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Hypertriglyceridemia JANEL LIANE CALA, RPH MEDICAL CENTER HOSPITAL - PowerPoint PPT Presentation

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Hypertriglyceridemia JANEL LIANE CALA, RPH MEDICAL CENTER HOSPITAL Objectives: To define hypertriglyceridemia To discuss pathophysiology behind hypertriglyceridemia To identify the diagnostic criteria for hypertriglyceridemia To

  1. Hypertriglyceridemia JANEL LIANE CALA, RPH MEDICAL CENTER HOSPITAL

  2. Objectives:  To define hypertriglyceridemia  To discuss pathophysiology behind hypertriglyceridemia  To identify the diagnostic criteria for hypertriglyceridemia  To tabulate the types of hypertriglyceridemia  To list the common causes of Hypertriglyceridemia  To state the clinical manifestations and physiologic effects of hypertriglyceridemia  To enumerate the possible pharmacologic and non-pharmacologic treatments behind hypertriglyceridemia  To summarize the guideline recommendations in dealing with hypertriglyceridemia

  3. Hypertriglyceridemia (HTG)  A condition in which the fasting plasma concentration of triglyceride exceeds a threshold value (eg, >1·7 mmol/L [>150 mg/dL])  Proposed definitions of HTG varies (see table below)  Usually asymptomatic until TG >1000-2000 mg/dL Reference: The polygenic nature of hypertriglyceridemia: implications for definition, diagnosis, and management triglyceridespanel.ajconline.org/Content/PDFs/4-Hegele-Polygenic.pdf

  4. Types of Lipoproteins Source: http://apoa1.org/2015/10/not-all-hdl-molecules-are-created-equal/

  5. APOLIPOPROTEINS Apolipoproteins- proteins that bind lipids to form lipoproteins -act as structural components of lipoproteins, cofactors for enzymes, and ligand for cell-surface receptors APOLIPOPROTEIN LIPOPROTEIN FUNCTIONS Apo A-I HDL Structural component of HDL Apo B-100 VLDL, IDL, LDL Assembly and secretion of VLDL from liver; Binding protein for LDL-R on cells Apo C-II Chylomicron, VLDL, HDL LPL activator Apo E Chylomicron, VLDL Ligand for receptor mediated clearance of VLDL and Chylomicron in Source: the circulation An Update on Hyperlipidemia and its Management http://jpma.org.pk/full_article_text .php?article_id=4665

  6. Lipid Metabolism Pathway Source : https://www.researchgate.net/figure/278524013_fig2_Figure-13-Schematic-of-the-exogenous-and-endogenous-lipid-metabolism-pathways

  7. Causes of HTG HTG Secondary Primary Predisposing Drug- Genetic Induced Disorders Conditions

  8. Primary Causes of HTG PRIMARY CAUSES DEFINITION Familial HTG High TG (200- 500 mg/dl) • May be due to VLDL overproduction and/or impaired VLDL catabolism • VLDL overproduced  unable to increase VLDL catabolism Strongly associated with hyperinsulinemia, hyperglycemia, and • hypertension Familial Combined Overproduction of hepatically derived ApoB-100 associated with VLDL • Hyperlipidemia (FCHL) Elevated TC and/or TG; Low HDL • Elevated ApoB and small dense LDL • Associated with Coronary risk - accounts for 1/3 to ½ of familial causes of • CHD

  9. Primary Causes of HTG PRIMARY CAUSES DEFINITION Hyperchylomicronemia Increased chylomicron and VLDL; Partial LPL deficiency • Usually presents with hepatosplenomegaly, eruptive xanthomas • Chylomicronemia Syndrome (TG >1000mg/dl) • + memory loss, abdominal pain, pancreatitis, lipemia retinalis Ultracentrifugal analysis • + creamy supernatant (Chylomicron); turbid infranatant (VLDL) Familial Presence of two Apo E2 alleles; (N= Apo 3/3 allele); • Dysbetalipoproteinemia Chylomicrons and VLDL with ApoE2- not cleared efficiently • Beta- VLDL formation (dense VLDL particle) • Premature CHD and PVD are common • Tuberoeruptive xanthomas, xanthoma palmare striatum •

  10. Clinical Manifestations of Primary HTG A. Eruptive cutaneous xanthomas B . Lipemic plasma C. Lipemia retinalis D. Tuberous xanthomas E. Palmar crease xanthomas Reference: Hypertriglyceridemia: its etiology, effects and treatment http://www.cmaj.ca/content/176/8/1113.full.pdf+html

  11. Secondary Causes of HTG  Obesity, Metabolic Syndrome, Diabetes  increased plasma concentrations of VLDL  deficient lipoprotein lipase activity  increased cholesteryl ester transfer protein activity  increased flux of free fatty acids to the liver  Acromegaly- decreased activity of Hepatic Lipase and LPL; increased insulin resistance  Pregnancy- estrogen-induced stimulation of the secretion of VLDL - decreased LPL and HL activity  Hypothyroidism- reduced LPL activity (Thyroid Hormones stimulate LPL)  Renal failure- reduced LPL activity; decreased clearance of TG-rich lipoprotein Reference: Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431581/ Hypertriglyceridemia: its etiology, effects and treatment http://www.cmaj.ca/content/176/8/1113.full.pdf+html

  12. Secondary Causes of HTG- Drugs  Alcohol- increased hepatic FA synthesis + decreased FA oxidation  hepatic VLDL secretion  Oral estrogen therapy – reduces levels of LPL and HL  decreased lipoprotein clearance  Tamoxifen- Selective Estrogen Receptor Modulator; reduction of LPL activity  Glucocorticoids - decreased clearance of TG rich lipoproteins - increased FA synthesis (synthesis of FA synthase) - insulin resistance - increased cholesterol production (HMG CoA reductase induction) Reference: Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431581/ Hypertriglyceridemia: its etiology, effects and treatment http://www.cmaj.ca/content/176/8/1113.full.pdf+html Hypertriglyceride Induced Pancreatitis http://cdn.intechopen.com/pdfs-wm/26197.pdf

  13. Correlation of HTG with CVD in Obesity Source: http://www.mdpi.com/1422-0067/15/4/6184/htm

  14. Treatment Goals of Hypertriglyceridemia HYPERTRIGLYCERIDEMIA Fasting TG level Treatment Goal Treatment (mg/dl) Mild 150-199 Reduction of Lifestyle changes • Moderate 200-999 Cardiovascular risk Statin Therapy • +/- TG lowering drugs • Severe 1000-1999 Prevent Acute Lifestyle Changes • Fibrates (1 st line)/ Very Severe >2000 Pancreatitis • Niacin/ Fish Oil +/- Statin • Lifestyle Changes = Weight loss (Obese patients), Aerobic Exercise, Strict Glycemic Control, Avoiding Medications that increase TG levels References: Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline https://www.endocrine.org/~/media/endosociety/Files/Publications/Clinical%20Practice%20Guidelines/082312_Hypertriglyceridemia_FinalA.PDF Hypertriglyceridemia, Journal of the American Board of Family Medicine http://www.jabfm.org/content/19/3/310.full

  15. Treatment Flowchart Source : Hypertriglyceridemia, American Academy of Family Physicians http://www.aafp.org/afp/2007/0501/p1365.html

  16. Non-Pharmacologic Treatment  Weight Loss for Obese Patients (BMI >= 30)  Mild-to-moderate weight loss (5 – 10% wt loss)  Reduce TG levels by 22%  Increase HDL-C by 9%.8  Decrease LDL by 40%  Lowers blood glucose  Diet and Exercise are the cornerstones of Weight loss  Excess calories are converted to TG then stored in adipose  To prevent this conversion (and eventually lower TG), decrease the caloric intake and increase physical activity Source: Hypertriglyceridemia-induced recurrent acute pancreatitis: A case-based review http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263185/ Hypertriglyceridemia Management in Patients With Diabetes, US Pharmacist http://www.uspharmacist.com/content/s/68/c/13446

  17.  DIET: Reduced calories, fat, and refined carbohydrate intake  Chylomicrons are the product of dietary fat absorption  Reduce fat to 10 – 15% of total energy intake (about 15 – 20 gm / day)  EXERCISE: 30 mins of Moderate Intensity Aerobic Exercise about 4x/wk can decrease TG and increase HDL Walking briskly (>=3mph) Water aerobics Bicycling (<10mph) Ballroom dancing General gardening  Alcohol should be avoided because it raises TG levels Source: Hypertriglyceridemia-induced recurrent acute pancreatitis: A case-based review http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263185/ Hypertriglyceridemia Management in Patients With Diabetes, US Pharmacist http://www.uspharmacist.com/content/s/68/c/13446 Measuring Physical Activity Intensity, Center for Disease Control and Prevention http://www.cdc.gov/physicalactivity/basics/measuring/

  18. Pharmacologic Treatment for Hypertriglyceridemia Source : Hypertriglyceridemia Management in Patients With Diabetes, US Pharmacist http://www.uspharmacist.com/content/s/68/c/13446

  19. Fibrates  modulate peroxisome proliferator activated receptors- α (PPAR - α) in the liver  Decreased hepatic secretion of VLDL  Increased lipolysis of the plasma triglyceride  PPAR-a activator; upregulate ApoCII and ApoAI  ApoAI - building block of HDL  Increased HDL levels  ApoCII activates LPL  Increased VLDL catabolism  Can lower TG significantly  However, if TG is high, it can increase LDL  Side Effects: Source:  Increased LFTs (Dose Related) Hypertriglyceridemia-induced recurrent acute pancreatitis: A case-based  GI disturbances- Abdominal Pain, N/V review http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263185/  Dyspepsia Hypertriglyceridemia Management in Patients With Diabetes, US Pharmacist http://www.uspharmacist.com/content/s/68/c/13446

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