Consistency of associations of systolic and diastolic blood pressure with white matter hyperintensities: A meta-analysis

Abstract

Background: White matter hyperintensities are the commonest manifestation of cerebral small vessel disease, associated with stroke, functional impairment, and cognitive decline. They are commonly preceded by hypertension, but the magnitude and clinical importance of this association is unclear.

Aims: Quantify the relationship between blood pressure and white matter hyperintensities across studies.

Methods: PubMed and EMBASE were searched for studies reporting associations between concurrent or historic blood pressure and white matter hyperintensities. Beta coefficients from linear models were extracted, whether standardized, unstandardized, unadjusted or adjusted for age, sex, and cardiovascular risk factors. Beta-coefficients were combined by fixed and random effects meta-analysis, combining standardized beta-coefficients or unstandardized coefficients measured by consistent methods.

Results: Twenty-five of 3230 papers were eligible, including 53,392 participants. Systolic blood pressure was significantly associated with white matter hyperintensity volume (WMHV) after maximal adjustment (standardized beta 0.096, 95%CI 0.06-0.133, p < 0.001, I² = 65%), including for concurrent readings (b = 0.106, p < 0.001) or readings five years previously (b = 0.077, p < 0.001), and for younger or older populations (mean age < 65: b = 0.114; >65 b = 0.069). Unstandardized, adjusted associations were similar for raw WMHV, log-transformed WMHV, or WMHV as percentage of intracranial volume. Unadjusted associations with systolic blood pressure (SBP) were greater (standardized beta = 0.273, 0.262-0.284, p < 0.0001). However, while associations with DBP were weaker than SBP (standardized beta = 0.065, p < 0.001), they were minimally affected by adjustment for age.

Conclusions: A standard deviation increase in SBP is associated with 10% of a standard deviation increase in WMHV, providing the current best estimate of the potential reduction in progression of white matter hyperintensities expected with good control of blood pressure.

Keywords: Hypertension; blood pressure; meta-analysis; white matter hyperintensities.

Figure 1.

Standardized association between SBP and white matter hyperintensity volume (WMHV). Results are shown for individual studies reporting standardized beta-coefficients, with the maximally adjusted value from each study shown, with all reports adjusted for at least age and sex. Results are combined by fixed and random effects meta-analysis, weighted by the inverse variance, with heterogeneity presented as I² statistics (I-sq), and the p-value for heterogeneity (p-het) determined by chi-squared test. StdBeta: standardized beta; N: number.

Figure 2.

Standardized association between diastolic blood pressure and white matter hyperintensity volume (WMHV). Results are shown for individual studies reporting standardized beta-coefficients, with the maximally adjusted value from each study shown, with all reports adjusted for at least age and sex. Results are combined by fixed and random effects meta-analysis, weighted by the inverse variance, with heterogeneity presented as I² statistics(I-sq), and the p-value for heterogeneity (p-het) determined by chi-squared test. StdBeta: standardized beta; N: number.

Figure 3.

Unstandardized, adjusted associations between systolic blood pressure and white matter hyperintensity volume (WMHV), stratified by whether WMHV were log-transformed or expressed as a percentage of intracranial volume. Results are shown for studies reporting standardized beta-coefficients, with the maximally adjusted value from each study shown, with all reports adjusted for at least age and sex. Results are combined by fixed and random effects meta-analysis, weighted by the inverse variance, with heterogeneity presented as I² statistics(I-sq), and the p-value for heterogeneity (p-het) determined by chi-squared test. StdBeta: standardized beta; N: number; ICV: intracranial volume. (a) WMHV not logged and not as proportion of ICV. (b) WMHV logged but not as proportion of ICV. (c) WMHV not logged, expressed as a percentage of ICV. (d) WMHV logged and expressed as a percentage of ICV.

Figure 4.

Standardized, adjusted associations between systolic blood pressure and white matter hyperintensity volume (WMHV), stratified by a mean age of greater than or less than 65. Results are shown for individual studies reporting standardized beta-coefficients, with the maximally adjusted value from each study shown, with all reports adjusted for at least age and sex. Results are combined by fixed and random effects meta-analysis, weighted by the inverse variance, with heterogeneity presented as I² statistics(I-sq), and the p-value for heterogeneity (p-het) determined by chi-squared test. StdBeta: standardized beta; N: number. (a) Systolic blood pressure, mean age less than 65. (b) Systolic blood pressure, mean age greater than 65.

Figure 5.

Standardized, adjusted associations between systolic blood pressure and white matter hyperintensity volume (WMHV), stratified by time interval between blood pressure measurement and MRI imaging. Results are shown for individual studies reporting standardized beta-coefficients, with the maximally adjusted value from each study shown, with all reports adjusted for at least age and sex. Results are combined by fixed and random effects meta-analysis, weighted by the inverse variance, with heterogeneity presented as I² statistics(I-sq), and the p-value for heterogeneity (p-het) determined by chi-squared test. StdBeta: standardized beta; N: number. (a) Concurrent systolic blood pressure. (b) Systolic blood pressure measured two or more years. (c) Systolic blood pressure measured five or more years previously.