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

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

doi:10.1161/CIRCULATIONAHA.115.020627

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

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

Authors

Roelof A J Smit¹, Stella Trompet¹, Behnam Sabayan¹, Saskia le Cessie¹, Jeroen van der Grond¹, Mark A van Buchem¹, Anton J M de Craen¹, J Wouter Jukema¹

Affiliation

¹ 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.).

PMID: 27436880
DOI: 10.1161/CIRCULATIONAHA.115.020627

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.

Keywords: atherosclerosis; lipoproteins; magnetic resonance imaging.

Publication types

Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Attention
Cardiovascular Diseases / drug therapy
Cardiovascular Diseases / prevention & control
Cerebrovascular Circulation*
Cholesterol, LDL / blood*
Cognition Disorders / blood*
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
Magnetic Resonance Imaging
Male
Mental Recall
Pravastatin / therapeutic use
Prognosis
Socioeconomic Factors
White Matter / diagnostic imaging*

Substances

Cholesterol, LDL
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pravastatin