Journal
CIRCULATION
Volume 134, Issue 3, Pages 212-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.115.020627
Keywords
atherosclerosis; lipoproteins; magnetic resonance imaging
Funding
- Bristol-Myers Squibb
- Netherlands Heart Foundation [2001 D 032]
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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.
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