1) A 43-year-old male presented with chest pain and was diagnosed with an acute inferior STEMI while in normal sinus rhythm. His medical history included atherosclerosis. 2) Atherosclerosis is caused by plaque buildup in arteries and accounts for over 70% of cardiovascular deaths in the US. Elevated LDL cholesterol increases the risk of atherosclerosis and heart disease. 3) Therapeutic lifestyle changes like diet and exercise can modestly lower LDL cholesterol by about 5% on average but response varies between individuals. High fat, low carb diets may improve glycemic control in diabetes without worsening lipids.

1. Pfizer Talk Family Medicine 13/1/2010Dr Ihab Suliman

2. 43 years old male with Chest Pain

3. Acute Inferior STEMI in NSR.

4. Atherosclerosis

6. The Impact of Elevated LDL-C and Associated AtherosclerosisAtherosclerosis is caused by a build-up of plaque in arterial walls, obstructing blood flowAtherosclerosis accounts for more than 70% of all deaths from cardiovascular disease in the USElevated LDL (low-density lipoprotein) cholesterol increases risk of atherosclerosis and coronary heart diseaseThe risk of coronary heart disease increases by about 2% for each 1% elevation in total cholesterolNational Center for Health Statistics. Health, United States, 2005.http://www.cdc.gov/nchs/hus.htm. Accessed May 17, 2006Kwiterovich PO Jr. Am J Cardiol. 1998,82:3U-17U

7. Cholesterol is important in so many metabolic activities , there fore it is more important in adults or infants????

8. What is the normal Cholesterol level in Infancy???.

9. Cholesterol Levels By SpeciesInfantAdult AmericanHunter-GathererHumans:HazdaInuitIKungPygmySanWild Primates:BaboonHowlerMonkeyNight MonkeyWild Mammals:HorseBoarPeccaryBlackRhinocerosAfricanElephantModern Human:507090110130150170190210Mean Total Cholesterol LevelJACC 2004;43:2142-6

10. Discovery of statinsSome drugs available but not effectiveIn 1971,Endo and Kuroda (Sankyo Pharmaceuticals in Japan) began search for better drugsCholesterol pathway known and they wanted to find a HMG-CoA reductase inhibitor – looked for a microorganism – screened over 6000Two (3rd later) cmpds identified - one was from Penicillium citrinum - named mevastatinIn 1976 isolated and crystallized Clinical trials started in 1978 and quickly stopped because of animal tumors

11. Modifiable Risk FactorsBehavioursCigarette smoking

12. Heavy alcohol use

13. Physical inactivity Medical conditionsHypertension

14. Diabetes mellitus

15. Hypercholesterolemia

16. Obesity

17. Insulin resistance?

18. Cardiac diseasesAtrial fibrillationCoronary artery diseaseCHF

19. Causes of death, 2001:USA1. Infectious and parasitic diseases: 14.9 million6.2. Heart diseases: 11.1 million1.3. Cancers: 7.3 million2.4. Stroke: 5.5 million3.5. Respiratory diseases: 3.6 million4.6. Accidents, fires, drowning, etc.: 3.5 million5.7. Maternal and perinatal: 3.0 million8. Violence (war, homicide, suicide): 1.6 million Population: 6,122,210,000Deaths: 56,554,000World Health OrganizationWorld Health Report 2002

20. Therapeutic lifestyle change is the cornerstone of the management of hyperlipidemia and dyslipidemia? LDL-C with AHA diet: ~ 5%Response variability: familial/geneticHypocaloric diets in overweight & obese

21. A high fat, low carb diet does not worsen serum lipids/lipoproteins and improves glycemic control in patients with diabetesLDL-C is unchangedHDL-C is unchanged or slightly higherTriglyceride is lower by~25%Variability in response?HbA1c better than with LFHC diet

22. Dietary NuancesFish: twice/wk; omega-3 fatty acids, 1000 mg/dEliminate/reduce trans FA Plant stanols/sterols reduce LDL-C by ~10%Antioxidant vitamins are not cardioprotective and interfere with effects of niacin on HDL-CHomocysteine: folic acid, vitamins B6 and B12not proven to be cardioprotective.

23. The 2004 NCEP LDL-C goal:lower may be betterAcute Coronary SyndromesMIRACL: LDL-C, 125 72 mg/dl

24. PROVE-IT: LDL-C, 106  62 mg/dlStable CHDHPS: benefit if basal LDL-C

25. ALLIANCE: 111  95 mg/dl

26. REVERSAL: 150  79 mg/dlHow low a LDL-C is safe?Newborn LDL-C is 35-50 mg/dl.Patients with hypobetalipoproteinemia are healthy and have enhanced survival

27. ATP III Treatment PrioritiesReduce LDL-C to goal (new goals)Correct residual lipid/lipoprotein abnormalities( non-HDL-cholesterol)Address the metabolic syndrome

28. Utility of the non-HDL-cholesterolTotal minus HDL-CIncludes all atherogenic lipoproteinsLDL-C, Lp(a), IDL, VLDLSurrogate for apoprotein BOptimum; add 30 mg/dl to LDL-C goals

29. All patients should receive TLC advise. Simultaneous drug therapy should be started in:Patients with symptomatic CHDAll high risk patientsIntermediate risk men@40-45 yrs

30. women@50-55 yrsOptions for reducing LDL-cholesterolStatins

31. Cholesterol absorption inhibitors

32. Bile acid binding resins

33. NiacinMuscle Adverse EffectsMyalgiaWeaknessFatigueMyopathy without CKPredisposing factors:Combined hyperlipidemia

34. Subclinical hypothyroidism

35. Suboptimum thyroxine replacementMODIFY RISK FACTORS

36. Hyperlipidemia in PregnancyTC & TG levels increase throughout pregnancyaverage cholesterol increase: 30 to 40 mg/dL around weeks 36 to 39TGs may increase as much as 150 mg/dLDrug therapy typically not initiated/continued during pregnancyTLC is the mainstay but BARs & absorption inhibitors may be considered in high risk patientsezetimibe: category C Statins: category X24

37. Statin Therapy Can Reduce the Risk of Coronary Heart Disease (CHD)Friday KE. Exp Biol Med. 2003,228:769-778Wilt TJ et al. Arch Intern Med. 2004;164:1427-1436

38. Diabetic DyslipidemiaCharacterized by hypertriglyceridemia, low HDL, & minimally elevated LDLDM ATP III CHD risk equivalentSmall, dense LDL (pattern B) in DM patients is more atherogenic than larger, more buoyant LDL (pattern A)1˚target: LDL Goal of treatment: LDL-C < 100 mg/dLLDL > 130 mg/dL: TLC + drug therapy often required Statins often considered initial drugs of choice26Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497.