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.
| Original language | English |
|---|---|
| Pages (from-to) | 3960-3967 |
| Number of pages | 8 |
| Journal | European Heart Journal |
| Volume | 43 |
| Issue number | 39 |
| DOIs | |
| Publication status | Published - 14 Oct 2022 |
Bibliographical note
FundingThe Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam; The Netherlands Organization for Scientific
Research; The Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the
Elderly; The Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports;
European Commission; and the Municipality of Rotterdam. Y.K. and E.S.G.S. were supported by the Netherlands Heart Foundation CVON
2017–20: generating the best evidence-based pharmaceutical targets for atherosclerosis (GENIUS II). D.B. was supported by a fellowship from
the BrightFocus Foundation (A2017424F). Amgen Netherlands BV funded part of this work and in particular the Lp(a) measurements.
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