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Overview of Dyslipidemia
Dr S K Agarwal
MBBS, MD, DM, FACC, CBCCT
Consultant cardiologist
Rashid Hospital
skagarwal@dha.go...
Magnitude of problem
• The estimated annual incidence of MI is 550,000 new
and 200,000 recurrent attacks
• According to da...
Total cholesterol levels for hunter-gatherers, wild primates, and wild
mammals, generally range from about 70 to 140 mg/dl...
Atherosclerotic Cardiovascular
Disease Risk Factors
Nontraditional risk
factors
Lipoprotein (a)
 Clotting factors
 Infl...
Atherosclerotic Cardiovascular
Disease Risk Factors
Nontraditional risk
factors
Lipoprotein (a)
 Clotting factors
 Infl...
Apolipoproteins
B/E receptor ligand *E2:IDL; *E4: Diet ResponsivityapoE
LpL inhibitor; antagonizes apoEapoC-III
LpL activa...
Cholesterol metabolism
Major sources of Liver cholesterol
Major routes by which cholesterol leaves liver
Ezetimibe
Fibrate...
Metabolism of Chylomicrons
Adipokines
TNFα, IL6
Leptin , PAI-1
NPC1L1
Role of raised plasma TG and remnant cholesterol in intimal low-
grade inflammation and development of atherosclerosis
Metabolism of VLDL, IDL & LDL
LDL receptor deficiency
Problem of Residual risk!
Non-HDL revisited
Lipoprotein subclasses and apoB–containing lipoproteins
Non-HDL cholesterol = ...
15
Patient populations recommended
for plasma lipid screening
Once every five years in patients ≥20 years old
T2DM
Arteri...
SCREENING TESTS RECOMMENDED FOR
DETECTING CV RISK
Fasting Lipid Profile-to ensure the most precise lipid assessment;
this ...
Schedule for screening
Adults With Diabetes
• Annually screen all adult individuals with T1DM or T2DM
Children and Adolesc...
Feast or famine lipids
Fasting sample must:
• Initiation of therapy
• Met s, DM, FCH
• Pediatric age
• Female sex
standard...
Secondary Causes of Dyslipidemia
↑ Total cholesterol and LDL-C
• Hypothyroidism
• Nephrosis
• Dysgammaglobulinemia (SLE, m...
Summary Part I
• Cholesterol metabolism
• Lipoproteins and apolipoproteins
• Mech of action of drugs
• Who need to be scre...
Framingham SCORE PROCAM (Men) Reynolds (Women) Reynolds (Men)
Sample size 5345 205,178 5389 24,558 10,724
Age, range (y) 3...
Risk categories
ESC 2016 ACC 2013------ATP III
Very high-risk Subjects with any of the following:
• Documented CVD, clinic...
Treatment targets and goals for
CVD prevention
primary
Target:
LDL-C
Very high-risk: LDL-C <70 mg/dL or a reduction of at ...
My cholesterol !!!!
What happened???
Oh no, nothing with your cholesterol level, our levels changed yesterday !
Treatment Recommendations
Lifestyle changes
Physical Activity:
• fitness therapy ( at least 30 minutes of moderate-intensi...
30 gm/day
Omega-3 Content of Frequently Consumed Seafood Products
SEAFOOD PRODUCT
OMEGA-3s PER 3
OUNCE COOKED
PORTION
Herring wild (...
6
4
2
0
-2
-4
-6
-8
-10
-12
-14
-16
-18
A Randomized, Controlled, Crossover Trial
The Almond magic Circulation. 2002;106
C...
#5 Drug therapy
Practical approach to reach LDL goal
ESC 2016
Starting
#5a
Relative LDL-lowering Efficacy of
Statin and Statin-based Therapies
Atorva Fluva Pitava Lova Prava Rosuva Vytorin* Simva %...
34
Recommendations for the pharmacological
treatment of hypercholesterolaemia
Recommendations Class Level
Prescribe statin...
CKx2wks
Monitor CK
Principal mechanisms involved in statin-induced
myopathy
44
Recommendations for lipid-lowering
therapy in patients with ACS
Recommendations Class Level
Initiate or continue high d...
Fasting TG
EPA/DHA
AHA Triglyceride Guidance
Miller et al. Circ 2011; 123: 2292
Impact of fibrates on macrovascular events
risk according to lipoprotein phenotype
N Engl J Med 2010
• An atherogenic lipoprotein
containing apo(a) and apoB.
• 20-30% of people have levels
suggesting C-V risk.
• Black subje...
Statin effect in other diseases
• Statin and gallstones
• Statin and open angle glaucoma
• Statin and VTE
• Statin in very...
slideshare.net/sanjeevkagarwal
Thank you
Best Wishes
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
Dyslipidemia overview 2017
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Dyslipidemia overview 2017

Dyslipidemia, specially high LDL cholesterol is the key risk factor for cardiovascular diseases. The presentation discusses metabolism and structure of lipoproteins, their screening and interpretation, risk assessment methods, targets for various lipoproteins and its step by step treatment.

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Dyslipidemia overview 2017

  1. 1. Overview of Dyslipidemia Dr S K Agarwal MBBS, MD, DM, FACC, CBCCT Consultant cardiologist Rashid Hospital skagarwal@dha.gov.ae
  2. 2. Magnitude of problem • The estimated annual incidence of MI is 550,000 new and 200,000 recurrent attacks • According to data from 2009-2012, >100 million U.S. adults ≥20 yrs of age have total cholesterol ≥200 mg/dL; 31 million have ≥240 mg/dL • 69% of U.S. adults have LDL-C concentrations above 100 mg/dL • Increasing evidence also points to insulin resistance —which results in ↑TG & LDL-C and ↓HDL-C AACE 2017
  3. 3. Total cholesterol levels for hunter-gatherers, wild primates, and wild mammals, generally range from about 70 to 140 mg/dl (corresponding to low-density lipoprotein levels of about 35 to 70 mg/dl
  4. 4. Atherosclerotic Cardiovascular Disease Risk Factors Nontraditional risk factors Lipoprotein (a)  Clotting factors  Inflammation markers (hsCRP; Lp-PLA2) Homocysteine levels Apo E4 isoform  Uric acid  TG-rich remnants Major risk factors Advancing age  Total cholesterol  Non–HDL-C  LDL-C Low HDL-C Diabetes mellitus Hypertension Chronic kidney disease Cigarette smoking Family history of ASCVD Additional risk factors Obesity, abdominal obesity Family history of hyperlipidemia  Small, dense LDL-C  Apo B LDL particle concentration Fasting/postprandial hypertriglyceridemia PCOS Dyslipidemic triad AACE 2017
  5. 5. Atherosclerotic Cardiovascular Disease Risk Factors Nontraditional risk factors Lipoprotein (a)  Clotting factors  Inflammation markers (hsCRP; Lp-PLA2) Homocysteine levels Apo E4 isoform  Uric acid  TG-rich remnants Major risk factors Advancing age  Total cholesterol  Non–HDL-C  LDL-C Low HDL-C Diabetes mellitus Hypertension Chronic kidney disease Cigarette smoking Family history of ASCVD Additional risk factors Obesity, abdominal obesity Family history of hyperlipidemia  Small, dense LDL-C  Apo B LDL particle concentration Fasting/postprandial hypertriglyceridemia PCOS Dyslipidemic triad AACE 2017
  6. 6. Apolipoproteins B/E receptor ligand *E2:IDL; *E4: Diet ResponsivityapoE LpL inhibitor; antagonizes apoEapoC-III LpL activatorapoC-II Inhibit Lp binding to LDL R; LCAT activatorapoC-I apoB-48 Structural protein of all LP except HDL Binding to LDL receptor apoB-100 Tg metabolism; LCAT activator; diet responseapoA-IV HL activationapoA-II HDL structural protein; LCAT activator;RCTapoA-I Fibrates
  7. 7. Cholesterol metabolism Major sources of Liver cholesterol Major routes by which cholesterol leaves liver Ezetimibe Fibrates Bile acid sequestrants Statins Lippincott’s Illustrated Reviews-Richard A. Harvey
  8. 8. Metabolism of Chylomicrons Adipokines TNFα, IL6 Leptin , PAI-1 NPC1L1
  9. 9. Role of raised plasma TG and remnant cholesterol in intimal low- grade inflammation and development of atherosclerosis
  10. 10. Metabolism of VLDL, IDL & LDL LDL receptor deficiency
  11. 11. Problem of Residual risk! Non-HDL revisited Lipoprotein subclasses and apoB–containing lipoproteins Non-HDL cholesterol = Total cholesterol-HDL Remnant cholesterol = Non HDL cholesterol - LDL
  12. 12. 15 Patient populations recommended for plasma lipid screening Once every five years in patients ≥20 years old T2DM Arterial hypertension Manifest ASCVD Central obesity Chronic inflammatory autoimmune disease CKD Family history of ASCVD Offspring of pts with severe disorders of plasma lipids (e.g. FH) ME 2016 Familial Hypercholesterolemia: Individuals should be screened for FH when there is a family history of • premature ASCVD • Elevated cholesterol levels (total, non-HDL and/or LDL) consistent with FH
  13. 13. SCREENING TESTS RECOMMENDED FOR DETECTING CV RISK Fasting Lipid Profile-to ensure the most precise lipid assessment; this include total cholesterol, LDL-C, TG, and non-HDL-C. non-fasting only if fasting is impractical LDL-C may be estimated using the Friedewald equation: LDL-C = (total cholesterol – HDL-C) – TG/5 Non-HDL-C (total cholesterol minus HDL-C) calculate to risk stratify individuals with moderately elevated TG (200 to 500 mg/dL), DM, and/or established ASCVD Additional Tests hsCRP, Lp-PLA2: routine measurement of homocysteine, uric acid, PAI-1, or other inflammatory markers is not recommended AACE 2017
  14. 14. Schedule for screening Adults With Diabetes • Annually screen all adult individuals with T1DM or T2DM Children and Adolescents • In children at risk for FH (e.g., family history of- premature CV disease or elevated cholesterol), screening should be at 3 yrs of age, again between ages 9 and 11, and again at age 18 • older than 16 years every 5 years or more frequently if they have ASCVD risk factors, have overweight or obesity, have other elements of the insulin resistance syndrome, or have a family history of premature ASCVD Young Adults (Men 20-45 Years, Women 20-55 Years) • Every 5 years as part of a global risk assessment Middle-Aged Adults (Men 45-65 Years, Women 55-65 Years) • In the absence of ASCVD risk factors, once every 1 to 2 years. More frequently when multiple global ASCVD risk factors are present Older Adults (Older Than 65 Years) • Annually for adults with 0 to 1 ASCVD risk factor • older women should be screened in the same way as older men AACE 2017
  15. 15. Feast or famine lipids Fasting sample must: • Initiation of therapy • Met s, DM, FCH • Pediatric age • Female sex standard lipids measured in the fasted state should continue as the benchmark for risk assessment, diagnosis, and therapy of lipid disorders, with consideration given to nonfasting samples in specific clinical circumstances and in the initial screening for dyslipidemias
  16. 16. Secondary Causes of Dyslipidemia ↑ Total cholesterol and LDL-C • Hypothyroidism • Nephrosis • Dysgammaglobulinemia (SLE, multiple myeloma) • Progestina or anabolic steroid treatment • Cholostatic diseases of the liver due to abnormal lipoproteins, as in primary biliary cirrhosis • Protease inhibitors for treatment of HIV infection ↑ TG and VLDL-C • Chronic renal failure • Type 2 diabetes mellitus • Obesity • Excessive alcohol intake • Hypothyroidism • Antihypertensive medications (thiazide diuretics and b-adrenergic blocking agents) • Corticosteroid therapy (or severe stress that increases endogenous corticosteroids) • Orally administered estrogens, oral contraceptives, pregnancy • Protease inhibitors for treatment of HIV infection AACE 2017
  17. 17. Summary Part I • Cholesterol metabolism • Lipoproteins and apolipoproteins • Mech of action of drugs • Who need to be screened • What need to be screened • Screening schedule • Fasting vs non fasting • Secondary causes
  18. 18. Framingham SCORE PROCAM (Men) Reynolds (Women) Reynolds (Men) Sample size 5345 205,178 5389 24,558 10,724 Age, range (y) 30 to 74; M:49 19 to 80; M:46 35 to 65; M:47 >45; M:52 >50; M:63 Mean follow-up (y) 12 13 10 10.2 10.8 Risk factors considered Age, sex, total cholesterol, HDL cholesterol, smoking, systolic blood pressure, antihypertensive Medications Age, sex, total- HDL cholesterol ratio, smoking, systolic blood pressure Age, LDL cholesterol, HDL cholesterol, smoking, systolic blood pressure, family history, diabetes, triglycerides Age, HbA1C (with diabetes), smoking, systolic blood pressure, total cholesterol, HDL cholesterol, hsCRP, parental history of MI at <60 y of age Age, systolic blood pressure, total cholesterol, HDL cholesterol, smoking, hsCRP, parental history of MI at <60 y of age Endpoints CHD (MI and CHD death) Fatal CHD Fatal/nonfatal MI or sudden cardiac death (CHD and CVD combined) MI, ischemic stroke, coronary revascularization, cardiovascular death (CHD and CVD combined) MI, stroke, coronary revascularization, cardiovascular death (CHD and CVD combined) URLs for risk calculators http://hp2010.nhlbi hin.net/atpiii/calcul ator.asp?usertype= prof http://www.heartsc ore.org/pages/welc ome.aspx http://www.chd- taskforce.com/co ronary_risk_asse ssment.html http://www.reynoldsris kscore.org/ http://www.reynoldsris kscore.org/ Global Coronary and Cardiovascular Risk Scores#1
  19. 19. Risk categories ESC 2016 ACC 2013------ATP III Very high-risk Subjects with any of the following: • Documented CVD, clinical or unequivocal on imaging. Clinical includes previous MI, ACS, PCI, CABG and other arterial revascularization procedures, stroke and TIA and PAD. Unequivocally documented CVD on imaging such as significant plaque on CAG or carotid ultrasound. • DM with TOD such as proteinuria or with a major risk factor such as smoking, HT or dyslipidaemia. • Severe CKD (GFR <30 mL/min/1.73 m2). • A calculated SCORE ≥10% for 10-year risk of fatal CVD 1. Patients with any form of clinical ASCVD 2. Patients with primary LDL- C levels of ≥190 mg/dl 3. Patients with DM, 40 -75 years of age, with LDL-C levels of 70-189 mg per dL 4. Patients without diabetes, 40 -75 years of age, with an estimated 10-year ASCVD risk ≥ 7.5% (10-year risk >20%) High-risk Subjects with: • Markedly elevated single risk factors, in particular cholesterol >310 mg/dL (e.g. in familial hypercholesterolaemia) or BP ≥180/110 mmHg. • Most other people with DM (some young people with type 1 diabetes may be at low or moderate risk) • Moderate CKD (GFR 30–59 mL/min/1.73 m2). • A calculated SCORE ≥5% and <10% 2+ risk factors (10-year risk 10% to 20%) Moderate-risk SCORE is ≥1% and <5% for 10-year risk of fatal CVD 2+ risk factors (10 year risk <10%) Low-risk SCORE <1% for 10-year risk of fatal CVD 0-1 risk factor https://www.framinghamheartstudy.org/risk-functions/coronary-heart-disease/hard-10-year-risk.php #2 ESC 2016 and ACC AHA 2013 / 2014 guidelines
  20. 20. Treatment targets and goals for CVD prevention primary Target: LDL-C Very high-risk: LDL-C <70 mg/dL or a reduction of at least 50% if the baseline is between 70 and 135 mg/dL High-risk: LDL-C <100 mg/dL or a reduction of at least 50% if the baseline is between 100 and 200 mg/dL Low to moderate risk: LDL-C <115 mg/dL secondary targets: Non-HDL-C 100, 130 and 145 mg/dL for very high-, high- and moderate-risk subjects, respectively HDL-C no target, but >40 mg/dL in men and >48 mg/dL in women indicates lower risk. TG no target but <150 mg/dL indicates lower risk and higher levels indicate a need to look for other risk factors. ESC 2016 #3
  21. 21. My cholesterol !!!! What happened??? Oh no, nothing with your cholesterol level, our levels changed yesterday !
  22. 22. Treatment Recommendations Lifestyle changes Physical Activity: • fitness therapy ( at least 30 minutes of moderate-intensity physical activity [consuming 4-7 kcal/min] 4 to 6 times weekly, with an expenditure of at least 200 kcal/day) • muscle-strengthening activity is recommended at least 2 days a week Medical Nutrition Therapy • Reduced-calorie diet of fruits and vegetables (combined ≥5 servings/day), whole grains, fish, and lean meats • plant stanols/sterols (~2 g/ day) and soluble fiber (10-25 g/day) • Limited intake of saturated fats, trans-fats, and cholesterol Primary preventive nutrition consisting of healthy lifestyle habits is recommended in all healthy children Smoking Cessation Pharmacologic Therapy #4
  23. 23. 30 gm/day
  24. 24. Omega-3 Content of Frequently Consumed Seafood Products SEAFOOD PRODUCT OMEGA-3s PER 3 OUNCE COOKED PORTION Herring wild (Atlantic & Pacific), Salmon farmed (Atlantic), Salmon wild (King), Mackerel wild (Pacific & Jack) ♥♥♥♥♥ >1,500 milligrams SEAFOOD PRODUCT Salmon canned (Pink, Sockeye & Chum) Mackerel canned (Jack), Mackerel wild (Atlantic & Spanish), Tuna wild (Bluefin) ♥♥♥♥ 1,000 to 1,500 milligrams Salmon wild (Sockeye, Coho, Chum & Pink), Sardines canned, Tuna canned (White Albacore), Swordfish wild , Trout farmed (Rainbow), Oysters wild & farmed, Mussels wild & farmed ♥♥♥ 500 to 1,000 milligrams Tuna canned (Light), Tuna, Wild (Skipjack), Pollock wild (Alaskan), Rockfish wild (Pacific) clams wild & Farmed, Crab wild (King, Dungeness & Snow), Lobster wild (Spiny), Snapper wild, Grouper wild, Flounder/Sole wild, Halibut wild (Pacific & Atlantic), Ocean Perch wild, Squid wild (Fried), Fish Sticks (Breaded) ♥♥ 200 to 500 milligrams Scallops wild , Shrimp wild & Farmed, Lobster wild (Northern), Crab wild (Blue), Cod wild, Haddock wild Tilapia farmed , Catfish farmed, Mahimahi wild, Tuna wild (Yellowfin), Orange Roughy wild , Surimi Product (Imitation Crab) ♥ < 200 milligrams
  25. 25. 6 4 2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 A Randomized, Controlled, Crossover Trial The Almond magic Circulation. 2002;106 Change in lipids from controls (in %) LDL HDL Total:HDL LDL:HDL Apo B:A1 Ox LDL Half: <0.018 0.034 0.004 <0.001 0.01 ----- Full: <0.001 0.047 <0.001 <0.001 <0.001 <0.001
  26. 26. #5 Drug therapy
  27. 27. Practical approach to reach LDL goal ESC 2016 Starting #5a
  28. 28. Relative LDL-lowering Efficacy of Statin and Statin-based Therapies Atorva Fluva Pitava Lova Prava Rosuva Vytorin* Simva %↓ LDL-C ----- 40 mg 1 mg 20 mg 20 mg ----- ----- 10 mg 30% 10 mg 80 mg 2 mg 40or80 mg 40 mg ----- ----- 20 mg 38% 20 mg ----- 4 mg 80 mg 80 mg 5 mg 10/10 mg 40 mg 41% 40 mg ----- ------ ----- ----- 10 mg 10/20 mg 47% 80 mg ----- ------ ----- ----- 20 mg 10/40 mg ----- 55% ----- ----- ------ ----- ----- 40 mg ----- 63% Source: US FDAWeng TC, et al. J Clin Pharm Ther 2010;35:139 #5b
  29. 29. 34 Recommendations for the pharmacological treatment of hypercholesterolaemia Recommendations Class Level Prescribe statin up to the highest recommended dose or highest tolerable dose to reach the goal. I A In the case of statin intolerance, ezetimibe or BAS or these combined, should be considered. IIa C If the goal is not reached, statin combination with a cholesterol absorption inhibitor should be considered. IIa B If the goal is not reached, statin combination with a bile acid sequestrant may be considered. IIb C In patients at very high-risk, with persistent high LDL-C despite treatment with maximal tolerated statin dose, in combination with ezetimibe or in patients with statin intolerance, a PCSK9 inhibitor may be considered. IIb C ESC 2016
  30. 30. CKx2wks Monitor CK
  31. 31. Principal mechanisms involved in statin-induced myopathy
  32. 32. 44 Recommendations for lipid-lowering therapy in patients with ACS Recommendations Class Level Initiate or continue high dose statins early after admission (1-4 d) in all ACS patients without contraindication or history of intolerance, regardless of initial LDL-C values. I A Lipids should be re-evaluated 4–6 wks after ACS to see whether target of LDL-C <70 mg/dL or a reduction of at least 50% (if the baseline is between 70 - 135 mg/dL) have been reached and whether there are any safety issues. The therapy dose should then be adapted accordingly. IIa C If the LDL-C target is not reached with the highest tolerable statin dose, ezetimibe should be considered in combination with statins in post-ACS patients IIa B If the LDL-C target is not reached with the highest tolerable statin dose and/or ezetimibe, PCSK9 inhibitors may be considered on top of lipid- lowering therapy; or alone or in combination with ezetimibe in statin intolerant patients or in whom a statin is contra-indicated. IIb C
  33. 33. Fasting TG EPA/DHA AHA Triglyceride Guidance Miller et al. Circ 2011; 123: 2292
  34. 34. Impact of fibrates on macrovascular events risk according to lipoprotein phenotype N Engl J Med 2010
  35. 35. • An atherogenic lipoprotein containing apo(a) and apoB. • 20-30% of people have levels suggesting C-V risk. • Black subjects have Lp(a) normal range twice as high as white and Asiatic subjects. • Apo(a) sequence similar to plasminogen, and Lp(a) interferes with spontaneous thrombolysis. • Lp(a) levels highly genetic, resistant to diet and drug therapy, although niacin may help. • PCSK9 has shown good results Apo(a) -S-S- Lipoprotein(a), or Lp(a) “LDL”
  36. 36. Statin effect in other diseases • Statin and gallstones • Statin and open angle glaucoma • Statin and VTE • Statin in very low LDL post MI • Statin and sepsis • Statin and NAFLD • Statin and H pylori
  37. 37. slideshare.net/sanjeevkagarwal Thank you Best Wishes

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