Lp(a) is associated with the onset but not the progression of aortic valve calcification: the Rotterdam Study (Kaiser et al., EHJ 2022)

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

Eur Heart J · 14 October 2022 · 6

Kaiser Y, van der Toorn JE, Singh SS, Zheng KH, Kavousi M, Sijbrands EJG, Stroes ESG, Vernooij MW, de Rijke YB, Boekholdt SM, Bos D

In 922 Rotterdam Study participants scanned twice 14 years apart, each 50 mg/dL higher Lp(a) raised the odds of prevalent aortic valve calcium (1.43) and of new-onset calcium (1.30) but did not predict progression once calcium was present, where the baseline score was the only predictor. Together with the Zheng 2019 stenosis cohort this suggests Lp(a) matters most for initiation and early disease, which is where a preventive trial should look. Amsterdam UMC and Erasmus MC.

Original abstract

Aim: 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.

Methods And Results: 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).

Conclusion: 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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.