Primary hypertriglyceridemia: Difference between revisions
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A lipid profile is usually done to diagnose the level of triglycerides in the blood. It is preferably diagnosed by estimating fasting triglyceride levels as compared to non-fasting levels.<ref name="pmid22962670">{{cite journal| author=Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH et al.| title=Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2012 | volume= 97 | issue= 9 | pages= 2969-89 | pmid=22962670 | doi=10.1210/jc.2011-3213 | pmc=3431581 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22962670 }} </ref> | A lipid profile is usually done to diagnose the level of triglycerides in the blood. It is preferably diagnosed by estimating fasting triglyceride levels as compared to non-fasting levels.<ref name="pmid22962670">{{cite journal| author=Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH et al.| title=Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2012 | volume= 97 | issue= 9 | pages= 2969-89 | pmid=22962670 | doi=10.1210/jc.2011-3213 | pmc=3431581 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22962670 }} </ref> | ||
==History and Symptoms== | ==History and Symptoms== | ||
The symptoms of hypertriglyceridemia can vary with respect to severity of the condition. These can include<ref name=" | The symptoms of hypertriglyceridemia can vary with respect to severity of the condition. These can include<ref name="pmid27678445">{{cite journal| author=Koopal C, Visseren FL, Marais AD, Westerink J, Spiering W| title=Tendon xanthomas: Not always familial hypercholesterolemia. | journal=J Clin Lipidol | year= 2016 | volume= 10 | issue= 5 | pages= 1262-5 | pmid=27678445 | doi=10.1016/j.jacl.2016.05.005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27678445 }} </ref><ref name="pmid18187065">{{cite journal| author=Leaf DA| title=Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. | journal=Am J Med | year= 2008 | volume= 121 | issue= 1 | pages= 10-2 | pmid=18187065 | doi=10.1016/j.amjmed.2007.10.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18187065 }} </ref> <ref name="pmid26796480">{{cite journal| author=Rachadi H, Ramli I, Touzani A, Hassam B, Ismaili N| title=[Spectacular presentation of tuberous xanthomas revealing a homozygous familial hypercholesterolemia]. | journal=Presse Med | year= 2016 | volume= 45 | issue= 2 | pages= 269-71 | pmid=26796480 | doi=10.1016/j.lpm.2015.09.027 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26796480 }} </ref> | ||
*Recurrent abdominal pain | *Recurrent abdominal pain | ||
*Creamy Appearance of the retina | *Creamy Appearance of the retina |
Revision as of 15:57, 7 November 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]
Overview
Primary hypertriglyceridemia, i.e. type 4 hyper lipidemia, is due to high concentration of triglycerides in the blood. It is also known as hypertriglyceridemia (or pure hypertriglyceridemia). According to the NCEP-ATPIII definition of high triglycerides (>200 mg/dl), prevalence is about 16% of the adult population.[1] Elevated levels of triglycerides can be detrimental for the normal cardiac functioning.[2]
Historical Perspective
- A study conducted in 1964 explained the post carbohydrate rise in triglycerides and the difference in the levels in patients with cirrhosis and metastasis.[3]
Classification
Hypertriglyceridemia can be classified in two ways
- As primary or secondary to another cause that can be obesity, diabetes type 2 or excessive alcohol consumption[4]
- Depending on the concentration [5] of triglyceride levels
- Normal <150 mg/dL
- Borderline-high triglycerides 150-199 mg/dL
- High triglycerides 200-499 mg/dL
- Very high triglycerides >500
Pathophisiology
Pathogenesis
Hypertriglyceridemia can occur through various mechanisms[6] that include
- Abnormal Very low density lipoprotein (VLDL) production in liver and synthesis of chylomicrons in the intestines
- Abnormal Lipoprotein lipase (LPL)-mediated lipolysis
- Abnornal remanant clearance
Genetics
Familial Hypertriglyceridemia has an autosomal dominant (AD) mode of inheritance.
Causes
- A diet high in carbohydrate content [7] [8]
- A diet high in fat content [9]
- Idiopathic
- Genetic causes (Autosomal Dominant)
- Obesity [4]
- Diabetes mellitus[4]
- Metabolic Syndrome [10]
- Paraproteinemic disorders
- Alcohol use [4]
- Estrogen therapy [9]
- Use of glucocorticoids [9]
- Medications like Zoloft, isotretinoin, some antihypertensive agents(e.g thiazides), tamoxifen [9]
- Nephrotic syndrome [11]
Differentiating Primary hypertriglyceridemia from Other Diseases
Primary hypertriglyceridemia differentiated from other hyperlipidemias.
- Familial Hyperchylomicronemia
- Familial hypercholesterolemia/familial combined hyperlipidemia
- Dysbetalipoprotenemia
- Mixed hyperlipoprotenemia
Different features can some times also have to be differentiated from similar conditions, e.g xanthomas[12] should be differentiated from
- Sitosterolemia
- Cerebrotendinous Xanthomatosis (CTX) - CYP27A1 recesive gene mutation
Epidemiology and Demographics
Type 4 hyperlipidemia i.e hypertriglyceridemia has a population prevalence of 5%–10%[4]
Risk Factors
Some of the risk factors include [4]
- Obesity
- Diabetes Melitis type 2
- Hypertension
Screening
There are no studies on benefits of screening on young adult population.[13] USPSTF guidelines for 2016 show no clear benefit for screening young adults.[14]
Natural History, Complications, and Prognosis
Complications
A large number of people in the US (approximately one fourth of the total population) have a high level of triglycerides (>150mg/dl) that can predispose and lead to numerous complications[15] including
- Cardiovascular diseases, particularly atherosclerosis of the coronary vessels.[16]
- Non Alcoholic Fatty Liver Disease (NAFLD)
- Pancreatitis caused by TG breakdown by pancreatic lipase and release of free fatty acids leading to production of free radicals[17]
Diagnosis
A lipid profile is usually done to diagnose the level of triglycerides in the blood. It is preferably diagnosed by estimating fasting triglyceride levels as compared to non-fasting levels.[2]
History and Symptoms
The symptoms of hypertriglyceridemia can vary with respect to severity of the condition. These can include[12][18] [19]
- Recurrent abdominal pain
- Creamy Appearance of the retina
- Eruptive xanthomas-yellow papules with erythemtous base demonstrating deposition of triglycerides in the cutaneous histiocytes, the majority of which are seen on the elbows and buttocks.
- Tendon xanthomas
- Tuberous xanthomas
Physical Examination
Severe hypertriglyceridemia can present[9]as
Laboratory Finding
The laboratory findings may include the following[9] [20]
Compenent | Effect |
---|---|
VLDL | Elevated |
Serum Triglycerides | Increased |
Glucose Tolerance | usually abnormal |
Carbohydrate Inducibility | usually abnormal |
Fat Intolerance | Normal |
Plasma appearance | Clear to cloudy |
Fasting Insulin levels | May be elevated
(Metabolic Syndrome) |
Blood indices | Pancytopenia and pseudo-Niemann
pick cells |
Imaging Findings
Biopsy
Treatment
Non Pharmacological
- The mainstay of therapy for hypertriglyceridemia includes lifestyle modifications to lower the triglyceride levels to below 150 mg/dl.
- A reduction of weight by 5-10 % can help decrease the triglyceride levels by 20%.[15]
- Other measures include reduction of fat content of food and high glycemic index foods.[21]
- Appropriate dietary changes and increase in aerobic activity can decrease triglyceride content in the body.
- Diet adjustment and weight loss can curtail the triglycerides by unto 25% [22]
- 4 grams daily of omega 3 fatty acids when taken along with these measures can also be helpful in reducing plasma levels by up to 20%.[23]
Medical Therapy
- If the triglyceride levels are excessively increased, control of blood levels can be achieved by various medical therapies varying according to the level of triglycerides found in the body.
- Moderate increase (i.e >500) can be treated by statins while severe increase that is >1000 or isolated hypertriglyceridemia needs to be treated by using a fibrate as the primary treatment.
- Extended release Niacin can be used in patients with low HDL and elevated triglyceride levels. [15][9]
Emerging treatment options
- Rimonabant a cannabinoid-1 (CB1) receptor antagonist works by decreasing appetite and consumption of food.[24] [25]
- Glitazar drugs have dual agonists on peroxisome proliferator-activated receptor-α (like fibrates) and -γ (like thiozolidinidiones).[26]
- LPL Gene Therapy can be helpful by treating monogenic LPL (lipoprotein lipase) deficiency[27].
Surgery
Prevention
Primary Prevention
The NCEP proposes dietary and behavioral measures to all Americans to reduce the burden of atherosclerosis.[28] [5][29] It devises two approaches
- Clinical approach includes provision of general advice and access to required resources to bring changes in lifestyle.
- Population based approach targets individual persons with changes meant to decrease individual risk of the person.
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) Final Report. Circulation 2002; 106; page 3240
- ↑ 2.0 2.1 Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH; et al. (2012). "Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 97 (9): 2969–89. doi:10.1210/jc.2011-3213. PMC 3431581. PMID 22962670.
- ↑ LEVERTON RM (1964). "CARBOHYDRATE INDUCED HYPERTRIGLYCERIDEMIA". Nutr Rev. 22: 328–30. PMID 14223171.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Yuan G, Al-Shali KZ, Hegele RA (2007). "Hypertriglyceridemia: its etiology, effects and treatment". CMAJ. 176 (8): 1113–20. doi:10.1503/cmaj.060963. PMC 1839776. PMID 17420495.
- ↑ 5.0 5.1 National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002). "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) final report". Circulation. 106 (25): 3143–421. PMID 12485966.
- ↑ Hassing HC, Surendran RP, Mooij HL, Stroes ES, Nieuwdorp M, Dallinga-Thie GM (2012). "Pathophysiology of hypertriglyceridemia". Biochim Biophys Acta. 1821 (5): 826–32. doi:10.1016/j.bbalip.2011.11.010. PMID 22179026.
- ↑ Silva ME, Pupo AA, Ursich MJ (1987). "Effects of a high-carbohydrate diet on blood glucose, insulin and triglyceride levels in normal and obese subjects and in obese subjects with impaired glucose tolerance". Braz J Med Biol Res. 20 (3–4): 339–50. PMID 3330460.
- ↑ McCarty MF (2004). "An elevation of triglycerides reflecting decreased triglyceride clearance may not be pathogenic -- relevance to high-carbohydrate diets". Med Hypotheses. 63 (6): 1065–73. doi:10.1016/j.mehy.2002.11.002. PMID 15504577.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Pejic RN, Lee DT (2006). "Hypertriglyceridemia". J Am Board Fam Med. 19 (3): 310–6. PMID 16672684.
- ↑ Ford ES, Giles WH, Dietz WH (2002). "Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey". JAMA. 287 (3): 356–9. PMID 11790215.
- ↑ Appel G (1991). "Lipid abnormalities in renal disease". Kidney Int. 39 (1): 169–83. PMID 2002630.
- ↑ 12.0 12.1 Koopal C, Visseren FL, Marais AD, Westerink J, Spiering W (2016). "Tendon xanthomas: Not always familial hypercholesterolemia". J Clin Lipidol. 10 (5): 1262–5. doi:10.1016/j.jacl.2016.05.005. PMID 27678445.
- ↑ Chou R, Dana T, Blazina I, Daeges M, Bougatsos C, Jeanne TL (2016). "Screening for Dyslipidemia in Younger Adults: A Systematic Review for the U.S. Preventive Services Task Force". Ann Intern Med. 165 (8): 560–564. doi:10.7326/M16-0946. PMID 27538032.
- ↑ US Preventive Services Task Force. Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW; et al. (2016). "Screening for Lipid Disorders in Children and Adolescents: US Preventive Services Task Force Recommendation Statement". JAMA. 316 (6): 625–33. doi:10.1001/jama.2016.9852. PMID 27532917.
- ↑ 15.0 15.1 15.2 Kushner PA, Cobble ME (2016). "Hypertriglyceridemia: the importance of identifying patients at risk". Postgrad Med. doi:10.1080/00325481.2016.1243005. PMID 27710158.
- ↑ Thompson WG, Gau GT (2009). "Hypertriglyceridemia and its pharmacologic treatment among US adults--invited commentary". Arch Intern Med. 169 (6): 578–9. doi:10.1001/archinternmed.2008.594. PMID 19307520.
- ↑ Tsuang W, Navaneethan U, Ruiz L, Palascak JB, Gelrud A (2009). "Hypertriglyceridemic pancreatitis: presentation and management". Am J Gastroenterol. 104 (4): 984–91. doi:10.1038/ajg.2009.27. PMID 19293788.
- ↑ Leaf DA (2008). "Chylomicronemia and the chylomicronemia syndrome: a practical approach to management". Am J Med. 121 (1): 10–2. doi:10.1016/j.amjmed.2007.10.004. PMID 18187065.
- ↑ Rachadi H, Ramli I, Touzani A, Hassam B, Ismaili N (2016). "[Spectacular presentation of tuberous xanthomas revealing a homozygous familial hypercholesterolemia]". Presse Med. 45 (2): 269–71. doi:10.1016/j.lpm.2015.09.027. PMID 26796480.
- ↑ Sandoval-Sus JD, Zhang L (2016). "Familial hypertriglyceridemia manifests with pancytopenia and bone marrow pseudo–Niemann-Pick cells". Blood. 127 (6): 787. PMID 27453965.
- ↑ Jenkins DJ, Kendall CW, Augustin LS, Franceschi S, Hamidi M, Marchie A; et al. (2002). "Glycemic index: overview of implications in health and disease". Am J Clin Nutr. 76 (1): 266S–73S. PMID 12081850.
- ↑ Gerhard GT, Ahmann A, Meeuws K, McMurry MP, Duell PB, Connor WE (2004). "Effects of a low-fat diet compared with those of a high-monounsaturated fat diet on body weight, plasma lipids and lipoproteins, and glycemic control in type 2 diabetes". Am J Clin Nutr. 80 (3): 668–73. PMID 15321807.
- ↑ Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ; et al. (2006). "Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review". BMJ. 332 (7544): 752–60. doi:10.1136/bmj.38755.366331.2F. PMC 1420708. PMID 16565093.
- ↑ Boyd ST, Fremming BA (2005). "Rimonabant--a selective CB1 antagonist". Ann Pharmacother. 39 (4): 684–90. doi:10.1345/aph.1E499. PMID 15755787.
- ↑ Gelfand EV, Cannon CP (2006). "Rimonabant: a cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors". J Am Coll Cardiol. 47 (10): 1919–26. doi:10.1016/j.jacc.2005.12.067. PMID 16697306.
- ↑ Nissen SE, Wolski K, Topol EJ (2005). "Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus". JAMA. 294 (20): 2581–6. doi:10.1001/jama.294.20.joc50147. PMID 16239637.
- ↑ Rip J, Nierman MC, Sierts JA, Petersen W, Van den Oever K, Van Raalte D; et al. (2005). "Gene therapy for lipoprotein lipase deficiency: working toward clinical application". Hum Gene Ther. 16 (11): 1276–86. doi:10.1089/hum.2005.16.1276. PMID 16259561.
- ↑ "Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II)". JAMA. 269 (23): 3015–23. 1993. PMID 8501844.
- ↑ Carleton RA, Dwyer J, Finberg L, Flora J, Goodman DS, Grundy SM; et al. (1991). "Report of the Expert Panel on Population Strategies for Blood Cholesterol Reduction. A statement from the National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health". Circulation. 83 (6): 2154–232. PMID 2040066.