ORIGINAL

PAPER

Ambulatory Arterial Stiffness Index Is Not Associated With Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Lacunar Stroke Patients Pim Klarenbeek, MD;1 Robert J. van Oostenbrugge, MD, PhD;1,2 Julie Staals, MD, PhD1,2 From the Department of Neurology;1 and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands2

Ambulatory arterial stiffness index (AASI) is associated with microvascular damage in other organs, but the association with microvascular brain damage is unknown. The association of AASI with magnetic resonance imaging (MRI) markers of cerebral small vessel disease in 143 patients with lacunar stroke was investigated. We performed 24-hour ambulatory blood pressure monitoring and scored the presence of lacunes, white matter hyperintensities, perivascular spaces, and cerebral microbleeds on brain MRI. In logistic regression analyses, AASI was associated with white matter hyperintensities, but, after

adjustment for age and sex, this association lost significance. AASI was not associated with lacunes, microbleeds, or perivascular spaces. Systolic and diastolic 24hour blood pressure values were associated with lacunes, perivascular spaces, and microbleeds independent of age and sex. Despite its significance and growing interest as a possible prognostic and therapeutic target in (micro)vascular diseases, AASI seems to have no added value over standard 24-hour blood pressure in cerebral small vessel disease. J Clin Hypertens (Greenwich). 2015;17:352–356. ª 2015 Wiley Periodicals, Inc.

Cerebral small vessel disease (cSVD) is a pathological process involving the small arteries and arterioles of the brain.1 Lacunes, white matter hyperintensities, perivascular spaces, and cerebral microbleeds (CMBs) have all been identified as markers of cSVD on brain magnetic resonance imaging (MRI).2 In general, assessment of asymptomatic end-organ damage has good prognostic significance for cardiovascular risk and may therefore be clinically relevant.3 Indeed, the markers of microvascular brain damage are associated with increased risk of stroke, higher mortality, and worse cognitive functioning.1,4–6 Elevated blood pressure (BP) is one of the main risk factors for cSVD.4,7 Increased arterial stiffness is considered another risk factor for cSVD. It is thought that abnormal flow pulsations extend deep into the microvasculature of the brain, damaging the vessels.8 Studies using arterial pulse wave velocity as a measure of arterial stiffness have found associations with lacunes, deep CMBs, and white matter hyperintensities.9–11 The ambulatory arterial stiffness index (AASI) was originally introduced as a new measure of arterial stiffness derived from 24-hour ambulatory BP monitoring data representing the dynamic relationship between systolic and diastolic BP.12 However, other factors such as heart rate and vascular resistance were shown to influence this measure as well.13 Despite the fact that the exact

pathophysiological background of this index remains unclear, AASI predicts cardiovascular outcome (especially stroke) and is associated with microvascular renal target organ damage.14–16 In contrast to these abundant data on the positive association with stroke and renal damage, the association between AASI and microvascular brain damage is unknown. In the present study we hypothesized that AASI is associated with microvascular brain damage. We investigated the association of AASI with MRI markers of cSVD in patients with a symptomatic small vessel (lacunar) stroke.

Address for correspondence: Pim Klarenbeek, MD, Department of Neurology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The Netherlands Email: [email protected] Manuscript received: September 29, 2014; revised: November 17, 2014; accepted: November 21, 2014 DOI: 10.1111/jch.12504

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The Journal of Clinical Hypertension

Vol 17 | No 5 | May 2015

METHODS Patient Recruitment For a lacunar stroke research project, we prospectively recruited patients who presented with a first-ever lacunar stroke at Maastricht University Medical Centre, the Netherlands, from May 2003 to January 2008 and at Orbis Medical Centre Sittard, the Netherlands, from September 2004 to April 2007. This study was approved by the local ethics committee and informed consent was obtained from all patients. The current research question was formulated after data collection in the lacunar stroke project. Therefore, no power analysis was performed and we used the data of all patients who met the inclusion criteria for the present study. As described earlier, we defined lacunar stroke as an acute symptomatic lacunar stroke syndrome with a recent, small, deep infarct on MRI (basal ganglia, thalamus, internal capsule, or brain stem) compatible with the clinical findings.17 We used established criteria of specific clinical lacunar syndromes if no symptomatic MRI lesion was visible.18 As we aimed to study patients

AASI and Markers of Small Vessel Disease | Klarenbeek et al.

who most likely had their stroke from small vessel disease, patients with a potential cardioembolic source (mostly atrial fibrillation [AF], which was defined as AF on electrocardiography or history of AF) and patients with carotid artery stenosis >50% on carotid ultrasound, were excluded. Electrocardiography and carotid ultrasound were performed in all patients. We documented the following vascular risk factors: age, sex, history of hypertension, diabetes mellitus, current smoking, and hypercholesterolemia (total cholesterol level >5 mmol/L).19 Ambulatory BP Monitoring Ambulatory BP was monitored noninvasively during a 24-hour period (with Mobil-O-Graph equipment, IEM GbmH, Stolberg, Germany, using the appropriate cuff size) after the acute stroke phase, between 1 and 6 months post-stroke (10243 days). Measurements were obtained every 15 minutes during the day (7 AM– 11 PM) and every 30 minutes during the night (11 PM–7 AM). Patients were encouraged to perform their normal daily activities but were instructed to keep their arm and hand motionless during the measurements. Patients continued their prescribed medications and the use of antihypertensive drugs was registered. Patients kept a record of their rising and retiring times. We determined day and night periods by excluding a 2-hour transition period around the reported rising and retiring times. Measurement data were not edited manually. Valid recordings required a minimum of 70% valid measurements. For each patient we calculated 24-hour systolic and diastolic BP and standard deviation (SD) of 24-hour systolic and diastolic BP. AASI was defined as one minus the regression slope of diastolic BP on systolic BP values according to previously published reports.12 As some studies argue that standard AASI is strongly influenced by nocturnal dipping and correlation between systolic and diastolic BP, we also determined a so-called “symmetric” AASI equivalent, calculated by 1–1/(systolic SD/diastolic SD) as proposed by Gavish and colleagues.20,21 MRI Scoring We acquired standard axial T2-weighted fast-spin echo images, axial fluid-attenuated inversion recovery images (FLAIR), and T2-weighted gradient echo images on a 1.5T or 3.0T MRI scanner within 6 months after stroke (4142 days). All images were independently rated by two vascular neurologists for the presence of lacunes, white matter hyperintensities, CMBs, and perivascular spaces. In case of disagreement, a consensus meeting was held. The interobserver agreement for the presence of the different markers of cSVD, determined before the study, was substantial to excellent.22,23 We defined lacunes as hyperintense lesions on T2-weighted images with corresponding hypointense lesions with a hyperintense rim on FLAIR, located in the basal ganglia, thalamus, internal or external capsule, or brainstem with a diameter

Ambulatory arterial stiffness index is not associated with magnetic resonance imaging markers of cerebral small vessel disease in lacunar stroke patients.

Ambulatory arterial stiffness index (AASI) is associated with microvascular damage in other organs, but the association with microvascular brain damag...
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