Cardiovascular Disease and Dialysis Patients: Is Therapeutic Nihilism Justified?

Cardiovascular disease is the major cause of death in patients who have end-stage renal disease (ESRD) and are receiving chronic dialytic therapy; the disease accounts for 44% of all-cause mortality (1). The risk of cardiac and all-cause death is greater in older patients, in patients with ESRD secondary to diabetes, and in patients on peritoneal dialysis (1). In the United States, the greatest increase in the incidence of ESRD has occurred in older patients and those with diabetic nephropathy. Accordingly, there has been a continuing increase in the burden of cardiovascular disease in the ESRD population. The staggering cardiovascular mortality in the U.S. dialysis population (as compared to the general population) is graphically summarized in Figure 1, which appropriately appeared on the front cover of the Special Reportfrom the National Kidney Foundation Task Force on Cardiovascular Disease (2). The burden of ischemic heart disease in ESRD patients has been independently confirmed by the European Dialysis and Transplant Association (EDTA) Registry. In the United Kingdom, the all-age death rate from myocardial ischemia and myocardial infarction for patients commencing renal replacement therapy in 1985–1990 was 16.6-fold greater in men and 17.7-fold greater in women, as compared to the general population (3). It is estimated from 1996 Medicare data that 287,515 patients in the United States were treated for ESRD, of whom 72.6% received dialysis and 27.4% had functioning renal transplants (4). The majority of dialysis patients in the United States receive hemodialysis for renal replacement therapy, as peritoneal dialysis patients account for only 14% of the chronic dialysis population (4). Past efforts to identify ischemic heart disease in ESRD patients have focused on “high-risk” (usually diabetic) renal transplant candidates. The American Society of Transplant Physicians has recommended that patients at high risk for ischemic heart disease be screened for coronary artery disease (CAD) before renal transplantation (5). However, no comparable strategy has been promoted for the largest group of ESRD patients with the highest risk of cardiovascular disease: patients receiving renal replacement therapy with chronic dialysis. The recent publication of the Special Report from the National Kidney Foundation Task Force on Cardiovascular Disease, chaired by Dr. Andrew Levey, is a benchmark, as it has focused sustained attention on the burgeoning epidemic of cardiovascular disease in patients with chronic renal failure. The reader is urged to review this work, as it frames all the important issues relating to cardiovascular disease in ESRD patients and, equally importantly, suggests proposed lines of research inquiry. The impact of multiple risk factors for the development of cardiovascular disease in patients with chronic renal failure, including hypertension, dyslipidemia, hyperglycemia, smoking, physical inactivity, enhanced thrombogenicity, and elevated homocysteine levels, can be ameliorated. In dialysis patients, anemia and a noncompliant vasculature may also contribute to the genesis of left ventricular hypertrophy. Aortic stiffness (assessed by aortic pulse-wave velocity) is an independent predictor of all-cause and cardiovascular mortality (6). The nonphysiologic nature of conventional hemodialysis schedules (usually administered thrice weekly in the United States on Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) may also contribute to excess cardiac mortality, on the basis of a recent publication detailing increased cardiac deaths of U.S. dialysis patients on Mondays (and, to a lesser extent, on the other dialysis day after the long weekend, Tuesday) (7). In my opinion, the most valuable contribution of the Task Force was to provide an informed synthesis of the literature on the epidemiology of cardiovascular disease in the ESRD patient and how the ESRD patient should be viewed from the perspective of cardiovascular risk stratification and management in the non-ESRD population. The Task Force applied to a patient population not previously well studied—ESRD and “pre-ESRD” patients—management strategies derived from welldesigned clinical trials in the non-ESRD population. Finally, considerably greater numbers of patients with chronic renal insufficiency do not yet require renal replacement therapy. Logically, targeting pre-ESRD patients for cardiovascular risk-factor reduction before the development of ESRD is more appealing, but this does not imply that dialysis patients are a lost cause from a cardiovascular standpoint. There may be opportunities to affect cardiovascular outcome by optimal medical therapy. For example, beta-blockers and angiotensinconverting enzyme (ACE) inhibitors improve survival in non-ESRD patients when used for congestive heart failure or after acute myocardial infarction (AMI). One surprising finding from the U.S. Renal Data System (USRDS) Dialysis Morbidity and Mortality Wave 2 Study was the disproportionately high percentage (52%) of calAddress correspondence to: Charles A. Herzog, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415. E-mail: herzo003@maroon.tc. umn.edu. Seminars in Dialysis—Vol 12, No 5 (September–October) 1999 pp. 285–287