Abstract WP181: Statin Usage Increases White Matter Hyperintensities: A Post-hoc Analysis Of SPRINT-MIND

Abstract

Introduction: White matter hyperintensity (WMH), a radiographic marker of cerebral small vessel disease, is typically treated by modification of conventional cerebrovascular risk factors. However, the influence of dyslipidemia and the impact of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) on WMH is less certain. The goal of this study was to evaluate the influence of statins on progression of WMH over a four-year interval. Methods: We performed a post-hoc analysis of the SPRINT-MIND database for participants who had completed a baseline and a 4-year follow-up brain MRI with volumetric WMH calculations. Follow-up visits within this time window included data on medications, including statins. We defined statin usage as no therapy (0% of visits), partial therapy (1 - 99% of visits) or full therapy (100% of visits) based on this self-reported data. WMH progression was calculated as the difference in WMH volume between the two scans and then segmented into tertiles. ANOVA and chi-squared tests were used for continuous and categorical variables with adjustments made for variables known to influence WMH development. Results: 425 individuals were included in this study: 53% (226/425) without statins use, 27% (115/425) with partial use and 20% (84/425) and full use. Demographic characteristics and baseline WMH volumes were similar amongst the cohort. With increasing statin use, a significant reduction in LDL was identified. Those with full statin use were significantly more likely to be in the top tertile of worse WMH progression (adjusted OR 2.30, 95% CI 1.11 - 4.77, p = 0.025). Conclusion: SPRINT-MIND participants prescribed a statin were nearly 2.5 times more likely to be within the top tertile of WMH progression over four years, despite adjustment for synergistic risk factors and improvement in LDL.

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

“…A longitudinal neuroimaging study of healthy, cognitively unimpaired, statin-naïve healthy adults randomized to simvastatin versus placebo found that simvastatin preserved white matter microstructure and volume at 18 months. 46 In contrast, a recent post hoc analysis of the SPRINT-MIND (Systolic Blood Pressure Intervention Trial) database found that nonrandomized (clinically prescribed) statin use was associated with worse white matter hyperintensities progression over a 4-year period despite adjustment for risk factors and LDL-C. 47 The question of how the overall effect of statins on these competing microvascular lesions would impact cognitive decline in ICH survivors remains open. Although observational datasets have suggested a reduction in cognitive decline with statin therapy in patients without ICH, 48 a handful of small targeted randomized trials and secondary outcomes of larger statin trials to date have not demonstrated an effect on incident dementia or cognitive outcomes with statin treatment.…”