Atherosclerosis 204 (2009) 503–508 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Albuminuria, metabolic syndrome and the risk of mortality and cardiovascular events Marit D. Solbu a,d,* , Jens Kronborg b,d , Trond G. Jenssen c,d , Inger Njølstad e , Maja-Lisa Løchen e,f , Ellisiv B. Mathiesen d,g , Tom Wilsgaard e , Bjørn O. Eriksen a,d , Ingrid Toft a,d a Department of Nephrology, University Hospital of North Norway, Tromsø, Norway b Department of Nephrology, Innlandet Hospital Trust, Lillehammer, Norway c Department of Nephrology, Rikshospitalet, National University Hospital, Oslo, Norway d Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway e Institute of Community Medicine, University of Tromsø, Tromsø, Norway f Department of Cardiology, University Hospital of North Norway, Tromsø, Norway g Department of Neurology, University Hospital of North Norway, Tromsø, Norway article info Article history: Received 10 September 2008 Received in revised form 21 October 2008 Accepted 2 November 2008 Available online 12 November 2008 Keywords: Albuminuria Metabolic syndrome Cardiovascular risk All-cause mortality Epidemiology abstract Aim: Increased urinary albumin-excretion is a cardiovascular risk-factor. The cardiovascular risk of the metabolic syndrome (MetS) is debated. The aim of the present prospective, population-based study of non-diabetic individuals was to examine the association between low-grade urinary albumin-excretion, MetS, and cardiovascular morbidity and all-cause mortality. Methods: 5215 non-diabetic, non-proteinuric men and women participating in the Tromsø Study 1994–1995 were included. Urinary albumin–creatinine ratio (ACR) was measured in three urine samples. The participants were categorized into four groups by the presence/absence of MetS (the International Diabetes Federation definition) and ACR in the upper tertile (≥0.75 mg/mmol). Results: Median follow-up time was 9.6 years for first ever myocardial infarction, 9.7 years for ischemic stroke and 12.4 years for mortality. High ACR (upper tertile)/MetS was associated with increased risk of myocardial infarction (hazard ratio (HR) 1.75; 95% confidence interval (CI): 1.30–2.37, p < 0.001), stroke (HR 2.48; 95% CI: 1.66–3.71, p < 0.001), and all-cause mortality (HR 1.63; 95% CI: 1.32–2.01, p < 0.001) compared to reference (low ACR/no MetS). Similar associations were found for the high ACR/no MetS group. Low ACR/MetS was associated with myocardial infarction only (HR 1.82; 95% CI: 1.39–2.37, p < 0.001). MetS predicted neither stroke nor mortality. Adjusted for its individual components, MetS was not associated with any end-point. Conclusions: ACR ≥ 0.75 mg/mmol was associated with cardiovascular morbidity and all-cause mortality independently of MetS. MetS was not associated with any end-point beyond what was predicted from its components. Thus, low-grade albuminuria, but not MetS, may be used for risk stratification in non- diabetic subjects. © 2008 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Microalbuminuria (albumin–creatinine ratio (ACR) 1.92 mg/ mmol in men and 2.83 mg/mmol in women or urinary albumin- excretion (UAE) 30–300 mg/d in both genders [1]) is associated with increased cardiovascular risk in diabetes [2], hypertension [3], and in non-diabetic populations [4]. Even low-grade increase in UAE, measured as ACR 0.6–0.9 mg/mmol, has been associated with cardiovascular disease (CVD) and mortality [4–6]. The clustering * Corresponding author at: Department of Nephrology, University Hospital of North Norway, N-9038 Tromsø, Norway. Tel.: +47 776 26000; fax: +47 776 69408. E-mail address: marit.solbu@unn.no (M.D. Solbu). of several cardiovascular risk-factors linked to obesity and insulin resistance, referred to as the metabolic syndrome (MetS), has also been shown by some authors to imply an increased risk for CVD and mortality [7]. However, others have stated that the MetS does not predict more than the sum of its components, and major criticism has been raised against the attempt to define a syndrome on the basis of a few selected variables with more or less arbitrary cut- off values and an unknown underlying pathophysiological process [8,9]. Nevertheless, MetS is a tool currently utilized by researchers and clinicians and therefore of interest. An association between UAE and the components of MetS has been described in many populations [10], and microalbuminuria is included in the World Health Organization (WHO) definition of MetS [11]. Other studies have not confirmed this association 0021-9150/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2008.11.002