Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Eur Heart J. 2013 Jan;34(4):286-91. doi: 10.1093/eurheartj/ehs376. Epub 2012 Nov 7.
Low HDL-C is a potent risk factor for cardiovascular disease (CVD). Yet, mutations in ABCA1, a major determinant of circulating HDL-C levels, were previously not associated with CVD risk in cohort studies. To study the consequences of low plasma levels of high-density lipoprotein cholesterol (HDL-C) due to ATP-binding cassette transporter A1 (ABCA1) dysfunction for atherosclerotic vascular disease in the carotid arteries.
We performed 3.0 Tesla magnetic resonance imaging (MRI) measurements of the carotid arteries in 36 carriers of high impact functional ABCA1 mutations and 36 normolipidemic controls. Carriers presented with 42% lower HDL-C levels (P < 0.001), a larger mean wall area (18.6 ± 6.0 vs. 15.8 ± 4.3 mm(2); P = 0.02), a larger mean wall thickness (0.82 ± 0.21 vs. 0.70 ± 0.14 mm; P = 0.005), and a higher normalized wall index (0.37 ± 0.06 vs. 0.33 ± 0.04; P = 0.005) compared with controls, retaining significance after adjustment for smoking, alcohol consumption, systolic blood pressure, diabetes, body mass index, history of CVD, LDL-C, and statin use (P = 0.002).
Carriers of loss of function ABCA1 mutations display a larger atherosclerotic burden compared with age and sex-matched controls, implying a higher risk for CVD. Further studies are needed to elucidate the full function of ABCA1 in the protection against atherosclerosis. These data support the development of strategies to up-regulate ABCA1 in patients with established CVD.
低 HDL-C 是心血管疾病（CVD）的一个强有力的危险因素。然而，在队列研究中，载脂蛋白 A1（ABCA1）是循环 HDL-C 水平的主要决定因素，其突变与 CVD 风险之前并无关联。本研究旨在研究由于 ABCA1 功能障碍导致的血浆高密度脂蛋白胆固醇（HDL-C）水平降低对颈动脉粥样硬化血管疾病的影响。
我们对 36 名高影响功能 ABCA1 突变携带者和 36 名血脂正常对照者进行了 3.0T 磁共振成像（MRI）颈动脉测量。携带者的 HDL-C 水平降低了 42%（P<0.001），平均壁面积增大（18.6±6.0 与 15.8±4.3mm²；P=0.02），平均壁厚度增大（0.82±0.21 与 0.70±0.14mm；P=0.005），归一化壁指数升高（0.37±0.06 与 0.33±0.04；P=0.005），与对照组相比差异有统计学意义，调整吸烟、饮酒、收缩压、糖尿病、体重指数、CVD 病史、LDL-C 和他汀类药物使用后仍有统计学意义（P=0.002）。
与年龄和性别匹配的对照组相比，丧失功能 ABCA1 突变携带者的动脉粥样硬化负担更大，提示 CVD 风险更高。需要进一步研究以阐明 ABCA1 在预防动脉粥样硬化方面的全部功能。这些数据支持开发针对已确诊 CVD 患者的 ABCA1 上调策略。
