Managing Hypertriglyceridemia in Daily Practice - Acta Medica

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CLINICAL PRACTICE

Managing Hypertriglyceridemia in Daily Practice Laurentius A. Pramono, Dante S. Harbuwono Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia Correspondence mail: Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo. Jl. Diponegoro no. 71, Jakarta 10430, Indonesia. email: [email protected], [email protected] ABSTRAK Hipertrigliseridemia merupakan salah satu jenis dislipidemia yang umumnya terjadi bersamaan dengan hiperkolesterolemia, kadar kolesterol LDL tinggi, atau kadar kolesterol HDL rendah. Sebagian besar penelitian menyebutkan bahwa hipertrigliseridemia berhubungan dengan berbagai kelainan metabolik, antara lain sindrom metabolik, diabetes, obesitas, dan penyakit kardio-serebrovaskular. Terapi terhadap hipertrigliseridemia seringkali tidak diberikan secara komprehensif oleh dokter yang hanya memberikan obat tanpa edukasi terhadap aktivitas fisik, diet sehat bagi pasien dislipidemia, dan penghentian merokok. Tinjauan ini mendiskusikan evaluasi, diagnosis, dan manajemen hipertrigliseridemia secara komprehensif, namun sederhana, yang dapat diaplikasikan sebagai panduan dalam praktek klinis sehari-hari. Kata kunci: hipertrigliseridemia, dislipidemia, manajemen, panduan klinis ABSTRACT Hypertriglyceridemia is a form of dyslipidemia, which usually occurs in combination with hypercholesterolemia, high-LDL or low-HDL cholesterol level. Most studies suggest that hypertriglyceridemia is associated with many metabolic disorders such as metabolic syndrome, diabetes, obesity, and also cardio-cerebrovascular diseases. Treatment of hypertriglyceridemia is often not comprehensively addressed by many physicians, who usually only include prescribing drugs without encouraging patients to perform physical activity, to take a true healthy diet for dyslipidemia and to stop smoking. This review article discusses evaluation, diagnosis and a comprehensive, yet simple management of hypertriglyceridemia, which can be easily applied in daily clinical practice. Key words: hypertriglyceridemia, dyslipidemia, management, clinical guidelines.

INTRODUCTION

Hypertriglyceridemia, a common form of dyslipidemia, is often stated as an independent risk factor for cardiovascular disease;1,2 however, several studies are still debating this statement.1,3 Almost all epidemiologic studies suggest that hypertriglyceridemia is associated with metabolic syndrome, diabetes, obesity, and coronary artery disease; while some clinical studies demonstrate that lowering triglyceride level can reduce the

risk of coronary artery disease.1,2,4-6 It is clear that hypertriglyceridemia is strongly associated with atherosclerosis.5,7,8 Hypertriglyceridemia is also associated with increased risk of acute pancreatitis.8-10 Nowadays, triglyceride level has become one of target biomarkers, which should be reduced in many patients at daily clinical practice. Several consensus recommend an optimal triglyceride level of less than 150 mg/dL.4-6 A

Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine

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report demonstrated that the mean triglyceride level among US population was 114 mg/ dL between 1976 and 1980. It was 116 mg/ dL in 1988-1994 and became 122 mg/dL in 1999-2002.3 A study conducted by Ford ES et al.3 showed that the unadjusted prevalence of triglyceride level of ≥150 mg/dL was 33.1%. The prevalence was 17.1% for triglyceride level of ≥200 mg/dL, 1.7% for triglyceride level of ≥500 mg/dL and 0.4% for triglyceride level of ≥1000 mg/dL. In conclusion, we can say that the prevalence of hypertriglyceridemia remains high in Western population. Very few studies have been done in Indonesian population. Kamso S et al.11 studied groups of executive workers in Jakarta and they found that the mean triglyceride levels in executive workers who had metabolic syndrome was 210.29 mg/dL; while in those without metabolic syndrome, the triglyceride level was 145.06 mg/dL. Another study has also been conducted in Indonesia. It was performed in Padang City, West Sumatera with a population, which is famous for its high cholesterol diet. The prevalence of hypertriglyceridemia (with cut off point of 200 mg/dL) in that particular population was 6.9% in elderly men and 5.7% in elderly women.12 Further study has also been done in Purwokerto, Central Java, which found that the mean triglyceride level in women with metabolic syndrome is 218.13 mg/dL.13 Those studies indicate that hypertriglyceridemia also affects populations of many cities in Indonesia. Hypertriglyceridemia is found more prominent in patients with type-2 diabetes.14,15 Soebardi S et al.15 found that the prevalence of hypertrigliseridemia was 54.3% in patients with newly diagnosed diabetes. Furthermore, the mean triglyceride level in subjects with normal glucose tolerance, newly diagnosed diabetes and those with diabetes were 124.5 mg/dL, 186.3 mg/ dL and 169.9 mg/dL, respectively.15 Untreated diabetes group, which was represented by newly diagnosed diabetes patient group, showed the highest triglyceride level. The high triglyceride level was improved following diabetes treatment, which suggests that providing diabetes treatment may have great contribution to improve lipid profiles.14,15

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Hypertriglyceridemia must be assessed completely, especially by history taking of other cardiovascular risks, physical examination, and laboratory data on lipid profiles.1 There are some criteria and consensus of triglyceride level for establishing the diagnosis of hypertriglyceridemia.4-6 Several management and treatment choices for hypertriglyceridemia can be seen in many reviews and guidelines. For severe cases, plasmapheresis can be an option. 10 Our review article emphasizes on the management of hypertriglyceridemia in daily practice based on several guidelines. Since there are many options of medication and non-pharmacological treatment in treating hypertriglyceridemia, it can be expected that physician not only treating hypertriglyceridemia with statin; but more options can be suggested for the patients. EVALUATION

The evaluation of hypertriglyceridemia always starts with an interview about family history of dyslipidemia and premature coronary artery disease,1,6 as well as secondary causes of hypertriglyceridemia such as untreated diabetes, other lipid metabolism disorders, drugs that can alter lipid metabolism, alcohol consumption, pregnancy, and renal disease.2,8 Brunzell JD2 stated that the presence of premature coronary artery disease in parents or sibling indicates familial combined hyperlipidemia or familial hypoalphalipoproteinemia. Special medications must be considered in this situation. Unfortunately, for patients with low to moderate socio-economic level, which are the majority in Indonesian population, family history are difficult to be obtained by physicians. Physician should ask patients about their past cardiovascular and medical history, prior medical tests or examinations, which have been performed earlier (electrocardiogram, echocardiography, treadmill test), their physical activity (frequency, duration, and type of sport or physical activity), diet profile, smoking habit, and simple anthropometry profile, which can be measured by the patients themselves. It seems that dyslipidemia patients also usually take over the counter (OTC) medicines

Vol 47 • Number 3 • July 2015

or traditional herbs to lower their cholesterol level or take medications from other physician or perform self-medication (buying medicine illegally in drug stores or drug markets). It is also important to ask their previous lipid profile found in their past laboratory data; they probably can remember the number of their cholesterol, LDL cholesterol, or triglyceride levels. Physical examinations that should be concerned in patients with dyslipidemia, diabetes, metabolic syndrome and risk factors for cardiovascular disease include blood pressure, body mass index (BMI) calculation (patient’s height and weight), and waist circumference.2 Large waist circumference, in Western population 101.6 cm for men and 88.9 cm for women;2 while in Indonesian population, we found 88 cm for men and 86 cm for women.16 The waist circumference may help the doctors to distinguish familial hypertriglyceridemia from familial combined hyperlipidemia or familial hypoalphalipoproteinemia.2 Lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride) are the most important laboratory data and other metabolic parameters must also be tested including fasting blood glucose level, 2 hours post-prandial blood glucose level, and kidney function (ureum and creatinin level).2,6 Apolipoprotein B is associated with metabolic syndrome; however, the use is still restricted for specific situation.2,17 Measurement of apolipoprotein B level may help doctors to estimate the total number of LDL particles (large and small). Elevated level is found in familial combined hyperlipidemia and lower level indicates familial hypertriglyceridemia. It is well-known that apolipoprotein B level provides better prediction for evaluating cardiovascular risk than non-HDL cholesterol.2 Other specific lipid parameters such as lipoprotein (a) and apolipoprotein A-I still have not been popular as laboratory tests for daily practice. Table 1 shows key points for evaluation of hypertriglyceridemia using history taking, physical examination, and other examinations. Lipid profile tests requires patients to fast in order to demonstrate the true endogenous triglyceride level.5,6 Indonesian Society for

Managing hypertriglyceridemia in daily practice Table 1. Key points for history taking, physical examination, and other examinations History taking Family history of dyslipidemia Family history of coronary artery disease History of diabetes, disorders of lipid metabolism Renal and liver disease Pregnancy Symptoms of angina Symptoms of peripheral artery disease Symptoms of pancreatitis Alcohol consumption Cigarrette smoking Physical activity Diet profile Medication history Physical examination Not specific Blood pressure Body mass index Waist circumference Other examinations Lipid profile (total cholesterol, LDL-C, HDL-C, triglyceride) Blood glucose and HbA1c Thyroid function tests (for suspected hypothyroidism) Renal function Liver function Electrocardiogram

Endocrinologists Concensus of Dyslipidemia recommends that patients who undergo lipid profiles examination to ideally fast 12-16 hours before blood withdrawal. 6 Nowdays, many clinical laboratory use direct LDL cholesterol examination, and if it is not possible, Friedwald calculation can be used only if the triglyceride level is less than 400 mg/dL.6 However, this calculation can still be used in many areas in Indonesia since there is still lack of lipid profiles examinations in many rural and suburban hospitals (district II hospitals) nowadays. Friedwald calculation: LDL cholesterol = Total cholesterol – HDL cholesterol – Triglyceride/5

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Acta Med Indones-Indones J Intern Med

or low level of HDL cholesterol, is called dyslipidemia or hyperlipidemia. In fact, the term ‘hyperlipidemia’ is not suitable for low-HDLcholesterol dyslipidemia type, which is should be simply known as the low-HDL. However, the terminology is a general diagnosis, which can be used for treatment in general and also for the purpose of education and socialization in the society. All types of dyslipidemia including hypertriglyceridemia must be categorized into primary and secondary dyslipidemia.6,8 Primary dyslipidemia is a term to point out the lipid disturbances caused by genetic factors, such as familial primary hypertriglyceridemia, remnant dyslipidemia, and familial hypercholesterolemia. In contrast, secondary dyslipidemia is caused by many other conditions such as hypothyroidism, nephrotic syndrome, diabetes mellitus, metabolic syndrome, and drugs like steroids, hormones, and beta-blockers.6,8

DIAGNOSIS

There are only several consensus have firmly defined the cut-off value for ‘hyper’ or high triglyceride level and one of them is the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), which recommends four categories for triglyceride level, i.e. optimal level is defined when triglyceride level is less than 150 mg/dL; while the level is 150-199 mg/dL, it is called borderline high. Triglyceride level between 200 and 499 mg/dL is called high level and when the level reaches more than (≥500 mg/dL), it is called very high level.4-6 Many physicians, including Indonesian physicians, and also clinical laboratories, use 150 mg/dL as the cut-off point for triglyceride level. 6 Small differences are described by Endocrine Society in 2010 which classifies hypertriglyceridemia as moderate, severe, and very severe hypertriglyceridemia.4 Table 2 shows the differences between NCEP ATP III and Endocrine Society classification for hypertriglyceridemia. Actually, for clinical application, aggressive LDL cholesterol lowering is more beneficial to reduce cardiovascular risk. 4,6 Treatment of LDL cholesterol with statins will also reduce triglyceride level further. For diabetic hypertriglyceridemia, the triglyceride level is considered high when the level is more than 150 mg/dL.14 Mild to moderate hypertriglyceridemia has a range of 150-499 mg/dL, while severe hypertriglyceridemia has a cut off point ≥500 mg/dL.14 Hypertriglyceridemia, either alone or in combination with hypercholesterolemia

MANAGEMENT

Before starting treatment for patients with dyslipidemia or hypertriglyceridemia, physician must always perform risk stratification of cardiovascular events that their patients about to have.6 The treatment target should follow the risk assessment. NCEP ATP III suggests that there are five risk factors for coronary heart disease, which must be assessed including cigarette smoking, hypertension (blood pressure above 140/90 mmHg, or those who are having anti-hypertensive medication), HDL cholesterol of less than 40 mg/dL, history of premature coronary heart disease (father
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Managing Hypertriglyceridemia in Daily Practice - Acta Medica

CLINICAL PRACTICE Managing Hypertriglyceridemia in Daily Practice Laurentius A. Pramono, Dante S. Harbuwono Department of Internal Medicine, Faculty ...

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