Department of Medicine, Division of Cardiology (A.E.B., C.J.R.), Albert Einstein College of Medicine, Bronx NY.
Division of Geriatrics (A.E.B.), Albert Einstein College of Medicine, Bronx NY.
Arterioscler Thromb Vasc Biol. 2022 Oct;42(10):1272-1282. doi: 10.1161/ATVBAHA.122.318004. Epub 2022 Aug 18.
Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC.
We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6784).
After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups.
In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.
主动脉瓣钙化（AVC）与动脉粥样硬化具有相同的病理特征。在主动脉瓣组织中已经检测到脂蛋白成分，包括高密度脂蛋白（HDL）。HDL 水平与心血管疾病呈负相关，但与长期 AVC 进展的关系尚不清楚。我们研究了 HDL 胆固醇、HDL 颗粒数和大小、载脂蛋白 C3 定义的 HDL 亚型以及其次的胆固醇酯转移蛋白（CETP）质量和活性与 AVC 的长期发生和进展之间的关系。
我们使用线性混合效应模型来评估基线 HDL 指数与 AVC 的关系。在动脉粥样硬化多民族研究（Multi-Ethnic Study of Atherosclerosis，MESA）中，在中位数为 8.9 年（最长 11.2 年）的随访中，通过对多达 3 次连续计算机断层扫描的 Agatston 评分来定量评估 AVC（n=6784）。
调整后，HDL-C（高密度脂蛋白胆固醇）、HDL-P（HDL 颗粒）、大 HDL-P 和载脂蛋白 C3 缺乏的 HDL-C 浓度较高与 AVC 的发生率/进展呈负相关。小或中等大小的 HDL-P 或载脂蛋白 C3 含量的 HDL-C 与 AVC 的发生率/进展均无显著相关性。当一起包含时，仅观察到 HDL-C 与 AVC 之间存在显著关联，而不是 HDL-P。二次分析显示 CETP 质量与 AVC 的发生率/进展呈负相关，但 CETP 活性则不然。在探索性评估中，HDL-C、HDL-P、大 HDL-P 和载脂蛋白 C3 缺乏的 HDL 与 AVC 的发生率/进展之间的负相关在年龄较大、男性和白人参与者中更为明显。在这些亚组中，载脂蛋白 C3 含量的 HDL-C 仅与 AVC 呈正相关。
在多民族人群中，HDL-C、HDL-P、大 HDL-P 和载脂蛋白 C3 缺乏的 HDL 与 AVC 的长期发生率和进展呈负相关。进一步研究 HDL 成分和机制可能有助于了解减缓 AVC 的途径。
