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Management Overview

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Management Overview

  1. 1. MANAGEMENT OVERVIEW DYSLIPIDEMIA DR / KHALID AL –HARBY FAMILY MEDICINE CONSULTANT MBBS, ABFM, SBFM DR/KHALID AL-HARBY 1
  2. 2. Prevalence in Saudi Arabia al –Nuaim AR 1997  The prevalence of HC, 5.2-6.2 mmol/l was 9% and 11% for all male and female (above 15 y.)respect.  The prevalence of HC, > 6.2 mmol/l was 7% and 8% for male and female (>15y.) respectively  The prevalence of HC, 5.2-6.2 for subjects aged 40-59 y. was 14% and 10% for male and female respectively  The prevalence of HC > 5.2 increase with BMI DR/KHALID AL-HARBY 2
  3. 3. Al – Awali PHC 1422 A pilot study on male adult diabetic patients High Cholesterol level Pie Chart yes 34.8 % 65.2 % no DR/KHALID AL-HARBY 3
  4. 4. Al – Awali PHC 1422 A pilot study on male adult diabetic patient High TG level Pie Chart yes 30.4 % 69.6 % no DR/KHALID AL-HARBY 4
  5. 5. Screening  National Cholesterol Education Program (NCEP): • Random TC and HDL for all adult > or = 20 years • Every 5 years  U.S.Preventive Task Force: • Men 36-65 y. and women 45-65y. Every 5 years • TC DR/KHALID AL-HARBY 5
  6. 6. Recommended algorithm for adults Measure total chol. And HDL chol. High: > or = 240 mg/dl Desirable: < 200 mg/dl Borderline high: 200-239 mg/dl HDL < 35 mg /dl or > HDL > or = 35 mg /dl HDL < 35 HDL > or = or = 2 risk factors And < 2 risk factors mg/dl 35 mg /dl Offer advice offer advice on risk on risk Measure fasting cholesterol and calculate LDL DR/KHALID AL-HARBY 6
  7. 7. Recommended algorithm for adults No evidence of CHD Evidence of CHD High LDL >optimal LDL Optimal LDL Desirable Borderline > 100 mg/dl < or = 100mg/dl LDL > or=160 LDL 130-159 Clinical evaluation Offer instru- < 2 R.F > or 2 R.F Clinical evaluat. ctions on diet Diet and activity therapy retest Diet Offer advice retest DR/KHALID AL-HARBY 7
  8. 8. Recommended algorithm for adults LDL > or = 190 LDL > or = 160 mg/dl LDL > 100 mg/dl and < 2 R.F and > or = 2 R.F Mg/dl Consider drug therapy DR/KHALID AL-HARBY 8
  9. 9. NCEP for cholesterol levels Risk category (mg/dl) LIPID Desirable Borderline High Total cholesterol < 200 200-239 >or=240 HDL cholesterol > 60 --- < 35 LDL cholesterol < 130 130-159 > or= 160 Triglycerides < 200 200-400 400-1000 DR/KHALID AL-HARBY 9
  10. 10. Friedewald Formula  LDL cholesterol = total cholesterol – HDL cholesterol + 0.16 TG  It is valid for estimating LDL cholesterol if the TG level is < 400 mg /dl and if the individual does not have familial dysbetalipoproteinemia DR/KHALID AL-HARBY 10
  11. 11. General Treatment Guidelines Status Initiation level (mg/dl) Goal level (mg/dl) No CHD and < 2 risk factors Diet > or = 160 < 160 Drugs > or = 190 < 160 No CHD and > or = risk factors Diet > or = 130 < 130 Drugs > or = 160 < 130 CHD Diet > 100 < or = 100 Drugs > or = 130 < or = 100 DR/KHALID AL-HARBY 11
  12. 12. The efficacy of primary prevention  AFCAPS/TexCAPS< RCT> (1998): 6605 men and women with average total cholesterol levels (mean 228mg/dl) and low HDL cholesterol (mean 40 mg/dl for women and 36 mg/dl for men), Lovastatin 20 or 40 mg /d reduced cardiovascular event by 37% DR/KHALID AL-HARBY 12
  13. 13. The efficacy of secondary prevention A. Scandinavian Simvastatin Survival Study (1994): • Decrease in cardiac mortality of 42%, and decrease in all-cause mortality of 30% • In 4444 pt.s with CHD over 5.4 years B. Cholesterol and Recurrent Event (CARE) (1996): • Decrease in coronary events of 24% with 5y. On Pravastatin 40mg/d, decrease in need for PTCA of 23% ,and decrease in need for CABG of 26% • In 4000 post MI with mean TC of 209 and LDL of 139 DR/KHALID AL-HARBY 13
  14. 14. 4444 with mild high chol. Simvastatin, placebo 5.4 years Reduce T.Chol, LDL , risk of major CAD Increase 6 y. survival DR/KHALID AL-HARBY 14
  15. 15. 4000 post MI Pravastatin, placebo 5 y. Reduce C events, need For PTCA, CABG DR/KHALID AL-HARBY 15
  16. 16. post CHD with high chol. LIPID Pravastatin, placebo 1y. 5.2 / 1000 live saved DR/KHALID AL-HARBY 16
  17. 17. The efficacy of secondary prevention C. The AVERT trial (1999): • 341 patient with stable CAD, LDL > or = 115 mg/dl and TG < or = 500mg/dl • Randomized to either aggressive lowering of LDL with atrovastatin (80mg/d), or PTCA and usual care • The atrovastatin group had a reduced but not statistically significant rate of ischemic events(13.4% vs. 10.1%) • This reassures that drugs are safe and as good as PTCA for pt.s with stable CAD DR/KHALID AL-HARBY 17
  18. 18. 341 for PTCA 177 PTCA, 164 LIPITOR 18 MONTHS LIPITOR reduces ischemia & need for PTCA DR/KHALID AL-HARBY 18
  19. 19. The role of dietary intervention A. Oslo Study Group (1981): established the recommendation of dietary intervention and smoking cessation to improve lipid profiles B. Physician Health Study: • Men who ate fish (including shellfish) at least once a week had a 52% reduction of sudden cardiac death compared with those who consumed fish < once/month • Data did not find an inverse association between fish consumption and the rate of MI DR/KHALID AL-HARBY 19
  20. 20. Comparison of step I and II diets Recommended intake Nutrient Step I Step II Total fat < 30 % of total calories Saturated fat 8% - 10% of total calories < 7% of total calories Polyunsaturated fat up to 10 % of total calories Monounsaturated fat up to 15 % of total calories Cholesterol < 300 mg/dl < 200 mg/dl Carbohydrates 50% - 60% of total calories Protein 10 % - 20 % of total calories Calories to achieve and maintain desired weight DR/KHALID AL-HARBY 20
  21. 21. Sources of dietary Fatty Acids  Cholesterol : egg yolk, organ meats (liver, sweetbreads, brain), animal meats (beef, pork, lamb), butter  Saturated Fatty Acids: animal fat (beef, pork), whole dairy products (milk, cream, ice cream, cheese), palm oil, coconut oil DR/KHALID AL-HARBY 21
  22. 22. Sources of dietary Fatty Acids  Polyunsaturated Fatty Acids: safflower oil, sunflower oil, soybean oil, corn oil  Monounsaturated Fatty Acids: olive oil, canola oil DR/KHALID AL-HARBY 22
  23. 23. Diet therapy guidelines Step I Diet Patient with CHD Monitor at 4-6 W, 3 Months Goal not achieved Step II Diet Goal achieved Monitor 4 times in 1st year, then 2 / year Goal achieved Monitor at 4-6 W, 3 Months Drug therapy Goal not achieved DR/KHALID AL-HARBY 23
  24. 24. Lipid-modifying drugs Drug class initial dosage maximum dosage monthly cost(S.R) LDL HDL VLDL S.Es HMG COA reductase inhibitors elevated LFT Atrovastatin 10 mg / d 80 mg / d 210- 783 GI upset Cerivastatin 0.3 mg / d 0.3 mg / d 150 myalgia/myosi. Fluvastatin 20 mg / d 40 mg bid 142- 281 Lovastatin 20 mg / d 40 mg bid 262- 941 Pravastatin 20 mg / d 40 mg / d 243- 398 Simvastatin 10 mg /d 40 mg /d 221- 735 Bile acid sequestrants drug interactions Cholestyramine 4 gm bid 20 gm (divided) 93- 686 GI upset Colestipol 5 gm / d 30 gm (divided) 108- 1233 dec. absorption of vit A,E,K DR/KHALID AL-HARBY 24
  25. 25. Lipid-modifying drugs Drug class initial dosage maximum dosage monthly cost(S.R) LDL HDL VLDL S.Es Niacin flushing/pruritus 50 – 100 mg bid 3 gm (divide) 6 – 187 rash/ GI upset gout exacerbation hyperglycemia elevated LFT Fibric acid derivatives pruritus/rash Gemfibrozil 300 mg bid 600 mg bid 40 – 303 GI upset Fenofibrate 67 mg / d 201 mg / d 75 – 228 myositis ( micronized) cholelithiasis DR/KHALID AL-HARBY 25
  26. 26. Probucol  Mechanism of action: not fully understood  It lowers LDL by 10-20% but also lowers HDL (neutral effect on total/HDL cholesterol ratio)  Dose: 500 mg BID  S.E: GI upset  C.I: prolonged QT interval or H/O ventricular dysrhythmia  Limited benefit on lipid profile but can be used as an anti- oxidant DR/KHALID AL-HARBY 26
  27. 27. ERT INCREASES: DECREASES: 1) HDL 1) LDL 2) TG 2) LIPOPROTEIN (a) DR/KHALID AL-HARBY 27
  28. 28. ERT  Recommended by NCEP II expert panel to all postmenopausal women with lipid disorder (but this is controversial: no support by clinical trials)  Meta-analysis of observational studies: 44% RR in primary prevention of CHD risk by ERT  The postmenopausal Estrogen/Progestin international (PEPI) trial (1995): combined HRT had a less desirable effect on HDL cholesterol than ERT alone DR/KHALID AL-HARBY 28
  29. 29. ERT  The Heart and Estrogen/Progestin replacement (HERS) 1998 <RCT> for secondary prevention : 2763 postmenopausal women with CHD, combined HRT or placebo, 4 years, no significance difference in the rate of non-fatal MI & CHD mortality between the groups despite significant improvement in LDL, HDL, TG, in the treatment group  For primary prevention: will be evaluated by the ongoing Women’s Health Initiative clinical trial (27500 women over 9 years) will be reported in 2005 DR/KHALID AL-HARBY 29
  30. 30. 2763 postmenop. + CHD Combined HRT & placebo 4 years HRT improved lipid but not CHD Increase S.E DR/KHALID AL-HARBY 30
  31. 31. Other drugs 1) Raloxifen : non steroidal benzothiopene that inhibits the growth of Estrogen receptor- dependent mammary tumors o It also lowers serum T.chol and LDL chol. o RCT of 601 postmenopausal women over 2 years: dose-dependent reduction of T. chol (9.7%) & LDL chol. (14.1%) in treatment group (Raloxifen 150 mg/ day) DR/KHALID AL-HARBY 31
  32. 32. Other drugs 2) D –thyroxin: lower LDL chol. 10 –15 % by enhancing its clearance from circulation , BUT : mild hyperthyroidism, cardiac S.Es 3) Neomycin : lower LDL by 10-15% by decreasing its intestinal absorption BUT: alter normal flora, ototoxicity, renal insufficiency 4) Olestra : non absorbable sucrose polyester fat substitute that interfere with chol. absorption, FDA approved as food not as a drug DR/KHALID AL-HARBY 32
  33. 33. Other drugs 5) Sitostanol-ester margarine: o A pine tree extract Stanol o RAISIO group (1995) in Finland <RCT> studied 153 non-obese subjects with mild dyslipidemia (TC > 216, TG > 265) : after 1 year – 10.2% reduction in TC, 14.1% reduction in LDL in treatment group DR/KHALID AL-HARBY 33
  34. 34. Combination therapy  To achieve a synergistic effect  Usually used in severe cases but can be used in less severe cases by using low doses of 2 agents rather than a high dose of single agent ( less toxicity, cost advantage)  The ideal regimen is bile acid sequestant + statin ( 50% reduction in LDL, good tolerability (bile acid seq. should be taken 1 h. prior to statin)  Statin and fibric acid derivative should not be combined (increase risk of myositis) DR/KHALID AL-HARBY 34
  35. 35. Patient Education  One study demonstrated that only approximately 50% of patients who were prescribed a lipid lowering drug were taking it 1 year later  Another study: 20-30 % of women given HRT never started on them, and only 40 % of those who started on HRT were still compliant with the regimen 1 year later DR/KHALID AL-HARBY 35
  36. 36. 875 healthy postmenop. Placebo, ERT, 3 HRT regimens 3 years ERT should be used if no uterus, CEE with Cyclic MP if uterus + DR/KHALID AL-HARBY 36
  37. 37. Controversies and future considerations (hypertriglyceridemia)  Large studies initially linked high TG levels with CHD, but it was associated with low HDL!! ( it might be due to the low HDL )  Until intervention data are available, TG– lowering agents should be reserved for patients with TG levels > or = 400 mg/dl and other cardiac disease DR/KHALID AL-HARBY 37
  38. 38. Controversies and future considerations small, Dense LDL and the Atherogenic Dyslipidemic syndrome LDL subclass Pattern B Pattern A (Small, dense) LDL-I LDL-III LDL-II LDL-IV ADS:- Dominant dyslipidemia In patient with CHD and familial combined type (H) TG ? Risk factor for development of type II DM (L) HDL (similar lipid profile) (B) TC Standard screening with total chol. And HDL Chol. Is not adequate for those with ADS “normal lipid profile” Treatment : combination Type II DM, HTN, central obesity, procoagulant state Syndrome X metabolic syndrome DR/KHALID AL-HARBY 38
  39. 39. Controversies and future considerations hyperpobetalipoproteinemia (Hyperapo B)  Apolipoprotein B is the component of LDL that serves as the ligand for its receptor  Hyperapo B : increased apo B levels in the absence of hyperlipidemia  It is found in hypertriglyceridemia  Analysis of some clinical trials has recognized that apo B is a strong predictor of CHD risk  Prospective studies are needed to determine if apo B is a better predictor of CHD risk than the current lipid measurements DR/KHALID AL-HARBY 39
  40. 40. Controversies and future considerations Lipoprotein (a)  Contains LDL + apoprotein (a)  Is considered an independent RF for premature CHD, but its importance appears to lessen with advancing age  Levels of Lp (a) are genetically determined (common in African-American), but external factors may account for up to 10% of the variation in concentration  No trials to support the view that lowering Lp (a) levels reduces CHD risk DR/KHALID AL-HARBY 40
  41. 41. Controversies and future considerations Diabetes Mellitus  CHD is the principal cause of death in DM pt.  Subgroup analysis of secondary prevention trials of statin therapy: decreased LDL in DM is beneficial  Unanswered Qs: 1) Should LDL goal of < 100 mg/dl in DM with CHD be further lowered? 2) How aggressively to treat pt.s with DM and no CHD?  At present NCEP II recommends : 1) a target LDL of 130mg/dl for primary prevention and < 100 for secondary 2) 200 and 150 for TG DR/KHALID AL-HARBY 41
  42. 42. Controversies and future considerations Cerebrovascular disease  Similar RF as CHD except for dyslipidemia  No large trials look to CVA as an endpoint  Secondary analysis of data from the CARE and the 4S trials : significant reduction in stroke among pt.s treated with statins  A systemic review of 16 trials using statin therapy: 25% reduction in all forms of stroke when total –chol. And LDL chol. were reduced 22% and 30% respectively DR/KHALID AL-HARBY 42
  43. 43. Controversies and future considerations Alcohol  It increases HDL and TG  Studies have shown that alcohol in moderation (2-6 drinks/wk) leads to 34-53% reduction in CHD  When heavy drinkers (> 2 drinks /d) were compared with the light drinkers, they had 51% increase in all-cause mortality  Helsinki Heart study: the beneficial effect of moderate alcohol consumption may be restricted to tobacco smokers only DR/KHALID AL-HARBY 43
  44. 44. Controversies and future considerations Nutritional supplement A. Fruits and vegetables: epidemiological data showed lower prevalence of CHD in populations with a higher intake of fruits and vegetables B. Antioxidant vitamins (vit. C&E): o Widespread belief: decrease risk of CHD (based on the belief that LDL oxidation reduce CHD risk) o GISSI-Prevenzione trial(1999): a RCT on secondary prevention, randomized 1324 pt. with recent MI to one of 3 groups (Omega-3-PUFAs, vit E, or both) DR/KHALID AL-HARBY 44
  45. 45. Controversies and future considerations Nutritional supplement after 42 months : (1) significant reduction of non-fatal MI + all-cause deaths + stroke in Omega-3 PUFAs group (2) neutral effect of Vit.E supplement o HOPE study 2000: no effect of vit. E on cardiovascular events in subjects with CAD or DM over 4.5 years C. Folic acid & vit.B6: o Widespread belief: dec. CHD risk by dec. high homocystein levels (another Atherogenic factors) o Have yet to be proven by large clinical trials DR/KHALID AL-HARBY 45
  46. 46. 1324 post MI on MDT diet Ở- PUVA, Vit E, both 1y. 5.7 / 1000 live saved DR/KHALID AL-HARBY 46
  47. 47. 1062 infant 540 dietary counseling, 522 control 5 y. Reduce T.Chol, Reduce LDL In boys only !!! DR/KHALID AL-HARBY 47
  48. 48. 1232 healthy men. With high chol. Dietary intervention & smoking cessation 5 y. Improve lipid, reduce CHD morb&mortality Even after 3 y. DR/KHALID AL-HARBY 48
  49. 49. 9297 at risk for CAD Ramipril , placebo 5 y. Reduce rate of death, MI, stroke DR/KHALID AL-HARBY 49
  50. 50. 4081 asymptomatic Dyslipidemeic men 2051 gemfibrozil, 2030 placebo Same death rate Increase HDL, reduce LDL, TChol, TG DR/KHALID AL-HARBY 50
  51. 51. 16608 healthy postmenop with Intact uterus Combined HRT, placebo Planed 8.5 y. (stopped at 5 y.) Risks exceed benefits DR/KHALID AL-HARBY 51
  52. 52. DM vs. control 20 years Increases 2-3 x Risk of clinical Atherosclerotic diseases Same in both sexes DR/KHALID AL-HARBY 52
  53. 53. 6605 with average chol. Lovastatin vs. diet + placebo 5.2 y. Reduce incidence 1st major CAD DR/KHALID AL-HARBY 53

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