White matter hyperintensities increase long-term risk for ischemic stroke, death

White matter hyperintensity volume, type and shape correlated with an increased risk for mortality and ischemic stroke among patients with manifest arterial disease, according to findings from the SMART-MR study published in Neurology.

“The relationship between advanced white matter hyperintensity markers and long-term clinical outcomes ... is not clear. Examining this relationship is of importance as [white matter hyperintensity] markers may aid in future patient selection for preventive treatment to ameliorate the risk [for cerebral small vessel disease]-related death and ischemic stroke,” Rashid Ghaznawi, MD, MSc, researcher in the department of radiology at University Medical Center Utrecht and Utrecht University, and colleagues wrote.

For this reason, Ghaznawi and colleagues sought to assess whether a relationship existed between volume, type and shape of white matter hyperintensities found on baseline MRI and long-term risk for mortality and ischemic stroke among 999 patients (median age, 59 years; 79% men) with manifest arterial disease. Most (78%) had periventricular white matter hyperintensities and 22% had confluent white matter hyperintensities.

The researchers reported results over a median follow-up period of 12.5 years, at which time 274 patients died and 75 patients experienced an ischemic stroke.

After adjusting for demographics, cardiovascular risk factors and cerebrovascular disease, Ghaznawi and colleagues found that greater periventricular or confluent white matter hyperintensity volume was independently associated with an increased risk for vascular death (HR = 1.29; 95% CI, 1.13-1.47 per 1 unit increase in natural log-transformed white matter hyperintensity volume) and ischemic stroke (HR = 1.53; 95% CI, 1.26-1.86).

They additionally observed an independent association between confluent white matter hyperintensity type and an increased risk for both vascular (HR = 2.05; 95% CI, 1.2-3.48) and nonvascular death (HR = 1.65; 95% CI, 1.01-2.73) as well as ischemic stroke (HR = 4.01; 95% CI, 1.72-9.35). Patients with a more irregular shape of periventricular or confluent white matter hyperintensity, as expressed by an increase in concavity index, were also at increased risk for vascular (HR = 1.20; 95% CI, 1.05-1.38 per standard deviation increase) and nonvascular death (HR = 1.21; 95% CI, 1.03-1.42) as well as ischemic stroke (HR = 1.28; 95% CI, 1.05-1.55).

“These findings suggest that white matter hyperintensity markers on MRI may be useful in determining [a] patient’s prognosis and may aid in future patient selection for preventive treatment,” the researchers wrote.

The study by Ghaznawi and colleagues “is an important addition to the literature in this field as it focuses not only on the absolute volume of [white matter hyperintensity], but on identifying additional geometric and topographic features which may convey an increased risk of stroke and death,” according to an editorial accompanying the study by Nawaf Yassi, PhD, and Bruce C.V. Campbell, PhD, both researchers in the department of medicine and neurology at Melbourne Brain Center at The Royal Melbourne Hospital in Australia.

“The study ... also builds upon a large and ever-growing body of literature confirming associations between imaging markers of cerebrovascular disease (including specifically [white matter hyperintensity] and adverse health outcomes,” they wrote. “However, the field is also in need of therapeutic strategies to attenuate the potential risk of [white matter hyperintensity] lesions on health outcomes in those predicted to be at the highest risk. To our knowledge, there are as yet no prospective randomized clinical trial data to support any specific interventions in patients selected based on the presence of significant white matter hyperintensity burden (notwithstanding that an agreed threshold is yet to be defined).”