Department of Epidemiology and Data Science, Amsterdam UMC-University of Amsterdam, Amsterdam, Netherlands; Department of Pediatrics, Amsterdam UMC-University of Amsterdam, Amsterdam, Netherlands.
Department of Pediatrics, Amsterdam UMC-University of Amsterdam, Amsterdam, Netherlands; Diabetes and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.
Lancet Diabetes Endocrinol. 2023 Sep;11(9):667-674. doi: 10.1016/S2213-8587(23)00156-0. Epub 2023 Jul 21.
Elevated lipoprotein(a) and familial hypercholesterolaemia are both independent risk conditions for cardiovascular disease. Although signs of atherosclerosis can be observed in children with familial hypercholesterolaemia, it is unknown whether elevated lipoprotein(a) is an additional risk factor for atherosclerosis in these young patients. Therefore, we aimed to assess the contribution of lipoprotein(a) concentrations to arterial wall thickening (as measured by carotid intima-media thickness) in children with familial hypercholesterolaemia who were followed up into adulthood.
We conducted a 20-year follow-up study of 214 children (aged 8-18 years) with heterozygous familial hypercholesterolaemia who were randomly assigned in a statin trial in Amsterdam (Netherlands) between Dec 7, 1997, and Oct 4, 1999. At baseline, and at 2, 10, and 20 years thereafter, blood samples were taken and carotid intima-media thickness was measured. Linear mixed-effects models were used to evaluate the association between lipoprotein(a) and carotid intima-media thickness during follow-up. We adjusted for sex, age, corrected LDL-cholesterol, statin use, and BMI.
Our study population comprised 200 children who had a carotid intima-media thickness measurement and a measured lipoprotein(a) concentration from at least one visit available. Mean age at baseline was 13·0 years (SD 2·9), 106 (53%) children were male, and 94 (47%) were female. At baseline, median lipoprotein(a) concentration was 18·5 nmol/L (IQR 8·7-35·5) and mean carotid intima-media thickness was 0·4465 mm (SD 0·0496). During follow-up, higher lipoprotein(a) concentrations contributed significantly to progression of carotid intima-media thickness (β adjusted 0·0073 mm per 50 nmol/L increase in lipoprotein(a) [95% CI 0·0013-0·0132]; p=0·017).
Our findings suggest that lipoprotein(a) concentrations contribute significantly to arterial wall thickening in children with familial hypercholesterolaemia who were followed-up until adulthood, suggesting that lipoprotein(a) is an independent and additional risk factor for early atherosclerosis in those already at increased risk. Lipoprotein(a) measurement in young patients with familial hypercholesterolaemia is crucial to identify those at potentially highest risk for cardiovascular disease.
Silence Therapeutics.
脂蛋白(a)升高和家族性高胆固醇血症都是心血管疾病的独立危险因素。尽管家族性高胆固醇血症患儿可观察到动脉粥样硬化的迹象，但脂蛋白(a)是否是这些年轻患者动脉粥样硬化的另一个危险因素尚不清楚。因此，我们旨在评估脂蛋白(a)浓度对成年后随访的家族性高胆固醇血症患儿的动脉壁增厚（通过颈动脉内膜中层厚度测量）的贡献。
我们对 1997 年 12 月 7 日至 1999 年 10 月 4 日在阿姆斯特丹（荷兰）进行的他汀类药物试验中随机分配的 214 名 8-18 岁杂合子家族性高胆固醇血症患儿进行了 20 年的随访研究。基线时以及此后 2、10 和 20 年时，采集血样并测量颈动脉内膜中层厚度。线性混合效应模型用于评估随访期间脂蛋白(a)与颈动脉内膜中层厚度之间的关联。我们调整了性别、年龄、校正后的 LDL 胆固醇、他汀类药物的使用和 BMI。
我们的研究人群包括 200 名至少有一次就诊时可测量脂蛋白(a)浓度和颈动脉内膜中层厚度的患儿。基线时的平均年龄为 13.0 岁（标准差 2.9），106 名（53%）患儿为男性，94 名（47%）为女性。基线时，脂蛋白(a)浓度中位数为 18.5 nmol/L（IQR 8.7-35.5），颈动脉内膜中层厚度平均值为 0.4465mm（SD 0.0496）。在随访期间，脂蛋白(a)浓度升高与颈动脉内膜中层厚度的进展显著相关（每增加 50nmol/L 的脂蛋白(a)，β 调整后增加 0.0073mm[95%CI 0.0013-0.0132]；p=0.017）。
我们的研究结果表明，脂蛋白(a)浓度对成年后随访的家族性高胆固醇血症患儿的动脉壁增厚有显著贡献，这表明脂蛋白(a)是这些已经处于高风险的患者早期动脉粥样硬化的独立和额外危险因素。在家族性高胆固醇血症的年轻患者中测量脂蛋白(a)对于确定那些具有潜在最高心血管疾病风险的患者至关重要。
Silence Therapeutics。
