What is the clinical evidence from this study?

Study design: Cohort. Population: Calcific aortic valve stenosis (CAVS) (n=1962). Intervention: Lp(a) levels ≥125 nmol/L vs. Lp(a) levels <125 nmol/L. Primary outcome: Aortic valve replacement (AVR) (HR 1.58, 95% CI 1.17-2.12).

March 13, 2025Open Access

Impact of Lipoprotein(a) on Valvular and Cardiovascular Outcomes in Patients With Calcific Aortic Valve Stenosis

Q: What are the key findings of this study?

In patients with calcific aortic valve stenosis, Lp(a) levels ≥125 nmol/L were associated with a higher risk of aortic valve replacement (HR 1.58; 95% CI 1.17-2.12) compared to levels <125 nmol/L.

Key Result

In patients with calcific aortic valve stenosis, Lp(a) levels ≥125 nmol/L were associated with a higher risk of aortic valve replacement (HR 1.58; 95% CI 1.17-2.12) compared to levels <125 nmol/L.

Study Design

Type

Cohort (n=1,962)

Multicenter

Yes

Structured PICO

Do elevated Lipoprotein(a) levels (≥125 nmol/L) increase the risk of valvular and cardiovascular events in patients with calcific aortic valve stenosis?

Population

1,962 patients from the UK Biobank with an electronic health record or self-reported calcific aortic valve stenosis (CAVS) diagnosis, no prior aortic valve replacement (AVR), and a minimal follow-up time of 2.5 years.

Intervention

Lipoprotein(a) levels ≥125 nmol/L

Comparator

Lipoprotein(a) levels <125 nmol/L

Outcome

Aortic valve replacement (AVR), composite of AVR or cardiac death, and composite of valvular or cardiovascular events (AVR, cardiac death, myocardial infarction, stroke, heart failure, or coronary artery bypass grafting) at up to 5 years follow-upcomposite

In patients with calcific aortic valve stenosis, elevated Lipoprotein(a) levels (≥125 nmol/L) are associated with a significantly increased risk of aortic valve replacement and cardiovascular events.

Main Result

Effect estimate: HR 1.58 (95% CI 1.17-2.12)

Abstract

BACKGROUND: Lp(a) (lipoprotein(a)) is an independent risk factor for calcific aortic valve stenosis (CAVS). Whether patients with CAVS and high Lp(a) levels are at higher risk of valvular or cardiovascular events is unknown. The aim of this study is to determine whether higher Lp(a) levels are associated with valvular and cardiovascular outcomes in patients with CAVS. METHODS AND RESULTS: We identified 1962 patients from the UK Biobank with an electronic health record or self-reported CAVS diagnosis but who did not previously undergo aortic valve replacement (AVR) and had a minimal follow-up time of 2.5 years. Cox proportional hazard regression was used to evaluate the effect of Lp(a) on AVR, AVR or cardiac death, and valvular or cardiovascular events (AVR, cardiac death, myocardial infarction, stroke, heart failure, or coronary artery bypass grafting). The maximal follow-up time was set to 5 years. During the follow-up, 198 patients underwent AVR, 260 had AVR or cardiac death, and 435 had at least 1 valvular or cardiovascular event. Patients with Lp(a) levels ≥125 versus <125 nmol/L were at higher risk of AVR (hazard ratio HR, 1.58 95% CI, 1.17-2.12), AVR or cardiac death (HR, 1.43 95% CI, 1.10-1.86), and cardiovascular or valvular events (HR, 1.36 95% CI, 1.11-1.68). Point estimates were comparable in men versus women, younger versus older patients, and in patients with higher versus lower plasma C-reactive protein levels. CONCLUSIONS: In patients with CAVS, Lp(a) levels predicted a higher risk of valvular and cardiovascular outcomes. The impact of Lp(a)-lowering therapies on valvular and cardiovascular health should be assessed in a long-term randomized clinical trial.