Review article
Chronic kidney disease and cardiovascular risk

https://doi.org/10.1016/j.jash.2007.01.010Get rights and content

Abstract

Chronic kidney disease (CKD) is a global public health concern, and there is emerging a strong relationship between CKD and increased cardiovascular disease (CVD) risk. CKD in the presence of other co-morbidities such as type 2 diabetes mellitus (T2DM) and hypertension (HTN) can lead to early progression to end-stage renal disease (ESRD/stage V CKD) and confer a greater risk for CVD morbidity and mortality. CVD events are the leading cause of premature death in patients with CKD, even before their progression to ESRD, with the rate of CVD progression being twice as common compared with the general population. The higher mortality from CVD persists even after adjusting for most of the traditional risk factors, suggesting the possible contributions of uremia-related, nontraditional risk factors. This has led to the current understanding that the pathophysiology of CVD in CKD involves a complex interplay of both the traditional as well as nontraditional, uremia-related risk factors. This review will elaborate on the pathophysiology of CVD in CKD and will discuss the role of microalbuminuria (MAU)-proteinuria as a potential diagnostic and prognostic tool for CVD in CKD risk assessment.

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

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    Conflict of interest: none.

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    Copyright © 2007 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.