Evaluation of Subclinical Organ Damage for Risk Assessment and Treatment in the Hypertensive Patient: Role of Microalbuminuria Roberto Pontremoli, Giovanna Leoncini, Francesca Viazzi, Elena Ratto, Valentina Vaccaro, Valeria Falqui, Angelica Parodi, Novella Conti, Cinzia Tomolillo, and Giacomo Deferrari Department of Internal Medicine, University of Genoa, and Department of Cardio-Nephrology, Azienda Opedaliera Universitaria San Martino, Genoa, Italy Microalbuminuria, i.e., abnormal urinary excretion of albumin, which is detectable by low cost and widely available tests, is a first-line tool for identifying hypertensive patients who are at higher cardiovascular (CV) risk. Numerous studies have provided evidence that microalbuminuria is a concomitant of cardiac and vascular damage as well as a strong, independent predictor of CV events. An important, emerging issue is that the risk for CV morbidity and mortality is linearly related to urinary albumin excretion and persists well below the currently used cutoff for defining microalbuminuria. Furthermore, late-breaking evidence suggests that a reduction of albuminuria under antihypertensive treatment is paralleled by changes in CV risk. The routine search for target organ damage by means of microalbuminuria could lead to a significant improvement in the evaluation and treatment of patients with primary hypertension. J Am Soc Nephrol 17: S112–S114, 2006. doi: 10.1681/ASN.2005121327 C ardiovascular diseases are the leading cause of death in Western countries, accounting for more than one third of all deaths. This is due mainly to the steady increase in the prevalence of hypertension and diabetes, which affect 30 and 8% of the general population, respectively, and have now reached the proportion of a worldwide epidemic. Unfortunately, the prevalence rates of these abnormalities are expected to increase in the next 2 decades, resulting in a further rise in the number of deaths from cardiovascular (CV) compli- cations (1,2). A similar scenario mandates the need for both better implementation of antihypertensive treatment and early identification of patients who are at increased CV risk. The assessment of global risk profile, including the severity of hypertension and the presence of concomitant CV risk fac- tors, represents a prerequisite for devising effective antihyper- tensive treatment (3). The National Health and Nutrition Ex- amination Survey Epidemiologic Follow-Up Study showed that reducing a given BP (by approximately 12 mmHg) over a 10-yr period is much more beneficial in patients with a worse global risk profile (4). Recently, international hypertension guidelines acknowledged the relevance of minor abnormalities in renal function for stratifying patients with arterial hypertension. The Seventh Report of the Joint National Committee, for example, considers the presence of microalbuminuria or a slight reduc- tion in GFR (60 ml/min) as major CV risk factors (5). Euro- pean guidelines go even further and list a slight elevation in serum creatinine (1.3 mg/dl in men and 1.2 mg/dl in women) and/or the presence of microalbuminuria among the signs of hypertensive organ damage (3). This brief review focuses on the role of microalbuminuria as an integrated marker of sub- clinical organ damage and its usefulness for global risk assess- ment and effective treatment. Microalbuminuria as a Marker of CV Risk The occurrence of microalbuminuria in patients who do not have diabetes but have primary hypertension was first de- scribed by Parving et al. (6) in 1974. Although 24-h urine col- lection is still considered the reference method for measuring urinary albumin excretion, evaluating the albumin to creatinine ratio in a first morning urine sample is easier but no less accurate and has rapidly become the method of choice in clin- ical practice. Since 1974, several studies have shown that mi- croalbuminuria, whose prevalence ranges from 5 to 40%, is a useful tool when evaluating CV risk in hypertensive patients. We and others have demonstrated that microalbuminuria is associated with extrarenal signs of hypertensive target organ damage, such as left ventricular hypertrophy and carotid ath- erosclerosis (7). Furthermore, a large body of data indicate that microalbuminuria is a strong, independent predictor of CV events both in patients with and in patients without diabetes. An important, emerging issue is that the risk for CV morbidity and mortality is linearly related to urinary albumin excretion, without any recognizable threshold or plateau. In the LIFE study, for example, the rate of the primary composite end point increased linearly four- to five-fold in patients from the lowest to the highest deciles of the albumin to creatinine ratio (8). On the basis of these findings, it was suggested recently that the cutoff value for defining microalbuminuria in essential hyper- tension be lowered to improve diagnostic sensitivity (9). Address correspondence to: Dr. Roberto Pontremoli, Department of Internal Medicine, University of Genoa, and Department of Cardio-Nephrology, Azienda Opedaliera Universitaria San Martino, Genoa Viale Benedetto XV 6, 16132 Genoa, Italy. Phone/Fax: +39-010-353-8932; E-mail: roberto.pontremoli@unige.it Copyright © 2006 by the American Society of Nephrology ISSN: 1046-6673/1704-0112