Cardiovascular disease

1. What is the relationship between the decrease in the glomerular filtration rate and cardiovascular disease?

Patients with chronic kidney disease (CKD) have a substantial increase in risk for death from cardiovascular disease. Even small decreases in kidney function, as measured by the estimated glomerular filtration rate (eGFR), are associated with this higher risk, and it increases progressively as kidney function declines. Patients with CKD are substantially more likely to die from heart disease than progress to dialysis. In patients with end-stage kidney disease (ESKD), the risk for death is 10- to 100-fold higher than age- and gender-matched individuals without kidney disease. Conversely, in patients with known heart disease (like coronary artery disease or heart failure), the greater the severity of kidney disease, the worse the patient outcome, including higher mortality and, in patients hospitalized for non-ST segment elevation myocardial infarction, a longer length of stay.

2. What is the relationship between albuminuria/proteinuria and cardiovascular disease?

The presence of albuminuria is also associated with a higher risk of death from cardiovascular disease. This risk begins even when the amount of urine albumin is not enough to meet the criteria for the diagnosis of microalbuminuria. As the amount of urine albumin increases, so does the risk for death from heart disease—the risk is higher in individuals with microalbuminuria and even higher among those with overt proteinuria.

3. Why is the risk for cardiovascular disease increased in CKD?

Both traditional and nontraditional risk factors are important contributors to cardiovascular disease. Diabetes mellitus and hypertension are the two most common causes of CKD—both are also known cardiovascular risk factors. Moreover, diseases like hypertension are more severe in the setting of CKD. However, traditional risk factors are insufficient to explain the high cardiovascular risk seen with CKD. A large number of nontraditional risk factors have been identified, such as systemic inflammation, high serum phosphorus, and oxidative stress (among others). However, at this time, it remains unclear if any of the traditional or nontraditional risk factors can be modified to reduce the risk of heart disease ( Table 21.1 ).

4. What types of cardiovascular disease are seen in patients with CKD?

There are two major overlapping categories of cardiovascular disease associated with CKD: disorders of cardiovascular perfusion, which includes atherosclerotic cardiovascular disease; and disorders of cardiac function, such as congestive heart failure and left ventricular hypertrophy. Disorders of vascular perfusion include coronary artery disease, cerebrovascular disease, peripheral vascular disease, and renovascular disease.

5. Are there other forms of cardiovascular disease seen in patients with CKD?

Cardiovascular calcification is a frequent contributor to cardiovascular disease in CKD; it can occur either in heart valves, the tunica intima, or the tunica media of the blood vessels. Calcified blood vessels can often be seen on plain x-rays in patients with CKD, particularly among the elderly or those being treated with dialysis. Though not fully understood, during vascular calcification, the smooth muscle cells of vessels express osteocytic phenotypes and the calcium phosphate deposition resembles hydroxyapatite seen in bone. The greater the severity of vascular calcification, the greater the risk of death. There are many reasons why patients with CKD develop vascular calcification; an increase in serum phosphorus is considered to be an important contributor, and this may be a potentially modifiable risk factor. Hence, the management of elevated phosphorus levels may reduce the risk for heart disease; however, this approach remains unproven.

Calciphylaxis, or cacificic uremic arteriolopathy, is an accelerated form of vascular calcification typically seen in patients with CKD stage 5. Risk factors include warfarin therapy, altered mineral metabolism, and obesity. The process can lead to nonhealing wounds and is often fatal. Parathyroidectomy and/or sodium thiosulfate therapy may be of benefit.

6. What are the clinical manifestations of cardiovascular disease in CKD?

Manifestations of cardiovascular disease include angina pectoris, myocardial infarction, congestive heart failure, stroke, peripheral vascular disease, arrhythmias, and sudden cardiac death. In advanced CKD, cardiovascular disease is often manifested by left ventricular hypertrophy, diastolic dysfunction, and heart failure. The national registry for dialysis patients—the United States Renal Data System—reports that about 30% of patients with CKD over 66 years of age have congestive heart failure. Left ventricular hypertrophy may be accompanied by left ventricular remodeling and fibrosis, and these changes, with or without coronary artery disease (in addition to electrolyte shifts and volume expansion), may contribute to the high incidence of sudden cardiac death in this population. Indeed, sudden cardiac death is the most common cause of death in dialysis patients.

The clinical manifestations of acute coronary syndrome are also atypical in patients with CKD, and the electrocardiographic findings may be obscured by the presence of left ventricular hypertrophy.