An Overview of High Triglycerides

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Triglycerides are a type of fat found in the blood and an important part of your body's metabolism. Any calories that you don't burn off are stored in the cells as triglycerides. When energy is needed, an enzyme known as pancreatic lipase will prompt the cells to release triglycerides into the bloodstream.

However, if you consume more triglycerides than you can burn off or store, they can accumulate excessively in the bloodstream and lead to an adverse condition known as hypertriglyceridemia. Persistent elevations are linked to serious illnesses, including pancreatitis (inflammation of the pancreas), atherosclerosis ("hardening of the arteries"), cardiovascular disease, and stroke.

Obesity and overeating are common causes of hypertriglyceridemia, but other genetic and health factors contribute as well. Fortunately, there are things you can do to help lower triglycerides, including an improved diet, exercise, and prescription medications.

Symptoms

Hypertriglyceridemia doesn't usually manifest with symptoms until triglycerides levels are excessively high. For the majority of people with elevated triglycerides, there will be no outward symptoms until pancreatitis or cardiovascular symptoms develop, often years down the road.

Generally speaking, symptoms will only appear when the triglyceride levels are between 1,000 and 2,000 milligrams per deciliter (mg/dL). At this level, episodes of pancreatitis may develop, manifesting with upper abdominal pain and nausea.

At these same levels, symptoms of atherosclerotic cardiovascular disease (ASCVD) can develop, including angina (chest pain), dyspnea (shortness of breath), and arrhythmia (irregular heartbeat).

Even levels at or above 443 mg/dL can increase the risk of a heart attack by more than three-fold.

As levels approach and exceed 5,000 mg/dL, other organ systems may be affected, leading to:

  • Hepatosplenomegaly (enlarged liver and spleen)
  • Eruptive xanthomas (small, painless nodules on the trunk, buttocks, and thighs)
  • Tuburoeruptive xanthomas (nodules on the elbows and knees)
  • Xanthoma striata palmaris (yellowish discoloration of the palms)
  • Xanthelasmas (yellowish, raised lesions around the eyelids)
  • Corneal arcus (a grayish-white opacity of the cornea)
  • Acute pancreatitis (manifesting fever, vomiting, rapid heart rate, loss of appetite, and radiating pain from the stomach to the back)
  • Neurological symptoms (including memory loss, depression, and dementia)

Severe manifestations like these are uncommon. They are typically seen with rare genetic disorders like familial dysbetalipoproteinemia and familial chylomicronemia, both of which cause extreme elevations in triglyceride and cholesterol levels.

According to a 2013 study in Clinical Lipidology, the median age of onset of cardiovascular disease in adults with hypertriglyceridemia was 57 years in women and 50 years in men. The age of onset of pancreatitis was similar.

Causes

Hypertriglyceridemia can be caused by many different things, broadly described as lifestyle causes, genetic causes, medical conditions, and medications:

  • Lifestyle causes include obesity, a high-fat diet, a lack of physical activity, and excessive alcohol consumption.
  • Genetic causes include familial hyperlipidemia, familial chylomicronemia, mixed hyperlipidemia, lipoprotein lipase deficiency, lysosomal acid lipase deficiency, glycogen storage disease, and cholesteryl ester storage disease.
  • Medical conditions include acute kidney failure, diabetes, hypothyroidism, pancreatitis, and lupus.
  • Medications include beta-blockers, estrogen replacement therapy, estrogen-based oral contraceptives, thiazide diuretics, HIV protease inhibitors, isotretinoin, steroids, and tamoxifen.

It is possible to have overlapping causes of hyperlipidemia in which, for example, lifestyle choices (like diet) paired with medications (such as beta-blockers) can complicate your genetic predisposition for high triglycerides.

Diagnosis

For most people, hypertriglyceridemia is diagnosed with a series of blood tests known as a lipid panel. In addition to triglycerides, the lipid panel will measure the major forms of cholesterol, such as total cholesterol, high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Prior to taking the lipid panel, you may be asked to fast for 12 to 14 hours.

Lab results are usually returned in one to two days. The triglyceride test results are described within a reference range of values established by the Endocrine Society Task Force:

  • Normal: less than 150 mg/dL
  • Borderline-high: between 150 and 199 mg/dL
  • High: between 200 and 499 mg/dL
  • Very high: 500 mg/dL or more
  • Severe hyperglyceridemia: between 1,000 to 1,999 mg/dL
  • Very severe hypertriglyceridemia: over 2,000 mg/dL

If triglyceride levels are higher than 500 mg/dL, additional tests may be performed to determine if there are genetic causes. A physical exam may also be conducted to check for skin and eye symptoms as well as the swelling of the liver and spleen.

In cases like these, the doctor will also want to differentiate between the primary causes of hypertriglyceridemia and the secondary causes (in which the elevation is a consequence of another condition).

The conditions explored in a differential diagnosis may include:

  • Alcohol abuse
  • Hormone replacement therapy
  • Hypothyroidism
  • Kidney failure
  • Pancreatitis
  • Type 1 diabetes
  • Type 2 diabetes

Treatment

Hypertriglyceridemia is typically treated with a combination of lifestyle and pharmaceutical interventions. If your triglyceride levels are borderline high, you may not need medication immediately but will instead begin a diet and exercise program to improve your overall health.

Lifestyle

The treatment of hypertriglyceridemia usually starts with an adjustment of lifestyle factors that give rise to elevations. This most often involves the use of a low-fat diet in tandem with routine exercise to achieve and sustain your ideal weight.

Depending on your current eating habits, fitness level, and weight, you may need to work a dietitian and/or personal trainer experienced in metabolic disorders.

Dietary interventions can vary based on your triglyceride levels but usually involve the restriction of dietary fats, the replacement of saturated and trans fats with polyunsaturated and monounsaturated fats, and a reduction in the consumption of carbohydrates (including simple carbohydrates like fructose).

Exercise programs should be of moderate intensity and involve a combination of aerobic exercise and resistance training. A personal trainer can design a program specific to your fitness status, ensuring that you are neither overtaxed nor undertaxed. The program would not be static but gradually increase in intensity and duration during the course of weeks and months.

The American Heart Association (AHA) recommends between 30 and 60 of aerobic exercise most days of the week and resistance training for at least 20 to 30 minutes twice weekly.

Smoking cessation should also be explored to reduce your risk of atherosclerosis and cardiovascular disease.

Medications

The decision to start medications is usually based on a review of your entire lipid profile, not just your triglyceride levels. Rarely do triglyceride levels increase while all other lipids remain normal.

To this end, the AHA in association with the American College of Cardiology (ACC) established guidelines to direct the appropriate treatment of hyperlipidemia (high blood lipids) as a whole. Among the medications used to reduce triglycerides and improve cholesterol levels are:

  • Statin drugs, such as Crestor (rosuvastatin), Lipitor (atorvastatin), Pravachol (pravastatin), and Zocor (simvastatin)
  • Zetia (ezetimibe), the first in a class of selective cholesterol-absorption inhibitors 
  • PCSK9 inhibitors, a class of injectable biologic drugs consisting of Praluent (alirocumab) and Repatha (evolocumab).
  • Fibrate acid derivatives, such as Atromid-S (clofibrate) and Lopid (gemfibrozil)
  • Bile acid sequestrants, such as Questran (cholestyramine) and Welchol (colesevelam)
  • Nicotinic acid, also known as niacin

Drug treatment should be considered when "bad" LDL levels reach a certain threshold. Though triglyceride levels will contribute to the decision (especially in people with diabetes and familial hypertriglyceridemia), the LDL values paired with the risk of atherosclerotic cardiovascular disease (ASCVD) are the two factors that will ultimately decide whether treatment is needed or not.

According to the AHA/ACC guidelines, the recommended treatment protocols are as follows:

  • For adults with clinically diagnosed ASCVD, start a statin drug at the maximally tolerated dose.
  • For adults with an LDL over 70 mg/dL and a moderate risk of ASCVD, start with a moderate-intensity statin.
  • For adults with an LDL over 70 mg/dL and diabetes, start with a moderate-intensity statin.
  • For adults with an LDL over 70 mg/dL and a very high risk of ASCVD, start with a high-dose statin with or without Zetia. A PCSK9 inhibitor can be added, as needed
  • For adults with an LDL greater than 190 mg/dL (but no ASCVD risk assessment), a high-dose statin with Zetia may be appropriate. A PCSK9 inhibitor can be added, as needed.

Hypertriglyceridemia is never treated with drugs alone. If medications are needed, it is all the more important that you reduce your intake of fat and sugar, exercise regularly, reduce alcohol consumption, and stop smoking.

Coping

Hypertriglyceridemia is not something you can "cure" but rather a condition that you need to manage for a lifetime. If treated appropriately, you can reduce your risk of heart disease and achieve an overall improvement in your health.

Among some of the tips that can help:

  • Set realistic goals. Do not start an aggressive weight-loss program if you are sedentary and 20 to 30 pounds overweight. Work with your doctor to establish incremental goals and a program you can sustain over the long term.
  • Learn good nutrition. Whatever your dietary restrictions may be, you need to maintain optimal nutrition to remain healthy and have enough energy to fuel your day. Avoid fad diets, and work with a dietitian to formulate a sensible, balanced approach.
  • Control all of your sugar. Excess calories from sugar are converted by the body into triglycerides. This includes the sugar in fruit known as fructose. Although it is important to obtain dietary fiber from fruit and other food sources, don't go overboard and use fruit to replace the candy and sweets you are used to eating. This includes fruit drinks made with high-fructose corn syrup.
  • Seek support. It is difficult to adhere to dietary and fitness programs without the support of family and friends. Educate them on why you need to make lifestyle changes and explain how they can help. Don't try to go it alone. If needed, ask your doctor to speak with your loved ones.
  • Seek treatment. If you have a drinking problem or are unable to stop smoking, ask your doctor about treatment options. The Affordable Care Act mandates that certain alcohol addiction and smoking cessation aids be made available free of charge as an Essential Health Benefit (EHB) of your insurance plan.
  • Seek financial assistance. PCSK9 inhibitors are expensive. Don't assume that you can't afford them in you are underinsured or have high copay or deductible costs. There are copay assistance programs available for both Praluent and Repatha that may reduce your out-of-pocket costs to $0.

Arguably, the most important thing to remember is to never treat hypertriglyceridemia in isolation. By managing your blood sugar, blood pressure, weight, bone health, lung health, and chronic medical conditions, you will almost invariably improve your blood lipid profile. It all starts with a positive attitude.

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