Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug;38(8):1578-1585.
doi: 10.1097/HJH.0000000000002440.

Functional health and white matter hyperintensities as effect modifiers of blood pressure-lowering on cognitive function and vascular events in older Secondary Prevention of Small Subcortical Strokes trial participants

Manuel R Blum  1   2   3 , Rebecca Scherzer  4   5 , Jesse C Ikeme  5   6 , Oscar R Benavente  7   8 , Leslie A McClure  9 , Carmen A Peralta  10 , Michelle C Odden  1
Affiliations

Functional health and white matter hyperintensities as effect modifiers of blood pressure-lowering on cognitive function and vascular events in older Secondary Prevention of Small Subcortical Strokes trial participants

Manuel R Blum et al. J Hypertens. 2020 Aug.

Abstract

Objective: To determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke.

Methods: Participants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (<130 mmHg) SBP target. The primary outcome was change in cognitive function (Cognitive Abilities Screening Instrument); secondary outcomes were incident mild cognitive impairment, stroke, major vascular events (all-stroke, myocardial infarction), and all-cause death. Results were stratified by severity of white matter hyperintensities (WMH; none/mild, moderate, severe) on baseline MRI, and by disability (no vs. at least one limitation in activities of daily living).

Results: One thousand, two hundred and sixty-three participants (mean age 73.8 ± 5.9 years, 40% women) were included. Participants with severe WMH or disability had worse cognitive function at baseline and after a mean follow-up of 3.9 years. No significant interactions existed between treatment group and effect modifiers (WMH, disability) for change in cognitive function (P for interaction 0.42 and 0.66, respectively). A lower SBP target appeared more beneficial among those with worse WMH burden for vascular outcomes (P for interaction = 0.01 for stroke and 0.03 for major vascular events).

Conclusion: There was no difference in the effect of lowering SBP to less than 130 mmHg on cognitive function by cerebral small vessel disease or disability among older adults with a history of lacunar stroke. Those with evidence of small vessel disease may derive greater benefit from lower SBP on prevention of subsequent vascular events.

Trial registration: Clinicaltrials.gov Identifier: NCT00059306.

PubMed Disclaimer

Conflict of interest statement

Declaration of interest: Carmen Peralta is the Chief Medical Officer and has ownership in Cricket Health.

Figures

Figure 1:
Figure 1:
Predicted mean CASI Z-scores by treatment group and effect modifier Panels: A: Stratified by white matter hyperintensities; B: Stratified by ADL limitations. Grey area represents 95% CI. Abbreviations: ADL, activities of daily living; BP, blood pressure; CASI, Cognitive Abilities Screening Instrument; CI, confidence interval
Figure 2:
Figure 2:
Effect modification of WMH and disability on incident mild cognitive impairment, vascular events, and death * Lower vs. higher target. Analysis was adjusted for age, sex and race. ** WMH was missing for 19 participants (5 in lower BP target group, 14 in higher BP target group). *** WMH was missing for 27 participants (9 in lower BP target group, 18 in higher BP target group). Abbreviations: ADL, activities of daily living; BP, blood pressure; CI, confidence interval; HR, hazard ratio; MCI, mild cognitive impairment; N, number; WMH, white matter hyperintensities; y, year
See this image and copyright information in PMC

References

    1. Regenhardt RW, Das AS, Lo EH, Caplan LR. Advances in Understanding the Pathophysiology of Lacunar Stroke: A Review. JAMA Neurol. 2018;75(10):1273. doi: 10.1001/jamaneurol.2018.1073 - DOI - PMC - PubMed
    1. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–2236. doi: 10.1161/STR.0000000000000024 - DOI - PubMed
    1. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665. doi: 10.1136/bmj.b1665 - DOI - PMC - PubMed
    1. O’Donnell MJ, Chin SL, Rangarajan S, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. The Lancet. 2016;388(10046):761–775. doi: 10.1016/S0140-6736(16)30506-2 - DOI - PubMed
    1. Williamson JD, Pajewski NM, Auchus AP, et al. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA. 2019;321(6):553–561. doi: 10.1001/jama.2018.21442 - DOI - PMC - PubMed

Publication types

Associated data