What are Lipids?

Dr. Thomas Knickelbine

Expert advice from Dr. Thomas Knickelbine, MD, FACC, FSCCT, a Minneapolis Heart Institute Foundation researcher and a cardiologist at the Minneapolis Heart Institute® at Abbott Northwestern Hospital.

This is a good question. People often hear the term “lipid profile” and are not sure what it means. Lipids are blood fats. We all have heard there are “good” fats and “bad” fats. It’s a bit more complicated, but basically the only “good” fat is HDL or high-density lipoprotein. High-density cholesterol brings the bad cholesterol from the body back to the liver for removal. All other cholesterols are “bad” in that they contribute to the formation of plaque, which can lead to heart attack and stroke. This includes LDL, IDL, VLDL and triglycerides. Thus, bad fats are often times represented as “non-HDL cholesterol” which can be easily calculated by subtracting HDL from the total cholesterol. Your doctor will provide you with a “goal” LDL cholesterol based on your risk. This may be < 100 for high-risk people or < 160 for lower risk people. Your non-HDL cholesterol should be no more than 30 points higher than your LDL cholesterol goal.

Hypertriglyceridemia. The triglyceride fat on the top layer in yellow.

Figure 1: Hypertriglyceridemia: The yellow layer on top is the triglyceride fat.

At the Minneapolis Heart Institute Lipid Clinic, we specialize in diagnosing and treating disorders related to blood fats. Here’s an example. Last year, a 26-year-old Asian man began experiencing severe abdominal pain. It turns out his pancreas was inflamed (called “pancreatitis”) and the cause was extremely high triglycerides (a type of blood fats) that irritate the pancreas. I took a photo of his blood sample after it was drawn and it shows the triglyceride fat layering out on the top. (Figure 1)

Interestingly, fish oils in very high doses can reduce triglyceride levels. I started the man on high dose fish oils (4 grams daily to start) and also a new medication called Fenofibrate. This medication works by increasing the natural substance (enzyme) that breaks down fats in the blood. He also met with a dietitian to adjust his eating habits. As a result, he was able to significantly decrease his triglyceride levels.

We also treat many people who may not tolerate medications used to treat lipid disorders. Sally is a patient who had a heart attack and angioplasty several years ago. She had not been able to take her “statin” medication, Zocor® (or Simvastatin) because it gave her muscle aches. She had tried multiple other statin medications including Lipitor, Pravachol and Crestor®. Muscle aches with these medications is actually very common, affecting about one in five people.

Because these medications can prevent further heart attack, we wanted to try another option to reduce her risk of a future event. So, we switched Sally to an alternative statin medication, Livalo (Pitavastatin), and were able to get her “bad” fat, or LDL, down to goal levels. Interestingly, we have found that vitamin D deficiency can sometimes make muscle aches more likely. We checked her level and it was “severely deficient” at 18 (“severely deficient” is defined as less than 20). In addition to the new statin, she was also started on a vitamin D supplement. She is now doing well and her LDL cholesterol is below her goal of 100.

We have some people in the lipid clinic that cannot control very high cholesterol values with any medications. Many of these people have an inherited disorder called “Familial Hypercholesterolemia” (FH). This affects about 1 in 500 Americans. This was the case for Cindy, a 48-year-old patient of mine whose father died from a heart attack at 50 years old. He had very high cholesterol, as does her brother. Her LDL cholesterol was over 300! She has FH. People with FH are at very high risk for heart attacks and strokes. Up to half will have one before the age of 50.

Figure 2: The Liposorber system that filters out all the “bad” fats and lets the HDL go through.

Sometimes, when the cholesterol is so high, we have to perform “Lipid Apheresis.” With this treatment, the person is hooked up to a dialysis-like machine that filters out the blood fats (Figure 2). While this treatment works, it’s time-consuming, expensive and fairly short-lived in effect.

For this reason, we wanted to try a new approach for Cindy. There are now two new medications on the market for FH, with many others on the way. JuxtapidTM and MipomersenTM are two new drugs that are FDA-approved for some patients with FH and have been shown to lower LDL cholesterol by as much as 60 to 70 percent. Time will tell if these medications are effective in the long term, but in many of these cases we may not have time to wait.

The mechanism of the new PSCK9 Inhibitors. They bind LDL receptors and cause them to become more abundant. LDL levels drop dramatically.

Figure 3: The mechanism of the new PCSK9 Inhibitors. They bind LDL receptors and cause them to become more abundant. LDL levels drop dramatically.

Finally, with the help of the Minneapolis Heart Institute Foundation, we are now starting clinical trials or studies to test newer cholesterol medications. These trials are called “Phase 3” Trials, which are usually the last set of trials before FDA approval for general use. One such trial is helping people who have had a heart attack or angioplasty control their cholesterol. Mr. M is a 65-year-old male who had a heart attack last month. All of his prior cholesterol treatments have failed. He is now enrolling in this trial to test whether we can lower his risk for heart disease with a new medication called a PCSCK9 inhibitor (Figure 3). PCSK9 is an enzyme involved in making cholesterol. We know that people who have a genetic defect and have no PCSK9 have extremely low LDL cholesterol and do not develop heart disease. This drug is an antibody to PCSK9. We are hoping that the antibody will inhibit PCSK9 and have the same effect.

Have a question or comment about cholesterol and new cholesterol medications? I am always interested in hearing your opinion and comments!