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

Abstract

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.

Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial

“…33 A post-hoc analysis of SPRINT-MIND further found angiotensin-converting enzyme inhibitors and dihydropyridine calcium channel blockers, but not selective β blockers, to be associated with reduced progression of white matter hyperintensities independent of blood pressure control and age. 34 However, the trial was not designed to compare different blood pressure-lowering drugs. CVR declines with ageing.…”

Associations of Cerebrovascular Regulation and Arterial Stiffness With Cerebral Small Vessel Disease: A Systematic Review and Meta‐Analysis

“…Although the vast majority of literature, to date, surrounding the risk of cSVD has focused on traditional vascular risk factors, specifically hypertension, their role as dominant factors in the pathogenesis of cSVD has been challenged. 12 , 202 , 203 Emerging theories propose complex vascular pathologies, including an impaired cerebrovascular function, as important factors mediating cSVD, alongside or independent of hypertension. 12 , 18 These relate to the varied complexities of the vascular pathologies proposed for cSVD subtypes, given cerebrovascular regulatory functions are mediated, in part, by local endothelial function 27 , 28 and arterial stiffness is, in part, dictated by vascular matrix composition and endothelial dysregulation of vascular smooth muscle tone.…”

Cerebral small vessel disease: a bibliometric analysis

“…A large area of necrosis can be seen in the left hemisphere, including the presence of neuro brillary tangles and amyloid plaques in the hippocampus and frequent amyloid plaques in the cerebral cortex, thickening of arterial walls, perivascular spaces are also found Enlargement, arteriosclerosis, microbleeds, and white matter thinning are consistent with features of CSVD and underscore the importance of the gut-vagus-brain axis in late-onset post-stroke dementia(Jiaerken et al, 2021). Furthermore, age-and hypertension-related cerebral small vessel disease are also major determinants of cognitive decline and disability in the elderly(Dobrynina et al, 2022;Goldstein et al, 2022).At present, treatment measures are mainly based on the characteristics of risk factors, the type and severity of biomarkers, and the severity of clinical sequelae. In clinical practice, blood pressure lowering, thrombolysis, and antiplatelet therapy are mostly used(Arba et al, 2019;Pan et al, 2022;Du H et al, 2022).…”