Intracranial Carotid Artery Atherosclerosis and the Risk of Stroke in Whites: The Rotterdam Study

IMPORTANCE Intracranial atherosclerosis represents a relatively unexplored, but potentially important, cause of stroke in a white population. OBJECTIVE To investigate the relationship between intracranial carotid artery calcification (ICAC) as a marker of intracranial atherosclerosis and the risk of stroke in whites. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort study in the general community with 6 years of follow-up was conducted (the Rotterdam Study). Between 2003 and 2006, a random sample of 2323 stroke-free persons (mean age, 69.5 years) underwent computed tomography scanning to quantify ICAC volume. All participants were continuously monitored for the occurrence of stroke until January 1, 2012. EXPOSURE Atherosclerotic calcification in the intracranial internal carotid arteries. MAIN OUTCOME AND MEASURE Incident stroke. RESULTS During 14 055 person-years of follow-up, 91 participants had a stroke, of which 74 were ischemic. Larger ICAC volume was related to a higher risk of stroke, independent of cardiovascular risk factors, ultrasound carotid plaque score, and calcification in other vessels (fully adjusted hazard ratio per an increase of 1 SD in ICAC volume, 1.43 [95% CI, 1.04-1.96]). Intracranial carotid artery calcification contributed to 75% of all strokes; for aortic arch and extracranial carotid artery calcification this incidence was only 45% and 25%, respectively. CONCLUSIONS AND RELEVANCE Our findings establish intracranial atherosclerosis as a major risk factor for stroke in the general white population and suggest that its contribution to the proportion of all strokes may be greater than that of large-artery atherosclerosis in more proximally located vessel beds.