Risk factors for microangiopathy-related cerebral damage in the Austrian stroke prevention study

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Abstract

Microangiopathy-related cerebral damage (MARCD) represents a common incidental MRI observation in the elderly. The risk factors of such findings are widely unknown. We therefore performed MRI in 349 randomly selected volunteers (ages 50 to 70 years) without neuropsychiatric disease, and evaluated the association of MARCD with conventional and recently suggested cerebrovascular risk factors such as apolipoprotein E genotypes, plasma concentrations of essential antioxidants and anticardiolipin antibody titres. MARCD was defined as evidence of early confluent and confluent deep white matter hyperintensities and lacunes. It was present in 71 (20.3%) subjects. Individuals with MARCD were older than those without such findings (62.7 years vs 59.6 years; P=0.0001). They had a higher rate of arterial hypertension (45.1% vs 28.1%; P=0.006) and cardiac disease (50.7% vs 37.1%; P=0.04), higher systolic blood pressure readings at exam (144.4 mmHg vs 136.7 mmHg; P=0.004), and higher serum fibrinogen concentrations (327.1 mg/dl vs 292.5 mg/dl; P=0.001). Their levels of total cholesterol (217.6 mg/dl vs 231.2; P=0.009), apolipoprotein A-I (167.3 mg/dl vs 177.4 mg/dl, P=0.02), lycopene (0.17μmol/l vs 0.24μmol/l; P=0.003), retinol (1.91μmol/l vs 2.10μmol/l; P=0.02) and alpha-tocopherol (27.55μmol/l vs 31.14μmol/l; P=0.001) were significantly lower. Forward stepwise regression analysis created a model of independent predictors of MARCD with age entering first (odds ratio 2.01/10 years), fibrinogen second (odds ratio 2.45/100 mg/dl), alpha-tocopherol third (odds ratio 0.55/10μmol/l), and arterial hypertension fourth (odds ratio 1.96). The association of MARCD with various treatable clinical conditions may have preventive implications.

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.

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