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Commencing Volume 19, Issue 1, MedReviews has ceased the publication of this journal. Reviews in Cardiovascular Medicine will continue to be published by IMRPress, Ltd. (www.imrpress.org)

Volume 4, Supplement 6, 2003

Volume 4, Supplement 6, 2003

Table of Contents

Epidemiology of Contrast-Induced Nephropathy
Decreasing levels of renal function act as a major adverse prognostic factor after contrast exposure with or without percutaneous coronary intervention. In chronic kidney disease, the most important risk factor for the development of contrast-induced nephropathy (CIN) is an estimated glomerular filtration rate = 60 mL/min/1.73 m2. Additional risk factors include diabetes, proteinuria, volume depletion, heart failure, and intraprocedural events. Overall, CIN occurs in approximately 15% of radiocontrast procedures, with < 1% requiring dialysis. CIN is directly related to increases in hospitalization length, cost, and long-term morbidity. For those patients who require dialysis, a 30% in-hospital mortality rate and 80% 2-year mortality rate can be expected. CIN is predictable and presents an opportunity to utilize preventive strategies, given the increasing numbers of patients undergoing contrast procedures worldwide. [Rev Cardiovasc Med. 2003;4(suppl 5):S3–S9]
Insulin Resistance: From Benign to Type 2 Diabetes Mellitus
Type 2 diabetes has become the most frequently encountered metabolic disorder in the world, currently affecting 5% to 10% of most populations, and the incidence continues to grow among developing nations. Two fundamental abnormalities are involved in the pathogenesis of type 2 diabetes: Resistance to the biologic activities of insulin in glucose and lipid metabolism and inadequate insulin secretion from the pancreatic ß cells. In genetically predisposed individuals, type 2 diabetes is pathogenically linked with progressive obesity, especially adiposity that is visceral or ectopic in distribution. While microvascular complications (retinopathy, nephropathy, neuropathy) continue to plague patients with longstanding type 2 diabetes, cardiovascular disease has assumed particular importance, accounting for more than 80% of adverse outcomes among patients. Since the aggressive management of diabetes and its complications poses a considerable challenge, large trials to prevent the progression to overt diabetes in persons at high risk have recently demonstrated that lifestyle modification and pharmaceutical therapy can be successful approaches. A better understanding of the complex relationship between obesity and both the development of type 2 diabetes and its cardiovascular complications may provide additional treatment targets in the future to prevent the devastating chronic morbidity of this disorder. [Rev Cardiovasc Med. 2003;4(suppl 6):S3-S10]
Diagnostic and Therapeutic Utility of B-Type Natriuretic Peptide in Patients With Renal Insufficiency and Decompensated Heart Failure
Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathophysiologically linked. A recent study in patients with severe CHF demonstrated that renal plasma flow was inversely correlated with pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction. This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessing cardiac function and volume status in patients with CKD and examines the safety and efficacy of BNP therapy in patients with renal insufficiency and decompensated heart failure. [Rev Cardiovasc Med. 2003;4(suppl 7):S3–S12]
Understanding the Consequences of Contrast-Induced Nephropathy
Several investigations have discovered important physiologic links in the development of contrast-induced nephropathy (CIN). Studies using a canine kidney model showed that contrast media produce a direct cytotoxic effect on the renal structures. Also, there is increasing evidence that apoptosis is involved in CIN as a result of cell injury. It has been suggested that hemodynamic changes resulting from administration of contrast media may contribute to the development of CIN, although the data are not conclusive. Several vasoactive substances, such as endothelin, prostaglandins, nitric oxide, and adenosine, have been implicated in the pathogenesis of CIN, as have immune mechanisms. Several factors contribute to the development of CIN, including preexisting renal insufficiency, older age, diabetes mellitus, reduced left ventricular systolic function, advanced heart failure, acute myocardial infarction, and shock. The authors also present the risk score they developed to help clinicians identify patients with different responses to contrast exposure. [Rev Cardiovasc Med. 2003;4(suppl 5):S10–S18]
The Relation of Insulin Resistance Syndromes to Risk of Cardiovascular Disease
Diabetes mellitus is one of the most common problems challenging physicians in the 21st century. Type 2 diabetes mellitus accounts for at least 90% of all cases, which can be attributed in part to an aging population and the prevalence of obesity and sedentary lifestyles. In addition to the major impact on quality of life, diabetes accounts for a significant proportion of global healthcare expenditure, with the majority of costs attributable to treatment of its long-term complications. The principal cause of diabetes mortality is cardiovascular disease (CVD). There is a long period, prior to clinical detection of the disease, in which insulin resistance and hyperglycemia gradually worsen, and vascular complications develop. This article reviews the relationship between diabetes and the risk of CVD. [Rev Cardiovasc Med. 2003;4(suppl 6):S11-S18]
Treatment of the Acute Decompensation of Heart Failure: Efficacy and Pharmacoeconomics of Early Initiation of Therapy in the Emergency Department
Most patients admitted with acute decompensated heart failure (ADHF) go through the emergency department as their initial point of care. New diagnostic tests hold the promise to improve the clinical accuracy of the emergency physicians’ diagnosis. Beyond that there is growing recognition that the treatment provided initially has an important impact on the subsequent inpatient course. Basic care for ADHF has involved oxygen as needed, diuretics, and, occasionally, topical or sublingual nitroglycerin. A substantial proportion of patients are treated with vasoactive agents including inotropes and vasodilators such as nitroglycerin and nesiritide. Unfortunately, inotropes have not been demonstrated to improve the outcome of heart failure and, in fact, may be deleterious. The newer agent, nesiritide, has the advantage of being a balanced vasodilator with favorable effects on diuresis, symptom relief, and neurohormones. Evidence from registries indicates that early initiation of nesiritide compared to delayed initiation leads to improved outcomes with shorter lengths of stay, shorter stays in the intensive care unit, and a lower mortality rate. This article reviews the initial management of ADHF, the role of early initiation of vasodilator therapy, and the pharmacoeconomics of nesiritide treatment. [Rev Cardiovasc Med. 2003;4(suppl 7):S13–S20]
What Every Cardiologist Should Know About Intravascular Contrast
Contrast-enhanced x-ray imaging remains essential to the diagnosis and treatment of many types of cardiac and vascular disease. Despite the rapid advancements in less invasive imaging techniques, only traditional angiography provides a high-resolution, real-time, dynamic view of vascular structures. Cardiologists have become concerned about contrast selection since the introduction of new agents over the last 2 decades. This concern has sparked three sequential debates within our community: the cost effectiveness of low osmolal contrast; whether nonionic agents are prothrombogenic; and whether the potential for nephrotoxicity differs between contrasts. Following is a summary of clinically relevant aspects of the cost effectiveness of low osmolal contrast and the prothrombogenicity of nonionic agents. These issues are important not only to those who perform angiography, but also to those who refer patients to, or follow them after, the procedure. [Rev Cardiovasc Med. 2003;4(suppl 5):S19–S27]
Treating the Diabetic Patient: Appropriate Care for Glycemic Control and Cardiovascular Disease Risk Factors
Diabetes, a leading cause of morbidity and mortality in the United States, is associated with a 2- to 4-fold increase in the risk of coronary artery disease. As the population in the United States has aged, the incidence of obesity, hypertension, glucose intolerance, and dyslipidemia has increased significantly, culminating in the current epidemic of type 2 diabetes mellitus. Strict glycemic control must, therefore, be accompanied with proven therapies (such as antihypertensives and lipid-lowering agents) to reduce cardiovascular events. Patients with type 2 diabetes have average low-density lipoprotein (LDL) levels but have an increased number of small, dense LDL particles, which are associated with a 3-fold increase in cardiovascular disease. Type 2 diabetes mellitus is also associated with increased triglyceride rich atherogenic particles, which trigger inflammation. In addition to glycemic control and drug therapy, lifestyle modifications (eg, diet, weight loss, and exercise) also play an important role in managing diabetes. Therefore, strict glycemic control, pharmacologic therapy, and lifestyle modifications are parts of a comprehensive strategy to prevent both microvascular and macrovascular events in patients with type 2 diabetes. [Rev Cardiovasc Med. 2003;4(suppl 6):S19-S28]
The Acute Decompensated Heart Failure National Registry (ADHERE): Opportunities to Improve Care of Patients Hospitalized With Acute Decompensated Heart Failure
Heart failure is a leading cause of hospitalization for adults in the United States. Patients hospitalized with acute decompensated heart failure (ADHF) face a substantial risk of in-hospital mortality and rehospitalization. Despite the large number of patients hospitalized and this substantial risk, data on these patients have been limited and there has been little effort to improve the quality of care for patients hospitalized with ADHF. The Acute Decompensated HEart Failure National REgistry (ADHERE™) was designed to bridge this gap in knowledge and care by prospectively studying characteristics, management, and outcomes in a broad sample of patients hospitalized with ADHF. Participating community and university hospitals identified patients with a primary or secondary discharge diagnosis of heart failure and collected medical history, management, treatments, and health outcomes via secure web browser technology. As of July 2003, 65,180 patients have been enrolled from 263 hospitals. Initial data have provided important insights into the clinical characteristics, patterns of care, and outcomes of these patients. ADHERE documents significant delays in diagnosis and initiation of ADHF therapies as well as substantial under-use of evidence-based, guideline-recommended chronic heart failure therapies at hospital discharge. As such, there are substantial opportunities to improve the quality of care for ADHF patients in the nation’s hospitals. The ADHERE Hospital Toolkit has been designed to provide hospital teams with effective proactive instruments to improve the quality of care for patients with ADHF. If successfully implemented, the improvements in shortand long-term clinical outcomes for ADHF patients are expected to be substantial. [Rev Cardiovasc Med. 2003;4(suppl 7):S21-S30]
Pathogenesis of Contrast-Induced Nephropathy: Experimental and Clinical Observations with an Emphasis on the Role of Osmolality
Experimental studies suggest that the pathogenesis of contrast media nephrotopathy is due to a combination of renal ischemia and direct tubular epithelial cell toxicity. Clinical studies to date have demonstrated a reduction in clinical contrast nephropathy with the introduction of low-osmolar and, more recently, iso-osmolar contrast media. Numerous experimental studies have examined the role of osmolality per se in the pathogenesis of contrast nephropathy, with conflicting results. Whether iso-osmolar contrast media are the least nephrotoxic iodinated contrast media needs to be determined with large prospective randomized clinical trials. [Rev Cardiovasc Med. 2003;4(suppl 5):S28–S33]
The Role of the Thiazolidinediones in the Practical Management of Patients With Type 2 Diabetes and Cardiovascular Risk Factors
The American Diabetes Association’s objective for treating patients with type 2 diabetes mellitus is to normalize glycemia and glycosylated hemoglobin concentrations while controlling blood pressure, cholesterol, and other cardiovascular risk factors. This article focuses on the role of thiazolidinediones (TZDs) in the management of patients with type 2 diabetes with comorbid cardiovascular disease. Insulin resistance is one of the earliest and main defects in type 2 diabetes and is strongly linked to comorbid cardiovascular conditions. The TZDs rosiglitazone and pioglitazone work mainly by reducing insulin resistance and may have the potential to alter the natural history of type 2 diabetes and reduce the cardiovascular mortality and morbidity associated with this condition. [Rev Cardiovasc Med. 2003;4(suppl 6):S29-S37]
A Review of Pharmacologic Interventions to Prevent Contrast-Induced Nephropathy
The serious clinical implications of contrast-induced nephropathy (CIN) have focused researchers on prevention strategies. Increased coverage of CIN in major medical journals and at major cardiovascular meetings, including the Transcatheter Cardiovascular Therapeutics (sponsored by the Cardiovascular Research Foundation), American College of Cardiology, and American Heart Association conferences, highlight this concern. Development of CIN prevention strategies is ongoing, but efforts have been hampered by an incomplete understanding of CIN pathophysiology. The most popular theories include contrast-induced renal tubular ischemia, free radical formation, and a direct tubular toxic effect. Proponents of an ischemia model direct clinical trials evaluating the efficacy of a variety of vasodilators, while those who favor a free radical or direct toxicity theory study antioxidants and free radical scavengers, or a variety of contrast agents varying in osmolality, ionicity, and viscosity. A comprehensive review of the more important and contemporary CIN prevention trials is provided to assist the cardiologist, radiologist, or nephrologist in developing his or her own data-driven approach to CIN prevention. [Rev Cardiovasc Med. 2003;4(suppl 5):S34–S42]
The Management of the Diabetic Patient With Prior Cardiovascular Events
Patients with diabetes are at high risk for cardiovascular (CV) events and heart failure. Approximately 2–3 million diabetics in the U.S. have had a history of prior CV events. The prevalence of diabetes in patients with heart failure ranges from 24% reported in clinical trials to 47% among hospitalized patients, and an estimated 1–2 million persons in the U.S. have diabetes and heart failure. Diabetes substantially increases the risk of mortality after acute coronary syndromes and also increases the risk of hospitalizations and mortality in patients with heart failure. It is now recognized that activation of multiple neurohormonal systems is central in the pathophysiology of diabetes, CV events, and heart failure. Pharmacologic intervention in these systems (eg, angiotensin-converting enzyme (ACE) inhibition, aldosterone-receptor antagonism, and ß-blockade) has been shown to decrease morbidity and mortality in diabetics with prior CV events and/or heart failure. Despite this awareness, ACE inhibitors, aldosterone antagonists, and ß-blockers are underutilized, and deaths and hospitalizations caused by CV events and heart failure in diabetic patients have steadily increased. Concerns about an increased incidence of hypoglycemia, worsening dyslipidemia, and decreased insulin sensitivity resulting from the use of ß-blockers may be preventing physicians from prescribing these agents for diabetic patients. ß-blockade in conjunction with ACE inhibition should be standard therapy for all diabetic patients. Optimal glycemic control therapy for patients with heart failure has not been well-defined, and there is an urgent need for randomized clinical trials to determine optimal treatment. [Rev Cardiovasc Med. 2003;4(suppl 6):S38-S49]
Recent Clinical Trials of Iodixanol
In patients with well-preserved renal function, the choice of contrast agent appears to have little impact on the development of contrast-induced nephropathy (CIN). However, in patients with underlying renal insufficiency and diabetes mellitus, it has been shown that the use of low-osmolar media is associated with a lower incidence of CIN compared with high-osmolar agents. Previously, it was unknown whether further benefit would be derived from the use of iso-osmolar contrast media. Recent studies, including Nephrotoxicity in High-Risk Patients Study of Iso-osmolar and Low-Osmolar Nonionic Contrast Media (NEPHRIC), have shown a reduction in the incidence of CIN with the iso-osmolar contrast agent iodixanol compared with low-osmolar agents in patients with renal insufficiency and diabetes. The peak rise in serum creatinine was significantly reduced with iodixanol (0.13 mg/dL vs 0.55 mg/dL, P < .001). The incidence of CIN, defined as a peak rise > 0.5 mg/dL, was decreased from 26% to 3%, P < .0002 when iodixanol was used. An ongoing, multicenter, prospective, double-blind, randomized study (Visipaque Angiography/Interventions with Laboratory Outcomes for Renal Insufficiency [VALOR]) is evaluating the potential benefit of iodixanol in reducing CIN in patients with preexisting renal impairment. Accumulating evidence suggests that the use of iso-osmolar contrast agents in conjunction with other proven measures, especially adequate intravenous hydration and contrast dosage limitation, can reduce the morbidity and mortality associated with CIN. These measures have the potential for a significant reduction in health care costs. [Rev Cardiovasc Med. 2003;4(suppl 5):S43–S50]
Insulin Resistance in Dilated Cardiomyopathy
The recognition that insulin resistance is an accompaniment to advanced dilated cardiomyopathy is a relatively recent revelation, but the consequences may be considerable for the failing heart. The failing heart develops a dependence on glucose as its preferred metabolic substrate, given the efficiency of glucose oxidation in the generation of highenergy phosphates. The increased preference for glucose oxidation requires that glucose transport and oxidation be highly regulated. Myocardial insulin resistance in advanced dilated cardiomyopathy limits both glucose uptake and oxidation and impairs the heart’s ability to generate much needed adenosine triphosphate. We provide evidence of insulin resistance in dilated cardiomyopathy and explore the relationship to increased sympathetic nervous system activation, lipolysis, and the subsequent alteration in the insulin signaling cascade. Together, these data provide a growing rationale for the development of clinical strategies to overcome insulin resistance in dilated cardiomyopathy. [Rev Cardiovasc Med. 2003;4(suppl 6):S50–S57]