Exploring the Latest on Lipids: Updates on Lp(a) in Preventative Cardiology

The European Society of Cardiology’s 2022 Congress explored the latest on lipids impacting the field of cardiology, including the biomarker lipoprotein(a), or Lp(a) for short. What do we need to know about this biomarker—and how is this changing the field of preventative cardiology?

Lp(a) is a highly prevalent cardiovascular risk factor, and emerging evidence suggests that while elevated Lp(a) levels could increase the risk of cardiovascular disease, lower levels of Lp(a) is associated with incident type 2 diabetes. Researchers have begun refocusing clinical efforts to better understand the role of Lp(a) in cardiovascular risk.

Clinical Data on the Degree of Risk

The Emerging Risk Factor Collaboration group conducted a study evaluating Lp(a) risk in relation to cardiovascular disease and all-cause mortality. The study evaluated 126,634 participants enrolled in 36 prospective studies, and researchers recorded a total of 22,076 first-ever fata or nonfatal vascular disease outcomes or nonvascular deaths. Of these deaths:

• 9,336 were from events related to coronary heart disease (CHD)
• 1,903 deaths were from ischemic stroke, 338 from hemorrhagic strokes, and 751 unclassified strokes
• 1,091 were from other vascular complications
• 8,114 were nonvascular deaths
• 242 were deaths of unknown cause

All of this data shows that in participants without prior CHD, Lp(a) is an independent predictor of CHD, even at levels less than 24 mg/dL.

Therapies for Lp(a) Risk Reduction

Given that Lp(a) rates are so closely tied with cardiovascular outcomes, clinicians have worked to evaluate how current therapeutic agents affect rates of Lp(a). Clinicians found the following regarding currently available treatment options:

• LDL apheresis can acutely decrease Lp(a) by up to 80 percent
• Mipomersen and PCSK9 can decrease Lp(a) by up to 40 percent
• Niacin and IL-6 antagonists can decrease Lp(a) by 30 percent
• Statins, on the flip side, can increase Lp(a) by up to 50 percent

Due to the variety of therapeutics used to manage cardiovascular risk, clinicians recommend an alternative approach to reducing Lp(a), specifically with apo(a) antisense oligonucleotides, which are single-stranded oligodeoxynucleotides that can modify protein expression. These antisense oligonucleotides can prevent the production of apolipoprotein(a) in the hepatocyte, which is the source of about 99 percent of plasma Lp(a), leading to a significant reduction of Lp(a).

An optimal apo(a) antisense oligonucleotides for patients, referred to as ISIS-APO(a), was evaluated in human volunteers. In these patients, clinicians saw a mean Lp(a) reduction of 78 percent and a maximum reduction of 92 percent. This trial is one of many paving the way for a potential therapy for high-risk patients in reducing Lp(a) levels. These trials also continue to demonstrate how Lp(a) reduction can decrease the risk of cardiovascular disease.

The Future of Cardiovascular Care

Incorporating therapeutics aimed at reducing the risk of Lp(a) into treatment, specifically for our high-risk patients, has shown to be an important part of preventative cardiology. As clinical data continues to emerge, our understanding of Lp(a) to be an independent, genetic risk factor for cardiovascular is something clinicians can use to inform care. And ongoing trials for antisense oligonucleotides, specifically targeting Lp(a), can help us normalize Lp(a) levels and change the way we reduce Lp(a)-contributable risk of cardiovascular disease.

References:

Tsimikas S. Lipoprotein(a): novel target and emergence of novel therapies to lower cardiovascular disease risk. Curr Opin Endocrinol Diabetes Obes. 2016 Apr;23(2):157-64. doi: 10.1097/MED.0000000000000237. PMID: 26825471; PMCID: PMC5061509.

Rinaldi, C., Wood, M. Antisense oligonucleotides: the next frontier for treatment of neurological disorders. Nat Rev Neurol 14, 9–21 (2018). https://doi.org/10.1038/nrneurol.2017.148