Dyslipidemia

1. Dyslipidemia WintanaTeklehaimanot 4th year Pharmacy student Florida A & M University Disease State Presentation

2. Objective • Define dsylipidemia with its risk factors, prevalence and pathophysiology • Describe the elements of diagnosis and the various non- pharmacological and pharmacological treatment options • Compare and contrast primary literature based on guideline recommendation • Discuss the clinical pearls and pharmacists role in managing patients with dyslipidemia

3. KEY to abbreviations • Total Cholesterol (TC) • Low Density Lipoproteins (LDL) • High Density Lipoproteins (HDL) • Very Low Density Lipoproteins (VLDL) • Triglycerides (TG)

4. Definition • Abnormalities of plasma lipoproteins in our body responsible for transporting major lipids: • LDL • HDL • Chylomicrons (TG) • VLDL • Elevation of TC ,LDL,TG, and low HDL or in some combination • Result in a predisposition to arterial diseases such as: • Coronary • Cerebrovascular • Peripheral Vascular

5. classification • Phenotype caterogy: I; Ila; IIb; III; IV; V • Clinically: • Isolated hypercholesterolemia: mostly due to LDL elevation • Mixed or combined dyslipidemia: elevations of TC or LDL, and TG • Isolated hypertriglyceridemia: elevation in TG only • Low HDL-cholesterol: either isolated or in association with hypercholesterolemia or hypertriglyceridemia

6. Prevalence • Direct relationship between LDL levels and new onset of CHD and recurrent coronary invents: • Framingham Heart Study • Multiple Risk Factor Intervention Trial (MRFIT) • Lipid Research Clinics (LRC) trial • About 46.8% American adults over age 20 are at borderline high risk with TC >200mg/dL • More than half are unaware • Only one-third are receiving treatment • Less than 20% have achieved their LDL goal

7. Prevalence • Major risk factor for mortality: • Coronary Heart Disease (70%deaths) • Ischemic heart disease (50% deaths) • Preexisting CHD or prior MI (5-7 times increased risk) • Leading cause of death for both men and women of all races and ethnicities • Incidence is higher in industrialized countries • LDL is a significant predictor of mortality and mobidity • Strong correlation between BMI and incidence of hypercholesterolemia

8. Etiology • Primary • Single or multiple gene mutations • Children and young adults • Small percentages • Secondary • Most adults cases • Sedentary lifestyle • Certain disease states • Alcohol dependence • Certain medication use

9. Pathophysiology • Atherosclerosis begins with injury to the endothelial cells that line the artery walls • LDL enters intima through intact endothelium (influx > eliminating capacity and formation of LDL extracellular pool) • Intimal LDL is oxidized into pro-inflammatory lipids • Oxidized LDL causes adhesion and entry of monocytes and T lymphocytes across endothelium • Monocytes differentiate into macrophages and then consume large amounts of LDL, transforming into foam cells • Foam cells release growth factors (cytokines) that encourage atherosclerosis

11. Risk factors • Additive effects to developing CV disease with: • Diabetes • Hypothyroidism • Excess body weight (BMI >25 kg/m2) • Cholestaticliver disease • Cigarette smoking • Low HDL • Hypertension • Electrocardiogram abnormalities • Hyperhomocystinemia • Autoimmune phenomena • Nephrotic syndrome • Use of certain medication

13. Complications • Myocardial Infaction • Ischemic cardiomyopathy • Sudden death • Stroke • Erectile dysfunction • Peripheral vascular disease • Acute limb ischemia

14. Tests • Lipid Profile • Total cholesterol (TC) >200 mg/dL; • LDL-cholesterol >100 mg/dL; • Non-HDL-cholesterol >130 mg/dL; • HDL-cholesterol <40 mg/dLfor men; <50 mg/dL for women • Triglycerides >150 mg/dL • TSH levels • 0.3 - 3.04 mIU/L

15. Diagnostic criteria

16. risk Stratification

17. Framingham risk score

18. Treatment approach

19. Non-pharmacological treatment • Dietary reduction total and saturated fat • Weight loss in overweight patients • Aerobic exercise • Addition of plant stanols/sterols to the diet • Dietary Recommendation: • Total fat intake 25% and 35% • Saturated fat <7% • Trans fat intake <1% of total daily calories • Cholesterol intake from food <300 mg/day • Increasing fish oil intake w/ omega-3 fatty acids may help lower TG levels

20. Pharmacological treatment

23. New controversial study • Use of Omega 3 fatty acid for hypertriglyceridemia due to increased risk of prostate cancer • Title: • Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial • Background: • Based on previous study, Prostate Cancer Prevention Trial (PCPT) claims high concentration of serum phospholipid long-chain ω-3 fatty acids are associated with large increase in the risk of high-grade prostate cancer • Method: • Case-cohort design nested within SELECT • Result: • Higher total long-chain ω-3 PUFA were associated with increased risks of total, low-, and high-grade cancer. Compared with men in the lowest quartile of total long-chain ω-3 PUFA, men in the highest quartile had 44% (95% CI= 8%- 93%), 71% (95% CI= 0%- 194%), and 43% (95% CI= 9%- 88%) increased risk for low-grade, high-grade and total cancer, respectively. • Conclusion: • This study does not prove fish oil supplementation to increase prostate cancer risk, however more investigation would be beneficial

24. Clinial pearls • Statins are once-daily dosing, unless otherwise specified. • Statins in severe renal impairment should be used in caution of doses over 40 mg daily • Statins if CrCl <30 mL/min should be used in caution of doses over 20 mg daily • Monitor for drug interactions when using antihyperlipidemia drugs • Combination therapy for non-therapeutic patients may be beneficial, however, must monitor for side effects • Lifestyle modification is the best approach to treating dyslipidemia

25. Pharmacists role

26. Reference