Chronic Kidney Disease (CKD) – An Important Risk Factor for Cardiovascular Disease

Article by Dr Tan Seng Hoe

Chronic Kidney Disease (CKD) – An Important Risk Factor for Cardiovascular Disease

Dr Tan Seng Hoe

Nephrologist
National University of Singapore
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The incidence and prevalence of chronic kidney disease is increasing worldwide. In the United Sates, more than 10% of the adult population is estimated to have varying levels of chronic kidney disease. Adults with hypertension, diabetes, or both have a higher risk of developing CKD than those without these diseases. Approximately 30% of diabetic patients and 20% of hypertensive patients have CKD. Other risk factors for CKD include cardiovascular disease, obesity, hypercholesterolemia, and a family history of CKD. The risk of developing CKD increases with age and is more common in men.


Increased risk of cardiovascular disease in CKD

Patients with CKD, irrespective of the cause, are at increased risk of cardiovascular disease, including coronary heart disease, cerebrovascular disease, peripheral vascular disease and heart failure. The number one cause of death in patients with CKD is cardiovascular disease and it accounts for 40 percent to 50 percent of all deaths in patients with end stage kidney disease. The mortality due to cardiovascular disease is up to 30 times higher in dialysis patients than the general population. The lifespan of patients receiving dialysis is reduced and is believed to be mainly as a consequence of premature cardiovascular death. All patients with CKD should be considered in the highest risk group for cardiovascular disease, irrespective of levels of traditional cardiovascular risk factors. Treatment recommendations based on cardiovascular risk stratification should take into account the highest risk status of patients with CKD.


Prevention of cardiovascular disease in CKD

Cardiovascular disease in CKD is preventable and treatable. Cardiovascular risk factors can be classified either “traditional” or “non-traditional”. The traditional risk factors have been identified in the Framingham Heart study to estimate the risk of developing symptomatic ischemic heart disease. Risk factors such as older age, diabetes mellitus, systolic hypertension, left ventricular hypertrophy, and low high-density lipoprotein cholesterol are highly prevalent in CKD. 

Many CKD related non-traditional cardiovascular risk factors are associated with atherosclerosis, which include hyperhomocysteinemia, oxidative stress, dyslipidemia, and elevated inflammatory markers. Other factor like anemia is associated with cardiomyopathy; and disorder in the calcium and phosphorus metabolism is associated with vascular remodeling and calcifications.


Proteinuria is associated with increased cardiovascular events

Proteinuria is a strong independent predictor of GFR decline in patient with and without diabetes mellitus. As such, many of the similar cardiovascular risk factors associated with a reduced GFR are associated with an increased urinary protein excretion. Microalbuminuria is associated with increased prevalence of cardiovascular risk factors, and is itself, an adverse prognostic indicator for clinical cardiovascular disease and all-cause mortality in patients with diabetes mellitus. Diabetic patients with microalbuminuria have increased prevalence of dyslipidemia, poor glucose control and increased blood pressure compared to diabetic patients without microalbuminuria. In the HOPE study, microalbuminuria in non-diabetic patients was associated with increased risk for composite end point of stroke, myocardial infarction and mortality. The presence of microalbuminuria in individuals with CKD may reflect generalized endothelial dysfunction, or abnormalities in the fibrinolytic and coagulation pathways, marker of inflammatory status or may represent the severity of end-organ damage.


Prevalence of cardiovascular risk factors is increased in CKD patients

Reduced glomerular filtration rate is associated with a high prevalence of CVD risk factors. Studies have shown that elevated systolic blood pressure, total cholesterol and the percentage of patients with low HDL are greater in patients with reduced renal function. Furthermore, the percentage of patients with diabetes mellitus, left ventricular hypertrophy, ischemic heart disease and heart failure are higher in patients with reduced glomerular filtration rate. The presence of chronic kidney disease is also an independent predictor of significant coronary disease.

Reduced glomerular filtration rate is associated with adverse clinical cardiovascular disease outcomes. A reduced renal function may result in more severe hypertension and dyslipidemia. The presence of CKD in itself is also an important independent risk factor for cardiovascular outcomes; as well as all-cause mortality in the high risk population. 


Summary 

There is a high prevalence of cardiovascular disease in CKD patients; and the presence of CKD is an independent risk factor for cardiovascular outcomes. The NKF KDOQI Guidelines recommend that patients with CKD should be considered in the highest risk group for cardiovascular events. The Eight Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood pressure includes CKD as an important indication for a lower target blood pressure to less than 140/90mmHg; and irrespective of race, diabetes, or proteinuria, initial or add-on drug treatment should include an Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker to improve kidney outcomes. The KDIGO Clinical Practice Guidelines on managing Dyslipidemia in chronic kidney disease recommend a lower target low-density lipoprotein cholesterol level since CKD patients are included in the highest risk group for cardiovascular events. Early detection and treatment of CKD and its associated co-morbid conditions is important to improve cardiovascular outcomes. In addition, routine evaluation of patients with CVD should include an evaluation for chronic kidney disease, such as detection of albumin or protein in the urine and the measurement of the serum creatinine to estimate the glomerular filtration rate.