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

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.

Conflict of interest statement

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

Figures

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:

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