Review articleChronic kidney disease and cardiovascular risk
Section snippets
Pathophysiology of CKD
CKD can result from several causes, including but not limited to T2DM and HTN. The pathophysiology of CKD may involve different initiating mechanisms depending on the underlying etiology, eventually leading to a set of common consequent mechanisms after a long-term decrease in the renal mass. This attrition of renal mass leads to an initial adaptive hyperfiltration that is mediated by increases in glomerular capillary pressure and flow, as well as by increases in the structural and functional
CKD as a Risk Factor for CVD
The correlation between raised serum creatinine levels and CVD mortality was first observed by Shulman et al in 19894 in the Hypertension Detection and Follow-up Program study. This concept received wide attention in 2003 after the scientific statement from the American Heart Association endorsed the fact that increased CVD mortality is noted in patients with CKD when compared with the general population.10 There is a strong continuous correlation between increased risk for CVD events and
Traditional and Nontraditional CVD Risk Factors in CKD
One can make an argument that the relationship between CVD and CKD is a result of the occurrence of many common traditional risk factors, such as HTN, T2DM, or dyslipidemia (CVD risk factors studied in the Framingham heart study). However, the Framingham risk equation has been shown to be insufficient in predicting the CVD risk in subjects with CKD in several cross-sectional studies, suggesting the presence of other risk factors that confer additional CVD risk in these patients. Sarnak and Levey
CKD and the Cardiometabolic Syndrome
Clustering of traditional CVD risk factors (T2DM, HTN, dyslipidemia) with obesity is observed in up to one in four people15 and is referred to as the cardiometabolic syndrome (CMS). Insulin resistance and compensatory hyperinsulinemia are considered integral to the development of the metabolic and vascular dysregulation that are seen in CMS, which leads to increased CVD and CKD risk. An association between CMS and CKD has been supported by several cross-sectional16, 17 and prospective studies.18
Role of Common Uremia-Related Co-Morbidities in the Pathogenesis of CKD-Related CVD
Reduced GFR and/or a raised creatinine level have been shown to be independent predictors of adverse outcomes. Impaired renal function has been associated with multiple CVD risk factors, such as increased levels of inflammatory factors and oxidative stress,17, 20 abnormal apolipoprotein levels,17 elevated plasma homocysteine,7 enhanced coagulability,20 anemia,21 endothelial dysfunction,22 arterial stiffness,22 and abnormal calcium and phosphorus metabolism.14
CKD and CVD Markers
The most common markers used in clinical practice for evaluation of CKD are serum creatinine, eGFR, and proteinuria. Go et al12 showed an independent graded association with a reduced GFR and risk of CVD events and hospitalization.
To overcome the cumbersome method of traditional GFR calculation (based on timed urine specimen collection), eGFR values can now be calculated from prediction equations that take into account serum creatinine as well as other variables like age, gender, race, and body
Risk-Reduction Strategies
Patients diagnosed with CKD should be further assessed for the severity of disease, complications related to CKD, and the presence of other CVD risk factors, including measurement of traditional as well as uremia-related CVD risk factors, so that appropriate risk-reduction therapies can be initiated.45 Also, the presence of CKD should prompt aggressive measures to reach goals for blood pressure and cholesterol that are recommended for the highest CV risk group, at the same time focusing on
Conclusion
The relationship between CKD and increased CVD risk is now well established and has led to the current recommendations by the NKF task force to consider patients with CKD to be in the highest-risk group for CVD.7 The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure also has endorsed this opinion by including CKD in its list of so-called compelling indications for aggressive blood pressure control.55
Recent studies have
References (55)
- et al.
Chronic kidney disease and cardiovascular disease in the Medicare population
Kidney Int
(2003) - et al.
A population-based study of the incidence and outcomes of diagnosed chronic kidney disease
Am J Kidney Dis
(2003) - et al.
Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here?
Am J Kidney Dis
(1998) - et al.
Clinical epidemiology of cardiovascular disease in chronic renal disease
Am J Kidney Dis
(1998) - et al.
Cardiovascular disease and chronic renal disease: a new paradigm
Am J Kidney Dis
(2000) - et al.
The impact of anemia on cardiomyopathy, morbidity, and mortality in end-stage renal disease
Am J Kidney Dis
(1996) - et al.
Aortic pulse wave velocity index and mortality in end-stage renal disease
Kidney Int
(2003) - et al.
Parathyroid hormone, vitamin D, and cardiovascular disease in chronic renal failure
Kidney Int
(1999) - et al.
Cardiovascular effects of recombinant human erythropoietin in predialysis patients
Am J Kidney Dis
(1997) - et al.
Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy
Kidney Int
(2000)
End-stage renal disease, atherosclerosis, and cardiovascular mortality: is C-reactive protein the missing link?
Kidney Int
Pretransplantation levels of C-reactive protein predict all-cause and cardiovascular mortality, but not graft outcome, in kidney transplant recipients
Am J Kidney Dis
Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): a position paper of the National Kidney Foundation
Am J Kidney Dis
JAMA
Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial
Ann Intern Med
High-normal serum creatinine concentration is a predictor of cardiovascular risk in essential hypertension
Arch Intern Med
Prognostic value of serum creatinine and effect of treatment of hypertension on renal functionResults from the hypertension detection and follow-up program
Hypertension
Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention
Circulation
Kidney-heart interactions: epidemiology, pathogenesis, and treatment
Clin J Am Soc Nephrol
Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization
N Engl J Med
Calcium phosphate metabolism and cardiovascular disease in patients with chronic kidney disease
Semin Dial
Prevalence of the metabolic syndrome among US adults findings from The Third National Health and Nutrition Examination Survey
JAMA
The metabolic syndrome and chronic kidney disease in U.S. adults
Ann Intern Med
Prevalence of non-traditional cardiovascular disease risk factors among persons with impaired fasting glucose, impaired glucose tolerance, diabetes, and the metabolic syndrome: analysis of the Third National Health and Nutrition Examination Survey (NHANES III)
Ann Epidemiol
Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults
J Am Soc Nephrol
The metabolic syndrome: time for a critical appraisal
Diabetologia
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Conflict of interest: none.