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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
HMG Co-A reductase is the rate limiting
enzyme in the cholesterol synthesis.
Rate Limiting Enzyme
 Elevated Total Cholesterol (TC)
 Elevated Low-density lipoproteins (LDL)
 Elevated triglycerides (TG)
 Decreased High-density lipoproteins (HDL)
 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.
Sedentary lifestyle
Excessive consumption of cholesterol –
saturated fats and trans-fatty acids.
Moderately common
Hypothyroidism
Pregnancy
Cholestatic liver disease
Drugs (diuretics, ciclosporin, corticosteroids, androgens)
Less common
 Nephrotic syndrome
Anorexia nervosa
Porphyria
Hyperparathyroidism
Secondary Dyslipidemia
Diabetes mellitus (type 2)
Chronic renal disease
Abdominal obesity
Excess alcohol
Hepatocellular disease
Drugs (β-blockers, retinoids, corticosteroids)
During routine health checkup
Clinical manifestation e.g. Xanthelesma
Associated diseases e.g. CHD,DM,HTN
At least 12 hrs fasting
Friedwald formula:
LDL-C= TC — HDL-C — ( TG/2.2) mmol/L
Applicable up to TG: 4mmol/L
TC= HDL + VLDL + LDL
TC = HDL + TG/5 + LDL
LDL= TC — ( HDL + TG/5)
Applicable up to TG: 350 mg/dl
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
LDL Cholesterol (mg/dl) HDL Cholesterol (mg/dl)
<100 Optimal < 40 Low
100-129 Near/Above Optimal > 60 High (Desirable)
130-159 Borderline High
160-189 High
>190 Very High
Categories of Risk that Modify LDL Goals
CHD and CHD risk equivalents <100
Multiple (2+) risk factors <130
Zero to one risk factor <160
Cigarette smoking
Hypertension (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
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
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)
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
Classification of Serum Triglycerides
Normal <150 mg/dl
Borderline High 150-199 mg/dl
High 200-499mg/dl
Very High >500 mg/dl
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
Atherosclerosis
 The main Consequence
Acute pancreatitis ( in High TG)
Risk assessment
Treat modifiable risk factors
Optimization of lifestyle factors
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
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
Achieve additional benefits with
supplementary intake of foods containing
lipid-lowering nutrients such as n-3 fatty
acids, dietary fibre and plant sterols.
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
HMG-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.
Atorvastatin
Simvastatin
Rosuvastatin
Pitavastatin
Fluvastatin
Pravastatin
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
Cholesterol 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
Nicotinic 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.
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.
After 6 weeks ( 12 weeks for fibrates)
Parameter:
1. Lipid response
2. Side effects- CK, LFT
3. Others-a) Dietary compliance
b) Exercise
c) Cardiovascular signs and symptoms
d) Wt.
e) BP
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

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Dyslipidemia and Management of Dyslipidemia | Muhammad-Nizam-Uddin

  • 1.
  • 2. 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
  • 3.
  • 4.
  • 5. HMG Co-A reductase is the rate limiting enzyme in the cholesterol synthesis. Rate Limiting Enzyme
  • 6.  Elevated Total Cholesterol (TC)  Elevated Low-density lipoproteins (LDL)  Elevated triglycerides (TG)  Decreased High-density lipoproteins (HDL)
  • 7.
  • 8.  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.
  • 9. Sedentary lifestyle Excessive consumption of cholesterol – saturated fats and trans-fatty acids.
  • 10. Moderately common Hypothyroidism Pregnancy Cholestatic liver disease Drugs (diuretics, ciclosporin, corticosteroids, androgens) Less common  Nephrotic syndrome Anorexia nervosa Porphyria Hyperparathyroidism Secondary Dyslipidemia
  • 11. Diabetes mellitus (type 2) Chronic renal disease Abdominal obesity Excess alcohol Hepatocellular disease Drugs (β-blockers, retinoids, corticosteroids)
  • 12.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17. During routine health checkup Clinical manifestation e.g. Xanthelesma Associated diseases e.g. CHD,DM,HTN
  • 18. At least 12 hrs fasting Friedwald formula: LDL-C= TC — HDL-C — ( TG/2.2) mmol/L Applicable up to TG: 4mmol/L
  • 19. TC= HDL + VLDL + LDL TC = HDL + TG/5 + LDL LDL= TC — ( HDL + TG/5) Applicable up to TG: 350 mg/dl
  • 20.
  • 21. 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
  • 22.
  • 23. LDL Cholesterol (mg/dl) HDL Cholesterol (mg/dl) <100 Optimal < 40 Low 100-129 Near/Above Optimal > 60 High (Desirable) 130-159 Borderline High 160-189 High >190 Very High Categories of Risk that Modify LDL Goals CHD and CHD risk equivalents <100 Multiple (2+) risk factors <130 Zero to one risk factor <160
  • 24. Cigarette smoking Hypertension (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
  • 25. 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
  • 26. 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)
  • 27. 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
  • 28. Classification of Serum Triglycerides Normal <150 mg/dl Borderline High 150-199 mg/dl High 200-499mg/dl Very High >500 mg/dl
  • 29. 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
  • 30. Atherosclerosis  The main Consequence Acute pancreatitis ( in High TG)
  • 31.
  • 32.
  • 33.
  • 34.
  • 35.
  • 36.
  • 37.
  • 38. Risk assessment Treat modifiable risk factors Optimization of lifestyle factors
  • 39. 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
  • 40. 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
  • 41. Achieve additional benefits with supplementary intake of foods containing lipid-lowering nutrients such as n-3 fatty acids, dietary fibre and plant sterols.
  • 42.
  • 43.
  • 44. 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
  • 45. HMG-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.
  • 47. 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
  • 48. Cholesterol 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
  • 49. Nicotinic 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.
  • 50. 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.
  • 51.
  • 52. After 6 weeks ( 12 weeks for fibrates) Parameter: 1. Lipid response 2. Side effects- CK, LFT 3. Others-a) Dietary compliance b) Exercise c) Cardiovascular signs and symptoms d) Wt. e) BP
  • 53. 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.
  • 54. Act Commission is Better than Omission