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肾移植受者中的小而密低密度脂蛋白:预防心血管并发症的潜在靶点?

Small dense low-density lipoprotein in renal transplant recipients: a potential target for prevention of cardiovascular complications?

作者信息

Badiou S, Garrigue V, Dupuy A M, Chong G, Cristol J P, Mourad G

机构信息

Biochemistry Laboratory, Hôpital Lapeyronie, University of Montpellier Medical School, 371 avenue du doyen Gaston Giraud, 34295 Montpellier 05, France.

出版信息

Transplant Proc. 2006 Sep;38(7):2314-6. doi: 10.1016/j.transproceed.2006.07.003.

Abstract

BACKGROUND

Immunosuppressive therapy is frequently associated with dyslipidemia, which is involved in cardiovascular morbidity and mortality in transplant patients. Beyond classical factors, such as low-density lipoprotein (LDL) cholesterol (LDL-C), qualitative abnormalities of lipoproteins, such as presence of the atherogenic factor, small dense LDL, may be of interest for a cardiovascular risk assessment. This study was designed to explore LDL size in renal transplant recipients in relation to quantitative lipid parameters and apolipoprotein (apo) CIII polymorphism.

METHODS

Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, apoA1, apoB, apoCIII, and LDL size were measured in 62 patients of mean age 45 +/- 13 years including 71% men at 2 +/- 0.5 years after renal transplantation. Thirty-two patients received cyclosporine (CsA), while 30 received tacrolimus (FK). ApoCIII Sstl genotype was determined by restriction fragment length polymorphism.

RESULTS

The CsA group exhibited higher TC (P = .001), LDL-C (P = .004), non-HDL-C (P = .009), HDL-C (P = .03), apoB (P = .008), and apoCIII (P = .002) levels than the FK group. However, LDL-C (CsA: 3.7 +/- 1.2, FK: 3.0 +/- 0.6 mmol/L) and triglyceride levels (CsA: 1.55 mmol/L, FK: 1.37 mmol/L) were near the normal range in both groups. Allelic frequency of the sparse A2 allele associated with hypertriglyceridemia was 6%, similar to the general population. LDL size, which was comparable in the CsA and FK groups (25.87 +/- 0.89 vs 25.75 +/- 0.62 nm, respectively), inversely correlated with TG/HDL ratio (P = 10(-4)). Prevalence of small dense LDL (defined as <25.5 nm) was 26% in the CsA group and 33% in the FK group.

CONCLUSION

After LDL-C goal has been achieved, LDL size modulation may be taken into account in order to prevent cardiovascular complications.

摘要

背景

免疫抑制治疗常与血脂异常相关,这与移植患者的心血管发病率和死亡率有关。除了经典因素,如低密度脂蛋白(LDL)胆固醇(LDL-C)外,脂蛋白的定性异常,如致动脉粥样硬化因子小而密LDL的存在,可能对心血管风险评估有意义。本研究旨在探讨肾移植受者的LDL大小与定量血脂参数及载脂蛋白(apo)CIII多态性的关系。

方法

对62例平均年龄45±13岁的患者进行了总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、LDL-C、apoA1、apoB、apoCIII和LDL大小的检测,其中男性占71%,检测时间为肾移植后2±0.5年。32例患者接受环孢素(CsA)治疗,30例接受他克莫司(FK)治疗。通过限制性片段长度多态性确定apoCIII Sstl基因型。

结果

CsA组的TC(P = 0.001)、LDL-C(P = 0.004)、非HDL-C(P = 0.009)、HDL-C(P = 0.03)、apoB(P = 0.008)和apoCIII(P = 0.002)水平均高于FK组。然而,两组的LDL-C(CsA组:3.7±1.2,FK组:3.0±0.6 mmol/L)和甘油三酯水平(CsA组:1.55 mmol/L,FK组:1.37 mmol/L)均接近正常范围。与高甘油三酯血症相关的稀少A2等位基因的等位基因频率为6%,与一般人群相似。CsA组和FK组的LDL大小相当(分别为25.87±0.89和25.75±0.62 nm),与TG/HDL比值呈负相关(P = 10⁻⁴)。小而密LDL(定义为<25.5 nm)的患病率在CsA组为26%,在FK组为33%。

结论

在达到LDL-C目标后,为预防心血管并发症,可考虑调节LDL大小。

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