Progression of Microvascular Brain Disease and Stroke Incidence in the Atherosclerosis Risk in Communities Study

Background and Purpose: Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts measures progression for the incidence of clinical stroke are scarce. We aimed to study associations between the progression in measures of microvascular brain disease over time and risk of stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: We analyzed data on 907 ARIC participants who underwent a brain MRI in 1993-95, a second brain MRI in 2004-6, and were subsequently followed for incident stroke through December 31 st , 2017 (median [IQR] follow-up of 12.6 [8.9-13.4] years from the second brain MRI in 2004-6). At each MRI, WMH was categorized according to the Cardiovascular Health Study 0-9 rating scale and scans were centrally reviewed for lacunar infarcts. A combined measure of microvascular brain disease was defined, and progression from the first to the second brain MRI, manifesting as new WMHs and lacunes at the second brain MRI, was categorized as: no progression; increase of ≥1 unit in WMH grade or incident lacune; increase of ≥1 unit in WMH grade and incident lacune. All fatal and non-fatal strokes occurring in the participants during the study period, and adjudicated as definite/probable ischemic or hemorrhagic incident stroke, were included in this analysis. Associations between progression of microvascular brain disease and incidence of stroke were studied with Cox proportional hazard models, adjusting for age, gender, race, education level, BMI, smoking, hypertension, diabetes and coronary heart disease. Results: At the second brain MRI (mean age 72y), no progression in the combined measure of microvascular disease was found in 38% of participants, while 57% showed ≥1 unit increase in WMH grade or new lacune, and 5% showed increased WMH grade and new lacune. Sixty-four incident strokes occurred during follow-up. Compared to no change in the combined measure, progression of microvascular brain disease expressed as ≥1 unit increase in WMH grade and incident lacune was significantly associated with higher risk of stroke (adjusted HR 3.01, 95% CI 1.30-6.95). Conclusion: Progression of combined measures of microvascular brain disease over a decade is associated with a significant increased risk of stroke.