Aspirin was associated with less aortic valve calcium in people with high lipoprotein(a)

Design

prospective observational cohort, exploratory stratified analysis

Population

up to 6,598 Multi-Ethnic Study of Atherosclerosis participants, mean age 62 years, 53% women

Primary outcome

incident aortic valve calcium and incident severe aortic stenosis

Effect

with Lp(a) ≥75 mg/dL, aspirin use HR 0.42 (95% CI 0.19–0.93) for valve calcium; no association at raised LDL-C

Lipoprotein(a) is causally linked to aortic valve calcium and aortic stenosis, and it has anti-fibrinolytic properties — which is the reasoning behind asking whether aspirin might matter specifically in this group. This analysis followed up to 6,598 participants in the Multi-Ethnic Study of Atherosclerosis, measuring aortic valve calcium on non-contrast cardiac computed tomography and comparing those reporting regular aspirin use, meaning at least three days a week, with those who did not.

Mean age was 62 years, 53% were women and 23% reported regular aspirin use. Over a median 8.9 years, 8% developed aortic valve calcium; over a median 16.7 years, 1% developed severe aortic stenosis. Among participants with lipoprotein(a) at or above 75 mg/dL, regular aspirin use was associated with lower incident valve calcium (HR 0.42, 95% CI 0.19–0.93), and at or above 100 mg/dL the estimate was 0.17 (0.04–0.67). For severe stenosis at lipoprotein(a) of 75 mg/dL or more the estimate was 0.02 (0.001–0.29). No comparable association appeared in participants with raised LDL cholesterol.

The authors call this exploratory and ask for confirmatory studies, and that is the right reading. Aspirin use was self-reported, the outcome events were few, and the intervals around the largest estimates are extremely wide. It is a reason to measure lipoprotein(a) in a patient with early valve calcification, not a reason to start aspirin on the strength of a valve finding.

• Measure lipoprotein(a) once in patients with aortic valve calcification or early stenosis
• Do not start aspirin for valve disease on the basis of this analysis
• Where a patient is already on aspirin for an established indication, this is reassurance rather than a new reason to continue
• Note that lipoprotein(a) testing remains inconsistently available and is often self-funded in Indian practice
• Record the lipoprotein(a) value in the notes — it does not need repeating, so it is worth finding

Why it matters

It raises the possibility that valve calcification in high lipoprotein(a) is a modifiable process, in a disease with no medical therapy at all.

Don't overread it

This was observational and exploratory — it cannot show that giving aspirin prevents aortic stenosis.

The statistics, in plain English

Look at the width of these intervals rather than the point estimates. A hazard ratio of 0.02 with an interval running from 0.001 to 0.29 comes from very few events, and an estimate that unstable should not be read as a 98% reduction in anything. The LDL cholesterol comparisons are the useful control: intervals such as 0.66 to 1.58 include 1.0 comfortably, which is what no association looks like. The contrast between the two strata is the finding here, not the size of the effect in either.

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