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22-07-2016 | Cardiometabolic | News | Article

LDL cholesterol variability has adverse neurocognitive effects

medwireNews: High variability in low-density-lipoprotein (LDL) cholesterol levels between visits is associated with poor cognitive performance, researchers report.

“Our findings underscore the potential of LDL-[cholesterol] variability as a useful prognostic marker for different clinical outcomes”, say Roelof Smit (Leiden University Medical Center, the Netherlands) and co-researchers.

Moreover, they found that this association was evident in both placebo-treated and pravastatin-treated patients.

“This advocates against increased LDL-[cholesterol] variability purely reflecting the known beneficial and harmful pleiotropic effects of statins or behavioral factors that may undermine response to lipid-lowering treatment, most notably nonadherence”, the team explains.

They investigated the effects of LDL cholesterol variability, defined as the intra-individual standard deviation over four LDL cholesterol measurements, on four cognitive domains in 4428 participants of the PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) study. Of these, 2202 were taking pravastatin and the remainder placebo.

In both groups, higher visit-to-visit LDL cholesterol variability was significantly associated with lower cognitive test scores. The most consistent of these was for memory measures.

For immediate recall on the 15-Picture Learning Test, scores ranged from 9.60 for placebo-treated patients in the lowest tertile for LDL cholesterol variability (0.02–0.22 mmol/L) to 9.36 for those in the highest (0.35–1.71 mmol/L), and from 9.38 to 9.08, respectively, in the pravastatin group. The findings were similar for delayed recall.

Significant associations were also seen for selective attention on the Stroop Color and Word Test among the placebo-treated patients, with scores ranging from 65.06 for patients with the lowest LDL cholesterol variability to 68.00 for those with the highest, and for information processing speed on the Letter-Digit Coding Test among pravastatin-treated patients, with scores ranging from 22.41 to 21.72, respectively.

The researchers note in Circulation that the associations remained robust when analyses were restricted to different subsets or adjusted for various common causes of LDL cholesterol variability and cognitive performance.

Also, in a subset of 535 participants with magnetic resonance imaging data available, higher LDL cholesterol variability was significantly associated with lower total cerebral blood flow in both treatment groups and greater white matter hyperintensity in the pravastatin group. There was no association with hippocampal volume in either group, however.

Given their findings, the researchers believe further investigation into the effects of lipid-lowering treatment on LDL cholesterol variability is need. And particularly warranted in patients taking proprotein convertase subtilisin-kexin type 9 inhibitors, high doses of which are known to produce substantial fluctuations in LDL cholesterol between doses, and among whom neurocognitive adverse events have been shown to occur more frequently.

By Lucy Piper

medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016

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