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.

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.

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.

Introduction: White matter hyperintensities (WMH) are a radiographic marker for cerebral small vessel disease (CSVD). Conditions altering cerebral venous outflow such as elevated central venous pressure and right atrial pressure in individuals with cardiac valvular disease have been implicated in the development of WMH. Hypothesis: We hypothesize that increased right-heart chamber size in individuals without significant cardiac valvular disease is associated with worse WMH. Methods: A retrospective chart review of adults with a brain MRI and a 2-dimensional transthoracic echocardiogram (TTE) was performed. Worst burden of WMH by way of Fazekas score, either periventricular or deep white matter, served as the primary outcome. Statistical analysis was performed using a multivariate ordinal logistic regression model. Results: A total of 132 individuals were included. Right atrial area (OR 0.93, 95% CI 0.87 to 1.00, p = 0.0041), right ventricular internal diameter (OR 0.48, 95%CI 0.27 to 0.83, p = 0.008) and left atrial area (OR 0.93, 95%CI 0.88 to 0.98, p = 0.007) was identified as being significant. Cardiac functional markers were not significant, including tricuspid annular plane systolic excursion (OR 0.99, 95%CI 0.93 to 1.05, p = 0.670), right ventricular ejection fraction (OR 0.99, 95%CI 0.96 to 1.02, p = 0.670) and left ventricular ejection fraction (OR 0.99, 95%CI 0.96 to 1.02, p = 0.567). Analysis of isolated DWM or PVWM Fazekas scores did not find significant predictors in relation to cardiac structure or function. Conclusions: Through non-invasive cardiac imaging, we identified that cardiac structural abnormalities as opposed to functional abnormalities were associated with worse WMH. Mechanistically this may result from altered intracerebral arteriovenous coupling or a shared pathophysiologic pathway between WMH and coronary microvascular disease.

Background and Purpose: Glucagon-like peptide-1 receptor agonists (GLP1-RA) are antihyperglycemic medications which may have a pleotropic benefit in reducing the risk of stroke. However, with ischemic stroke being the most common stroke subtype in diabetic individuals, it is currently unknown if this benefit remains present when evaluating ischemic stroke in isolation. The aim of this study was to identify whether GLP1-RA medications lower the risk of ischemic stroke. Methods: A 1:1 propensity score matched analysis of a retrospective cohort of patients from the TriNetX platform was performed with the outcome of ischemic stroke, defined with ICD-10-CM codes, during 5 years of follow-up. The exposure was prescription of a GLP1-RA, after which follow-up began. Subgroup propensity matched analyses were performed on individual GLP1-RA medications. Results: 256,938 diabetic individuals prescribed a GLP1-RA were matched with an equal cohort of unexposed diabetics. Demographic and diabetic parameters were equally matched (mean age 57.4 years, 52.5% using insulin concurrently, mean hemoglobin A1c 8.3%). Composite ischemic stroke was lower in the GLP1-RA cohort (3.5%; 8,961/256,938 versus 5.8%; 14,806/256,938) with a risk ratio of 0.61 (95% 0.59-0.62), odds ratio of 0.59 (95% CI 0.58-0.61), hazard ratio of 0.71 (95% CI 0.60-0.87), without violation of the PH assumption (p=0.4). Rate of first-time incident stroke followed a similar pattern: (1.9%; 4,746/246,735 versus 3.3%; 8,044/241,891), risk ratio of 0.58 (95% CI 0.56 - 0.60), odds ratio of 0.57 (0.57 - 0.59), hazard ratio of 0.76 (0.67 - 0.86) with preservation of the PH assumption (p= 0.25). All four GLP1-RA medications lowered the event rate of ischemic stroke. Conclusions: In our study of a large cohort of adults with diabetes, the use of a GLP1-RA reduced the risk of ischemic stroke, consistent with post-hoc analyses of randomized controlled trials.