较高的就诊间低密度脂蛋白胆固醇变异性与老年受试者较低的认知表现、较低的脑血流量以及较高的白质高信号负荷相关。

Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects.

作者信息

Smit Roelof A J, Trompet Stella, Sabayan Behnam, le Cessie Saskia, van der Grond Jeroen, van Buchem Mark A, de Craen Anton J M, Jukema J Wouter

机构信息

From Department of Cardiology (R.A.J.S., S.T., J.W.J.), Section of Gerontology and Geriatrics, Department of Internal Medicine (R.A.J.S., S.T., B.S., A.J.M.d.C.), Department of Radiology (B.S., J.v.d.G., M.A.v.B.), Department of Clinical Epidemiology (S.l.C.), Department of Medical Statistics and Bioinformatics (S.l.C.), and Einthoven Laboratory for Experimental Vascular Medicine (J.W.J.), Leiden University Medical Center, Leiden, The Netherlands; and Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands (J.W.J.).

出版信息

Circulation. 2016 Jul 19;134(3):212-21. doi: 10.1161/CIRCULATIONAHA.115.020627.

DOI:10.1161/CIRCULATIONAHA.115.020627

PMID:27436880

Abstract

BACKGROUND

Recently, it was shown that intraindividual variation in low-density lipoprotein cholesterol (LDL-C) predicts both cerebrovascular and cardiovascular events. We aimed to examine whether this extends to cognitive function and examined possible pathways using a magnetic resonance imaging substudy.

METHODS

We investigated the association between LDL-C variability and 4 cognitive domains at month 30 in 4428 participants of PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). Additionally, we assessed the association of LDL-C variability with neuroimaging outcomes in a subset of 535 participants. LDL-C variability was defined as the intraindividual standard deviation over 4 postbaseline LDL-C measurements, and all analyses were adjusted for mean LDL-C levels and cardiovascular risk factors.

RESULTS

Higher LDL-C variability was associated with lower cognitive function in both the placebo and pravastatin treatment arms. Associations were present for selective attention (P=0.017 and P=0.11, respectively), processing speed (P=0.20 and P=0.029), and memory (immediate recall, P=0.002 and P=0.006; delayed recall, P=0.001 and P≤0.001). Furthermore, higher LDL-C variability was associated with lower cerebral blood flow in both trial arms (P=0.031 and P=0.050) and with greater white matter hyperintensity load in the pravastatin arm (P=0.046). No evidence was found for interaction between LDL-C variability and pravastatin treatment for both cognitive and magnetic resonance imaging outcomes.

CONCLUSIONS

We found that higher visit-to-visit variability in LDL-C, independently of mean LDL-C levels and statin treatment, is associated with lower cognitive performance, lower cerebral blood flow, and greater white matter hyperintensity load.

摘要

背景

最近的研究表明，低密度脂蛋白胆固醇（LDL-C）的个体内变异可预测脑血管和心血管事件。我们旨在研究这种关联是否延伸至认知功能，并通过一项磁共振成像子研究来探究可能的途径。

方法

我们在4428名PROSPER（老年高危人群普伐他汀前瞻性研究）参与者中，调查了第30个月时LDL-C变异性与4个认知领域之间的关联。此外，我们在535名参与者的子集中评估了LDL-C变异性与神经影像学结果的关联。LDL-C变异性定义为基线后4次LDL-C测量值的个体内标准差，所有分析均对平均LDL-C水平和心血管危险因素进行了校正。

结果

在安慰剂组和普伐他汀治疗组中，较高的LDL-C变异性均与较低的认知功能相关。在选择性注意力方面存在关联（分别为P = 0.017和P = 0.11）、处理速度方面（P = 0.20和P = 0.029）以及记忆方面（即时回忆，P = 0.002和P = 0.006；延迟回忆，P = 0.001和P≤0.001）。此外，在两个试验组中，较高的LDL-C变异性均与较低的脑血流量相关（P = 0.031和P = 0.050），在普伐他汀组中与更高的白质高信号负荷相关（P = 0.046）。未发现LDL-C变异性与普伐他汀治疗之间在认知和磁共振成像结果方面存在相互作用的证据。