What is Hypertriglyceridemia?
Hypertriglyceridemia, which means having high levels of triglycerides (a type of fat) in your blood, is getting more common. It has been linked with an increased risk of heart disease and inflammation of the pancreas, known as pancreatitis. If your triglyceride levels are really high, you’re at an even bigger risk of developing pancreatitis. To lower this risk, you might need to make lifestyle changes or take medication. The root cause of the high triglyceride levels also needs to be addressed.
Medications that target low-density cholesterol (LDL-C) – a “bad” type of cholesterol that can build up in your arteries – have helped to improve outcomes for patients with atherosclerotic cardiovascular disease (ASCVD). This is a condition where fat, cholesterol, and other substances build up in the artery walls and can lead to dangerous clots. However, these medications don’t remove the risk completely.
For those who still have a risk of atherosclerotic cardiovascular disease after treatment, multiple studies have shown that even mild to moderate hypertriglyceridemia can independently increase the risk for heart disease. However, there’s no definitive evidence that heart disease risk decreases with the treatment of hypertriglyceridemia.
What Causes Hypertriglyceridemia?
Hypertriglyceridemia, a condition that means having too much triglyceride (a type of fat) in your blood, can be caused by a variety of things. Triglycerides in the blood can come from the fats in your food, but the body can also make them. Genetic factors can play a role, as well as issues with how the body makes or gets rid of triglyceride-rich lipoproteins, a type of protein that transports fat in your blood.
Some people might inherit conditions that cause hypertriglyceridemia. Certain syndromes lead to having too many triglycerides, called Very Low-Density Lipoprotein (VLDL), in your blood but not affecting the normal cholesterol levels. Some genetic conditions cause a rare type of hypertriglyceridemia known as chylomicronemia – such as the deficiency of certain proteins important for fat metabolism in the body.
There are also various medical conditions and habits that can lead to this condition. Obesity, type 2 diabetes, thyroid problems, hormonal diseases, kidney disease, HIV, pregnancy, and certain autoimmune conditions like systemic lupus erythematosus are all associated with hypertriglyceridemia. Certain medications, like some high blood pressure drugs (thiazides, beta-blockers), hormone treatments (oral estrogens, tamoxifen), contraceptive pills, drugs used for HIV (anti-retroviral protease inhibitors), certain psychiatric medications, skin medications (like isotretinoin), steroids, drugs that bind to bile acid and immune system drugs (like sirolimus) can lead to hypertriglyceridemia.
Your diet plays a role too: eating too much alcohol, food heavy in saturated fats, or food with a high glycemic index (foods that raise your blood sugar level quickly) can causes increased triglycerides.
Risk Factors and Frequency for Hypertriglyceridemia
The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) has defined categories for triglyceride levels, known as HTG. They define mild HTG as a triglyceride level of 150-199 mg/dL, high HTG as 200-499 mg/dL, and very high HTG as anything above 500 mg/dL. Ideally, for management purposes, an individual’s triglyceride level should be below 150 mg/dL.
The National Health and Nutrition Examination Survey (NHANES) studied risk factors for heart disease over several decades. Part of their research was based on triglyceride levels across the US population. They found that triglyceride levels were generally higher in men, particularly up to the age of 70, and levels increased in both sexes with increasing age. The study also highlighted an increase in high triglyceride levels among young people and teenagers, linked to growing obesity and diabetes rates. About a third of participants from 1999 to 2008 had triglyceride levels above the desired 150 mg/dL, and roughly 42% of those aged 60 or older also had high levels. In around 2% of the individuals studied, the triglyceride levels were very high, surpassing 500 mg/dL.
- Rates of high triglyceride levels were particularly high among Mexican-Americans, more so than white Americans.
- African-Americans had the lowest rates of high triglyceride levels.
While it’s still debated whether high triglyceride levels are a standalone risk factor for heart disease, it’s known that individuals with high levels often have low HDL-C (good cholesterol) and high LDL-C (bad cholesterol), a combination known to increase heart disease risk. Studies demonstrate that reducing triglyceride levels can decrease this risk, regardless of the drug class or lipid fraction used in treatment.
Signs and Symptoms of Hypertriglyceridemia
Hypertriglyceridemia is a condition marked by an abnormal level of triglycerides, a type of fat, in your blood. It could be triggered by various things like alcohol consumption, metabolic syndrome, endocrine disorders, and certain medications. If you have primary hypertriglyceridemia, which means it’s not caused by another medical condition, it’s important to check for other factors that could increase your risk of heart disease. These might include obesity, diabetes, high blood pressure, and tobacco use. If you have a family history of lipid disorders such as dyslipidemia and heart disease, this should also be investigated.
People with familial dysbetalipoproteinemia, a certain type of lipid disorder, might have specific symptoms like palmar xanthomas, which appear as orange or yellow deposits along the creases of the palms, and eruptive xanthomas, which show up at pressure points like the elbows, buttocks, and knees.
Chylomicronemia syndrome is another lipid disorder, which can cause symptoms such as:
- Abdominal pain in the upper middle part of the abdomen
- Eruptive xanthomas on the buttocks and the outer surfaces of the upper limbs
- Enlarged liver and spleen
- Acute pancreatitis, an inflammation of the pancreas
- Temporary memory loss
- Lipemia retinalis, a change in the color of the blood vessels in the eyes
- Occasionally, specific neurological issues
Testing for Hypertriglyceridemia
Hypertriglyceridemia, or high levels of triglycerides (a type of fat) in the blood, is diagnosed by a fasting lipid panel, which is a blood test done after you’ve fasted for a set number of hours. The guidelines set by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) divide hypertriglyceridemia into three categories based on triglyceride levels: mild (150-199 mg/dL), high (200-499 mg/dL), and very high (>500 mg/dL).
When triglyceride levels exceed 400 mg/dL, LDL cholesterol (the “bad” cholesterol) levels can be calculated using a specific equation called the Friedewald equation. However, since this equation might not provide a completely accurate LDL cholesterol level, an alternative is to calculate non-HDL cholesterol levels (total cholesterol minus HDL cholesterol, the “good” cholesterol) or if possible, directly measure LDL cholesterol levels.
Though measuring the size or density of LDL cholesterol isn’t very helpful in managing heart-related events, apolipoprotein B (Apo B) and lipoprotein(a) (Lp(a)) might be useful in assessing heart disease risk in people with high triglycerides. There are some effective treatments for reducing Apo B levels. But while niacin and estrogen can lower Lp(a) levels, there’s no direct evidence that doing so can prevent heart disease related to the hardening and narrowing of the arteries. High levels of Lp(a) have been linked to early-onset heart disease, so managing LDL cholesterol is strongly recommended when Lp(a) is high.
Another condition associated with high triglycerides due to insulin resistance is hepatic steatosis or non-alcoholic steatohepatitis (NASH), which is a type of fatty liver disease. It’s often suspected when liver function tests show high levels of enzymes called aminotransferases. If this is suspected, an ultrasound of the liver may be recommended for further evaluation.
Treatment Options for Hypertriglyceridemia
If pancreatitis is associated with high levels of triglycerides (a type of fat) in your blood, a few treatments are often used. The first step is usually giving fluids through an IV (directly into your veins) and asking patients to rest their bowels by not eating anything. Sometimes, a slow IV infusion of insulin could also help, because it can limit the creation of new triglycerides. If your triglyceride levels are incredibly high, a process called plasmapheresis, which removes some blood and filters out the excess triglycerides, might be used. Finally, once you’ve recovered from pancreatitis, it’s important to focus on getting your triglycerides down as much as possible to prevent another flare-up.
For medication, fibrates are often used since they can help reduce triglyceride levels by 30% to 50%. They do so by decreasing triglyceride production in the body, increasing the breakdown of fatty acids, and enhancing the synthesis of certain proteins involved in metabolizing fats. The effect of fibrates on LDL-C (or “bad cholesterol”) can differ based on your current triglyceride levels. If your levels are very high, LDL-C might increase, but if your levels are only slightly high, LDL-C could instead decrease. Fibrates are typically avoided in patients with liver or kidney disease, and are known to interact with other medications, so your doctor would take these factors into account.
Another option for treating high levels of triglycerides are omega-3 fatty acids (OM3FA). These are often used when triglyceride levels surpass 1000 mg/dL. OM3FA can reduce the amount of triglycerides by 20% to 50%, but the exact reduction depends on the dosage. OM3FA may also slightly increase the levels of low-density lipoprotein cholesterol (LDL-C), a.k.a. “bad cholesterol”, but this isn’t as marked with the EPA-only prescription products.
Moreover, there’s a drug called niacin, which comes in two types, immediate release and extended-release. It can decrease triglycerides levels, increase HDL-C (“good cholesterol”) and slightly decrease LDL-C. However, some side effects of niacin, like flushing (a feeling of warmth and redness on the face), are common. Other possible side effects include problems with blood sugar control, liver damage, and increases in uric acid level. Additionally, they should be avoided in patients with active peptic ulcer disease – a painful sores or ulcers in the lining of the stomach.
Statins are another class of drugs that help lower fats like triglycerides in the blood. They can reduce the amount by about 10% – 30% which is dependent on the dosage. However, statins are more effective when the triglycerides values are more than 500 mg/dL and it’s imperative to lower cardiovascular risk. In the past, fibrates and statins were used together, but this combination is now avoided due to the increased risk of muscle damage. Lastly, a drug called ezetimibe can lower fats by about 5-10%, but it’s not as effective as the others in lowering triglycerides, particularly in people with very high triglyceride levels.
What else can Hypertriglyceridemia be?
When your doctor checks for illnesses that cause high levels of chylomicronemia (fat droplets in the blood) or hypertriglyceridemia (high levels of a type of fat called triglycerides), they might consider the following conditions:
- Lipoprotein lipase deficiency
- Apo C II deficiency
- Apo AV homozygosity
- Mutations in the GPIHBP1 gene
Furthermore, there are several syndromes that could also trigger high triglyceride levels:
- Familial combined hyperlipidemia, which results in high levels of very-low-density lipoprotein (VLDL) and/or low-density lipoprotein (LDL). This condition could lead to early onset of heart disease.
- Familial hypertriglyceridemia, a more common syndrome, often causes an overproduction of large VLDL particles. In this case, the patient usually has low LDL and high-density lipoprotein (HDL) levels. This illness does not usually bring about early heart disease, unless the triglyceride levels are exceptionally high, but it is associated with pancreatitis.
Another condition that might be considered is Familial dysbetalipoproteinemia (type III hyperlipoproteinemia). This disease is due to a defect in Apo E, a protein that helps clear chylomicrons and VLDL remnants from your body. This causes an accumulation of these particles and triggers high cholesterol and high triglycerides levels. This condition is associated with early heart disease and peripheral vascular disease, which affects blood vessels away from the heart.
