Show 1306: The Best-Kept Secret in Heart Disease

In our nationally syndicated radio show this week you’ll learn about a cardiac risk factor you may never have heard mentioned. Although scientists identified lipoprotein a as an important problem in the 1970s, your doctor may never have measured your level. We ask one of the country’s leading experts why Lp(a) has been overlooked for so long. It seems to be the best-kept secret in heart disease.

The Best-Kept Secret in Heart Disease:

When you think about preventing heart disease, you probably can name the ways in which you are attempting to control your cholesterol with diet or a statin, lower your blood pressure and stay physically active. Those are all excellent steps, but none of them have a big effect on your Lp(a) (pronounced ell-pee-little-ay). This is genetically determined, for the most part, and 20 to 30 percent of us have elevated levels.

Possibly one reason your doctor may not have mentioned Lp(a) is that they can’t write a prescription for it. Although there are drugs under development, none are available yet. What’s more, the statin drugs that most people take to prevent heart disease lower LDL cholesterol, but they actually raise Lp(a). This is a little bit like driving with one foot on the brake and the other on the gas pedal. However, no one taking a statin should stop taking it on their own.

Is Lp(a) Linked to Other Risk Factors?

In cardiology, many risk factors seem to travel together, like a herd of buffalo. When triglycerides are high, there’s a good chance that blood sugar will be elevated as well. Hypertension is not unusual when cholesterol is above normal. If a lot of these risk factors team up together, the doctor may diagnose metabolic syndrome. That indicates an elevated risk for cardiovascular disease.

We wondered if Lp(a) also rises when other risk factors do. Our guest expert, Dr. Sam Tsimikas, pointed out that it is independent of them. Some people with high cholesterol also have high Lp(a), but others do not. Likewise, some of us with low cholesterol might have high Lp(a). Unless you measure it, you will not know.

Treating Lp(a):

There aren't yet medications for lowering lipoprotein levels. Instead, doctors try to help patients get all their other cardiac risk factors in good shape. That may be all they can do for now.

Without drugs explicitly designed to lower the best-kept secret in heart disease, doctors have a challenge. Pharmacological doses of niacin can lower lipoprotein a somewhat, but we don’t have studies showing that it can reduce heart disease and improve longevity. Moreover, patients taking niacin should be under a doctor’s expert supervision. At high doses, niacin can sometimes cause troublesome side effects.

PCSK9 Inhibitors:

While statins raise Lp(a) by 10 to 25 percent, another category of cholesterol-lowering drugs can lower it by 15 to 30 percent. Those are the PCSK9 inhibitors, also known as alirocumab (Praluent) and evolocumab (Repatha). Doctors often prescribe these injectable medications for people who need lower LDL cholesterol than statins can produce. Although these drugs don’t lower Lp(a) for everyone, they may be an option for some people with very elevated levels.

Antisense Oligonucleotides:

Some new drugs being developed to lower Lp(a) are antisense oligonucleotides. These interfere with mRNA producing the proteins that they code for. Dr. Tsimikas has helped Ionis Pharmaceuticals develop its drug pelacarsen to help lower Lp(a) levels.

What Are Normal Levels of Lp(a)?

For the Lp(a) HORIZON study of pelacarsen, researchers recruited volunteers with elevated Lp(a) levels over 70 mg/dL. Sometimes Lp(a) is measured as nanomols per liter. By that measurement, 125 nmol/L is high. Ideally, we’d want normal Lp(a) levels at or under 30 mg/dL or 75 nmol/L. Dr. Tsimikas urges his colleagues to consider cascade screening. That is, if they identify a patient with elevated Lp(a), urge their family members to be screened as well. Because of the genetics of Lp(a), close family members have a 50/50 chance of also having high lipoprotein a. When testing is readily available, Lp(a) will stop being the best-kept secret in heart disease.

This Week's Guest:

Sotirios Tsimikas, MD, FACC, FAHA, FSCAI, is Professor of Medicine/Cardiology and Director of Vascular Medicine at the Sulpizio Cardiovascular Center in the Division of Cardiovascular Medicine of the University of California, San Diego. You will find some of his recent articles in the European Heart Journal, Jan. 1, 2020; European Heart Journal, Oct. 21, 2020; European Heart Journal, Nov. 21, 2020; and Journal of Thrombosis and Thrombolysis, Jan. 2022.

Dr. Tsimikas has a following on the Twitter educational forum @Lpa_doc. There you will find a Twittorial of 24 topics explaining Lp(a), each with a quiz to help understanding. It is modeled after the Breakfast Club.

When asked about conflicts of interest, Dr. Tsimikas mentioned Ionis Pharmaceuticals, the company developing pelacarsen. He has been involved with its development.