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1 Role of Triglycerides. 2 Objectives  Explain the metabolism of triglycerides and the relationship between triglycerides and HDL-C  Discuss the role.

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Presentation on theme: "1 Role of Triglycerides. 2 Objectives  Explain the metabolism of triglycerides and the relationship between triglycerides and HDL-C  Discuss the role."— Presentation transcript:

1 1 Role of Triglycerides

2 2 Objectives  Explain the metabolism of triglycerides and the relationship between triglycerides and HDL-C  Discuss the role of triglycerides in the metabolic syndrome  Describe the relationship between serum triglycerides and CVD risk HDL-C=high-density lipoprotein cholesterol; CVD=cardiovascular disease

3 3 Role of Triglycerides Properties and Metabolism of Triglycerides

4 4 Properties of Triglycerides  Triglycerides are a vehicle for energy storage, primarily in adipose tissue  Triglycerides have both exogenous and endogenous sources –The liver synthesizes triglycerides from free fatty acids (FFAs) –The Western diet contains vast amounts of triglycerides that are absorbed into the body via the intestine  Triglycerides circulate primarily in very low-density lipoproteins (VLDLs) and chylomicrons Sarwar N et al. Circulation. 2007;115:450–458; Castelli WP. Am Heart J. 1986;112:432–437.

5 5 Triglyceride Metabolism LPL=lipoprotein lipase; FFA=free fatty acid; HL=hepatic lipase; LDL-C=low-density lipoprotein cholesterol; VLDL=very low-density lipoprotein; IDL=intermediate density lipoprotein; apo E=apolipoprotein E; apo B=apolipoprotein B from Mahley RW et al. In: Larsen PR et al, eds. Williams Textbook of Endocrinology. 10th ed. Philadelphia, Pa; Saunders: 2003;1642–1705; Castelli WP. Am J Heart. 1986;112:432–437. Liver Intestine Dietary fat + cholesterol Chylomicrons Chylomicrons remnants Bile acids VLDLIDL apo E mediated apo B mediated apo E mediated Adipose tissue Peripheral tissue (with LDL-C receptors) LPL HL LPL LDL-C receptors Remnant receptors FFA LDL-C

6 6 The Relationship Between Triglycerides and HDL-C  HDL-C concentrations depend on the metabolism of triglyceride-rich lipoproteins.  A rise in chylomicrons and VLDL allows increased translocation of cholesterol esters from HDL-C particles, decreasing the measured HDL-C level.  Elevated triglyceride levels thus help drive reduced levels of HDL-C.  This inverse relationship between triglycerides and HDL-C complicates analysis of their contributions to CAD risk. HDL-C=high-density lipoprotein cholesterol; VLDL=very low-density lipoprotein; CAD=coronary artery disease Patsch JR et al. Arterioscler Thromb. 1992;12:1336–1345.

7 7 NCEP III Factors Contributing to Elevated Triglycerides High Triglyceride Risk Factors Obesity/overweight Physical inactivity Cigarette smoking Excess alcohol intake High carbohydrate diet Type 2 diabetes, renal failure, underactive thyroid Certain drugs Genetic factors  Most often elevated in metabolic syndrome NCEP III=National Cholesterol Education Program Adult Treatment Panel III Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486–2497; De Backer G et al. Eur J Cardiovasc Prev Rehabil. 2003;10(suppl 1):S1–S78; Pejic RN et al. J Am Board Fam Med. 2006;19:310–316.

8 8 The Metabolic Syndrome a Risk FactorDefining Level Abdominal obesity (waist circumference) Men Women >102 cm (>40 in) >88 cm (>35 in) Triglycerides≥1.7 mmol/L (≥150 mg/dL) HDL-C Men Women <1.03 mmol/L (<40 mg/dL) <1.3 mmol/L (<50 mg/dL) Blood pressure≥130/85 mm Hg Fasting glucose≥6.1 mmol/L (≥110 mg/dL) Clinical Identification of the Metabolic Syndrome a Patients are diagnosed with the metabolic syndrome if they have 3 or more of these risk determinants HDL-C=high-density lipoprotein cholesterol from Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486– 2497; Adapted from De Backer G et al. Eur J Cardiovasc Prev Rehabil. 2003;10(suppl 1):S1–S78.

9 9 Triglycerides, Atherogenic Dyslipidemia, and the Metabolic Syndrome  Elevated serum triglycerides combined with low HDL-C is referred to as atherogenic dyslipidemia.  Atherogenic dyslipidemia often occurs with small, dense LDL-C particles and is also referred to as the “lipid triad.”  Clinically, atherogenic dyslipidemia is seen most often with the metabolic syndrome.  The metabolic syndrome is strongly associated with the development of type 2 diabetes and clinical CHD. HDL-C=high-density lipoprotein cholesterol; LDL-C=low-density lipoprotein cholesterol; CHD=coronary heart disease Szapary PO et al. Am Heart J. 2004;148:211–221.

10 10 Role of Triglycerides Triglycerides and CVD Risk

11 11 Triglyceride Levels as an Independent Risk Factor for CHD? StudyResults PROCAMHigh triglyceride levels predict major coronary events independent of HDL-C Copenhagen Male StudyHigh triglyceride levels predict major coronary events independent of HDL-C Lipid Research Clinics Follow-up Study Coronary mortality related to triglyceride levels, but not independent of HDL-C and LDL-C Helsinki Heart StudyThe effect of triglyceride levels on CHD is jointly influenced by LDL-C and HDL-C levels COLTS“Normal” triglyceride levels (1.1–2.2 mmol/L [100–199 mg/dL]) predict new cardiovascular events independent of HDL-C Framingham Heart StudyTriglycerides were a CHD risk factor only when HDL-C was1.03 mmol/L (  40 mg/dL) PROCAM=Prospective Cardiovascular Münster Study; HDL-C=high-density lipoprotein cholesterol; LDL-C=low-density lipoprotein cholesterol; COLTS= Baltimore Coronary Observational Long-Term Study; CHD=coronary heart disease To convert triglycerides from mg/dL to mmol/L, divide by 88.57 Assmann G et al. Am J Cardiol. 1996;77:1179–1184; Jeppesen J et al. Circulation. 1998;97:1029–1036; Criqui MH et al. N Engl J Med. 1993;328:1220–1225; Manninen V et al. Circulation. 1992;85:37–45; Miller M et al. J Am Coll Cardiol. 1998;31:1252–1257; Castelli WP. Am Heart J. 1986;112:432–437.

12 12 High Triglyceride Levels and CAD Risk in the Framingham Heart Study N=5127 people aged 30–62 years CAD=coronary artery disease Miller M. Am J Cardiol. 2000;86(suppl):23L–27L; Castelli WP. Can J Cardiol. 1988;4:5A–10A.

13 13 High Triglycerides and CHD Risk in Patients With Diabetes 10 40 30 20 0 mmol/L<1.511.51–2.60>2.60 Total Triglycerides P<0.001 CHD mortality All CHD events 7-Year Incidence of CHD in Type 2 Diabetes, % N=1059 CHD=coronary heart disease from Lehto S et al. Diabetes. 1997;46:1354–1359.

14 14 Triglycerides and CHD Risk: Meta-Analysis in Western Populations CHD=coronary heart disease; CI=confidence interval; EPIC=European Prospective Investigation of Cancer; APCSC=Asia Pacific Cohort Studies Collaboration from Sarwar N et al. Circulation. 2007;115:450–458.  This meta-analysis involves >260,000 participants and includes information from a total of >10,000 CHD cases

15 15 Cumulative Incidence of MI and IHD by Levels of Nonfasting Triglycerides a MI=myocardial infarction; IHD=ischemic heart disease. from Nordestgaard BG et al. JAMA. 2007;298:299–308. Age, y Cumulative Incidence, % Age, y Cumulative Incidence, % a Prospective cohort study of 13,981 individuals in Copenhagen followed from 1976 to 2004

16 16 Association of Fasting vs Nonfasting Triglyceride Levels With Future Cardiovascular Events a a Prospective study of 26,509 initially healthy women HR and 95% CI adjusted for age, blood pressure, smoking, hormone use, total cholesterol level, diabetes mellitus, BMI, and high-sensitivity C-reactive protein level, using triglyceride levels <1.7 mmol/L (<150 mg/dL), and HDL-C levels ≥1.3 mmol/L (≥50 mg/dL) as the reference group HDL-C=high-density lipoprotein cholesterol; HR=hazard ratio; CI=confidence interval; BMI=body mass index from Bansal S et al. JAMA. 2007;298:309–316. 0.51.010 HDL-C ≥1.3 mmol/L Triglycerides <1.7 mmol/L Triglycerides ≥1.7 mmol/L HDL-C <1.3 mmol/L Triglycerides <1.7 mmol/L Triglycerides ≥1.7 mmol/L FastingNonfasting Fully Adjusted HR (95% CI) 0.51.010

17 17 Summary  The metabolism of triglyceride-rich chylomicrons and VLDL lowers HDL-C, creating an inverse relationship between triglycerides and HDL-C.  Low HDL-C and high triglycerides commonly occur together in the metabolic syndrome.  Many studies have found triglyceride levels to be positively correlated with coronary events. The significance of this association may often be weakened by the influence of HDL ‑ C.  Nonfasting triglycerides may be an independent predictor of CVD and fasting triglycerides are not. VLDL=very low-density lipoprotein; HDL-C= high-density lipoprotein cholesterol; CVD=cardiovascular disease

18 18 Bibliography

19 19 Role of Triglycerides Before prescribing, please consult the manufacturers’ prescribing information. Merck does not recommend the use of any product in any different manner than as described in the prescribing information. Copyright © 2007 Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved. 12-08 M524A-2007-W-1245913-SS 02-10-CVT-2009-IT-2690-SS VISIT US ON THE WORLD WIDE WEB AT www.merck.com


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