Cardiovascular Disease in End-Stage Renal Disease Patients

Allan J. Collins, MD, FACP, Shuling Li, MS, Jennie Z. Ma, PhD, and Charles Herzog, MD
This study evaluates risk factor monitoring in end-stage renal disease (ESRD) patients with cardiovascular disease. Death rates from cardiovascular disease in ESRD patients are 20 to 40 times higher than in the general population, and 72% of ESRD patients with an acute myocardial infarction (AMI) are dead within 2 years of follow-up. Patients who have sustained an AMI rarely receive denitive testing to assess coronary circulation, and cardiac catheterization rates and revascularization rates are low, even after the high-risk event of an AMI. Risk factor intervention to treat lipid disorders in the ESRD population has received little attention, with the USRDS reporting that in 1998, 58% of dialysis and 64% of transplant patients had no lipid monitoring performed within a year. Of those tested, only 33% of dialysis and 27% of transplant patients had two or more tests within 1 year. Glycemic control monitoring in the form of HbA1c, recommended for diabetes management, is also underutilized in ESRD patients, with fewer than half receiving a single test within 1 year and only 10% receiving three or more tests. This raises concerns that diabetic glycemic control monitoring may be suboptimal in the ESRD population. The use of diabetic eye examinations and diabetic glucose monitoring is also low, as are inuenza vaccination rates. These data suggest that the clinical care of cardiovascular disease in the ESRD patients needs more attention. 2001 by the National Kidney Foundation, Inc. INDEX WORDS: End-stage renal disease (ESRD); cardiovascular disease (CVD); acute myocardial infarction; diabetes; risk factors; preventive health care.

ARDIOVASCULAR disease has been known for many years to be the leading cause of death in end-stage renal disease (ESRD) patients, as shown in Tables H.18 through H.37 of the 2000 USRDS Annual Data Report,1 yet the magnitude of the impact of cardiovascular mortality had not been appreciated until Sarnak and Levey2 published comparisons of cardiovascular mortality between dialysis patients and the general population. The differences in death rates range from approximately a 120-fold difference between patients 25 to 34 years of age, to a 15-fold difference between patients 55 to 64 years of age, and to as much as a 3-fold difference in patients who are more than 85 years of age. These dramatic differences in cardiovascular death rates between the general population and the dialysis patient population raise questions relative not only to the underlying etiology of the increased cardiovascular death rate, but also whether factors that may be amenable to treatment are being pursued. The recent study by Herzog et al3 showed that mortality after acute myocardial infarct in paFrom the Minneapolis Medical Research Foundation, University of Minnesota, Minneapolis, MN; and the University of Tennessee, Memphis, TN. Address reprint requests to Allan J. Collins, MD, FACP, Minneapolis Medical Research Foundation, University of Minnesota, 914 South Eighth St, Minneapolis, MN 55404. 2001 by the National Kidney Foundation, Inc. 0272-6386/01/3804-0105$35.00/0 doi:10.1053/ajkd.2001.27392
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tients on dialysis is exceedingly high, with 72% of patients dead 2 years after the acute myocardial infarction index event and with 60% of deaths due to cardiovascular causes. More recently, the US Renal Data System (USRDS) presented information at the American Society of Nephrology 2000 annual meeting showing that the degree of lipid monitoring in dialysis and transplant patients for the year 1998 appears to be substantiated. They studied all period-prevalent dialysis patients who survived at least 90 days in 1998, with Medicare as the primary payor and the patients surviving the entire year (Fig 1). The study included 203,065 patients for whom lipid tests were identied using current procedural terminology (CPT)-coded services billed to the Medicare system. Of the 124,916 dialysis patients, 58% had no lipid monitoring during the entire year, 10% had only 1 test, and 33% had 2 or more tests. Of the 70,994 transplant patients identied, 64% had no lipid tests, 9% had only 1 test, and 27% had 2 or more tests. From these data, it appeared that, even though the cardiovascular death rate in dialysis patients is known to be between 20 and 40 times higher than that of the general population, little is done to monitor risk factors, which may be amenable to interventions for these highly vulnerable patients. The reasons for the lack of monitoring are unknown, but may reect the fact that there are no outcome-based clinical trials demonstrating the efcacy of lipid treatment in ESRD patients. Alternatively, drug therapy to intervene is be-

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Fig 1. Dialysis versus transplant: percentage of patients having 1 or more lipid tests, 1998. Patients who remained on the same modality for the entire year.

yond the scope of Medicare coverage, which limits the prescription drug benets of dialysis patients; therefore, monitoring of these tests would not lead to direct intervention because patients cannot afford the treatment. Another possibility centers around the care delivery system, in which nephrologists focus their efforts on providing primarily ESRD care in the areas of dialytic therapy, anemia management, and blood pressure control in the dialysis units. This leaves other areas of preventive care (such as risk factor interventions) outside the scope of practice included in the monthly capitation payment for US nephrologists. To determine whether risk factor monitoring for cardiovascular disease was an isolated phenomenon or a more general area of concern, the USRDS evaluated the diabetic population to determine the frequency of glycosylated hemoglobin monitoring for diabetics who survived 1 full year (Fig 2). It was noted that for diabetics with Medicare as the primary payor, almost 70% of patients had no glycosylated hemoglobin control testing in 1998. This number was down from almost 82% in 1995, showing slight improvement, but it was clear that fewer than 10% of the patients actually had 3 or more glycosylated hemoglobin tests performed in 1 year, as shown in Fig 9.11 of the USRDS 2000 Annual Data Report.1 Other evidence of reduced components of care has been shown by the USRDS in the area of diabetic eye examinations. This parameter has been used by the National Council of Quality Assurance in the United States as a benchmark for employer group health plan insurance to determine whether care is delivered to

certain populations. In this area, the USRDS showed that, overall, fewer than 35% of patients received diabetic eye testing during a year, including examinations for eye hemorrhages, neovascularization, retinal detachments, and blindness. The groups of patients who received the lowest amount of diabetic testing were Native Americans and Blacks, as shown in Fig 9.1 of the USRDS 2000 Annual Data Report.1 Other preventive health care measures include inuenza vaccinations, which also showed in 1998 that fewer than 45% of ESRD patients received vaccinations in the fall of 1998. There was considerable variation in vaccination rates, ranging from a low of less than 36% to a high of more than 50% of patients, or an almost 2-fold difference. These general measures of medical care, as well as cardiovascular and diabetic care, raise questions relative to the consistency of services delivered to this vulnerable population and how that may adversely effect cardiovascular death rates. The largest discrepancy between the general population death rates and dialysis patient death rates exists in the younger age population, with a more than 150-fold difference in the cardiovascular death rates. In the pediatric population, although cardiovascular death rates in prevalent hemodialysis patients from 1996 through 1998 were as low as fewer than 10 deaths per 1,000 treatment years compared with the adult population at over 200 deaths per 1,000 treatment years, there were signicant gender and racial differences, as shown in Fig 6.38 of the USRDS 2000 Annual Data Report.1 Death rates in the pediatric peritoneal dialysis population have raised concerns, particularly regarding the female population. It appears that deaths due to cardiac arrest were over 3 times higher in the female pediatric peritoneal dialysis population between 1996 and

Fig 2. Results: HbA1c tests in diabetic ESRD patients surviving 1 full year.

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1998 compared with their male counterparts, as shown in Fig 6.39 of the USRDS 2000 Annual Data Report.1 These higher cardiovascular death rates in the peritoneal dialysis population appear to be associated with Black children, as shown in Fig 6.42 of the USRDS 2000 Annual Data Report.1 The reasons for these associated cardiovascular death rates in pediatric peritoneal dialysis patients are unknown but may reect uid management and/or ultraltration control leading to persistent hypertension and subsequent left ventricular hypertrophy, predisposing these children to arrhythmic deaths. It is not clear why the female pediatric population would be at adverse risk compared with the male population; however, other differences in care need to be carefully reviewed. For example, the female pediatric population may be vulnerable to increasing levels of anemia, which has received little attention. Because the pediatric population rarely initiates dialysis with histories of other known cardiovascular risks (such as diabetes, history of smoking, or long history of lipid disorders), this patient population may be more amenable to risk factor intervention compared with the adult population, particularly in the area of anemia treatment. Cardiovascular disease in the adult population continues to be an area of concern. Recently, the USRDS cardiovascular symposium at the American Society of Nephrology 2000 annual meeting presented information on revascularization rates in the adult dialysis population, showing an increase in the rst, second, and third year of ESRD survival over the period 1991 through 1997. Unfortunately, it appears that few patients are evaluated for revascularization after the index event of an acute myocardial infarction. It appears that monitoring of lipids within 6 months before and after the acute myocardial infarction event did not change over the 5-year period studied, with fewer than 20% of patients receiving these tests either before or after the acute myocardial infarction event. This would be in contrast to the current recommendations of the American Heart Association that patients with acute myocardial infarction are a high-risk group requiring aggressive risk factor intervention.4 Under the direction of Charles A. Herzog, MD, the USRDS Cardiovascular Special Studies Center presented two abstracts at the American

Society of Nephrology 2000 annual meeting, one focusing on the improvement in survival of dialysis patients after coronary bypass surgery with internal mammary artery grafts5 and the second on the outcome of dialysis patients after cardiac valve replacement surgery. In the rst study, Herzog et al5 showed a signicant early survival advantage for those patients who receive coronary bypass grafting using an internal mammary artery, compared with saphenous vein grafting. This advantage was present in all-cause mortality as well as in cardiac mortality. From the same group, Ma et al6 showed that survival after the rst coronary revascularization procedures was different between hemodialysis and peritoneal dialysis patients.6 In this study, which was adjusted for age, gender, race, and comorbid conditions, with peritoneal dialysis as the baseline group, hemodialysis patients had a 28% to 30% lower risk of death after coronary revascularization procedures, compared with their peritoneal dialysis counterparts. Cardiovascular deaths were 20% to 30% lower in the hemodialysis patient group. Because cardiovascular disease occurs more commonly in the older population, the observations may help explain the higher reported mortality of peritoneal dialysis patients in diabetics 55 years of age or older, who have previously been shown to have a high mortality risk compared with comparable hemodialysis patients.7 Valvular heart disease continues to be an area of concern in the hemodialysis population, yet the types of prostheses used in the valve replacement appear to be controversial. Current American College of Thoracic Surgeons recommendations suggest that bio-prosthetic valves are contraindicated in dialysis patients. Herzog et al5 studied this area, as reported at the American Society of Nephrology 2000 annual meeting, evaluating 5,500 patients who had aortic, mitral, or combined aortic/mitral valve replacements. Of the group, 881 had tissue valves and 2,000 patients had their valve replacements as part of the coronary artery bypass graft. When comparing survival after the valve procedures, the Kaplan-Meier all-cause survival was not different between the nontissue- and tissue-based valve replacement patients. Here, the curves were indistinguishable between each other, with a logrange test P value of 0.79. Cardiac death was

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also indistinguishable between the 2 groups. This evaluation suggests that, in fact, the current recommendations by the American College of Thoracic Surgeons regarding bio-prosthetic valves should be reconsidered based on these studies. The high cardiovascular death rate in the dialysis population compared with that of the general population spans the full age spectrum from the pediatric group all the way up to the most elderly patients on ESRD treatment. It appears that signicant improvement in care may be obtained if risk factor interventions are pursued in both dialysis and transplant patients. In the area of acute coronary events, it appears that there is signicant room for improvement in evaluating the high-risk dialysis patients after acute myocardial infarction and that risk factor intervention should receive increased attention. Some of the concerns over long-term survival of peritoneal dialysis patients may be related to treatment of cardiovascular disease. Whether adequate risk factor intervention was performed on this population requires further study. Lastly, in the area of valve replacement surgery, expanded use of bioprosthetic valves in this population may actually be indicated to reduce the requirements for anti-

coagulation and potentially reduced hemorrhagic complications. In the current era, considerable improvements in the treatment of cardiovascular disease are needed that may reduce the high death rate of this vulnerable population.
REFERENCES
1. US Renal Data System: USRDS 2000 Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2000 2. Sarnak MJ, Levey AS: Epidemiology of cardiac disease in dialysis patients. Semin Dial 12:69-76, 1999 3. Herzog CA, Ma JZ, Collins AJ: Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 339:799-805, 1998 4. Gage TW, Pallasch TJ: American Heart Association guidelines. Pediatr Dent 20:380-381, 1998 5. Herzog CA, Ma JZ, Collins AJ: Is there improved survival of dialysis patients after coronary artery bypass surgery with internal mammary artery grafts? J Am Soc Nephrol 11:272A, 2000 (abstr) 6. Ma JZ, Collins A, Herzog CA: Survival of dialysis patients after coronary revascularization procedures: Hemodialysis vs. peritoneal dialysis. J Am Soc Nephrol 11:285A, 2000 (abstr) 7. Vonesh EF, Moran J: Mortality in end-stage renal disease: A reassessment of differences between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol 10:354-365, 1999