White Matter Hyperintensity and Cardiovascular Disease Outcomes in the SPRINT MIND Trial

Abstract

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal systolic blood pressure (SBP) <120 mm Hg vs. <140 mm Hg. In a subset of participants, the SPRINT MIND ancillary study performed a baseline MRI and measured white matter hyperintensity volume (WMHv). In this secondary analysis, we evaluated the association between baseline WMHv and cardiovascular events during follow-up in the overall sample.

Methods: The primary outcome was the same as SPRINT, a composite of stroke, myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, or cardiovascular death. We fit Cox models to the primary outcome and report adjusted hazard ratios (HR) for log-transformed WMHv and quartiles of WMHv.

Results: Among 717 participants, the median (IQR) baseline WMHv was 1.62 (0.66-3.98) mL. The primary outcome occurred in 51/719 (7.1%). The median WMHv was higher in patients with the primary outcome (3.40 mL versus 1.56 mL, p < 0.001). In adjusted models, WMHv as a log-transformed continuous variable was associated with the primary outcome (HR 1.44, 95% CI 1.15-1.80). The highest quartile of WMHv, compared to the lowest, was also independently associated with the primary outcome (HR 3.21, 95% CI 1.27-8.13).

Conclusions: We found that the baseline volume of WMH was associated with future CVD risk in SPRINT MIND. Prospective clinical trials with larger sample sizes than the current study are needed to determine whether intensive BP lowering can reduce the high cardiovascular risk in patients with WMH.

Keywords: Cardiovascular diseases; Outcome; SPRINT MIND; White matter hyperintensity.

Figure 1.

Kaplan-Meier curve for the quartiles of white matter hyperintensity volume, fit to the primary outcome (composite of stroke, myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, or death from cardiovascular disease).