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可溶性 LR11 与家族性高胆固醇血症无症状治疗男性患者的主动脉根部钙化相关。

Soluble LR11 associates with aortic root calcification in asymptomatic treated male patients with familial hypercholesterolemia.

机构信息

Department of Internal Medicine, Laboratory of Vascular Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

Atherosclerosis. 2017 Oct;265:299-304. doi: 10.1016/j.atherosclerosis.2017.06.018. Epub 2017 Jun 9.

Abstract

BACKGROUND AND AIMS

Despite statin treatment, a high prevalence of severe vascular calcification is found in patients with familial hypercholesterolemia (FH). We assessed the relation between the circulating soluble form of low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11), a risk factor for cardiovascular disease, and vascular calcification in asymptomatic statin-treated heterozygous FH patients.

METHODS

In 123 asymptomatic heterozygous FH patients (age 40-69 years), aortic root (ARC), aortic valve (AVC) and coronary artery calcification (CAC) were determined with CT-based calcium scoring expressed in Agatston units. Plasma sLR11 levels were measured by sandwich ELISA.

RESULTS

Seventy-three patients displayed ARC, 48 had AVC and 96 CAC. Plasma sLR11 levels were positively correlated with the presence of ARC (r = 0.2, p = 0.03), but not with AVC or CAC. The correlation between sLR11 levels and ARC was restricted to male FH patients (r = 0.31, p = 0.006). Multivariate logistic analyses showed that the association of plasma sLR11 with the presence of ARC was independent of other determinants (Adjusted Odds Ratio, 2.01 (95% CI = 1.28-3.16) p = 0.002).

CONCLUSIONS

Plasma sLR11 is associated with ARC in male FH patients and may be mechanistically involved in the differential distribution of atherosclerotic lesions in the vasculature.

摘要

背景与目的

尽管进行了他汀类药物治疗,家族性高胆固醇血症(FH)患者仍存在高发的严重血管钙化。我们评估了循环中 LDL 受体可溶性形式(sLR11)与心血管疾病风险因素之间的关系,以及无症状他汀类药物治疗的杂合子 FH 患者的血管钙化。

方法

在 123 名无症状的杂合子 FH 患者(年龄 40-69 岁)中,使用 CT 基于钙评分法以 Agatston 单位表示评估主动脉根部(ARC)、主动脉瓣(AVC)和冠状动脉钙化(CAC)。通过夹心 ELISA 法测量血浆 sLR11 水平。

结果

73 例患者显示 ARC,48 例患者显示 AVC,96 例患者显示 CAC。血浆 sLR11 水平与 ARC 的存在呈正相关(r=0.2,p=0.03),但与 AVC 或 CAC 无关。sLR11 水平与 ARC 之间的相关性仅限于男性 FH 患者(r=0.31,p=0.006)。多变量逻辑分析表明,血浆 sLR11 与 ARC 的存在之间的关联独立于其他决定因素(调整后的优势比,2.01(95%CI=1.28-3.16),p=0.002)。

结论

血浆 sLR11 与男性 FH 患者的 ARC 相关,并且可能在血管中动脉粥样硬化病变的差异分布中具有机制作用。

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