1. This lecture was conducted during the Nephrology Unit Grand Ground by Nephrology Registrar under Nephrology Division, Department of Medicine in King Saud University. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. Eman Saad Algadi 427200141 presented on Wed 23-11-2011

3. Definition Elevation of measured serum lipid components: Total cholesterol. LDL cholesterol Friedewald formula is LDL = total cholesterol - HDL - (triglycerides/5). Triglycerides (TGs) Or low HDL. Accelerate development of atherosclerosis. A modifiable major risk of CAD.

4. Why? (causes) primary Inborn derangement of lipid metabolism and/or transport. The most common cause of dyslipidemia in children, do not cause a large percentage of cases in adults. Secondary Hypothyroidism. Sedentary lifestyle with excessive dietary intake of saturated fat, cholesterol, & trans fats. Obesity Diabetes mellitus Alcohol overuse Cigarette smoking chronic kidney disease. cholestatic liver disease. Drugs (thiazides, βblockers, retinoids, glucocorticoids).

5. When to screen? ✽ All men older than 35 & all women older than 45. (level A evidence by USPSTF) ✽ Men age 20-35 & women age 20-45 in the presence of risk factors: Type 2 diabetes FHx early CAD Possibility of familial hyperlipidemia Any combination of cardiac risk factors: smoking, obesity, hypertension, or sedentary lifestyle.

6. Routine screening of TC and HDL every 5 years is recommended by National Institutes of Health (NIH) & the American Heart Association (AHA)

7. Steps to Approach hyperlipidemia recommended by The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program

8. Complete lipid profile after 9- 12 hour fast 1

9. Determine CHD risk category 2

10. 1- Identify CHD/ CHD risk equivalent (high risk) If the patient have Clinical CHD Symptomatic carotid artery disease Peripheral arterial disease Abdominal aortic aneurysm. Diabetes is regarded as a CHD risk equivalent

11. 2- Identify major risk factors (other than LDL-C) Cigarette smoking Hypertension (BP >140/90 mmHg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dL) HDL cholesterol >60 mg/dL is a “negative” risk factor; it removes one risk factor from the total count 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)

12. If 2+ risk factors (other than LDL) present without CHD/CHD risk equivalent: assess 10-year Framingham risk score >20% — CHD risk equivalent 10-20% <10% 10 yr CHD risk score Gender Age Smoking Total cholesterol HDL level SBP

13. Risk categories High risk CHD or risk equivalent (10-year CHD risk > 20 %) Moderately high risk ≥ 2 risk factors (10-year CHD risk of 10 -20 %) Moderate risk ≥ 2risk factors (10-year CHD risk < 10 %) Low risk One or no risk factors

14. Risk CategoryLDL Goal LDL Level at Which to Initiate Therapeutic lifestyle changes LDL Level at Which to Consider Drug Therapy HIGH RISK: CHD or CHD Risk Equivalents (10-year risk >20%) <100 mg/dL≥100 mg/dL≥130 mg/dL (100-129 mg/dL: drug optional) MODERATLY HIGH RISK: ≥ two risk factors (10-year risk 20-10 %) <130 mg/dL ≥130 mg/d≥130 mg/dL MODERATE RISK: ≥ two risk factors (10-year risk < 10 %) ≥160 mg/dL LOW RISK: One or no risk factors <160 mg/dL≥160 mg/dL≥190 mg/dL (160-189 mg/dL: LDL- lowering drug optional)

15. Therapeutic lifestyle changes lipid-lowering diet: Reduce Saturated fat <7% of calories. Reducing cholesterol <200 mg/day. Consider increased soluble fiber (10-25 g/day) Weight management Increased physical activity Smoking cessation (increases HDL by 4 mg/dL and reduces total mortality in patients with CAD).

16. Statins reduce overall mortality in primary and secondary prevention of CAD. (level A evedince) Statins HMG-CoA reductase inhibitors. LDL ↓ 18-55% HDL ↑ 5-15% TG ↓ 7-30% Myopathies (<1% # fibrates) Rhabdomyolysis (< 0.2%) Abnormal Liver function test (< 2%) Contraindicated in active liver disease and pregnancy Drug therapy

17. Bile acid sequestrants (Cholestyramine) LDL ↓ 15-30% HDL ↑ 3-5% TG No change or increase GI distress Constipation Decreased absorption of other drugs Contraindicate d in hyperTG Drug therapy

18. Nicotinic acid LDL ↓ 5-25% HDL ↑ 15-35% TG ↓ 20-50% Flushing Hyperglycemia Hyperuricemia (or gout) Upper GI distress Hepatotoxicit Contraidicated in: Chronic liver disease Severe gout Diabetes Hyperuricemia Peptic ulcer disease Drug therapy

19. Fibrates (Gemfibrozil) LDL ↓ 5-20% (may be increased in patients with high TG) HDL ↑ 10-20% TG ↓ 20-50% Dyspepsia Gallstones Myopathy Contraindicated in: Severe renal disease Severe hepatic disease Drug therapy

20. Lacks clinical outcome data (monotherapy or combined with a statin) EzetimibeLDL ↓ 18%Contraindicated in active liver disease when combined with a statin Drug therapy

21. Omega-3 fatty acids do not clearly demonstrate reductions in mortality ( level A evidence ) Omega-3 fatty acids Dyspepsia. Burping. Fishy taste Drug therapy

22. If TGs are greater than 500 mg/dL, they become the primary target of therapy due to the risk of acute pancreatitis. Niacin, fibrates, or omega-3 fatty acids should be used until the TG level is less than 500 mg/dL.

23. If the LDL goal has been achieved and the TC level is greater than 200 mg/dL: non-HDL (TC - HDL) becomes the secondary goal of treatment. Niacin, fibrates, and omega-3 fatty acids along with diet and exercise to achieve this goal.

24. Complementary/Alternative Therapy Garlic. Red yeast rice. Artichoke. may modestly reduce cholesterol, but patient-oriented evidence is lacking. Vitamin E does not reduce mortality, recurrent events, or nonfatal stroke after an acute myocardial infarction

25. References: 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;285:2486-97. Pignone MP,, et al. Screening for lipid disorders. Systematic Evidence Review No. 4 Rockville, Md.: Agency for Healthcare Research and Quality, 2001. Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med.2003;37:283- 90. Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ.2006;332:752-60. hekelle PG, Morton SC, Jungvig LK, et al. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med.2004;19:380-9.

26. THANK YOU!