Statin Usage Increases White Matter Hyperintensities: A Post Hoc Analysis of SPRINT-MIND.

BACKGROUND: Progression of white matter hyperintensities (WMHs), a radiographic marker of cerebral small vessel disease, occurs with uncontrolled conventional cerebrovascular risk factors. Less certain, however, is the influence of dyslipidemia and the impact of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) on WMH progression. The goal of this study was to evaluate the influence of statins on the progression of WMH over a 4-year interval. METHODS: We performed a post hoc analysis of the SPRINT-MIND database on those with serial volumetric WMH data. WMH progression was calculated as the difference in WMH volume between the 2 scans and then segmented into tertiles due to rightward skew. We defined statin usage as no therapy (0% of visits), partial therapy (1% to 99% of visits) or full therapy (100% of visits) as logged during study visits. Analysis of variance and χ 2 tests were used for continuous and categorical variables with adjustments made for variables known to influence WMH development. RESULTS: A total of 425 individuals were included in this study: 53% without statins use, 27% partial use, and 20% full use. Demographic characteristics and baseline WMH volumes were similar among the cohort. Those with full statin use were significantly more likely to be in the top tertile of WMH progression (adjusted odds ratio: 2.30, 95% confidence interval: 1.11-4.77, P =0.025), despite improvement in dyslipidemia. CONCLUSIONS: SPRINT-MIND participants prescribed a statin were nearly 2.5 times more likely to be within the top tertile of WMH progression over 4 years, despite adjustment for synergistic risk factors and improvement in low-density lipoprotein.

Effect of Antihypertensives by Class on Cerebral Small Vessel Disease: A Post Hoc Analysis of SPRINT-MIND.

BACKGROUND: Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, although it is unclear whether this reduction occurs due to blood pressure control or class-specific pleiotropic effects, such as improved beat-to-beat arterial pressure variability with calcium channel blockers. The goal of this study was to investigate the influence of antihypertensive medication class, particularly with calcium channel blocker, on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. METHODS: We completed an observational cohort analysis of the SPRINT-MIND trial (Systolic Blood Pressure Trial Memory and Cognition in Decreased Hypertension), a large randomized controlled trial of participants who completed a baseline and 4-year follow-up brain magnetic resonance image with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the magnetic resonance images. A percentage of follow-up time participants were prescribed each of the 11 classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between 2 scans and, to address skew, dichotomized into a top tertile of the distribution compared with the remaining. RESULTS: Among 448 individuals, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 versus 65.7±7.3 years; P<0.001) and systolic blood pressure (128.3±11.0 versus 126.2±9.4 mm Hg; P=0.039). Seventy-two (48.3%) of the top tertile cohort and 177 (59.2%) of the remaining cohort were in the intensive blood pressure arm. Those within the top tertile of progression had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL (P<0.001). Use of angiotensin-converting enzyme inhibitors (odds ratio, 0.36 [95% CI, 0.16-0.79]; P=0.011) and dihydropyridine calcium channel blockers (odds ratio, 0.39 [95% CI, 0.19-0.80]; P=0.011) was associated with less WMH progression, although dihydropyridine calcium channel blockers lost significance when WMH was treated as a continuous variable. CONCLUSIONS: Among participants of SPRINT-MIND trial, angiotensin-converting enzyme inhibitor was most consistently associated with less WMH progression independent of blood pressure control and age.

The association between transthoracic echocardiogram parameters and white matter hyperintensities.

OBJECTIVE: Identify abnormal cardiac chamber size and hemodynamic parameters on transthoracic echocardiogram (TTE) as predictors of advancing cerebral small vessel disease (CSVD) on brain magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective chart review of adults with a brain MRI and a 2-dimensional TTE was performed. WMH measured by the Fazekas score served as the primary outcome. We fit multivariate ordinal logistic regression models to the Fazekas score with the individual predictors of the TTE measurements and adjusted for potential confounders. RESULTS: 132 individuals were included. Cardiac functional markers were not significant, including tricuspid annular plane systolic excursion (p = 0.818), right ventricular ejection fraction (p = 0.818) and left ventricular ejection fraction (p = 0.673). Cardiac structural markers included right atrial area (p = 0.247), right ventricular internal diameter (RVID, p = 0.020) and left atrial area (LAA, p = 0.041). RVID and LAA were identified as being predictors, although the direction of the association suggested that normal values resulted in more WMH. Analysis of isolated DWM or PVWM Fazekas scores were not associated with cardiac structure or function. CONCLUSIONS: In our study, we found that normal LAA and RVID values were associated with an increased degree of WMH on MRI. This finding may represent earlier identification of WMH prior to TTE cardiac changes. Future studies are needed for more robust quantitative comparison as well as evaluation prospectively of the association between cardiac chamber sizes and development of WMH.