Abstract
AimsWhite matter hyperintensities (WMH) progress with age and hypertension, but the key period of exposure to elevated blood pressure (BP), and the relative role of systolic BP (SBP) vs. diastolic BP (DBP), remains unclear. This study aims to determine the relationship between WMH and concurrent vs. past BP. Methods and results UK Biobank is a prospective community-based cohort of 40–69-year olds from 22 centres, with magnetic resonance imaging in a subgroup of over 40 000 people at 4–12 years after baseline assessment. Standardized associations between WMH load (WMH volume normalized by total white matter volume and logit-transformed) and concurrent vs. past BP were determined using linear models, adjusted for age, sex, cardiovascular risk factors, BP source, assessment centre, and time since baseline. Associations adjusted for regression dilution bias were determined between median WMH and usual SBP or DBP, stratified by age and baseline BP.In 37 041 eligible participants with WMH data and BP measures, WMH were more strongly associated with concurrent SBP [DBP: β = 0.064, 95% confidence interval (CI) 0.050–0.078; SBP: β = 0.076, 95% CI 0.062–0.090], but the strongest association was for past DBP (DBP: β = 0.087, 95% CI 0.064–0.109; SBP: β = 0.045, 95% CI 0.022–0.069), particularly under the age of 50 (DBP: β = 0.103, 95% CI 0.055–0.152; SBP: β = 0.012, 95% CI −0.044 to 0.069). Due to the higher prevalence of elevated SBP, median WMH increased 1.126 (95% CI 1.107–1.146) per 10 mmHg usual SBP and 1.106 (95% CI 1.090–1.122) per 5 mmHg usual DBP, whilst the population attributable fraction of WMH in the top decile was greater for elevated SBP (19.1% for concurrent SBP; 24.4% for past SBP). Any increase in BP, even below 140 for SBP and below 90 mmHg for DBP, and especially if requiring antihypertensive medication, was associated with increased WMH.ConclusionsWMH were strongly associated with concurrent and past elevated BP with the population burden of severe WMH greatest for SBP. However, before the age of 50, DBP was more strongly associated with WMH. Long-term prevention of WMH may require control of even mildly elevated midlife DBP.
Highlights
White matter hyperintensities (WMH) are associated with an increased risk of stroke,[1,2] dementia,[1,2,3] refractory depression,[4] and functional decline in older age.[4]
Participants were not included if they had diagnoses that could confound WMH assessment (N = 492) or missing blood pressure (BP) values at baseline and at follow-up (N = 17 and 822), resulting in 37 026 people included in the longitudinal analyses and 37 041 in cross-sectional analyses
WMH were more strongly associated with past diastolic BP (DBP) than with past systolic BP (SBP), especially under the age of 50
Summary
White matter hyperintensities (WMH) are associated with an increased risk of stroke,[1,2] dementia,[1,2,3] refractory depression,[4] and functional decline in older age.[4] They are present in >50% of patients over the age of 65 and almost everyone over the age of 80.5However, the underlying pathophysiological mechanisms are still unclear[2] despite evidence for a strong genetic component.6Hypertension (HT) is the single strongest treatable risk factor,2,7–9and despite evidence from post hoc analyses of randomized controlled trials suggesting that antihypertensive treatment reduces the progression of WMH,[10] there is a lack of conclusive evidence that lowering blood pressure (BP) reduces the risk of stroke and dementia or which patient groups are most likely to benefit from this treatment. Concurrent associations with arterial stiffness,[11] endothelial dysfunction,[2] impaired cerebrovascular reactivity, and cerebral pulsatility[11,12] suggest the importance of long-term BP changes, but the longitudinal interactions between WMH, age, HT, and the pulsatile [systolic BP (SBP)] vs the steady-state [diastolic BP (DBP)] component of BP are unclear.[11]. These studies have analysed small- to moderatesized populations, at different ages, different BP levels, and different durations of follow-up, limiting the ability to determine the role of midlife BP levels on mid- and late-life WMH
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