High Lp(a) Signals Risk Beyond The Coronaries
Elevated levels of lipoprotein(a) [Lp(a)] were associated with significantly increased risks for incident peripheral artery disease and carotid artery stenosis. Among patients with peripheral artery disease, those with high levels of Lp(a) (≥ 150 nmol/L) had a high risk of progressing to major adverse limb events.
METHODOLOGY:
Despite lifestyle interventions and therapies for lowering levels of cholesterol, a residual risk for major atherosclerotic complication persists.
Researchers analyzed data from a large prospective biobank (2006-2010) to investigate whether baseline levels of Lp(a) predict the risk for onset and progression of extracoronary atherosclerotic vascular disease — a combination of peripheral artery disease and carotid artery stenosis.
The UK biobank data included 460,544 individuals (average age at enrollment, 57 years; 54.2% men; 94.9% European) and followed them for a median duration of 13.6 years.
Data on baseline serum levels of Lp(a) were retrieved, with levels ≥ 150 nmol/L (about 70 mg/dL) defined as high.
The analysis assessed the incidence of peripheral artery disease and carotid artery stenosis and the progression to both the first major adverse limb event and first stroke.
TAKEAWAY:
Individuals with high levels of Lp(a) were older and more often men than those with normal levels of Lp(a) (P < .001 for both).
Each 75-nmol/L (35 mg/dL) increase in levels of Lp(a) was associated with a 1.18-fold elevated risk for incident peripheral artery disease and a 1.17-fold increased risk for incident carotid artery stenosis (P < .0001 for both).
Among patients with peripheral artery disease, those with high levels of Lp(a) had a 1.6-fold higher risk of developing major adverse limb events than those with normal levels of Lp(a) (P = .004).
IN PRACTICE:
'Participants with established atherosclerotic vascular disease and elevated Lp(a) concentrations may represent the ideal group to benefit from targeted preventive interventions,' the researchers noted.
'[The study's] findings make a strong case to explore the effect of therapies to lower Lp(a) in participants with PAD [peripheral artery disease] and carotid stenosis towards the goal of slowing disease progression and reducing major complications of amputation and stroke,' they added.
SOURCE:
This study was led by Tiffany R. Bellomo, MD, of Broad Institute of Harvard and MIT, Cambridge, Massachusetts. It was published online on July 28, 2025, in Circulation.
LIMITATIONS:
Measuring Lp(a) using immunoassays may be inaccurate for individuals with large Lp(a) isoforms. This study lacked measurement of ankle-brachial index to define peripheral arterial disease. The analysis may not have accounted for all potential confounding factors.
DISCLOSURES:
This study received grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute. One author reported receiving research grants and personal fees from several pharmaceutical and healthcare companies and holding equity in multiple healthcare data and biotech firms. The same author reported spousal employment at a pharmaceutical company.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
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