Hypertriglyceridemia – Causes, Symptoms, Treatment

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Hypertriglyceridemia (HTG) increases the total amound of  triglyceride in the blood that are associated with an increased risk of cardiovascular disease and pancreatitis, obesity. A severe elevation of triglycerides (TG) increases the risk for pancreatitis and requires lowering by lifestyle change and pharmacotherapy. Although statin therapy targeting low-density cholesterol (LDL-C) has improved atherosclerotic cardiovascular disease (ASCVD) outcomes, residual risk remains..   

The triglycerides found in our bloodstream are a mixture of triglycerides that have been obtained from the diet and those produced in the body to provide an energy source. Hypertriglyceridemia is often caused or worsened by factors such as obesity, poorly controlled diabetes and a sedentary lifestyle.

Hypertriglyceridemia denotes high (hyper-) blood levels (-emia) of triglycerides, the most abundant fatty molecule in most organisms. Elevated levels of triglycerides are associated with atherosclerosis, even in the absence of hypercholesterolemia (high cholesterol levels), and predispose to cardiovascular disease.

Types of Hypertriglyceridemia

Hypertriglyceridemia is a disorder with high levels of triglycerides in the blood. Five main disorders result in hypertriglyceridemia

  • Familial hypertriglyceridemia – An autosomal dominant disorder that results in elevated VLDL levels in plasma
  • Familial combined hyperlipidemia –¬† An autosomal dominant disorder, characterized by the excessive synthesis of lipoproteins containing apolipoprotein B
  • Congenital lipoprotein lipase deficiency – An autosomal recessive disorder, which results in low to no lipoprotein lipase activity; typically, chylomicrons build up in the blood and eruptive xanthomas develop
  • Apoprotein CII deficiency – An autosomal recessive disorder, characterized by the lack of apoprotein CII, an essential cofactor for lipoprotein lipase activity; there is usually chylomicron and VLDL accumulation in the plasma
  • Familial dysbetalipoproteinemia – A disorder in which there is a defect in apolipoprotein E; due to the buildup of remnant VLDL particles in the blood, there are higher plasma levels of cholesterol and triglyceride

Causes of Hypertriglyceridemia

  • Unknown Cause – Hypertriglyceridemia is usually multifactorial. A combination of genetic factors, increased production, and or impaired clearance of triglyceride-rich lipoproteins (TRLP) are known to play a role in hypertriglyceridemia.
  • Genetic causes – include syndromes that present primarily with HTG (common) or chylomicronemia (rare). Familial hypertriglyceridemia (excess Very Low-Density Lipoprotein but normal cholesterol) and Familial combined hyperlipidemia (polymorphisms of apolipoprotein C-II (apoC-II), apolipoprotein C-III (apoC-III), etc.) present predominantly with HTG. ¬†Lipoprotein lipase deficiency, Apolipoprotein C-II deficiency, Apolipoprotein AV deficiency, and dysbetalipoproteinemia are examples of genetic syndromes that present with chylomicronemia.¬†
  • Secondary causes – of HTG include certain medical conditions, drugs, and dietary causes. Obesity, metabolic syndrome, Diabetes mellitus type 2, hypothyroidism, Cushing’s syndrome, chronic kidney disease, Human Immunodeficiency virus, pregnancy, and some autoimmune conditions such as systemic lupus erythematosus have been associated with HTG. ¬†Medications that cause HTG include thiazides, beta-blockers, oral estrogens, tamoxifen, OCPs, anti-retroviral protease inhibitors, atypical antipsychotics, isotretinoin, corticosteroids, bile acid-binding resins, and immunosuppressive agents such as sirolimus.¬†¬†Dietary causes of HTG include excessive alcohol intake and foods rich in saturated fat or with a high glycemic index.¬†
  • Obesity, metabolic syndrome, diabetes – People with excess visceral adipose tissue often have elevated triglycerides and low HDL-C levels. About 80% of men with a waist girth of 90 cm or more and a plasma triglyceride level of 2 mmol/L or more typically have a metabolic triad of nontraditional cardiovascular-disease markers: hyperinsulinemia and increased levels of apo B and small, dense LDL particles. This triad can increase the risk of cardiovascular disease by up to 20 times.[rx]
  • Alcohol – Hypertriglyceridemia associated with alcohol intake also mainly results from increased plasma VLDL, with or without chylomicronemia. In some alcohol users, plasma triglyceride measurements can remain within the normal range because of an adaptive increase in lipolytic activity. However, alcohol can also impair lipolysis, especially when a patient has a pre-existing functional deficiency of lipoprotein lipase, which leads to markedly increased plasma triglycerides.
  • Renal disease¬†Although elevated LDL-C is the dominant abnormality, nephrotic syndrome is also characterized by increases in apo B‚Äďcontaining lipoproteins, including VLDL. The complex relation between renal disease and lipoprotein metabolism is reviewed in depth elsewhere,[rx] but the underlying mechanisms probably include overproduction by the liver, which concurrently increases albumin synthesis to compensate for renal protein wasting. Uremia is associated with elevated VLDL, which reflects impaired lipolysis, possibly from the toxic effect of uremic metabolites.
  • Pregnancy –¬†During the third trimester of pregnancy, plasma triglyceride levels normally rise to as much as threefold,[rx] but this physiologic triglyceride increase has little clinical consequence. Marked triglyceride increases also result, however, when lipoprotein lipase activity is compromised. Although chylomicronemia during pregnancy is very rare, it can be complicated by pancreatitis, which can be fatal to both mother and fetus.[rx]
  • Nonalcoholic fatty-liver disorder – This disorder may affect up to one-third of North Americans, which reflects the increasing prevalence of obesity, insulin resistance and metabolic syndrome.[rx,rx] Among affected patients, up to one-third may also have nonalcoholic steatotic hepatitis.[rx,rx]
  • Other medical conditions Although hypothyroidism is usually associated with elevated LDL concentrations, triglycerides may also be elevated. Paraproteinemias (e.g., hypergammaglobulinemia in macroglobulinemia, myeloma, lymphoma, and lymphocytic leukemias) and autoimmune disorders (e.g., systemic lupus erythematosus) can also cause hypertriglyceridemia, probably through immune-mediated interference of lipolysis.
  • Medications –¬†Many drugs increase triglyceride concentrations. If one is considered to cause hypertriglyceridemia, the indications for that medication should be reviewed. If dosage reductions, changes in the route of administration, or substitution with another class of medication are not practical, then marked elevations of triglycerides should be treated with diet or pharmacologic agents.
  • Overeating
  • Obesity
  • Diabetes mellitus¬†and¬†insulin resistance¬†– it is one of the defined components of¬†metabolic syndrome¬†(along with¬†central obesity,¬†hypertension, and¬†hyperglycemia)
  • Excess¬†alcohol consumption
  • Kidney failure,¬†nephrotic syndrome
  • Genetic predisposition; some forms of familial¬†hyperlipidemia¬†such as familial¬†combined hyperlipidemia¬†i.e. Type II hyperlipidemia
  • Lipoprotein lipase deficiency¬†– Deficiency of this water-soluble¬†enzyme, that hydrolyzes¬†triglycerides¬†in¬†lipoproteins, leads to elevated levels of triglycerides in the blood.
  • Lysosomal acid lipase deficiency¬†or¬†Cholesteryl ester storage disease
  • Certain medications e.g.¬†isotretinoin,¬†hydrochlorothiazide¬†diuretics,¬†beta blockers,¬†protease inhibitors
  • Hypothyroidism¬†(underactive thyroid)
  • Lupus¬†and associated autoimmune responses¬†[rx]
  • Glycogen storage disease type 1.
  • Propofol
  • HIV medications
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Symptoms of Hypertriglyceridemia

Blood samples of a young patient with extreme hypertriglyceridemia. Most people with elevated triglycerides experience no symptoms. Some forms of primary hypertriglyceridemia can lead to specific symptoms:
  • Both familial chylomicronemia and primary mixed hyperlipidemia include skin symptoms (eruptive xanthoma),
  • Eye abnormalities (lipemia retinalis),
  • Hepatosplenomegaly (enlargement of the liver and spleen), and neurological symptoms.
  • Some experience attacks of abdominal pain that may be mild episodes of pancreatitis. Eruptive xanthomas are 2‚Äď5¬†mm papules, often with a red ring around them, that occur in clusters on the skin of the trunk, buttocks and extremities.[rx]
  • Familial dysbetalipoproteinemia¬†causes larger, tuberous xanthomas; these are red or orange and occur on the elbows and knees. Palmar crease xanthomas may also occur.[rx][rx]
  • Acute pancreatitis¬†may occur in people whose triglyceride levels are above 1000¬†mg/dL (11.3¬†mmol/L).[rx][rx][3]¬†Hypertriglyceridemia is associated with 1‚Äď4% of all cases of pancreatitis. The symptoms are similar to pancreatitis secondary to other causes, although the presence of xanthomas or risk factors for hypertriglyceridemia may offer clues.[rx]

Diagnosis of Hypertriglyceridemia

The diagnosis is made on¬†blood tests, often performed as part of¬†screening. The normal triglyceride level is less than 150¬†mg/dL (1.7¬†mmol/L).[rx][rx] Once diagnosed, other blood tests are usually required to determine whether the raised triglyceride level is caused by other underlying disorders (“secondary hypertriglyceridemia”) or whether no such underlying cause exists (“primary hypertriglyceridemia”). There is a hereditary predisposition to both primary and secondary hypertriglyceridemia.[rx]

You may recommend testing the following 

  • CBC, ESR, HB
  • Seram lipid profile. Weight and body mass index,
  • CRP
  • Metabolic examination
  • Food habit
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 According to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, HTG is classified into

  • mild: TG level 150-199 mg/dL,
  • high:¬† TG 200-499 mg/dL and
  • very high: TG > 500 mg/dL.
  • When triglycerides are above 400 mg/dL, LDL-C levels are calculated using the Friedewald equation.¬†
  • Since the calculation can underestimate LDL-C, the alternative is to calculate non-HDL-C levels (total cholesterol minus HDL cholesterol) or obtain direct LDL-C levels if possible.¬†

The diagnosis is made on¬†blood tests, often performed as part of¬†screening. Once diagnosed, other blood tests are usually required to determine whether the raised triglyceride level is caused by other underlying disorders (“secondary hypertriglyceridemia”) or whether no such underlying cause exists (“primary hypertriglyceridaemia”). There is a hereditary predisposition to both primary and secondary hypertriglyceridemia.[rx]

Treatment of Hypertriglyceridemia

Lifestyle Recommendations for Triglyceride Lowering in Children and Adolescents

  • Lose Some Weight. Whenever you eat more calories than you need,¬†your¬†body turns those calories into¬†triglycerides and stores them in fat cells.
  • Limit¬†Your Sugar Intake.
  • Follow a Low-Carb Diet.
  • Eat More Fiber.
  • Exercise Regularly.
  • Avoid Trans Fats.
  • Eat Fatty Fish Twice Weekly.
  • Increase¬†Your¬†Intake of Unsaturated Fats.
  • Daily caloric intake should be < 25%‚Äď30% of calories from fat, <7% from saturated fat, <200 mg/d of cholesterol*, decrease trans fat
  • Avoid sugar intake (ice cream, candy, baked goods) and sugar sweetened beverages (pop, juice, sports drinks)
  • Replace simple carbohydrates (white bread, white pasta, white rice) with complex carbohydrates (wheat bread, whole grain pasta, brown rice)
  • Replace carbohydrates with monounsaturated fat (olive oil, canola oil, nuts, seeds)
  • Increase omega 3 fatty acids (fish)
  • 30-60 minutes of vigorous exercise daily
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Medication

  • Very high levels that would increase the risk of pancreatitis is treated with a drug from the fibrate¬†class.
  • Niacin¬†and¬†omega-3 fatty acids¬†as well as drugs from the¬†statin¬†class may be used in conjunction, with statins being the main drug treatment for moderate hypertriglyceridemia where reduction of cardiovascular risk is required.[rx]
  • Medications are recommended in those with high levels of triglycerides that are not corrected with lifestyle modifications, with¬†fibrates¬†being recommended first.[rx][rx][rx]
  • Epanova (omega-3-carboxylic acids)¬†is another prescription drug used to treat very high levels of blood triglycerides.

Lowering triglycerides without medication

Unless your triglycerides are extremely high, lifestyle changes are the best place to start. These simple steps can significantly lower triglyceride levels.

  • Beware of¬†bad fats –¬†Cutting back on saturated fat (in red meat and full-fat dairy foods) and trans fats (in restaurant fried foods and commercially prepared baked goods) can lower triglycerides.
  • Go for good carbs –¬†Easily digested carbohydrates (such as white bread, white rice, cornflakes, and sugary sodas) give triglycerides a definite boost. Eating whole grains and cutting back on soda can help control triglycerides.
  • Check your alcohol use – In some people, alcohol dramatically boosts triglycerides. The only way to know if this is true for you is to avoid alcohol for a few weeks and have your triglycerides tested again.
  • Go fish – Omega-3 fats in salmon, tuna, sardines, and other fatty fish can lower triglycerides. Having fish twice a week is fine.
  • Aim for a healthy weight – If you are overweight, losing just 5% to 10% of your weight can help drive down triglycerides.
  • Get moving –¬†Exercise lowers triglycerides and boosts heart-healthy HDL cholesterol.
  • Stop smoking –¬†It isn‚Äôt good for triglyceride levels ‚ÄĒ or for anything else.

References

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