Association between Arterial Stiffness and Cerebral White Matter Lesions in Community-Dwelling Elderly Subjects

75 Hypertens Res Vol.31 (2008) No.1 p.75-81 Original Article Association between Arterial Stiffness and Cerebral White Matter Lesions in Community-Dwelling Elderly Subjects Takahiro OHMINE1),2), Yoshikazu MIWA1),3), Hiroshi YAO3),4), Takefumi YUZURIHA4), Yuki TAKASHIMA4), Akira UCHINO5), Fumi TAKAHASHI-YANAGA1), Sachio MORIMOTO1), Yoshihiko MAEHARA2), and Toshiyuki SASAGURI1) The presence of cerebral white matter lesions (WMLs) on MRI is suggested to be a predictive factor for vascular dementia and stroke. To investigate the relationship between arterial stiffness and WMLs, we performed brain MRI to evaluate the presence of two subtypes of WML—periventricular hyperintensities (PVH) and deep white matter lesions (DWML)—and furthermore, determined the brachial-ankle pulse wave velocity (ba-PWV) as a marker of arterial stiffness in 132 elderly asymptomatic subjects (49 men and 83 women, 70.3±9.0 years). PVH and DWML were observed in 41 (31.0%) and 53 (40.2%) subjects, respectively. The baPWV values were significantly greater in subjects with PVH than in those without. DWML also tended to be associated with ba-PWV, but the correlation was not statistically significant. In multiple logistic regression analysis, age and decreased DBP were independently associated with PVH. ba-PWV was also detected as an independent factor for the appearance of PVH (adjusted odds ratio: 2.84, p = 0.015) but not DWML. These results indicate that the increase in arterial stiffness contributes to the pathogenesis of PVH rather than DWML. Although further study is needed to clarify the difference between WML subtypes, our study suggests that the measurement of ba-PWV is a simple and useful tool for detecting cerebral arterial dysfunction. (Hypertens Res 2008; 31: 75–81) Key Words: white matter lesion, magnetic resonance imaging, pulse wave velocity, arterial stiffness, periventricular hyperintensity Introduction Cerebral white matter lesions (WMLs), detected as areas of hyperintensity in T2-weighted scans and of isointensity in T1weighted scans on MRI, are frequently seen in elderly people without apparent neurological symptoms (1, 2). Although the clinical importance of WMLs has not been fully elucidated, the presence of WMLs on MRI was reported to correlate with mental deterioration or cognitive impairment (3, 4), mood disorder (5), and gait disturbance (6). Previous reports suggested that WMLs are associated with chronic hypoperfusion or ischemia in the white matter (7, 8). It has been shown that WMLs are frequently observed in subjects with traditional cerebrovascular risk factors such as aging, hypertension, or diabetes (1, 2, 9, 10) and that the presence of WMLs is an From the 1)Department of Clinical Pharmacology and 2)Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 3)Second Department of Internal Medicine, Kyushu University Hospital, Fukuoka, Japan; 4)Center for Emotional and Behavioral Disorders, National Hospital Organization Hizen Psychiatric Center, Saga, Japan; and 5)Department of Radiology, Saga University of Medicine, Saga, Japan. This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research of Japan. Address for Reprints: Yoshikazu Miwa, M.D., Ph.D., Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812–8582, Japan. E-mail: Received April 11, 2007; Accepted in revised form August 5, 2007. 76 Hypertens Res Vol. 31, No. 1 (2008) T1 T2 FLAIR PVH DWML Fig. 1. MRI of PVH (upper) and DWML (lower): T1-weighted (left), T2-weighted (middle), and FLAIR (right). PVH and DWML were determined as described in the Methods section. Arrowheads and arrows indicate PVH and DWML, respectively. independent risk factor for stroke (11). WMLs are more frequent in vascular dementia than in other dementias (12). Furthermore, several pathological studies reported a thickened intima or atherosclerotic changes of the cerebral arteries in regions containing WMLs (13, 14). These observations suggest that the pathogenesis of WMLs is closely associated with arteriosclerosis or atherosclerosis. However, from the perspectives of time and cost, it is not realistic to use MRI for screening early cerebrovascular damage. Recently, pulse wave velocity (PWV) measurements have been found useful for assessing early atherosclerotic change (especially in vascular stiffness) of the vascular wall. An increase in aortic PWV was reported in patients with end-stage renal disease (15) and diabetes (16), and as a risk factor for cardiovascular and all-cause mortality (17). Aortic PWV is also reportedly elevated in patients with stroke (18) and a prognostic factor for vascular dementia or cerebral infarction (19). Thus, estimations of PWV can be used for both the screening of atherosclerosis and as a predictor of cardiovascular events. Nevertheless, the relationship between PWV and WMLs has not been examined. In the present study, therefore, to test whether or not PWV values are associated with the prevalence of WMLs, we assessed the presence of two distinct types of cerebral WML—periventricular hyperintensities (PVH) and deep white matter lesions (DWML)—in elderly asymptomatic subjects. We also determined the brachialankle PWV (ba-PWV), a noninvasive measure of arterial stiffness using an automatic device, and examined its association with the presence of WMLs on MRI. Methods Participants Between August and November in both 2003 and 2004, we examined 144 elderly asymptomatic subjects (52 men and 92 women) living in the rural community of Sefuri village, population 600, in Saga Prefecture, Japan. We randomly contacted inhabitants through the village office by mail, and only those who agreed to participate were enrolled in the study. The positive response rate was 92.3% (144/156). All participants were living independently at home and had a MiniMental Status examination score > 24. Subjects with an apparent history of stroke, silent brain infarction on MRI, or arrhythmia including atrial fibrillation, or who were suspected of having peripheral arterial disease (ankle-brachial index [ABI, the ratio of ankle pressure to brachial pressure] < 0.9) were excluded. Finally, 132 subjects were analyzed. At the time of physical examination, blood pressure (BP), body mass index (BMI), and hematological and biochemical profiles were determined. Smoking status and medical histories were recorded for all participants at the same time. Blood was drawn in the morning after an overnight fast. Fasting blood glucose, HbA1c, triglyceride, total cholesterol, and high-density lipoprotein (HDL)–cholesterol levels were measured using routine laboratory methods. Low-density lipoprotein (LDL)–cholesterol levels were calculated using Friedewald’s formula. Hypertension was defined as either systolic BP (SBP) ≥ 140 mmHg or diastolic BP (DBP) ≥ 9 (...truncated)