Risk factors for microangiopathy-related cerebral damage in the Austrian stroke prevention study
Introduction
Microangiopathy-related cerebral damage (MARCD) is commonly noted on Magnetic Resonance Imaging (MRI) in the elderly and includes white matter hyperintensities (WMH) and lacunar lesions (Brant-Zawadzki et al., 1985; Drayer, 1988; Manolio et al., 1994). The exploration of the risk factors of clinically silent MARCD may hold important preventive implications, since MARCD probably identifies a group of individuals at high risk for clinically overt cerebrovascular disease (Chimowitz et al., 1989; Meyer et al., 1992). Previous studies yielded conflicting results (Awad et al., 1986a; Lechner et al., 1988; Kertesz et al., 1988; Schmidt et al., 1992; Bots et al., 1993; Breteler et al., 1994). There existed a consistent and strong association with advancing age (Awad et al., 1986a; Sarpel et al., 1987; Kertesz et al., 1988; Fazekas et al., 1988; Schmidt et al., 1992; Bots et al., 1993; Manolio et al., 1994), yet it remained unclear which additional factors may contribute to the evolution of such changes. Hypertension has been considered most often (Awad et al., 1986a; Kertesz et al., 1988; Bots et al., 1993; Schmidt et al., 1993) but there were also studies suggesting cardiac disease (Sarpel et al., 1987; Fazekas et al., 1988; Bots et al., 1993), diabetes mellitus (Schmidt et al., 1992) or hypercholesterolemia (Manolio et al., 1994). Some authors even failed to detect any relationship with well-documented risk factors for stroke and therefore assumed that such abnormalities are linked to other age-related and yet unappreciated causative clinical conditions or simply represent a normal part of the cerebral aging (Hendrie et al., 1989; Sullivan et al., 1990; Meyer et al., 1992). So far virtually all studies towards clinical conditions predisposing to incidental MARCD on MRI focused on conventional risk factors only. The present investigation evaluated the risk profile for MARCD in a large cohort of randomly selected middle-aged and elderly normals and for the first time included several newly suggested cerebrovascular risk factors such as the apolipoprotein E polymorphism (Pedro-Botet et al., 1992; Couderc et al., 1993), serum concentrations of ten naturally occurring antioxidants (Gey et al., 1993) and anticardiolipin antibody titres (Hess et al., 1991; Ginsburg et al., 1992).
Section snippets
Subjects and methods
Individuals aged 50 to 75 years and stratified by gender and 5 year age groups were randomly selected from the official register of residents of the city of Graz, Austria. They received a written invitation to participate in the Austrian Stroke Prevention Study (ASPS), a single-center prospective follow-up study in our community. The study has been approved by the Medical Ethics Committee of the Karl-Franzens University of Graz. Written informed consent was obtained from all study participants.
Results
A total of 71 (20.3%) individuals had MARCD. There were 8 (2.3%) subjects with both types of ischemic lesions. Early confluent and confluent WMH and lacunes were noted in 57 (16,3%) and 24 (6.3%) subjects, respectively. With the exception of 2 lesions involving the brain stem, lacunes were always located in the basal ganglia-internal capsule area.
As can be seen from Table 1 study participants with MARCD were significantly older, had higher frequencies of arterial hypertension and cardiac
Discussion
One fifth of our study participants had MARCD on MRI. Because of the low response rate in our study, the cohort presented here may not be truly representative of the entire population. Yet, all individuals were randomly selected from the official community register and a subgroup of nonresponders did not differ in terms of sociodemographic variables and history of major vascular risk factors on telephone interview. Moreover, the frequency of early confluent and confluent WMH, the most common
Acknowledgements
The authors are indebted to Prof. H. Lechner who inaugurated the Austrian Stroke Prevention Study. The current investigation was supported by the `Steiermärkischen Krankenanstalten GmbH' and the Austrian National Bank Projects # 3905 and # 4484.
References (56)
- et al.
Cerebral white matter lesions and atherosclerosis in the Rotterdam study
Lancet
(1993) - et al.
Risk of angina pectoris and plasma concentrations of vitamin. A.,C, and E and carotene
Lancet
(1991) - et al.
MR imaging of the aging brain
AJNR Am. J. Neuroradiol.
(1985) Imaging of the aging brain
Radiology
(1988)- et al.
Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study
Stroke
(1994) - et al.
Periventricular lesions on MRI. Facts and theories
Stroke
(1989) - et al.
White matterlesions in the elderly
J. Neurol. Sci.
(1992) - et al.
Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors
Stroke
(1986) - et al.
Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals
Stroke
(1988) - et al.
Periventricular and subcortical hyperintensities on magnetic resonance imaging. Rims, caps and unidentified bright objects
Arch. Neurol.
(1988)
Magnetic resonance imaging signal hyperintensities in the deep and subcortical white matter. A comparative study between stroke patients and normal volunteers
Arch. Neurol.
Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: The Rotterdam Study
Neurology
Magnetic resonance imaging periventricular hyperintensity in a veterans administration hospital population
Arch. Neurol.
White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors
Stroke
Neuropsychologic correlates of MRI white matter hyperintensities: a study of 150 normal volunteers
Neurology
Foci of increased T2 signal intensity on brain MR scans of healthy elderly subjects
AJNR Am. J. Neuroradiol.
Risk factors for white matter changes detected by magnetic resonance imaging in the elderly
Stroke
Lipoprotein and apolipoprotein Profile in men with ischemic stroke. Role of lipoprotein(a), triglycerid-rich lipoproteins, and apolipoprotein E polymorphism
Stroke
Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case-control study
Stroke
Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study
Clin. Invest.
Anticardiolipin antibodies: a study of frequency in TIA and stroke
Neurology
Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis
Ann. Intern. Med.
Assessment of cerebrovascular risk profiles in healthy persons: definition of research goals and the Austrian Stroke Prevention Study (ASPS)
Neuroepidemiology
The sensitivity and specificity of MRI in stroke
Neurology
Foci of MRI signal (pseudo lesions) anterior to the frontal horns: histological correlations of a normal finding
AJR Am. J. Roentgenol.
The morphologic correlate of incidental punctate white matter hyperintensities on MR images
AJNR Am. J. Neuroradiol.
Infarcts with a cardiac source of embolism in the NINCDS stroke data bank: historical features
Neurology
The diagnosis of ischemic heart pain and intermittent claudication in field surveys
Bull. WHO
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