DYSLIPIDEMIAS: TYPES I-V

1. DYSLIPIDEMIAS:TYPES I-V Thomas F. Whayne, Jr, MD, PhD, FACC Professor of Medicine (Cardiology) University of Kentucky March 2011. E-Mail: twhayn0@uky.edu. No conflicts to declare.

3. THE MAJOR LIPOPROTEINS • CHYLOMICRONS. • VERY LOW DENS. LIPOPROT. (VLDL). • LOW DENS. LIPOPROT. (LDL) . • HIGH DENS. LIPOPROT. (HDL) .

4. Type I Type IIA Type IIB Type III Type IV Type V Normal

7. Before UC After UC VLDL Tube Plain LDL HDL

8. VLDL Tube with KB LDL HDL

9. TYPE I • RARE GENETIC DISORDER. • HYPERCHYLOMICRONEMIA. • LIPOPROTEIN LIPASE DEFICIENCY.

12. TYPE I: TREATMENT • RESTRICTION OF FATS. • PANCREATITIS: NPO. • MEDIUM CHAIN FATTY ACID TRIGLYCERIDES.

13. TYPE II-A HYPERLIPOPROTEINEMIA AUTOSOMAL DOMINANT. • HETEROZYGOTES: 1 IN 500. • HOMOZYGOTES: 1 IN 1,000,000.

15. TYPE II-A IS ALSO: • POLYGENIC. • SPORADIC. • POSSIBLY ACQUIRED

16. TYPE II-A • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY CORONARY. • TENDON XANTHOMAS. • TUBEROUS XANTHOMAS. • XANTHELASMA. • CORNEAL ARCUS.

20. EXTREME EXAMPLE OF TYPE II-A HYPERLIPOPROTEINEMIA STORMY JONES: AGE 10.

21. TYPE II-B ACCELERATED ATHEROSCLEROSIS: CORONARY AND PERIPHERAL

23. TYPES IIA/IIB: TREATMENT • STATINS ESPECIALLY. • BILE ACID BINDING RESINS, ESPECIALLY COLESEVELAM. • NICOTINIC ACID (NIASPAN®). • ZETIA. • POLICOSANOL. • LDL APHERESIS.

24. TYPE III • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY PERIPHERAL. • PALMAR XANTHOMAS. • TUBEROUS XANTHOMAS.

26. TYPE III APO E IN LIVER RECEPTORS IS ABNORMAL OR DEFICIENT FOR: • LOW DENS. LIPOPROTEINS (LDL). • INTERMED. DENS. LIPOPROTEINS (IDL). • CHYLOMICRON REMNANTS.

28. TYPE III TREATMENT • LOW CHOLESTEROL UNSATURATED FAT DIET. • SOME CARBOHYDRATE (SIMPLE SUGARS) RESTRICTION. • CLOFIBRATE (ATROMID). • GEMFIBROZIL (LOPID). • FENOFIBRATE (TRICOR). • STATIN.

29. TYPE IV HYPERLIPOPROTEINEMIA • ALSO CALLED FAMILIAL HYPERTRIGLYCERIDEMIA. • ACCELERATED ATHEROSCLEROSIS, ESPECIALLY PERIPHERAL.

31. TYPE IV: TREATMENT • FENOFIBRATE. • NICOTINIC ACID (NIASPAN®). • OMEGA FATTY ACIDS (LOVAZA®). • METFORMIN. • PIOGLITAZONE. • STATINS. • EZETIMIBE. • INSULIN.

32. TYPE V • INCREASED CHYLOMICRONS AND VLDL. • CAN BE RARE GENETIC DISORDER. • CAN BE MORE FREQUENTLY SEEN IN DIABETES, EVEN WITH MILD INCREASE IN PLASMA GLUCOSE.

35. TYPE V: TREATMENT • CONTROL DIABETES. • FENOFIBRATE. • NICOTINIC ACID (NIASPAN®). • OMEGA FATTY ACIDS (LOVAZA®). • METFORMIN. • PIOGLITAZONE. • INSULIN.

36. DYSLILPIDEMIA IN DIABETES:TYPICAL PATTERN • HIGH LEVELS OF TRIGLYCERIDES. • LOW LEVELS OF HDL. • PREPONDERANCE OF SMALL DENSE LDL.

37. SMALL, DENSE LDL • ASSOCIATED WITH 3X  RISK OF CHD. • INCREASED ATHEROGENICITY: • FASTER ENTRY INTO BLD. VESSEL WALL. •  BINDING TO LDL RECEPTOR. • INCREASED SUSCEPTIBILITY TO OXIDATION.

38. TRIGLYCERIDES IN DIABETES • HIGH TRIGLYCERIDE LEVELS OCCUR MAINLY IN VLDL BUT ALSO IN CHYLOMICRONS. • ELEVATED TRIGLYCERIDE LEVELS RESULT FROM: • OVERPRODUCTION OF VLDL. • IMPAIRED LIPOLYSIS OF TRIGLYCERIDES (INSULIN IS AN LPL COFACTOR).

39. ADA RATIONALE FOR Rx OF DYSLIPIDEMIA IN DIABETES • THERE IS  RISK OF CHD BECAUSE OF DYSLIPIDEMIA. • DIABETIC DYSLIPIDEMIA FREQUENTLY CHARACTERIZED BY  TRIGLYCERIDES,  HDL AND  SMALL, DENSE LDL. • Rx OF DIABETIC DYSLIPIDEMIA MAY REDUCE RISK OF CHD.

40. IMPROVED CONTROL OF HYPERGLYCEMIA • CAN REDUCE DYSLIPIDEMIA. • MAY RESULT IN  ATHEROGENIC DENSE LDL. • COMPLETE REVERSAL OF DYSLIPIDEMIA USUALLY NOT ACHIEVABLE.

41. RESPONSE OF DENSE LDL TO MEDICATION • FIBRATES AND NICOTINIC ACID (NIASPAN®) SHIFT THESE DENSE LDL TO A LARGER SIZE LDL PARTICLE. • STATINS ARE NOT EFFECTIVE IN FAVORABLE SHIFT OF DENSE LDL TO LARGER, LESS DENSE LDL PARTICLE.

42. FIBRATES IN TYPE II DIABETICS

43. Syndrome X, Metabolic Syndrome or Cardiovascular Dysmetabolic Syndrome • Obesity. • Hypertriglyceridemia. • Low HDL. • Increased Dense LDL. • Hypertension. • Insulin Resistance. • Hyperuricemia. • Increased PAI-1.

44. METABOLIC SYNDROME, SYNDROME X or CV DYSMETABOLIC SYNDROME AT LEAST 3 OF THE FOLLOWING 5 PRESENT†: TG  150 mg/dl. HDL < 40 mg/dl in men and < 50 mg/dl in women . BP  130/85 mm/Hg. Waist girth > 102 cm (men) and > 88 cm (women). Fasting glucose  100 mg/dl. OTHER COMPONENTS:  dense LDL, Insulin resistance, Hyperuricemia,  PAI-1,  hsCRP,  Tissue necrosis factor-α Interleukin-6,  Resistin, and  Adiponectin. †Grundy SM, et al. Circulation 2005;112:2735-2752.

45. Metabolic Syndrome: Prevalence Increases with Age 47 million or 23% of US adults have the metabolic syndrome Adapted from: Ford ES, et al. JAMA2002;287:356-359.

46. MARKED HYPERTRIGLYCERIDEMIA CAN OCCUR FROM RETROVIRUS Rx IN HIV PATIENTS

47. Thiazides: • Marked elevation of triglycerides and VLDL can occur. • Increased total cholesterol and LDL. • Little effect on HDL.

48. ESTROGEN SPORADICALLY AND UNPREDICTABLY, ESTROGEN MAY CAUSE A MARKED ELEVATION IN TRIGLYCERIDES.

49. BETA BLOCKERS • Increase triglycerides and VLDL. • Decrease HDL. • Less significant increase in Total Cholesterol and LDL. • Beta Blockers with ISA may have a less pronounced effect.

50. CONCLUSION MULTIPLE APPROACHES AVAILABLE TO ACHIEVE GOOD BLOOD LIPID CONTROL AND THEREBY AVOID MULTIPLE CLINICAL PROBLEMS INCLUDING SEQUELAE OF CORONARY ATHEROSCLEROSIS.