Atherosclerosis 187 (2006) 372–377 The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: The Cardiovascular Health Study Jie J. Cao a , Joshua I. Barzilay b , Do Peterson c , Teri A. Manolio a , Bruce M. Psaty d , Lewis Kuller e , Jason Wexler f , Anthony J. Bleyer g , Mary Cushman h,∗ a National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA b Kaiser Permanente of Georgia and the Division of Endocrinology, Emory University School of Medicine, Atlanta, GA, USA c Department of Biostatistics, University of Washington, Seattle, WA, USA d Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA e Department of Epidemiology, University of Pittsburgh, PA, USA f Department of Medicine, University of California at Davis, Davis, CA, USA g Department of Medicine, Wake Forest University, Winston-Salem, NC, USA h Departments of Medicine and Pathology, University of Vermont, College of Medicine, Burlington, VT, USA Received 1 March 2005; received in revised form 31 August 2005; accepted 15 September 2005 Available online 20 October 2005 Abstract Purpose: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events. Methods: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age ≥65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33%), those with hypertension (52%) and those with diabetes, with or without hypertension (15%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass. Results: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70–1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95% CI 1.08, 2.30]) or diabetes (OR 2.51 [95% CI 1.27, 4.94]). Conclusion: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Microalbuminuria; Cardiovascular disease; Hypertension; Diabetes mellitus ∗ Corresponding author. Present address: University of Vermont, 208 South Park Drive, Suite 2, Colchester, VT 05446, USA. Tel.: +1 802 656 8959; fax: +1 802 656 8965. E-mail address: mary.cushman@uvm.edu (M. Cushman). 1. Introduction Microalbuminuria is a risk factor for clinical cardiovascu- lar disease (CVD) [1–5]. Whether this association represents a causal mechanism is unknown. It is possible that microal- buminuria is related to CVD because it is associated with 0021-9150/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2005.09.015