Aspirin May Play Key Role in Reducing Risk for Aortic Disease in People With High Lipoprotein(a)

 Aspirin’s use in primary prevention has narrowed sharply in recent years, but new findings suggested an important new role: reducing risk for aortic stenosis in people with elevated lipoprotein(a) (Lp[a]).

A study in the European Heart Journal showed regular aspirin use was associated with markedly lower risk of developing aortic valve calcium and severe aortic stenosis. For those with high low-density lipoprotein (LDL) cholesterol, however, this same course showed no defense against these conditions.

The prospective observational analysis included 6598 participants enrolled in the US-based cohort Multi-Ethnic Study of Atherosclerosis (MESA). Participants were men and women aged 45-84 years (mean age, 62 years) with available measures of aspirin intake and with no known clinical cardiovascular disease at enrollment. The racial and ethnic breakdown was 39% White, 28% Black, 22% Hispanic, and 12% Chinese American individuals.

Who Takes Aspirin? Did it Lower Risk?

Twenty-three percent of participants reported regular aspirin use, defined as at least 3 days per week, at baseline (2000-2002), though the exact duration of use was unknown. Participants underwent noncontrast cardiac CT to measure aortic valve calcium and were followed for a median of 8.9 years for incident aortic valve calcium and for up to 16.7 years for severe aortic stenosis.

Investigators used multivariable Cox regression modeling to determine whether baseline aspirin use was associated with new aortic valve calcium or severe aortic stenosis across prespecified Lp(a) and LDL cholesterol thresholds.

Baseline aspirin use was not linked to a lower risk for new aortic valve calcium or severe aortic stenosis in the cohort as a whole. However, among participants with elevated Lp(a), aspirin use was tied to a substantially lower risk.

Those with Lp(a) ≥ 75 mg/dL had a 58% lower risk for incident aortic valve calcium, and those with Lp(a) ≥ 100 mg/dL had an 83% lower risk. Over longer follow-up, aspirin use was also associated with an 87% lower risk for severe aortic stenosis among participants with Lp(a) ≥ 50 mg/ dL. No protective association was observed across LDL cholesterol categories.

During follow-up, 8% of participants without baseline valve calcium developed incident aortic valve calcium, and 1.3% progressed to severe — underscoring that both outcomes were relatively uncommon but clinically meaningful in a primary prevention cohort. The consistency of the association across higher Lp(a) thresholds, coupled with the absence of any signal in LDL cholesterol strata, strengthens the case for a biologically distinct Lp(a)-driven pathway in valve disease.

Importantly, increasing Lp(a) levels were independently associated with incident valve calcification, whereas LDL cholesterol levels did not show a significant trend with incident aortic valve calcium. The apparent protective association was not seen in participants with lower Lp(a) levels and was not observed with non-aspirin nonsteroidal anti-inflammatory drug use. This finding suggests a potentially Lp(a)-specific, platelet-mediated mechanism rather than a broad anti-inflammatory effect.

Lp(a), Aortic Valve Calcium Protection?

Because aspirin use was not randomized, these findings suggest a potential protective effect in people with markedly elevated Lp(a) (≥ 75-100 mg/dL). While the link between Lp(a) and calcific aortic valve disease has already been established, the Lp(a)-stratified observation that regular aspirin use was associated with lower long-term risk of developing new aortic valve calcium and severe aortic stenosis creates a solid hypothesis.

Erin Michos, MD, MHS

Erin Michos, MD, MHS, a professor of medicine in the Division of Cardiology at Johns Hopkins University School of Medicine in Baltimore, expressed excitement about what this study suggests — and how future randomized trials could provide tools for practitioners.

The findings are “really fascinating and suggest that some of the risk of valve calcification may be related to prothrombotic properties of Lp(a) because aspirin does not lower LDL cholesterol or [apolipoprotein B],” she said.

Michos also believes clinicians could conservatively apply the results of the study in their practice today.

“For patients with high Lp(a) who are not at high risk for bleeding but are at high risk for vascular or calcific valvular disease, aspirin is something we can cautiously consider offering them to help mitigate this risk,” she said. “It is a discussion I am already having with my patients with high Lp(a) about risks vs potential benefits with low-dose aspirin. But we need a dedicated aspirin trial to confirm this benefit before more concrete guidance can be issued.”

Seamus Whelton, MD

Seamus Whelton, MD, an assistant professor at the Johns Hopkins School of Medicine and a co-author of the study, agreed future findings could be a game changer in preventive therapy for aortic stenosis.

“Aortic stenosis is one of the very few cardiovascular diseases without a preventive therapy,” he said. “A randomized clinical trial that showed a reduced risk of severe aortic stenosis with low-dose aspirin for patients with very high Lp(a) would change the entire paradigm for identifying and treating aortic stenosis. It would also have the benefit of being a low-cost medication, which would reduce barriers to treatment.”

Michos and Whelton reported having no relevant financial relationships.

https://www.medscape.com/viewarticle/aspirin-may-play-key-role-reducing-risk-aortic-disease-2026a100074w