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*Department of Internal Medicine, University of Maastricht, Maastricht, The Netherlands; Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Departement Moleculair en Cardiovasculair Onderzoek, Katholieke Universiteit, Leuven, Belgium; Erasmus University, Rotterdam, The Netherlands; Department of Internal Medicine and Hypertension Unit, General Hospital of Athens, Athens, Greece; ¶Istituto Auxologico Italiano and the Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, Universitá di Milano, Milan, Italy; ||Department of Internal Medicine, Alexandrov’s University Hospital, Sofia, Bulgaria; #Department of Medicine and Therapeutics, University of Aberdeen, Abderdeen, Scotland; **Unidad de Hypertensión, Hospital 12 de Octubre, Madrid, Spain; Sackler School of Medicine, Tel Aviv, Israel; and National Public Health Institute, Helsinki, Finland.
Correspondence to Dr. Peter W. de Leeuw, Department of Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Phone: 31-43-387-7005; Fax: 31-43-387-5006; E-mail: p.deleeuw{at}intmed.unimaas.nl
ABSTRACT. Several reports suggest that markers of renal function such as serum creatinine, serum uric acid, and urinary excretion of protein may be related to cardiovascular complications and mortality. This study analyzed the data from the Syst-Eur trial, which was a randomized, placebo-controlled, double-blind intervention trial in elderly patients with isolated systolic hypertension. The purpose was to evaluate whether serum levels of creatinine and uric acid and urinary protein excretion at entry are related to subsequent morbidity and mortality. Incidence rates of total mortality, cardiovascular mortality, stroke (fatal as well as nonfatal), coronary events, and all cardiovascular endpoints were calculated for each quintile of serum creatinine or serum uric acid or for each category of protein excretion (none, trace, and overt). Crude and adjusted relative hazard rates were also determined for each 20 µM increase in serum creatinine, each 50 µM increase in serum uric acid, and for each protein excretion category. Even when adjusted for age, gender, and various other covariates, serum creatinine was significantly associated with a worse prognosis. There was an U-shaped relationship between serum uric acid and total mortality, but otherwise no obvious relationships were detected between serum uric acid levels and complications when appropriate adjustments were made for confounding variables. Proteinuria at entry was a significant predictor of total mortality and all cardiovascular endpoints. It is concluded that higher levels of serum creatinine and trace or overt proteinuria are associated with an increased number of cardiovascular events and with a higher mortality in patients with isolated systolic hypertension.
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