The Trouble With Triglycerides

In the classic Star Trek episode, “The Trouble with Tribbles”, the crew find themselves on an alien planet. A trader gives a tribble to one of the officers, who brings it on board the Enterprise. The tribbles are purring balls of fluff that ease human anxieties. They are instantly loved by the crew. Unfortunately, the tribbles reproduce rapidly, taking over all of the space on the ship and eating all of the food on board. Because the tribbles are killing their hosts, they have to be removed.

 

Triglycerides transport the fat that we eat to the cells in the body to use for energy. Unlike tribbles, triglycerides are not cute and fuzzy, although high levels of triglycerides make the blood look milky and cloudy. Also, like tribbles, as triglycerides accumulate (the blood level goes up) it can kill its host (the risk for heart disease goes up). Elevated levels of triglycerides are either primary (genetic, running in families) or secondary to other medical conditions or lifestyle choices. Secondary causes include type 2 diabetes, thyroid disease, or fatty liver disease. Lifestyle factors include obesity, being sedentary, smoking, alcohol use, or a diet high in saturated fats or processed sugars. Hypertriglyceridemia is defined as blood levels above 150 mg/dl. World-wide more than 25% of people have high triglycerides. High triglyceride levels have been strongly and significantly associated with elevated cardiovascular risk, independent of LDL (“bad cholesterol”) levels. People can have normal or low LDL values, but if their triglycerides are high, they are still at risk for a heart attack. In addition, a very high level of triglycerides is a risk factor for pancreatitis (a potentially life-threatening inflammation of the pancreas). The trouble with triglycerides is how to treat them or whether to treat them at all.

 

The first step in treating elevated triglycerides is lifestyle modification. This starts with reducing excess weight, alcohol intake and dietary carbohydrates. Additional measures include exercise, smoking cessation and diabetes control. Together, these interventions can lower triglycerides by 60%. Medications for high triglycerides include statins, fibrates and omega-3 fatty acids. Certain statins (for example, atorvastatin) lower triglycerides as well as LDL cholesterol and should always be the initial agent chosen. Atorvastatin (Lipitor) reduces triglycerides by about 25%. Fibrates (such as fenofibrate) have the highest potency in reducing triglycerides. However, despite lowering triglycerides by 30-50%, fenofibrates have not been shown to reduce the risk of cardiac events. There are three omega-3 fatty acid formulations in clinical use. These are: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and icosapent ethyl (IPE, a highly purified form of EPA).  EPA is found in plants and fish. Medications with high dose EPA reduce triglycerides by 14-33%. One study showed that EPA reduced cardiac events by 19%. Another study looked at IPE in patients with heart disease or diabetes on a statin. High dose IPE reduced cardiac events by 25%. However, triglycerides were only modestly reduced in the study and it was felt that other factors improved the outcomes (possibly anti-inflammation or anti-oxidant effects of IPE). On the other hand, a large review of multiple trials did not show a reduction in cardiac events with omega-3 fatty acid therapy. In addition, a study of EPA and DHA did not show a reduction in outcomes. The reason for this discrepancy is currently being hotly debated in the cardiology community. 

  

It is well established that higher triglyceride levels are associated with higher cardiac events. However, while there is strong evidence for lowering LDL (the current principle is lower is better) to reduce cardiac risk, the data regarding triglyceride treatment is less conclusive. So, what should we do about high triglycerides? Should we ignore them and not treat them since there is no therapy that unequivocally reduces outcomes? Should we treat them with our current agents and hope that future research proves these therapeutics useful? Should we beam up to the Enterprise and find a new planet? Right now, there is no definite answer, but a few recommendations can be made. The first and strongest recommendation is to start atorvastatin (Lipitor) in patients with established heart artery disease or high risk for heart artery disease (for example diabetics) and elevated LDL and triglyceride levels. A second recommendation can be made for the high-risk patient (as defined above) who has triglyceride levels above 150 mg/dl and whose LDL is at goal with a statin. This type of patient should be started on high dose IPE. Lastly, patients with triglyceride levels over 300 mg/dl should start fenofibrate to reduce the risk for pancreatitis. What about the lack of data? Never fear, the science officers are combing the galaxy, doing the research, trying to find an answer to the triglyceride question. Stay tuned.