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脂蛋白(a)水平升高的无症状个体中,杂合子家族性高胆固醇血症患者与非患者相比,冠状动脉微血管功能障碍的发生率更高。

Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia.

机构信息

Cardio Metabolic Unit, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

出版信息

Atherosclerosis. 2024 Feb;389:117439. doi: 10.1016/j.atherosclerosis.2023.117439. Epub 2023 Dec 30.

Abstract

BACKGROUND AND AIMS

Microvascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH).

METHODS

Four groups of asymptomatic individuals aged 30-59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry.

RESULTS

The groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups.

CONCLUSIONS

Coronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.

摘要

背景与目的

微血管功能障碍是许多心血管疾病的基础;然而,目前对于脂蛋白(a) [Lp(a)]水平较高的个体中是否存在这种功能障碍知之甚少。本研究旨在确定伴有或不伴有家族性高胆固醇血症(FH)的此类个体中微血管功能障碍的发生频率。

方法

招募了四组年龄在 30-59 岁、无明显心血管疾病的无症状个体(每组 30 人):脂蛋白(a) < 30 nmol/L 的对照组、脂蛋白(a) < 30 nmol/L 但突变确认的 FH 组、脂蛋白(a) > 125 nmol/L 的 FH 组,以及脂蛋白(a) > 125 nmol/L 的单纯脂蛋白(a)升高组。通过经胸多普勒超声心动图测量冠状动脉血流储备(CFR)评估心肌微血管功能,并通过外周动脉张力测定评估外周微血管内皮功能。

结果

各组在年龄、性别和体重指数方面平衡。三个血脂异常组中,有更多的个体存在冠状动脉血流储备受损,分别为 30%,而对照组为 6.7%(p = 0.014)。然而,四组间的 CFR 中位数水平无显著差异。FH + Lp(a) > 125 组中,CFR 正常者的降脂治疗时间长于 CFR 受损者(p = 0.023),而 FH + Lp(a) < 30 组中降脂治疗时间无差异(p = 0.468)。各组间的外周内皮功能无差异。

结论

与健康对照组相比,单纯脂蛋白(a)升高的无症状个体以及杂合性 FH 患者,无论是否伴有高脂蛋白(a),其冠状动脉微血管功能障碍更为常见。降脂治疗可能有助于预防微血管功能障碍的发生。

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