ardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) regardless of stage. 1 Forty percent to 50% of all deaths in the end-stage renal disease (ESRD) population are of cardiovascular origin. 1 Car- diovascular causes also account for the majority of deaths among patients with predialysis kidney dis- ease. 1,2 The burden of cardiovascular disease in this pa- tient population is evident upon the initiation of renal replacement therapy. As shown in a Canadian cohort, 40% of patients starting dialysis already had evidence of coronary heart disease (CHD), and only 16% had normal echocardiographic studies. 3 Early intervention is required to minimize the bur- den of cardiovascular disease in CKD. Risk reduction strategies are likely to be effective in reducing cardiovas- cular morbidity and mortality in CKD patients in the same way these interventions improve outcomes in the general population. However, the pathogenesis of car- diovascular damage in CKD patients is far more com- plex than in the general population and includes tradi- tional risk factors as well as risk factors typical of chronic renal failure (Table 1). 1 Thus, risk reduction in these patients should target both traditional and CKD-specific risks for cardiovascular disease. Traditional cardiovascular risk factors are highly prev- alent in patients with chronic renal insufficiency. Diabetes is the most common cause of kidney disease in the United States and is the primary diagnosis in 45% of ESRD patients. 4 The total burden of diabetes in patients surviving 1 year on dialysis was actually 60%. 4 Similarly, hypertension and dyslipidemia are rampant in this popu- lation. In a cross-sectional analysis involving patients enrolled in the Modification of Diet in Renal Disease trial, 64% were hypertensive despite being on therapy, 64% had low-density lipoprotein (LDL) cholesterol lev- els greater than 130 mg/dL, and 38.3% had high-density lipoprotein (HDL) cholesterol levels less than 35 mg/dL. 5 CKD-related risk factors for cardiovascular disease include the hemodynamic and metabolic abnormalities associated with renal insufficiency and the complications of decreased renal function. These risk factors are some- times divided into those altered by the uremic state (eg, hypertension, dyslipidemia) and those characteristic of the uremic state (eg, anemia, oxidative stress) (Table 1). 1 Whether renal insufficiency itself is an independent risk factor for cardiovascular disease is unclear. The Heart Outcomes and Prevention Evaluation study dem- onstrated an increased incidence of cardiovascular death, myocardial infarction (MI), or stroke in patients with renal insufficiency, and this incidence increased with serum creatinine concentration. 6 Other data from intervention studies in patients with hypertension, coro- nary disease, and congestive heart failure show a consis- tent role of renal dysfunction in predicting worse cardio- vascular outcomes and death. 7 Conversely, Garg et al 8 found no independent association between moderate renal insufficiency and total as well as cardiovascular mortality after adjustment for coexisting risk factors in a large prospective cohort. Despite these conflicting data, we believe that a sufficient number of studies suggest an independent role of CKD in predicting cardiovascular risk, such that patients with CKD should be considered at highest risk for subsequent cardiovascular events. This article outlines relevant cardiovascular risk factors in patients with CKD and summarizes the available evidence supporting the role of these factors C Dr. Zaldivar is a Fellow, Division of Nephrology, University of Connect- icut Health Center, Farmington, CT. Dr. Peixoto is an Assistant Professor of Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, CT; and Director, Hypertension Clinic, VA Connecticut Healthcare System, West Haven, CT. Dr. Perazella is an Associate Professor of Medicine, Section of Nephrology; and Director, Acute Dialysis Program, Yale University School of Medicine; he is also a member of the Hospital Physician Editorial Board. www.turner-white.com Hospital Physician June 2003 29 Clinical Review Article Series Editor: Mark A. Perazella, MD, FACP CKD Series: Cardiovascular Risk Reduction in Patients with Chronic Kidney Disease Maria Criselda Zaldivar, MD Aldo J. Peixoto, MD