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Morbidity and Mortality Associated with Dyslipidemia

Morbidity and Mortality Associated with Dyslipidemia. By: David Tran, Mercer University, 2013 Pharm.D. Candidate Prececptor: Dr. Ali Rahimi. Dyslipidemia. An imbalance of any or all lipid concentrations in the plasma, including hyperlipidemia, hypertriglyceridemia, and hypercholesterolemia

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Morbidity and Mortality Associated with Dyslipidemia

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  1. Morbidity and Mortality Associated with Dyslipidemia By: David Tran, Mercer University, 2013 Pharm.D. Candidate Prececptor: Dr. Ali Rahimi

  2. Dyslipidemia • An imbalance of any or all lipid concentrations in the plasma, including hyperlipidemia, hypertriglyceridemia, and hypercholesterolemia • Puts you at risk of developing heart disease which is the leading cause of death in the United States (~620,000 deaths in 2008) • People of all ages and backgrounds can have high cholesterol

  3. CDC Statistics • 71 million American adults (33.5%) have high LDL • 1 out of every 3 adults with high LDL cholesterol has the condition under control • Less than half of adults with high LDL cholesterol get treatment • People with high total cholesterol have approximately twice the risk of heart disease as people with optimal levels. A desirable level is lower than 200 mg/dL • The average total cholesterol level for adult Americans is about 200 mg/dL, which is borderline high risk

  4. Hyperlipidemia by Ethnicity (LDL >130 mg/dL)

  5. Lipid Goals

  6. NCEP/ATP III Recommendations • Recommend all adults ≥ 20 years old have a fasting lipid panel obtained every 5 years • LDL is the primary target • TG should be targeted first if TG are >500 mg/dL • Once LDL goal is achieved, attention should be focused on other parameters (non-HDL cholesterol)

  7. Risk Factors • Age: male >45; female >55 • Family history: premature CHD in 1st degree relative • Male <55; female <65 • Current cigarette smoking • HTN (>140/90 mmHg or on antihypertensive medications) • Low HDL (<40 mg/dL) • Abdominal obesity

  8. CHD and CHD Risk Equivalents Established CHD • Myocardial ischemia • MI • Coronary angioplasty and/or stent placement • CABG • Prior unstable angina CHD Risk Equivalents • CAD • Stroke history • TIA • Carotid stenosis >50% • Peripheral Artery Disease • Abdominal Aortic Aneurysm • Diabetes Mellitus

  9. Dyslipidemia and Coronary Risk • Continuous, graded relationship between serum total plasma cholesterol concentration and coronary risk • Meta-analysis of 38 primary and secondary prevention trials found that for every 10% reduction in serum cholesterol, CHD mortality would be reduced by 15% and total mortality risk by 11% • High LDL levels associated with an increased incidence of CHD in a large number of studies • Framingham Heart Study found that the risk of myocardial infarction increases by about 25% for every 5 mg/dL decrement below median values • Meta-analysis of prospective population-based studies evaluating the association between serum triglyceride concentration and incidence of cardiovascular disease showed significant risk ratios • Lipid Research Clinics Program found that differences of 30 mg/dL in non-HDL corresponded to 19% and 11% increases in mortality in men and women, respectively

  10. LDL Target Goals

  11. Lipid Synthesis

  12. Lipid Components

  13. Lipoproteins • Apo-B48 is required for the formation of the chylomicron and secretion for general circulation • Apo-B100 is required for VLDL assembly • Lipoprotein lipase (LPL)- forms free fatty acids that can be used for energy in the periphery. Also, responsible for the formation of remnants which is taken up by the liver for breakdown into cholesterol • Apo-C2 is responsible for activating LPL • Apo-E binds to LDL-related protein receptors for lipids to be taken up into the liver to be broken down into cholesterol and phospholipids

  14. Apolipoprotein B • Acts as a ligand for LDL receptors in various cells throughout the body to deliver cholesterol • High levels of ApoB can lead to plaques that cause atherosclerosis which can thereby lead to heart disease • ApoB is a marker for CHD risk • The AMORIS study found that measurement of ApoB improved the prediction of fatal MI at all levels of total cholesterol, LDL, and triglycerides • In multivariate analysis, the concentration of ApoB was more highly significant than LDL in determining outcomes and added predictive power to LDL cholesterol

  15. Apolipoprotein E • Serves as a transporter of lipoproteins, fat-soluble vitamins, and cholesterol • Variant alleles of ApoE are genetic risk factors for Alzheimer disease • Defects in ApoE result in familial hyperlipidemia which is characterized by increased plasma cholesterol and triglycerides • Cardiovascular biomarker with a positive dose-response association with ischemic stroke

  16. Heart Protection Study • Randomized, placebo-controlled trial of effects of simvastatin and antioxidant vitamins on morbidity and mortality • >20,536 men and women 40–80 yr at increased risk of CHD due to prior disease with total cholesterol >135 mg/dL • Simvastatin 40 mg daily vs placebo • Duration of greater than 5 years

  17. Heart Protection Study • Primary endpoint • The effect of simvastatin on total and cause-specific mortality • Secondary endpoints • Treatment effect on CHD morbidity and mortality in special patient populations • Treatment effect on incidence of cancer, strokes, major vascular procedures, and other conditions requiring hospitalization • Treatment effect on cause-specific mortality and cancers during longer-term follow-up

  18. Heart Protection Study: Vascular Events by Baseline Disease

  19. Heart Protection Study: Vascular Event by LDL

  20. References • CDC. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol. United States, 1999–2002 and 2005–2008. MMWR. 2011;60(4):109–14. • Khan et al. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals. International Journal of Epidemiology. 2013 Apr;42(2):475-492. • MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002 Jul 6;360(9326):7-22. • National Institute of Health. Morbidity and Mortality: 2012 Chart Book on Cardiovascular, Lung, and Blood Diseases. Online. 4/16/2013. http://www.nhlbi.nih.gov/resources/docs/2012_ChartBook.pdf • Pereira, Telmo. Dyslipidemia- From Prevention to Treatment: Dyslipidemia and Cardiovascular Risk: Lipid Ratios as Risk Factors for Cardiovascular Disease. Pgs 279-298. • Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–220. • Uptodate. Screening Guidelines for Dyslipidemia. Online. 4/10/2013. http://www.uptodate.com/contents/screening-guidelines-for-dyslipidemia?topidKey=PC%

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