RISK FACTORS

2. RISK FACTORS

3. IRREVERSIBLE • Masculine gender • Increasing age • Genetic traits • Body build POTENTIALLY REVERSIBLE • Smoking • Dyslipidaemia • Obesity • Hypertension • Physical in activity • Diabetes GEOGRAPHICAL • Climate and season

4. PSYCHOLOGICAL • Low socioeconomic class • Stressful situation • Coronary prone behavior pattern

5. LIPOPROTEINS AND LIPID METABOLISM

6. LIPOPROTEINS Blood lipids and lipoproteins Lipoproteins are molecular complex that consist of lipids and proteins(conjugated proteins) They functions as transport vehicles for lipids in blood plasma. Lipoproteins deliver the lipid components to various tissues for utilization.

7. STRUCTURE OF LIPOPROTEINS A lipoprotein basically consist of neutral lipid core surrounded by a coat shell or phospholipids, apoprotein and cholesterol. Lipoprotein is soluble in aqueous solution.

8. The protein components lipoprotein are known as apolipiproteins. THEY PERFORM THE FOLLOWING FUNCTIONS Act as structural components of lipoprotein. Recognize the cell membrane surface receptor. APOLIPOPROTEINS(APOPROTEINS)

9. 1.Apolipoproteins B form low-density lipoprotein particles. These proteins have mostly beta-sheet structure . 2.Other apolipoproteins form high-density lipoprotein particles. These proteins consist of alpha-helices. There are six classes of apolipoproteins and several sub-classes: A (apo A-I, apo A-II, apo A-IV, and apo A-V) B (apo B48 and apo B100) C (apo C-I, apo C-II, apo C-III, and apo C-IV) D E H Classes

10. CHOLESTEROL 60-70% is carried on LDL, 20%-30% on HDL, and 10-15% on VLDL Population that consume diets high in saturated fatty acids have increased blood cholesterol levels.

11. Functions- Major constitute of all cell membranes Precursor of bile acid Precursor of adrenal and reproductive steroids. Essential component of plasma lipoprotein. Precursor of vitamin D synthesis. FACTORS- age, diet high in fat, saturated fat and cholesterol, genetics, endogenous sex hormones, body weight, presence of other diseases.

12. Total Triglyceride The triglyceride-rich lipoproteins include chylomicrons, LDLs, and any remnants or intermediary products formed in metabolism. All contain the apo B lipoprotein Fasting triglyceride Levels are classified as normal (<150 mg/dl), borderline high (150 to 199 mg/dl), high (200 to 499 mg/dl), and very high (>500 mg/dl)

13. METABOLISM Lipid transport can be understood as the- water insoluble lipids water soluble forms water insoluble lipids. Remember, fat floats on water, because it is lighter than water

14. TRIGYLYCERIDES FROM GUT TO ADIPOCYTE- Chylomicrons. • Monoglycerides and fatty acids are re-esterified triglycerides within the mucosal cell. • The lipid rich particles leave the mucosal cell and travel through lymphatic channels to the thoracic duct that empties into the right side of the heart. • Chylomicrons leaves the heart through the aorta and are transported to the adipocyte.

15. Lipoprotein lipase(LPL), an enzyme bind chylomicrons (c)and cleave triglycerides monoglycerides +fatty acids re-esterified into triglycerides hydrophobic storage

16. TRIGLYCERIDES FROM LIVER TO ADIPOCYTE- very low-density lipoprotein. • The liver receive fat from a number of sources- • From chylomicrons remnants • From circulating fatty acids • From uptake of intermediate lipoproteins • From endogenous body synthesis.

17. The liver re-esterifie from all sources and wraps in a heavier coat of protein and phospholipids to form VLDL. • This lipoprotein is richer in cholesterol than chylomicrons. • In the fed state, large no of VLDL are formed and then sported to adipocyte. • Insulin-facilates large storage

18. CHOLESTEROL FROM DIET AND LIVER TO ALL CELL- Low density lipoprotein • After LPL has cleaved additional triglyceride from VLDL, the remnant remaining is called an intermediate density lipoprotein. • The endocyte vesicles containing LDL receptors is fused with lysosome, there by breaking it down • The protein is recycles to the cellular amino acids pool and cholesterol is released for use by the cell.

19. CHOLESTEROL FROM CELL TO THE LIVER- High density lipoproteins • The HDL facilitates cholesterol turnover by removing free cholesterol from cell membrane and scavenging cholesterol from other lipoproteins. • HDL particles are formed in the liver as protein-PHOSPHOLIPIDS disk.

20. The ability of HDL, to function as a cholesterol transporter is dependent on the activity of Cu-dependent enzyme-LECITHIN CHOLESTEROL ACYL TRANSFERASE.

23. LIPOPROTEIN LIPASE • It is an enzyme that hydrolyzes lipids in lipo-protein, such as those found in chylomicrons, VLDL, into two FFA and one monoacylglycerol. • LPL is specifically found in endothelial cell linning. • LPL functions as homodimer, and had dual function of • Triglyceride hydrolyses • Bridging factor for receptor. • Insulin is known to reduce LPL synthesis in adipocyte

24. Include measurement of total cholesterol, LDL cholesterol, and total triglyceride levels and thus should be measured after a person has fasted for 8-12 hours. The friedewald formula is. LDL-C = (TC) – (HDL-C) – (TG/5) LIPOPROTEIN PROFILE

25. LOW DENSITY LIPOPROTEIN A decrease in 1 mg/dl in LDL cholesterol results in about a 1% to 2% decrease in relative risk for CHD. LDL cholesterol levels for children and adult are- 100 mg/dl and 123mg/dl

26. FACTORS THAT INCREASE LDL CHOLESTEROL Aging Genetics Diet Reduced estrogen levels Diabetes obesity

27. During the acute phase response, serum triglyceride are increased, and HDL cholesterol is decreased in an effort to move nutrients to the cell that need them in host defense. TRIGLYCERIDE LEVELS

28. Diet(excessively low-fat, high refined carbohydrates) Estrogens Alcohol Obesity Untreated diabetes Chronic renal failure And liver diseases Factors that increase triglyceride levels are

29. HDL as good cholesterol A HDL cholesterol levels (> 60 mg/dl) considered a negative risk factor for CHD. HIGH DENSITY LIPOPROTEIN CHOLESTEROL

30. Exogenous estrogen Intensive exercise Loss of excess body fat Moderate consumption of alcohol The consumption of alcoholic beverages, in particular red wine, results in reduction in cardiovascular risk factor and decrease mortality. Factors that increase hdl cholesterol levels

31. PROPERTIES AND FUNCTIONS OF MAJOR PLASMA LIPOPROTEIN

33. ATP III GUIDLINES

34. Since 1988,the National Cholesterol Education Program(NCEP) has issued guidelines identifying LDL cholesterol as the primary target of cholesterol therapy. ATP III guidelines issued in May 2001, emphasizes the role of diet and exercise in decreasing for developing CHD.

35. A change in minimum accepted level of HDL. A new set of therapeutic lifestyle changes. Identifying diabetes as CHD risk equivalent . Increase attention to the treatment of high TG levels.. A sharper focus on cluster of heart disease risk factor known as the metabolic syndrome. KEY FEATURES OF ATP III GUIDELINES-

36. STEP 1 Determine lipoprotein levels–obtain complete lipoprotein profile after 9 to 12 hour fast. ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dl)Identify LDL Cholesterol – Primary Target of Therapy

37. Total cholesterol HDL cholesterol

38. STEP 2- Identify presence of clinical atherosclerotic disease that confers high risk for coronary heart disease- • Clinical CHD • Symptomatic carotid artery disease. • Peripheral arterial disease. • Abdominal aortic aneurysm.

39. Determine presence of major risk factors (other than LDL). Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals Cigarette smoking Hypertension (BP >140/90 mmHg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dl) Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years) Age (men >45 years; women >55 years) STEP 3

40. If 2+ risk factors (other than LDL) are present without CHD or CHD risk equivalent, assess 10-year (short-term) CHD risk Three levels of 10-year risk: >20% — CHD risk equivalent n 10-20% n <10% STEP 4

41. Determine risk category: Establish LDL goal of therapy. Determine need for therapeutic lifestyle changes (TLC) Determine level for drug consideration. STEP 5

42. Initiate therapeutic lifestyle changes (TLC) if LDL is above goal. TLC Features TLC Diet: Saturated fat <7% of calories, cholesterol <200 mg/day Consider increased viscous (soluble) fiber (10-25 g/day) and plant stanols/sterols (2g/day) as therapeutic options to enhance LDL lowering Weight management Increased physical activity. STEP 6

43. Consider adding drug therapy if LDL exceeds levels. Consider drug simultaneously with TLC for CHD and CHD equivalents Consider adding drug to TLC after 3 months for other risk categories. STEP 7

44. STEP - 8 Identify metabolic syndrome and treat, if present, after 3 months of TLC.

45. Treatment of the metabolic syndrome Treat underlying causes (overweight/obesity and physical inactivity): Intensify weight management Increase physical activity. Treat lipid and non-lipid risk factors if they persist despite these lifestyle therapies: Treat hypertension Use aspirin for CHD patients to reduce prothrombotic state Treat elevated triglycerides and/or low HDL

46. STEP 9 ATP III Classification of Serum Triglycerides (mg/dL)

47. Treat elevated triglycerides. Treatment of elevated triglycerides (>150 mg/dl) Primary aim of therapy is to reach LDL goal Intensify weight management Increase physical activity If triglycerides are >200 mg/dl after LDL goal is reached, set secondary goal for non-HDL cholesterol.

48. GENETIC HYPERLIPIDEMIAS