76 A therosclerotic plaques in the carotid arteries represent an important cause of cerebral ischemia. The compo- sition of an atherosclerotic plaque is an important predictor for plaque rupture and subsequent thromboembolic events. Intraplaque hemorrhage (IPH) is considered as a high-risk component of the vulnerable plaque through contribution of cholesterol to the necrotic core of the plaque and by increas- ing macrophage iniltration, making the plaque more unsta- ble. 1–3 Several studies have indicated a strong association of IPH with cerebrovascular events. 3–5 Furthermore, even in atherosclerotic lesions of asymptomatic subjects, IPH was shown to contribute to plaque progression and destabiliza- tion. 6,7 Magnetic resonance imaging (MRI) has emerged as a reliable and accurate tool for discriminating plaque com- ponents in vivo and for detecting IPH. 7,8 However, only few studies have investigated determinants of plaque composition in the carotid artery 9,10 and, speciically, studies relating risk factors to IPH are scarce. We recently reported that sex, age, smoking, and hypertension are associated with IPH in the gen- eral population. 11 Hypertension is a highly prevalent condi- tion and a major contributor to atherosclerotic cardiovascular disease. However, the pathophysiology of the contribution of high blood pressure to atherosclerotic plaques is still not fully elucidated. For a long time, hemodynamic forces have been linked to atherosclerosis formation and plaque destabilization. 12 Plaque instability is, in part, determined by local factors, but it has been suggested that systemic factors are also important. 13 Atherosclerotic plaques form at positions of disturbed blood low and concomitant low and oscillating wall shear stress, 14 whereas all structures of the arterial wall are inluenced by blood pressure luctuations. As a continuation of our previous study, 11 the current study was designed to determine the association of various blood pressure parameters with the presence of carotid IPH in a large population-based study. Abstract—Intraplaque hemorrhage (IPH) is a characteristic of the vulnerable atherosclerotic plaque that has been associated with ischemic stroke. Not much is known about determinants of IPH. We studied whether blood pressure parameters are associated with presence of IPH. Within the framework of a prospective population-based cohort study, The Rotterdam Study, the carotid arteries of 1006 healthy participants ≥45 years and with intima-media thickening (≥2.5 mm) on ultrasound were imaged with a 1.5-T magnetic resonance imaging scanner. IPH was deined as a hyperintense signal on a 3D-T1w-GRE magnetic resonance sequence. Generalized estimation equation analysis, adjusted for age, sex, carotid wall thickness, and cardiovascular risk factors, was used to assess the association between blood pressure parameters and IPH. Magnetic resonance imaging of the carotid arteries revealed presence of IPH in 444 of 1860 plaques (24%). Systolic blood pressure and pulse pressure (PP) were signiicantly associated with IPH after adjustment for age and sex. In multivariate analysis, PP yielded the strongest association, with an odds ratio per SD increase in PP of 1.22 (95% CI, 1.07–1.40). The odds ratio per SD for systolic blood pressure was 1.13 (0.99–1.28). Only PP remained signiicant after additional adjustment for other blood pressure components. The combination of smoking and isolated systolic hypertension was associated with 2.5 times increased risk of IPH (1.2–5.2). In conclusion, PP was the strongest determinant of IPH independent of cardiovascular risk factors and other blood pressure components. The association between pulsatile low and IPH may provide novel insights in the development of the vulnerable plaque. (Hypertension. 2013;61:76-81.) Key Words: blood pressure ■ carotid artery ■ intraplaque hemorrhage ■ MRI ■ pulse pressure Received May 4, 2012; irst revision May 18, 2012; accepted October 21, 2012. From the Departments of Epidemiology (M.S., Q.J.A.v.d.B., G.C.V., A.D., F.U.S.M.-R., M.V., O.H.F., A.H., J.C.M.W.), Biomedical Engineering (M.S., J.J.W.), Radiology (M.S., Q.J.A.v.d.B., M.V., A.v.d.L.), and Internal Medicine (G.C.V., F.U.S.M.-R.), Erasmus Medical Center, Rotterdam, The Netherlands. Drs Selwaness and Bouwhuijsen contributed equally to this work. Correspondence to Jacqueline C.M. Witteman, Department of Epidemiology, Erasmus Medical Center, Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail j.witteman@erasmusmc.nl Blood Pressure Parameters and Carotid Intraplaque Hemorrhage as Measured by Magnetic Resonance Imaging The Rotterdam Study Mariana Selwaness, Quirijn J.A. van den Bouwhuijsen, Germaine C. Verwoert, Abbas Dehghan, Francesco U.S. Mattace-Raso, Meike Vernooij, Oscar H. Franco, Albert Hofman, Aad van der Lugt, Jolanda J. Wentzel, Jacqueline C.M. Witteman © 2012 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.112.198267 by guest on September 4, 2016 http://hyper.ahajournals.org/ Downloaded from