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.

中文翻译：

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脂蛋白（a）与主动脉瓣钙化的发生有关，但与进展无关

目的 脂蛋白 (a) [Lp(a)] 是主动脉瓣疾病发病机制中的潜在致病因素。然而，Lp(a) 与主动脉瓣钙化 (AVC) 的新发作和进展之间的关系尚未得到研究。该研究的目的是评估高血清 Lp(a) 水平是否与 AVC 发生率和进展相关。方法和结果 来自基于人群的鹿特丹研究的 922 名个体（平均年龄 66.0±4.2 岁，47.7% 为男性），其 Lp(a) 测量可用，在基线和中位随访时间为 14.0 [四分位数间距 (IQR) 13.9–14.2] 年。新发 AVC 定义为在第一次扫描没有 AVC 的情况下，后续扫描的 AVC 评分＞0。进展被定义为基线和后续扫描之间 AVC 评分的绝对差异。进行逻辑和线性回归分析以评估 Lp(a) 与 AVC 的基线、新发和进展之间的关系。所有分析都针对年龄、性别、体重指数、吸烟、高血压、血脂异常和肌酐进行了校正。AVC 进展分析以基线 AVC 分数为条件，表示为受限三次样条。在基线时没有 AVC 的 702 名个体中，415 名 (59.1%) 在后续扫描中出现了新发的 AVC。在具有基线 AVC 的患者中，年进展中位数为 13.5 (IQR = 5.2–37.8) Agatston 单位 (AU)。脂蛋白 (a) 浓度与基线 AVC 独立相关 [比值比 (OR) 每升高 50 mg/dL Lp(a) 为 1.43；95% 置信区间 (CI) 1.15–1。79] 和新发 AVC（Lp(a) 每升高 50 mg/dL，OR 为 1.30；95% CI 1.02–1.65），但不伴随 AVC 进展（β：Lp 每升高 50 mg/dL，-71 AU（ a); 95% CI -117; 35). 只有基线 AVC 评分与 AVC 进展显着相关 (P < 0.001)。结论 在基于人群的鹿特丹研究中，Lp(a) 与基线和新发 AVC 密切相关，但与 AVC 进展无关，这表明降低 Lp(a) 的干预措施可能在主动脉瓣钙化前阶段最有效疾病。