Chronic Kidney Disease, Cardiovascular Events, and the Effects of Perindopril-Based Blood Pressure Lowering: Data from the PROGRESS Study Vlado Perkovic,* † Toshiharu Ninomiya,* Hisatomi Arima,* Martin Gallagher,* Meg Jardine,* Alan Cass,* ‡ Bruce Neal,* Stephen MacMahon,* ‡ and John Chalmers* ‡ *George Institute for International Health, University of Sydney, † Royal North Shore Hospital, and ‡ Royal Prince Alfred Hospital, Sydney, Australia ABSTRACT Chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease, but evidence regarding the effectiveness of interventions to reduce that risk is lacking. The Perindopril Protection against Recurrent Stroke Study (PROGRESS) study enrolled 6105 participants with cerebrovascular disease and randomly allocated them to perindopril-based blood pressure–lowering therapy or placebo. Individuals with CKD were at approximately 1.5-fold greater risk of major vascular events, stroke, and coronary heart disease, and were more than twice as likely to die (all P0.002). Perindopril-based treatment reduced the risk of major vascular events by 30% and stroke by 35% among subjects with CKD, and the absolute effects of treatment were 1.7-fold greater for those with CKD than for those without. Considering patients with CKD and a history of cerebrovascular disease, perindopril prevented one stroke or other cardiovascular event among every 11 patients treated over five years. In conclusion, kidney function should be considered when determining the need for blood pressure lowering therapy in patients with cerebrovascular disease. J Am Soc Nephrol 18: 2766 –2772, 2007. doi: 10.1681/ASN.2007020256 Chronic kidney disease (CKD) is being increasingly recognized as a leading public health problem. CKD, most commonly defined by a reduction in GFR or the presence of proteinuria, affects 10 to 15% of the adult population in Western countries and a much higher proportion of individuals who are older than 65 yr. 1,2 Individuals with CKD are at significantly in- creased risk for cardiovascular events as well as pro- gression to end-stage kidney disease. This relation- ship has been confirmed in a large number of observational analyses 3 and persists after adjust- ment for other known risk factors. There is, how- ever, a lack of data regarding the effects of interven- tions such as BP lowering on cardiovascular risk in the CKD population. BP is an important determinant of cardiovascu- lar risk in the general population, 4 in which inter- ventions that lower BP have been clearly shown to prevent cardiovascular events. 5 BP levels are com- monly elevated in people with CKD, raising the possibility that BP lowering may offer significant benefit in this group. BP-lowering agents acting via the renin-angiotensin system have been demon- strated to have renoprotective effects in the protein- uric subgroup of people with CKD. 6,7 The few BP- lowering trials that have been conducted in a broader range of participants with CKD 8 –10 have not demonstrated clear benefits for either cardio- vascular events or kidney function overall. Subsid- iary analyses of one large clinical trial 11 suggested Received February 28, 2007. Accepted May 24, 2007. Published online ahead of print. Publication date available at www.jasn.org. Correspondence: Dr. Vlado Perkovic, George Institute for Inter- national Health, PO Box M201, Sydney, Australia, 2050. Phone: +612-9993-4523; Fax: +612-9993-4501; E-mail: vperkovic@ thegeorgeinstitute.org Copyright © 2007 by the American Society of Nephrology CLINICAL RESEARCH CLINICAL RESEARCH www.jasn.org 2766 ISSN : 1046-6673/1810-2766 J Am Soc Nephrol 18: 2766 –2772, 2007