Krzesińska Aleksandra, Kłosowska Anna, Sałaga-Zaleska Kornelia, Ćwiklińska Agnieszka, Mickiewicz Agnieszka, Chyła Gabriela, Wierzba Jolanta, Jankowski Maciej, Kuchta Agnieszka
Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
Department of Paediatrics, Haemathology and Oncology, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
J Clin Med. 2022 Jul 27;11(15):4356. doi: 10.3390/jcm11154356.
The improvement in the lifespan of individuals with Down syndrome (DS) has created interest in the context of the development of age-related diseases. Among them is atherosclerosis-based cardiovascular disease (CVD), which seems to be an especially urgent and important issue. The aim of the present study was to evaluate the lipid markers that may clarify cardiovascular risk profiles in individuals with DS. To this end, we analyzed lipid profile parameters, including lipoprotein(a) (Lp(a)) levels, protein composition, and the antioxidative properties of high-density lipoprotein (HDL), in 47 adolescents with DS and 47 individuals without DS. Compared with the control group (C), subjects with DS had significantly increased concentrations of low-density lipoprotein cholesterol (105 ± 31 vs. 90 ± 24 mg/dL, p = 0.014), non-high-density lipoprotein cholesterol (120 ± 32 vs. 103 ± 26 mg/dL, p = 0.006), and triglycerides (72 [55−97] vs. 60 [50−77] mg/dL, p = 0.048). We found that patients with DS were characterized by significantly higher Lp(a) levels (31.9 [21.5−54.3] vs. 5.2 (2.4−16.1) mg/dL, p < 0.001). In fact, 57% of individuals with DS had Lp(a) levels above 30 mg/dL, which was approximately four times higher than those in the control group (DS 57% vs. C 15%). Apart from decreased high-density lipoprotein cholesterol levels in the subjects with DS (53 ± 11 vs. 63 ± 12 mg/dL, p < 0.001), differences in parameters showing the quality of HDL particles were observed. The concentrations of the main proteins characterizing the HDL fraction, apolipoprotein A-I and apolipoprotein A-II, were significantly lower in the DS group (144 ± 21 vs. 181 ± 33 mg/dL, p < 0.001; 33 ± 6 vs. 39 ± 6 mg/dL, p < 0.001, respectively). No significant differences between the groups were observed for the concentration of paraoxonase-1 (DS 779 ± 171 vs. C 657 ± 340 ng/mL, p = 0.063), enzyme activities toward paraoxon (DS 219 [129−286] vs. C 168 [114−272] IU/L, p = 0.949), or phenyl acetate (DS 101 ± 20 vs. C 93 ± 21 kIU/L, p = 0.068). There were no differences in myeloperoxidase activity between the study groups (DS 327 [300−534] vs. C 426 [358−533] ng/mL, p = 0.272). Our results are the first to demonstrate an unfavorable lipid profile combined with higher Lp(a) levels and quality changes in HDL particles in individuals with DS. This sheds new light on cardiovascular risk and traditional healthcare planning for adolescents with DS.
唐氏综合征(DS)患者寿命的延长引发了人们对其与年龄相关疾病发展情况的关注。其中,基于动脉粥样硬化的心血管疾病(CVD)似乎是一个尤为紧迫且重要的问题。本研究的目的是评估可能阐明DS患者心血管风险状况的脂质标志物。为此,我们分析了47名DS青少年和47名非DS个体的脂质谱参数,包括脂蛋白(a)(Lp(a))水平、蛋白质组成以及高密度脂蛋白(HDL)的抗氧化特性。与对照组(C)相比,DS患者的低密度脂蛋白胆固醇浓度显著升高(105±31 vs. 90±24 mg/dL,p = 0.014)、非高密度脂蛋白胆固醇浓度显著升高(120±32 vs. 103±26 mg/dL,p = 0.006)以及甘油三酯浓度显著升高(72 [55 - 97] vs. 60 [50 - 77] mg/dL,p = 0.048)。我们发现DS患者的Lp(a)水平显著更高(31.9 [21.5 - 54.3] vs. 5.2 (2.4 - 16.1) mg/dL,p < 0.001)。事实上,57%的DS个体Lp(a)水平高于30 mg/dL,这大约是对照组的四倍(DS为57%,C为15%)。除了DS患者的高密度脂蛋白胆固醇水平降低(53±11 vs. 63±12 mg/dL,p < 0.001)外,还观察到了显示HDL颗粒质量的参数差异。DS组中表征HDL组分的主要蛋白质载脂蛋白A-I和载脂蛋白A-II的浓度显著更低(分别为144±21 vs. 181±33 mg/dL,p < 0.001;33±6 vs. 39±6 mg/dL,p < 0.001)。两组之间对氧磷酶-1的浓度(DS为779±171 vs. C为657±340 ng/mL,p = 0.063)、对氧磷酶活性(DS为219 [129 - 286] vs. C为168 [114 - 272] IU/L,p = 0.949)或苯乙酸酯(DS为101±20 vs. C为93±21 kIU/L,p = 0.068)未观察到显著差异。研究组之间髓过氧化物酶活性没有差异(DS为327 [300 - 534] vs. C为426 [358 - 533] ng/mL,p = 0.272)。我们的结果首次证明了DS个体存在不利的脂质谱,伴有更高的Lp(a)水平以及HDL颗粒的质量变化。这为DS青少年的心血管风险和传统医疗保健规划提供了新的见解。