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Severity of White Matter Hyperintensities and Effects on All-Cause Mortality in the Mayo Clinic Florida Familial Cerebrovascular Diseases Registry



      To compare all-cause mortality rates across the severity range of white matter hyperintensities (WMH).

      Patients and Methods

      Between October 26, 2010, and October 5, 2017, the ongoing Mayo Clinic Florida Familial Cerebrovascular Diseases Registry prospectively enrolled 1011 diverse participants with and without cerebrovascular disease. T2-weighted magnetic resonance imaging of the brain was used to evaluate WMH in 455 participants using the Fazekas scale. Fazekas deep WMH (FD) and periventricular WMH (FPV) scores (0-3 points) were assigned on the basis of WMH severity. Kaplan-Meier survival analyses, Cox proportional hazards models, and estimated hazard ratios compared survival rates across FD and FPV categories. The Fisher exact and χ2 tests evaluated the relationship of categorical variables, and the Kruskal-Wallis test measured the relationship of continuous variables across FD and FPV categories. All tests were performed at a P<.05 significance level.


      Over a median follow-up of 3.06 years (range, 0.00-6.96 years), 96 deaths occurred. Higher FD scores corresponded to a higher likelihood of mortality (P<.001). Participants with an FD score of 3 were 4.69 (95% CI, 2.60-8.46) times more likely to die compared with those with an FD score of 0. Participants with higher FPV scores had a higher likelihood of mortality (P<.001). Participants with an FPV score of 3 were 7.04 (95% CI, 3.39-14.62) times more likely to die compared with those with an FPV score of 0. Once adjusted, age and baseline functional status explained most of the survival differences among the FD scores.


      Associations between all-cause mortality rates across the severity range of WMH were observed in the Registry. Further studies are warranted to understand the clinical importance of WMH in other clinical populations.

      Abbreviations and Acronyms:

      CVD (cerebrovascular disease), FD (Fazekas deep white matter hyperintensity), FLAIR (fluid-attenuated inversion recovery), FPV (Fazekas periventricular white matter hyperintensity), GFR (glomerular filtration rate), MRI (magnetic resonance imaging), mRS (modified Rankin Scale), SBP (systolic blood pressure), WMH (white matter hyperintensities)
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