathways
Of the total cholesterol available for
absorption, 50 is absorbed through the
intestinal wall and 50 is excreted in the feces.
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• Cholesterol cant dissolve in the blood. It has
  to be transported to and from the cells by
  carriers called lipoproteins. Low-density
  lipoprotein, or LDL, is known as bad
  cholesterol. High-density lipoprotein, or HDL, is
  known as good cholesterol. These two types of
  lipids, along with triglycerides and Lp(a)
  cholesterol, make up your total cholesterol
  count, which can be determined through a blood
  test.

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LDL (Bad) Cholesterol

• When too much LDL (bad) cholesterol circulates in
  the blood, it can slowly build up in the inner
  walls of the arteries that feed the heart and
  brain. Together with other substances, it can
  form plaque, a thick, hard deposit that can
  narrow the arteries and make them less flexible.
  This condition is known as atherosclerosis. If a
  clot forms and blocks a narrowed artery, heart
  attack or stroke can result.

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HDL (good) Cholesterol

• About one-fourth to one-third of blood
  cholesterol is carried by high-density
  lipoprotein (HDL). HDL cholesterol is known as
  good cholesterol, because high levels of HDL
  seem to protect against heart attack. Low levels
  of HDL (less than 40 mg/dL) also increase the
  risk of heart disease. Medical experts think that
  HDL tends to carry cholesterol away from the
  arteries and back to the liver, where it's passed
  from the body. Some experts believe that HDL
  removes excess cholesterol from arterial plaque,
  slowing its buildup.

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Hyperlipidemia

• An elevated concentration of plasma cholesterol
  or triglycerides, or both.
• It may be
• Primary (genetic defect and diet)
• Secondary
• DM
• Hypothyroidism
• Nephrotic syndrome renal failure
• Alcohol abuse

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Hyperlipidemias
Primary 5 Familial genetic
Secondary 95
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Causes of Low HDL

• Smoking
• Obesity (visceral fat), Physical inactivity
• Very high Carbohydrate diet
• Type II Diabetes
• Hyper-triglyceridemia
• Drugs like beta-blockers, androgenic steroids
• and androgenic progestins

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Approach to Hyperlipidemic patients

• History
• Family history (familiar hypercholesterolemia)
• Causes of 2ry hyperlipidemia (DM, obstructive
  liver disease, chronic renal failure,
  hypothyroidism)
• Drugs that alter lipid levels (ex. beta-blockers,
  thiazides)
• Physical examination
• Signs of CVD, DM
• Investigations
• Lipid profile, blood markers
• ECG, angiograms

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Hyperlipidemia

• The Adult Treatment Panel (ATP) of the National
  Cholesterol Education Program (NCEP) published
  guidelines for the treatment of
  hypercholesterolemia in 1987 that were revised in
  1993 as ATP II and again in 2001 as ATP III.
• These guidelines classify patients according to
  their cholesterol levels

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ATP III classification

• ATP III recognized that elevated triglycerides
  are also an important risk factor for CHD and
  classified them as follows
• Triglycerides
• Normal lt150 mg/dl
• Borderline high 150199 mg/dl
• High 200499 mg/dl
• Very high 500 mg/dl
• Several factors contribute to elevated
  triglycerides obesity, physical inactivity,
  excessive alcohol intake, certain diseases
  (diabetes, chronic renal failure), and genetic
  disorders.

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ATP III classification

• LDL cholesterol (mg/dl)
• lt100 Optimal
• 100129 Near or above optimal
• 130159 Borderline high
• 160189 High
• gt190 Very high
• Total cholesterol (mg/dl)
• lt200 Desirable
• 200239 Borderline high
• 240 High
• HDL cholesterol (mg/dl)
• lt40 Low
• 60 High

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Two Types of Lipids
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Clinical Photoes
Tuberous xanthoma. Flat-topped,
yellow, firm tumor
Xanthelasma. Multiple, longitudinal,
creamy-orange, slightly elevated papules on
eyelids .
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Clinical Photoes
Tendinous xanthomas. Large sub-cutaneous tumors
adherent to the Achilles tendons.
Papular eruptive xanthomas. Multiple, discrete,
red-to-yellow confluent papules
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Therapeutic Lifestyle Changes - TLC

• Nutrient Recommended Intake
• Saturated fat lt 7 of calories
• PUFA fat Up to 10 of calories
• MUFA fat Up to 20 of calories
• Total fat 2535 of calories
• Carbohydrate 5060 of calories
• Fiber 2030 grams per day
• Protein Approx. 15 of calories
• Cholesterol Less than 200 mg/day

DIETARY THERAPY
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Our dietary fats

• SFA (saturated) meet and diary products,
  coconut oil, Kernel, Ghee, Butter, Palm oil,
• Trans fatty acids in chocolates , baked, deep
  fat fried food
• MUFA Olive oil, Gingili oil
• PUFA Soya, Sun Flower oil, GN oil
• PUFA Fish oils Twice a wk ? 76 CAD
• Legumes, fruits, olive oil ? all cause
  mortality

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Initial Lipoprotein Analysis

• In all adults aged 20 years or older
• A fasting lipoprotein profile (Total-C, LDL-C,
  HDL-C, and triglycerides). Or nonfasting levels
  of total-C and HDL-C should be obtained once
  every 5 years
• A follow-up lipoprotein analysis is needed for
  appropriate management based on LDL-C.

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ATP III LDL-C cutpoints for TLC and drug therapy
Risk Category LDL-C Goal LDL-C Level for Initiating TLC Consider Drug Therapy
CHD or CHD risk equivalents (10 yr. CHD risk gt20) lt100 mg/dL ³100 mg/dL ³130 mg/dL (100-129 mg/dL drug optional)
Multiple (2) risk factors(10 yr. CHD risk 20) lt130 mg/dL ³130 mg/dL 10-yr risk 10-20 ³130 mg/dL10-yr risk lt10 ³160 mg/dL
0-1 Risk factor lt160 mg/dL ³160 mg/dL ³190 mg/dL (160-189 mg/dL drug optional)
Therapeutic Lifestyle Changes
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Treatment of Hyperlipidemia

• Therapeutic Lifestyle Changes (TLC)
• Diet control
• Plant stansols/sterols (2g/day) and increased
  soluble fiber (10-25 g/day)
• Weight reduction, if appropriate
• Increase physical activity
• Drug Treatment
• Statins
• Bile acids sequestrants
• Nicotinic acids
• Fibric acids

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The Three Canons
DYSLIPIDEMIA
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Lipid lowering classes
Module 3
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Cholesterol Absorption Inhibitor (CAI)