Why test for lipoprotein-a when there’s not much doctors can do?

While the Canadian Cardiovascular Society (CCS) most recent lipid guidelines introduced a recommendation for once in a lifetime testing of lipoprotein-a (Lp(a)), the burning question for doctors is why test for something that has no direct therapy available? According to Dr. George Thanassoulis, one of the guideline’s authors, there are multiple reasons. Among them are that this sticky protein is an independent risk factor for cardiovascular disease (CVD) (even if usual cholesterol measures are healthy), that there are things that can be done to help patients, and that direct treatments are under study and in the pipeline. Read: Moderate and late preterm birth linked to later cardiometabolic disorders “Lp(a) has a lot of similar features to LDL cholesterol but it’s worse for you. It’s stickier and more likely to adhere to the artery wall, and is associated with more atherosclerosis in the artery than typical cholesterol,” Dr. Thanassouli, a preventive cardiologist and genetic epidemiologist at McGill University, told the Medical Post in an interview. Elevated Lp(a) occurs in people who have a gene mutation in the LPA gene. This means the levels in an individual tend to remain fairly stable, which is why the recommendations suggest testing only once when patients undergo initial cholesterol screening. But the mutation is not uncommon. In fact, an estimated 20% of the population has elevated Lp(a) levels which translates to about six million people in Canada. “And if you look at patients who have had a heart attack, the prevalence is closer to 30%,” he said. Genetic studies have shown that populations with the mutation have higher rates of heart attacks, strokes, and earlier mortality. One large epidemiologic study found that people of African, Latin American and South Asian decent tend to have the highest levels and are at the greatest risk for CVD, making it even more important to offer testing for them. Indeed, of these groups, elevated Lp(a) levels occur in 20% of individuals of European and South Asian descent, 40% of African American individuals, and fewer than 10% of East Asian individuals. People with Chinese ancestry generally have the lowest levels While Lp(a) has similarities to low-density lipoprotein (LDL), it is not in the usual panel for cholesterol screening and has to be ordered separately—though that may soon change now that the guidelines recommend adding it to screening tests. The test costs about $25, and several provinces are making the move to cover it. The CCS guidelines recommend patients whose Lp(a) is 50 mg/dL or greater (or 100 nmol/L and above) should undergo earlier and more intensive health behaviour modification counselling and management of other CVD risk factors. One study showed that Lp(a) above this level is associated with 1.5-fold increased risk of MI, independent of other CVD risk factors including DM, smoking, high blood pressure “Most patients don’t know they have this type of cholesterol that’s elevated, but if they know it’s elevated they can work harder at getting other risk factors under control,” he said. Reducing those risks reduces the risk for CVD events overall. Risk factors can be viewed as a collective: reducing some risks reduces overall risk. Another challenge is that Lp(a) is stealthy. A person can have elevated Lp(a) while other cholesterol measures are in a normal healthy range. Testing alerts the physician and patients that there is a risk factor. But a downside is that for just Lp(a), lifestyle, dietary changes, blood pressure medications and cholesterol lowering agents don’t affect the levels (though statins have been found to actually slightly raise Lp(a) levels in some patients). Still, they help with overall cardiovascular health. For people at high risk and who have had CVD events, PCSK9 inhibitors can be used for secondary prevention. Reports suggest they can lower Lp(a) by as much as 20% to 30%. However, they are expensive, and people in many parts of Canada don’t have access to them, Dr. Thanassoulis said. Another possibility is apheresis which “can be used in select patients with very high levels of Lp(a) who have had recurrent vascular events,” he said. It used in the U.S. and parts of Europe, but few places in Canada offer it outside of academic hospitals. It is also expensive and time-consuming for the patient. Dr. Thanassoulis added that the evidence for apheresis is relatively weak. While there have been some studies, but they weren’t randomized, he said. In the pipeline The good news is that trials are underway for new therapies to treat elevated Lp(a). According to a report in Nature Biotechnology, there are four trials in progress of RNA-related injectable treatments that target Lp(a) production. Pelacarsen (Novartis) is being studied in a randomized control trial with 8,300 patients (the HORIZON trial) and is the furthest along with an estimated completion date of 2025. Olpasiran (Amgen) was found in a phase-2 trial to lower Lp(a) levels and will move on a phase-3 clinical trial, likely later this year. SLN360 (Silence Therapeutics) is in phase-1 studies. LY3819469 (Eli Lilly) is in phase-1 trials.

Why test for lipoprotein-a when there’s not much doctors can do?

Register for free access or login.

Related Topics