Cardiovascular disease in patients on chronic hemodialytic therapy

D URING the early 1970s it became apparent that patients maintained on chronic hemodialysis programs died of cardiovascular disease with an incidence greatly in excess of the age-adjusted expected rate. As a larger number of patients with diabetes, severe hypertension, and preexisting heart disease have become candidates for chronic hemodialysis, elucidation of the exact causes of and factors contributing to the development and progression of cardiovascular disease in end-stage renal failure has become an issue of practical significance. Several earlier reviews of mortality in highly selected, “better risk” dialysis patients reveal an extremely high incidence of cardiovascular complications.‘*2 Lindner et a1.2 reported a sharp increase in the cause-specific mortality from cardiac problems beginning 4 yr after the institution of hemodialysis. Included in this report were three patients with intractable congestive heart failure, as well as eight with myocardial infarction and three patients with stroke. When considered as a single risk factor, the death rate from myocardial infarction rose steeply after 6 yr. A comparison of these data with the incidence of coronary artery disease in the Framingham study3 demonstrates that young dialysis patients have a mortality 2.5 times that reported for older men with severe levels of hypertension.4 Data collected from European centers indicate a similar pattern.’ Among 12,000 deaths occurring in patients on chronic dialysis programs through 1976, 58% were due to cardiovascular disease. Of these, almost half were attributed to “hypertensive cardiac failure,” cardiac arrest, and “other causes of cardiac failure.” Lazarus et a1.,4 after reviewing these data, data from the U.S. National Registry, and data from their own series, concluded that “hemodialysis patients are dying from complications of vascular disease. ” “Accelerated atherosclerosis” was the term used by Lindner et al.* to characterize this unexpected increase in cardiovascular deaths. Although several physical and metabolic abnormalities associated with cardiovascular disease can be shown to be prevalent in the hemodialysis population, there is no direct evidence that these abnormalities can either cause or accelerate atherosclerosis in this patient group. Indeed, a more recent study by Burke et al.’ indicates that patients who do not have diabetes, underlying heart disease, or malignant hypertension before entering dialysis programs have a very low incidence of subsequent atherosclerotic complications. None of the 24 deaths in this group was due to cardiac disease, although 7 deaths occurred after more than 5 yr on dialysis. Almost half of the deaths Burke et al. reported were due to infection, while small numbers were due to dialysis dementia, hyperkalemia, voluntary discontinuance, and miscellaneous other causes. In contrast, 8 of 10 deaths occurring after more than 5 yr of dialysis in Lindner’s group were due directly to cardiac disease, and 7 of these were “coronary deaths.“* Burke et al.* suggested that the discordant experiences may be due to a fundamental change in the physical composition of the dialysis population. They point out that case selection greatly influences the conclusions drawn from these retrospective studies, since the incidence of myocardial infarction and stroke was 34% in a group of patients excluded from their analysis (Table 1). In order to estimate the contribution of chronic hemodialysis to cardiovascular disease, it is necessary to evaluate the cardiac status of patients before entry into dialysis programs. Studies of cardiac function have the disadvantage that day-to-day alterations in diet, fluid balance, or compliance with medical therapy may be responsible for large fluctuations in a