Blood Pressure Variation and Subclinical Brain Disease

Abstract

Background: Large blood pressure (BP) variability may contribute to stroke and dementia, but the mechanisms are largely unknown.

Objectives: This study investigated the association of BP variation, considering its magnitude and direction, with the presence and progression of subclinical brain disease in the general population.

Methods: This study included 2,348 participants age ≥55 years from a prospective cohort study. BP was measured at each visit every 3 to 4 years from 1990 onward. Brain magnetic resonance imaging (MRI) was performed at all visits from 2005 onward. The authors primarily assessed variation as the absolute difference in BP divided by the mean over 2 sequential visits for both systolic BP (SBP) and diastolic BP (DBP), and further assessed the direction of the variation. The authors investigated the multivariate-adjusted associations of BP variation with subsequent measurements of MRI markers of cerebral small vessel disease, brain tissue volumes, and white matter microstructural integrity. Longitudinal changes in these markers also were assessed.

Results: A large SBP variation (top vs. bottom tertiles), measured on average 7 years preceding brain MRI, was associated with higher odds of having severe white matter hyperintensities (WMH) (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.21 to 1.43), lacunes (OR: 1.25; 95% CI: 1.04 to 1.48), and microbleeds (OR: 1.16; 95% CI: 1.03 to 1.31). Similarly, this variation was associated with smaller total brain volume and worse white matter microstructural integrity (all p < 0.001). A large SBP variation was also associated with the progression of WMH (rate ratio [RR]: 1.14; 95% CI: 1.02 to 1.27). Higher burdens of these brain imaging markers were observed with both large rises and falls in SBP. Similar findings were observed for DBP variation.

Conclusions: Elevated BP variation was associated with a wide range of subclinical brain structural changes, including MRI markers of cerebral small vessel disease, smaller brain tissue volumes, and worse white matter microstructural integrity. These subclinical brain changes could be the underlying mechanisms linking BP variation to dementia and stroke.

Keywords: blood pressure; cerebral small vessel disease; cerebrovascular disease; dementia; magnetic resonance imaging; prospective cohort study.

FIGURE 1. The Association of SBP Variation With the Presence of Cerebral Small Vessel Disease

*SBP variation was <1.4%/year (bottom tertile), 1.4% to 3.3% (middle tertile), and >3.3% (upper tertile). †Association estimates after adjusting for age, sex, smoking habits, body mass index, APOE genotype, and history of diabetes. CI = confidence interval; SBP = systolic blood pressure.

FIGURE 2. The Association of SBP Variation With Brain Tissue Volumes

*SBP variation was <1.4%/year (bottom tertile), 1.4% to 3.3% (middle tertile), and >3.3% (upper tertile). †Association estimates after adjusting for age, sex, smoking habits, body mass index, APOE genotype, and history of diabetes. Abbreviations as in Figure 1.

FIGURE 3. The Association of SBP Variation With White Matter Microstructural Integrity

*SBP variation was <1.4% per year (bottom tertile), 1.4% to 3.3% (middle tertile), and >3.3% (upper tertile). †Association estimates after adjusting for age, sex, smoking habits, body mass index, APOE genotype, and history of diabetes. Abbreviations as in Figure 1.

CENTRAL ILLUSTRATION. The Association of Systolic Blood Pressure Variability With the Subsequent Magnetic Resonance Imaging Measurements of Subclinical Brain Disease

*Represents the absolute difference in SBP divided by mean SBP over 2 sequential visits on average 4 years apart scaled to percentage per year. SBP = systolic blood pressure; WMH = white matter hyperintensities.