Managing Cardiovascular Risk: Special Considerations in Patients with Chronic Kidney Disease
Paper Symposium
Activity Date: July 2005  — Activity Info: Volume 5, (7A)
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Managing Cardiovascular Risk: Special Considerations in Patients with Chronic Kidney Disease
Mohamed G. Atta, MD, MPH,* and Norman Lepor, MD, FACC, FAHA†

More than 1 in 5 adults in the United States have the metabolic syndrome, a cluster of cardiovascular and metabolic abnormalities that include obesity, atherogenic dyslipidemia, insulin resistance, and hypertension. The metabolic syndrome is a risk factor for 2 major diseases that have high mortality rates: type 2 diabetes mellitus and cardiovascular disease (CVD). This monograph discusses recognition and management of the metabolic syndrome with a focus on dyslipidemia.

The National Kidney Foundation has a 5-stage classification system for ranking the severity of kidney disease. Stage 5 is the most severe, and patients in this stage require dialysis. The Third National Health and Nutrition Examination Survey estimates the number of patients with stage 2 kidney disease at 5.3 million, and the number of patients with stage 3 kidney disease at 7.6 million.1 The number of patients progressing to the more severe stages of kidney disease falls off sharply, with only about 0.3 million surviving to reach stage 5.1 Outcomes data for patients with chronic kidney disease (CKD) show that these patients have a poor long-term prognosis. As the survey estimates show, most of these patients are not likely to reach end-stage renal disease (ESRD). The reason patients die rather than progress to ESRD is evident: these patients are at a greatly increased risk for cardiovascular events compared with patients with normal kidney function. The specific mechanism by which CKD increases cardiovascular risk is not entirely understood. However, CKD has been linked to vascular endothelial dysfunction and has been associated with increased risk for stroke, coronary artery disease, and congestive heart failure. The various cardiovascular events occurring in patients with CKD suggests that the diseases interact through an underlying systemic disorder.

Risk factors for the progression of CKD, such as diabetes mellitus, hypertension, and anemia, are also factors that increase the risk of CVD. The complexity of the interaction between CKD and CVD necessitates a multidisciplinary approach to disease management. Our panel convened to discuss this complex issue and to provide insight into management strategies that may help reduce the cardiovascular impact of CKD.

The first article, by Norman Lepor, MD, FACC, FAHA, features clinical evidence that suggests a causal link between the cardiovascular and renal manifestations of CKD. The outcomes data he includes in his article suggest that the onset and progression of CKD are largely driven by novel risk factors, such as inflammation, which underlie and are perhaps exacerbated by traditional risk factors, such as diabetes mellitus and anemia. Results of trials analyzing the effect of anemia on outcomes for patients with CVD collectively show that among other risk factors, anemia is an independent predictor of increased cardiovascular mortality.

In the following article, Jeffrey Brinker, MD, discusses clinical evidence of increased cardiovascular risk among patients with renal insufficiency. He explores methods for assessing cardiovascular risk in this population, in which CVD is prevalent and progresses quickly. Dr Brinker shows evidence that patients with CKD present with a variety of cardiovascular conditions, suggesting that CKD affects the cardiovascular system as a whole. Dr Brinker also discusses evidence that renal and cardiovascular risk assessments and effective treatments are underutilized, especially in the early stages of kidney disease, when the probability of preventing a poor outcome is the greatest.

In his article, Steven Fishbane, MD, discusses outcomes data from observational and interventional trials that investigated the role of anemia in the progression of CKD and CVD. Obser-vational data showed that anemia significantly increases the risk of mortality in patients with CKD and CVD, although the specific mechanism by which anemia increases mortality risk remains unknown. The interventional data he discusses show that anemia can be treated effectively and safely with erythropoietin therapy. Although these trials did not show benefit from correction of relatively mild or moderate anemia, patient quality of life was improved. The results of these trials suggest treatment benefits may sometimes be difficult to quantify in patients with advanced kidney disease, in whom multiple comorbidities contribute to the outcome.

The final article, by Jeffrey S. Berns, MD, addresses clinical evidence that illustrates that effective treatment of the major risk factors for CKD progression also reduce the relative risk of cardiovascular events. These data show that treating dyslipidemia and calcium-phosphorous imbalances in patients with CKD may reduce the risk of cardiovascular disease. Dr Berns also discusses promising data from interventional studies in patients with severe anemia. Erythropoietin treatment in these patients improved quality of life and benefited measurable cardiovascular endpoints, such as left ventricular mass index. The data suggest that patients treated with erythropoietin in the early stages of CKD may experience slower disease progression compared with patients whose treatment is delayed.

Each article is followed by a panel discussion, in which it was generally agreed that prospective trials are needed to provide evidence of the specific mechanism by which CKD and CVD compound one another’s detrimental effects. In the case of conditions that greatly increase mortality risk, such as anemia, patients should be identified and treated early in the disease process. The practical realities of early treatment are reviewed herein, in the context of the recommendations made in the Kidney Disease Outcomes Quality Initiative guidelines. Limiting the effects of known risk factors may help slow the progression of CKD and CVD and, hence, reduce mortality risk.


1. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2, suppl 1):S1-S266.

*Assistant Professor of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
†Associate Clinical Professor of Medicine, David Geffen School of Medicine at UCLA; Attending Cardiologist, Cedars-Sinai Medical Center, Los Angeles, California.
Address correspondence to: Mohamed G. Atta, MD, Johns Hopkins University School of Medicine, 1830 East Monument St, Ste 416, Baltimore, MD 21205.

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