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Dyslipidemia and Management of Dyslipidemia
Prepared by:
Muhammad Nizam Uddin
CHOLESTEROL A soft waxy substance found among
lipids (fats) in the bloodstream and all cells
Needed for digesting fats, making hormones, building cell walls
Carried in particles called lipoproteins that act as transport vehicles delivering cholesterol to various body tissues to be used, stored or excreted
Excess circulating cholesterol can lead to plaque formation- Atherosclerosis
Structure of Lipoprotein
Metabolism of Plasma Lipid
HMG Co-A reductase is the rate limiting enzyme in the cholesterol synthesis.
Rate Limiting Enzyme
DYSLIPIDEMIA
(A consequence of abnormal lipoprotein metabolism)
Elevated Total Cholesterol (TC) Elevated Low-density lipoproteins (LDL) Elevated triglycerides (TG) Decreased High-density lipoproteins (HDL)
Causes of Dyslipidemia
SINGLE OR MULTIPLE GENE MUTATION –RESULTING IN DISTURBANCE OF LDL, HDL AND TRIGYLCERIDE, PRODUCTION OR CLEARANCE.
Should be suspected in patients with premature heart disease family hx of atherosclerotic dx. Or serum cholesterol level >240mg/dl. Physical signs of hyperlipidemia.
Primary Dyslipidemia
Secondary Dyslipidemia
Sedentary lifestyle Excessive consumption of cholesterol
– saturated fats and trans-fatty acids.
Moderately commonHypothyroidism Pregnancy Cholestatic liver disease Drugs (diuretics, ciclosporin, corticosteroids,
androgens)
Less common Nephrotic syndrome Anorexia nervosa Porphyria Hyperparathyroidism
Secondary Dyslipidemia
Secondary hypertriglyceridaemia
Diabetes mellitus (type 2) Chronic renal disease Abdominal obesity Excess alcohol Hepatocellular disease Drugs (β-blockers, retinoids,
corticosteroids)
Classification of Dyslipidemia and Risk
Clinical manifestation of Dyslipidemia
Different ways of detection of dyslipidemia
During routine health checkup
Clinical manifestation e.g. Xanthelesma
Associated diseases e.g. CHD,DM,HTN
BY DOCTOR BY PATIENT
Lipid measurement
At least 12 hrs fasting
Friedwald formula:LDL-C= TC — HDL-C — ( TG/2.2)
mmol/L
Applicable up to TG: 4mmol/L
Calculation of LDL
TC= HDL + VLDL + LDL
Þ TC = HDL + TG/5 + LDL
Þ LDL= TC — ( HDL + TG/5)
Applicable up to TG: 350 mg/dl
Different Types of Cholesterol
LDL- (“bad” cholesterol) The major cholesterol carrier in the blood. Excess most likely to lead to plaque formation. Goal: LOW
HDL- (“good” cholesterol) Transports cholesterol away from arteries and back to the liver to be eliminated. Removes excess cholesterol from plaques, slowing growth. Goal: HIGH
Normal Level
LDL Cholesterol (mg/dl) HDL Cholesterol (mg/dl)
<100 Optimal < 40 Low100-129 Near/Above Optimal > 60 High (Desirable)130-159 Borderline High160-189 High>190 Very High
Categories of Risk that Modify LDL GoalsCHD and CHD risk equivalents <100Multiple (2+) risk factors <130Zero to one risk factor <160
Major Risk Factors For CHD That Modify LDL Goals
Cigarette smokingHypertension (BP >140/90 or on BP
med)Low HDL cholesterol (<40mg/dl)Family Hx premature CHD- CHD in male 1st degree relative <55 years old- CHD in female 1st degree relative <65 years old
Age (men >45 yrs. women >55 yrs) HDL >60 counts as a “negative” risk factor. It’s presence removes
one risk factor from the total count
Risk Assessment for CHD
DM regarded as a CHD equivalent
For patients with multiple (2+) risk factors
-Perform 10 year risk assessment
For patients with 0-1 risk factor-Most have 10 year risk assessment
<10%; risk assessment scoring unnecessary
Current ATP III Guidelines for Treating LDL Cholesterol
Risk Category
LDL Goal(mg/dl)
LDL level to initiate TLC
LDL level to consider Rx therapy
CHD or Equivalents
<100<70 Ideal
> 100 > 130(100-129 Rx optional)
2+ Risk Factors
<130 > 130 > 130 (10 Year risk 10-20%)> 160 (Risk <10%)
0-1 Risk Factor
<160 > 160 > 190(160-189 Rx optional)
A Model of Steps in Therapeutic Lifestyle Changes (TLC)
Visit 1
Begin TLC
• Emphasize reduction in saturated fat & chol.
• Encourage moderate Physical activity
• Consider referral to dietician
Visit 2 (6 wks)
Eval. LDL response
Intensify Tx if not to goal
• Reinforce dietary recommendations
• Consider adding plant stanols/sterols
• Increase fiber intake
• Consider dietician
Visit 3 (6 wks)
Eval LDL response
Consider adding Rx if not to goal
• Evaluate for Metabolic syndrome
• Intensify wt mgmt & physical activity
• Consider dietician
Visit N
Monitor adherence to
TLC Q4-6 mos
Specific Dyslipidemias: Elevated Triglycerides
Classification of Serum Triglycerides
Normal <150 mg/dl Borderline High 150-199 mg/dl High 200-499mg/dl Very High >500 mg/dl
Specific Dyslipidemias: Elevated Triglycerides
Management of Very High Triglycerides (>500 mg/dl)
Goal of therapy: Prevent acute pancreatitis Very low fat diets (< 15% of caloric intake) Triglyceride-lowering drug usually required
(fibrate or nicotinic acid) Reduce triglycerides before lowering LDL
Consequences of dyslipidemia
Atherosclerosis The main Consequence
Acute pancreatitis ( in High TG)
Pathogenesis of Atherosclerosis
Early Atherosclerosis
Early Atherosclerosis
Early Atherosclerosis
Stable Atherosclerotic Plaque
Advanced Atherosclerosis
Unstable Coronary Artery Disease
Management of Dyslipidemia
Risk assessment Treat modifiable risk factors Optimization of lifestyle factors
Non pharmacologic management
Reduce intake of saturated and trans-unsaturated fat to less than 7-10% of total energy
Reduce intake of cholesterol to < 250 mg/day
Replace sources of saturated fat and cholesterol with alternative foods such as lean meat, low-fat dairy products, polyunsaturated spreads and low glycaemic index carbohydrates
Non pharmacologic management
Reduce energy-dense foods such as fats and soft drinks
Increase consumption of cardioprotective and nutrient-dense foods such as vegetables, unrefined carbohydrates, fish, pulses, nuts, legumes, fruit etc.
Adjust alcohol consumption, reducing intake if excessive or if associated with hypertension, hypertriglyceridaemia or central obesity
Non pharmacologic management
Achieve additional benefits with supplementary intake of foods containing lipid-lowering nutrients such as n-3 fatty acids, dietary fibre and plant sterols.
Pharmacologic Management
Nutrient Recommendations of TLC Diet
Nutrient Recommended Intake
Saturated fat < 7% of total calories Polyunsaturated fat Up to 10% of total calories Monounsaturated fat Up to 20% of total calories Total fat 25-30% of total calories Carbohydrates 50-60% of total calories Fiber 20-30 grams/day Protein Approx. 15% of total calories Cholesterol <200 mg/day Total calories Balance energy intake and
expenditure to maintain desirable body
weight/prevent weight gain
Lipid Lowering DrugsHMG-CoA Reductase Inhibitors (Statins)
Partially block an enzyme necessary for formation of cholesterol
Speed removal of LDL from blood 18%-60% reduction in LDL Most effective at lowering LDL; esp. HS dosing Liver enzymes MUST be monitored. Check
baseline, 3mos., then semi-annually (D/C if > 3x normal limits)
Side effects: Myalgias (D/C if total CK >10x normal), rhabdomyolysis
Metabolized by CP450 (watch for drug interactions)
Contraindicated in pregnancy.
Different statins
AtorvastatinSimvastatinRosuvastatinPitavastatinFluvastatin
Pravastatin
Lipid Lowering Drugs
Bile Acid Sequestrants:Cholestyramin , Cholestipol
Convert cholesterol to bile acids Bind bile acids and prevent
reabsorption in the gut May increase triglyceride levels Most common side effects: GI-
constipation Alternative for statins
Lipid Lowering DrugsCholesterol Absorption Inhibitor(Ezetimibea):
Monotherapy or in combination with statin Not recommended with fibrates Reduces LDL number : esp. Lp(a)
hepatic LDL receptor,Inhibit intestinal mucosa transporter NPCILT.
Lipid-Regulating Agent: Omega 3 acid ethyl esters
Omega 3 Fish oil (salmon, herring, mackerel, swordfish, albacore tuna, sardines, lake trout)
Only FDA approved supplement for tx of dyslipidemias
Decreases hepatic production of TG and VLDL Increases LDL size to large buoyant particles
Lipid Lowering DrugsNicotinic Acid/Niacin (B3)
Inhibition of lipolysis
Reduces production and release of LDL Effective in reduction of triglycerides
(<400mg/dl) Increases HDL Very effective in increasing LDL particle
size Monitor liver enzymes and glucose Most common side effect: FLUSHING (take
ASA/ibuprofen 30 min. prior and take with light snack). Decreased with time released formulas
Liver function disterbance Exacerbation of gout and hyperglycemia.
Lipid Lowering Drugs
Fibric Acid Derivatives/Fibrates
M/A: PPAR∞- stimulation metabolism of TG & LDL Very effective in reducing triglycerides
(>400) Increase HDL SIE: Myolgia,Myopathy,Abnormal LFT,Choleclithiasis Containdications: Gallbladder disease,
hepatic disease, renal dysfunction Increase LDL particle size but not
quantity Caution with statins Gemfibrozil, Benza fibrates, feno fibrates.
Monitoring of therapy After 6 weeks ( 12 weeks for fibrates) Parameter:1. Lipid response2. Side effects- CK, LFT3. Others-a) Dietary compliance
b) Exercise c) Cardiovascular signs and
symptomsd) Wt. e) BP
Summary Dyslipidemia(Silent killer)
Artherosclerosis MI,Stroke At least 12 hrs fasting for the
measurement of lipid profile. TLC-very important But usually
ignored Statin-(Commission is better than
omission)widely well tolerated Other risk factors should be
addressed appropriately.
Act Commission is Better than
Omission
THANK YOU