# Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification

## TL;DR

High levels of lipoprotein(a) are linked to the start but not the worsening of aortic valve calcification, suggesting early interventions may help prevent the condition.

## Contribution

This study is the first to show that lipoprotein(a) influences the onset but not the progression of aortic valve calcification in a population-based cohort.

## Key findings

- Lipoprotein(a) is independently associated with baseline and new-onset aortic valve calcification.
- Lipoprotein(a) levels are not significantly linked to the progression of aortic valve calcification.
- Baseline aortic valve calcification score is strongly associated with its progression over time.

## Abstract

Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression.

A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9–14.2] years. New-onset AVC was defined as an AVC score >0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2–37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15–1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02–1.65), but not with AVC progression (β: −71 AU for each 50 mg/dL higher Lp(a); 95% CI −117; 35). Only baseline AVC score was significantly associated with AVC progression (P < 0.001).

In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease.

Structured Graphical Abstract

In the population-based Rotterdam Study, lipoprotein(a) [Lp(a)] was associated with aortic valve calcification (AVC) onset in multivariable analysis adjusted for age, sex, body mass index, smoking, dyslipidaemia, hypertension, and creatinine. In contrast, progression of AVC was only associated with baseline AVC score, implying that disease progression may take place independently of initiating risk factors. AVC, aortic valve calcification; Lp(a), lipoprotein(a).