Identifying individuals with elevated levels of lipoprotein(a) (Lp[a]) remains a key objective in preventive cardiology. New data addressing the importance of Lp(a) testing with DNA technology in research settings were presented at the American College of Cardiology 75th Annual Scientific Session & Expo (ACC.26).

Following this presentation, featured expert Christie M. Ballantyne, MD, was interviewed by Conference Reporter Associate Editor-in-Chief Mona Shah, PharmD. Clinical perspectives from Dr Ballantyne on these findings are presented here.

When we talk about the genetics of Lp(a), it is important to understand why the recently published American College of Cardiology/American Heart Association (ACC/AHA) multisociety guidelines say that we should check Lp(a) in every adult. The main reason is because it is an autosomal dominant risk factor, and Lp(a) levels are genetically determined at a rate of approximately 70% to upwards of 90%.

Monogenic pathogenic variants for genes that regulate the levels of low-density lipoprotein cholesterol, such as familial hypercholesterolemia, are also very important. However, familial hypercholesterolemia affects approximately 1 in 250 people, whereas approximately 1 in 5 individuals worldwide are estimated to have high Lp(a) levels. So, high Lp(a) is probably the most common hereditary risk factor. A level of 50 mg/dL (125 nmol/L) is considered high, at least by US guidelines; less than 30 mg/dL (75 nmol/L) is considered within the desirable range. Atherosclerotic cardiovascular disease risk actually starts to go up at around 30 mg/dL (75 nmol/L) and is increased by approximately 1.4 at or above 50 mg/dL (125 nmol/L).

One of the things that we look at is how to identify patients with high Lp(a) levels. Since it is genetic, what about DNA? At the recent ACC.26 meeting, Michael G. Levin, MD, and colleagues reported the results from a haplotype-based prediction model they developed looking at 1408 common genetic variants flanking the LPA locus on chromosome 6 using data from the All of Us Research Program. External validation was performed among the Penn Medicine, Mass General Brigham, and BioMe (Icahn School of Medicine at Mount Sinai) biobank participants with available Lp(a). Dr Levin et al found that the model effectively identified individuals with elevated Lp(a) levels among these 3 biobanks, with an overall r² of the model being 0.51. The overall positive predictive value was 80%, so they could predict with about 80% accuracy who was going to have an elevated Lp(a) level, which is pretty good. So, if you have already had a patient’s DNA tested in a health care system, you could analyze the results and advise these patients to get their Lp(a) checked.

The more pragmatic approach is to check Lp(a) in everybody. You do not need to use DNA to predict the level of something when you can measure it in your plasma, and it is not an expensive test. DNA testing is important for genetic research, but in terms of actual clinical practice, I would recommend that you just measure the Lp(a) level. The commercial laboratories are now quite good. If someone has a high Lp(a) level, it is important to remember that this has an autosomal dominant inheritance pattern. This means that there is a 50% chance that their children will inherit it and that their siblings have it. You should test the whole family with cascade screening to identify individuals with high Lp(a) levels. I always tell my patients that, if they have children, they need to get their children’s Lp(a) levels checked. I also ask them to have their siblings and other first-degree relatives get their levels checked.

That leads to the next obvious question: If you find a high Lp(a) level, what do you do about it? If a patient has a high Lp(a) level, we do a lot of common-sense interventions for the general prevention of cardiovascular disease, such as exercise and diet and lifestyle modification. We also know that other certain preventive measures are helpful, such as smoking cessation and the treatment of hypertension. We would also consider being more aggressive with lipid-lowering therapy in higher-risk individuals. Finally, in patients with obesity, we might treat their obesity more aggressively. These are some of the common-sense interventions and factors to be considered when you see a high Lp(a) level.