Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
JAMA Cardiol. 2024 Sep 1;9(9):826-834. doi: 10.1001/jamacardio.2024.1874.
Lipoprotein(a) (Lp[a]) is a causal risk factor for cardiovascular disease; however, long-term effects on coronary atherosclerotic plaque phenotype, high-risk plaque formation, and pericoronary adipose tissue inflammation remain unknown.
To investigate the association of Lp(a) levels with long-term coronary artery plaque progression, high-risk plaque, and pericoronary adipose tissue inflammation.
DESIGN, SETTING, AND PARTICIPANTS: This single-center prospective cohort study included 299 patients with suspected coronary artery disease (CAD) who underwent per-protocol repeated coronary computed tomography angiography (CCTA) imaging with an interscan interval of 10 years. Thirty-two patients were excluded because of coronary artery bypass grafting, resulting in a study population of 267 patients. Data for this study were collected from October 2008 to October 2022 and analyzed from March 2023 to March 2024.
The median scan interval was 10.2 years. Lp(a) was measured at follow-up using an isoform-insensitive assay. CCTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography).
The association between Lp(a) and change in percent plaque volumes was investigated in linear mixed-effects models adjusted for clinical risk factors. Secondary outcomes were presence of low-density plaque and presence of increased pericoronary adipose tissue attenuation at baseline and follow-up CCTA imaging.
The 267 included patients had a mean age of 57.1 (SD, 7.3) years and 153 were male (57%). Patients with Lp(a) levels of 125 nmol/L or higher had twice as high percent atheroma volume (6.9% vs 3.0%; P = .01) compared with patients with Lp(a) levels less than 125 nmol/L. Adjusted for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% (95% CI, 0.04-0.60) increment in percent atheroma volume during the 10 years of follow-up. Every doubling of Lp(a) resulted in an odds ratio of 1.23 (95% CI, 1.00-1.51) and 1.21 (95% CI, 1.01-1.45) for the presence of low-density plaque at baseline and follow-up, respectively. Patients with higher Lp(a) levels had increased pericoronary adipose tissue attenuation around both the right coronary artery and left anterior descending at baseline and follow-up.
In this long-term prospective serial CCTA imaging study, higher Lp(a) levels were associated with increased progression of coronary plaque burden and increased presence of low-density noncalcified plaque and pericoronary adipose tissue inflammation. These data suggest an impact of elevated Lp(a) levels on coronary atherogenesis of high-risk, inflammatory, rupture-prone plaques over the long term.
脂蛋白(a)（Lp[a]）是心血管疾病的因果风险因素；然而，其对冠状动脉粥样硬化斑块表型、高危斑块形成和冠状动脉周围脂肪组织炎症的长期影响仍不清楚。
研究脂蛋白(a)水平与长期冠状动脉斑块进展、高危斑块和冠状动脉周围脂肪组织炎症之间的关系。
设计、地点和参与者：这是一项单中心前瞻性队列研究，纳入了 299 名疑似冠心病（CAD）患者，这些患者接受了计划内重复冠状动脉计算机断层扫描血管造影（CCTA）成像，两次扫描之间的间隔为 10 年。由于冠状动脉旁路移植术，32 名患者被排除在外，因此研究人群为 267 名患者。本研究的数据收集于 2008 年 10 月至 2022 年 10 月，并于 2023 年 3 月至 2024 年 3 月进行分析。
中位扫描间隔为 10.2 年。在随访时使用同型不敏感测定法测量脂蛋白(a)。CCTA 扫描使用先前验证的基于人工智能的算法（动脉粥样硬化成像定量计算机断层扫描）进行分析。
在调整临床危险因素的线性混合效应模型中，研究了脂蛋白(a)与斑块体积百分比变化之间的关系。次要结果是在基线和随访 CCTA 成像时存在低密斑块和存在冠状动脉周围脂肪组织衰减增加。
纳入的 267 名患者平均年龄为 57.1（SD，7.3）岁，其中 153 名为男性（57%）。脂蛋白(a)水平为 125 nmol/L 或更高的患者的动脉粥样硬化体积百分比为 6.9%，而脂蛋白(a)水平低于 125 nmol/L 的患者为 3.0%（P = .01）。调整其他危险因素后，脂蛋白(a)每增加一倍，在 10 年的随访期间，动脉粥样硬化体积百分比就会额外增加 0.32%（95%CI，0.04-0.60）。脂蛋白(a)每增加一倍，与基线和随访时存在低密斑块的比值比分别为 1.23（95%CI，1.00-1.51）和 1.21（95%CI，1.01-1.45）。脂蛋白(a)水平较高的患者在基线和随访时，右冠状动脉和左前降支周围的冠状动脉周围脂肪组织衰减都增加了。
在这项长期前瞻性系列 CCTA 成像研究中，较高的脂蛋白(a)水平与冠状动脉斑块负担的增加以及低密非钙化斑块和冠状动脉周围脂肪组织炎症的存在有关。这些数据表明，在长期内，升高的脂蛋白(a)水平对高风险、炎症性、易破裂的冠状动脉粥样硬化斑块的动脉粥样形成有影响。
