Inter. J. of Pharmacotherapy / 4(1), 2014, 32-35.

International Journal of Pharmacotherapy

www.ijopjournal.com ISSN Print ISSN 2249 - 7765 2249 - 7773

HYPERTRIGLYCERIDEMIA: WHAT IS IT AND HOW IT IS MANAGED- A REVIEW

Atta Abbas
Department of Pharmacy, Health and Well Being, University of Sunderland, England, United Kingdom.

ABSTRACT Hypertriglyceridemia is a condition in which the triglycerides are raised in the blood and the disease is often seen associated with diabetes mellitus, a disease more common in developed countries. It is one type of dyslipidemia; there are several other types too. Different guidelines around the world define hypertriglyceridemia with reference to the levels of triglycerides in the blood. The diagnosis of hypertriglyceridemia must be taken into special consideration in order to understand the underlying secondary disease i.e. diabetes mellitus if present and its particular type. The lab analysis of serum or plasma is helpful in that case. The disease can be managed on the basis of the extent to which the levels of TG are raised in the body. A review of different approaches to treat the disease is the objective of the article. Key words: Hypertriglyceridemia, Triglycerides, Diabetes Mellitus.

INTRODUCTION Hypertriglyceridemia is a state in which the triglyceride levels are raised in the blood. It is often resulted and aggravated by uncontrolled diabetes mellitus, life style and obesity, which are more common in civilized societies than in developing countries and it as a risk factor for coronary artery disease [1]. Fredrickson classification of the disease is as under. In this system, all types are hTG except type IIa[5]. Type I is very uncommon condition which is marked by highly incremented levels of triglycerides and topping higher than 1000 milligram per deciliter [1]. Type IIb is resulted by rise in lipoproteins which have low density (LDL) and lipoprotein of much more lower density (VLDL) [2], and it is the characteristic assorted hyperlipidemia i.e. high cholesterol and triglyceride levels. Type III is a condition in which the patients total cholesterol and triglyceride is high. The state is also called dysbeta-lipoproteinemia. The patients of type III hypertriglyceridemia are mixed without doubt with their counterparts with phenotype IIb. Increase in intermediate

density lipoprotein (IDL) levels is seen in the patients with phenotype III. Phenotype IV can be easily distinguished by unusual increment in level of very low density lipoproteins (VLDL), and triglyceride levels are always in a smaller amount i.e. <1000 mg/dL. However, the cholesterol in serum is normal [2]. In phenotype V, chylomicrons and very low density lipoproteins (VLDL) are elevated. The level of triglyceride is always >1000 mg/dL, and the total cholesterol echelon at all times is steeped. The level of low density lipoproteins (LDL) cholesterol is less most of time. Considering uncommonness of the phenotype type I of the disease, when the level of triglyceride is noted to be >1000 mg/dL, there is a possibility of phenotype V[1]. There is a risk of acute pancreatitis incase the level of triglyceride is augmented to >1000 mg/dL [2] and because triglycerides are so labile, the initial target of the therapy should be around 500 mg/dL or more than that. The National Cholesterol Education Program[6] (NCEP) defines hypertriglyceridemia as triglycerides with levels 150mg/dl as or higher than that [2]. The incidence Email: bg33bd@student.sunderland.ac.uk

Corresponding Author:-Atta Abbas

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of the disease occurring in patients aging more than twenty years both male and female was in the region of 35% and 25% respectively [2,6]. Elaborated as follows: National Cholesterol Education Program [6] (NCEP) defines stern hypertriglyceridemia as the triglycerides >2000 mg/dL [2,6] and it is predictable to be 1.8 cases in 10,000 [2] in white adolescents, with high incidence in those having history of alcohol intake or diabetes mellitus. The deficiency of lipoprotein lipase occurs in the region of 1 case in a million; apo C-II deficiency occurrence is even lower [2,8]. In context of the whole world, the prevalence of the deficiency of lipoprotein lipase is identical to the USA[1]. The apo C-II deficiency is rare in all populations which have been studied till now. Triglycerides are relatively lower in Blacks than in Whites [2]. An observational study was conducted known as Prospective cardiovascular Munster study which found out that mild hypertriglyceridemia i.e. TG levels of greater than 200mg/dL is more common in the males which accounts for 18.6% as compared to females which is just 4.2%. The levels of triglycerides normally increase till age of 40years in males and then tapper down to some extent. However, in females it continues to top up along with the age. Lipoprotein lipase and apo C-II mutations of genetic origin occur in equal number in both sexes and they are normally detected in young age. However, the ailment may exhibit in adulthood also. Furthermore, mild hypertriglyceridemia i.e. TG levels greater than 150mg/dL has slightly more incidence of occurring in males aging 30 years and in females of age 60 years [1-2]. The symptoms of hypertriglyceridemia are typically whitening of retina (lipemia retinalis) and dermatological problems such as skin lumps (lipid xanthomas), they are mostly present on the chest, back, proximal extremities and buttocks. They are as a result of the buildup of chylomicrons inside macrophages and fade away slowly when the TG levels are maintained to less than 1000 mg/dL [1]. Other symptoms include abdominal pain, memory loss, dementia and depression to a lesser part. The diagnosis of hypertriglyceridemia is thought out when TG levels recorded to be elevated [2]. The most important thing is to check fasting blood sugar to eliminate the most common cause i.e. uncontrolled diabetes. Also the eating habits and carbohydrate-rich diet can lead to hypertriglyceridemia [2] and should be determined. The lab examination of the serum or plasma after a ten to twelve hour fast can also determine the level of triglycerides and confirm its diagnosis but to determine which lipoprotein is the cause of the disease is not so easy [1,2]. Klinicheskaia Meditsina [4] in 2012 also highlighted the diagnostic significance of different apolipoprotein levels during hypertriglyceridemia. The basic diagnosis route is explained by the following chart:

On the other hand, distinguishing between these entities is not so compulsory since the treatment is similar for both [1-2]. The target for patients having high levels of triglycerides are; For patients having triglycerides levels ranging from 150199 mg/dL, the levels of VLDL are not increased enough to call for a non-HDL cholesterol aim but on the other hand, patients with triglyceride level topping 200499 mg/dL with 0 or 1 CAD coronary artery disease risk which is quiet low risk factor or greater than or equal to 2 which is an average CAD risk, the aim for non-HDL cholesterol is less than 190 mg/dL for 0 and 1, and <160 mg/dL, in that order [6]. The involvement of therapeutic lifestyle changes (TLC) is intended to promote loss of weight and it is done by decreasing the dietary saturated fats intake i.e. less than 7% calories in total, less than 200 mg/day of cholesterol intake and exercise. It is supposed to be a integral component of the plan to manage the patients having high levels of triglyceride and is a primary option for patients having marginal levels of triglycerides ranging from 150 to 199 mg/dL. Patients having little and normal risk for coronary artery disease with a topping level of triglycerides i.e. 200 to 499 mg/dL, the prime or 1 st line medications therapy can be started if intended non-HDL cholesterol target is not fulfilled in a span of 12 to 24 weeks of undergoing the TLC program [3,6]. Furthermore, the need to start medications straight away in patients at an elevated danger of coronary artery disease with triglycerides <500 mg/dL. Increased cholesterol levels (non-HDL) in patients having triglycerides levels ranging 200-499 mg/dL are characteristically the outcome of both major LDL cholesterol or triglyceride elevations. As of this point of view, the first preference of drugs in the afore said patients depends upon the prime source of cholesterol (non-HDL) increase, which is either triglyceride or LDL to take full advantage of the potential of non-HDL cholesterollowering effect [6]. Patients having very high triglycerides i.e. greater than or equal to500 mg/dL, the 1st line drugs comprise of fibrates and/or n-3 PUFAs to be started without delay. Even though the best target is to decrease triglycerides to <150 mg/dL which is normally unrealistic. The goal which seems to be reasonable is to lower down and sustain the triglyceride levels in fasting to <500 mg/dL to trim down the possibility of acute pancreatitis [6]. Patients who are diagnosed with chylomicronemia having TG levels >1000 mg/dL and abdominal pain must be taken as an emergency because there is a fear of acute pancreatitis [6]. The primary aim of treating chylomicronemia is most excellently done in a healthcare setting [6]. The disease management with regard to the increase in triglycerides levels which is as under [3].

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Table 1. Classification of hyperlipoproteinemia Type Serum Elevation Lipoprotein Elevation I Cholesterol & triglycerides Chylomicrons IIa Cholesterol LDL IIb Cholesterol & triglycerides LDL, VLDL & remnants III Cholesterol & triglycerides IDL IV Triglycerides VLDL V Cholesterol & triglycerides VLDL, Chylomicrons[1,2] Where, VLDL refers to very low density lipoproteins IDL refers to intermediate density lipoproteins LDL refers to low density lipoproteins Table 2. Incidence of hypertriglyceridemia in different segments of the American population Triglyceride Levels S.No Ethnicity Male Female African American 21% 14% 1 Mexican American 40% 35% 2 White American 37% 25% 3 Table 3. Diagnosis of hypertriglyceridemia S.No Condition 1 TG elevated but below 1000mg/dL TG elevated but less than 1000mg/dL, Total 2 Cholesterol elevated [2] Type IIb or Type III 3 4 Type III

i) ii)

Inference Increased VLDL Type IIb Type III hyperlipidemia (Distinguished by direct LDL-c analysis or beta quantification from lab) If direct LDL-c is significantly lower than calculated LDL-c[2]

Table 4. Disease management of hypertriglyceridemia S.No TG Levels Actions &Comments 1 Less than 177.14792 mg/dl (2mmol/L) Continue current management Reassess lipid profile regularly 2 Greater than 177.14792 mg/dl (2mmol/L) 1. Therapeutic life style measures but less than 442.8698 mg/dl (5mmol/L) Weight control Increase physical activity Reduce dietary fat, alcohol intake, sugars Reassess lipid profile regularly 2. Manage other secondary factors Control glycemia (if diabetic) Reassess medications 3. Consider Pharmacologic treatment Statin therapy Omega 3 (fish oil) Niacin 3 Greater than 442.8698 mg/dl (5mmol/L) but 4. Intensify steps 1-3 above less than 885.73959 mg/dl (10mmol/L) Apolipoprotein B determination might be helpful 5. Consider fibrate therapy Benzafibrate 400mg/d Fenofibrate 145mg/d, 160mg/d or 200mg/d Gemfibrozil 600-1200mg/d 4 Greater than 885.73959 mg/dl (10mmol/L)6. Further intensify steps 1-3 above With acute pancreatitis

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Very low fat diet Alcohol cessation Insulin for diabetes Admit to hospital IV administration (fluid replacement) 7. Initiate fibrate therapy Monitor serum creatinine 8. Consider specialist referral consideration in order to understand the underlying secondary disease i.e. diabetes mellitus if present and its particular type. The lab analysis of serum or plasma is helpful in that case. The disease can be managed on the basis of the extent to which the levels of TG are raised in the body. Research is going on various aspects associated with the disease which might one day become helpful in managing it more effectively.

CONCLUSION In conclusion, it is very essential to understand the complexities of hypertriglyceridemia, its epidemiology, types, symptoms and its association with uncontrolled diabetes. The symptoms of hypertriglyceridemia are mainly dermatological and can be easily seen on the skin. Moreover, the diagnosis of hypertriglyceridemia must be taken into special

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