Risk factors for metabolic syndrome independently predict arterial stiffness and endothelial dysfunction in patients with chronic kidney disease and minimal comorbidity

OBJECTIVE

Metabolic syndrome (MS) is common in patients with chronic kidney disease (CKD), but its contribution to arterial stiffness and endothelial dysfunction in CKD is not well defined. We hypothesized that risk factors for MS would independently predict arterial stiffness and endothelial dysfunction in CKD patients.

RESEARCH DESIGN AND METHODS

Risk factors for MS, carotid-femoral pulse wave velocity (CF-PWV) and flow-mediated dilation (FMD) as measures of arterial stiffness and endothelial dysfunction, respectively, were assessed in 113 minimally comorbid CKD patients and in 23 matched control subjects.

RESULTS

CF-PWV correlated with systolic blood pressure (SBP), waist circumference, and plasma glucose (r² = 0.25, 0.09, and 0.09; P < 0.01 for all). FMD correlated with SBP (r² = 0.09; P < 0.01) and waist circumference (r² = 0.03; P < 0.05). CF-PWV increased progressively (r² = 0.07; P < 0.01) with increasing number of risk factors for MS. In multiple linear regression, SBP and waist circumference were independent determinants of CF-PWV, whereas only SBP predicted FMD.

CONCLUSIONS

The number of MS risk factors is an important determinant of arterial stiffness in CKD patients irrespective of the degree of renal impairment. Although BP remains the major determinant of arterial stiffness and endothelial dysfunction, waist circumference independently predicts arterial stiffness. MS risk factors, particularly abdominal girth, are potential targets for future interventional studies in patients with CKD.Chronic kidney disease (CKD) is common and associated with an increased risk of cardiovascular disease (CVD) (1). Conventional (Framingham) CVD risk factors, including high blood pressure (BP), hypercholesterolemia, and diabetes, all of which are common in CKD patients, only partly explain the high cardiovascular risk (2). CKD is now regarded as an independent risk factor for CVD (1,3), and we have recently shown that renal dysfunction also contributes to arterial stiffness and endothelial dysfunction in a group of minimally comorbid CKD patients (4).Increased arterial stiffness, as measured by pulse wave velocity (PWV), is a commonly recognized feature of CKD (4), a marker of cardiovascular risk (5,6), and an independent predictor of mortality and survival in dialysis patients (6). The vascular endothelium is an important regulator of arterial stiffness (7), and endothelial dysfunction is also a common feature of CKD (8) and a predictor of CVD (9).Metabolic syndrome (MS) is a clustering of metabolic abnormalities and risk factors for CVD and includes abdominal obesity, hyperglycemia, hypertension, hypertriglyceridemia, and reduced HDL cholesterol (10). As MS is associated with increased risks of diabetes and CVD (11,12), its treatment and prevention have become one of the major public health challenges worldwide. The risk factors for MS, either together or individually, are also associated with arterial stiffness and endothelial dysfunction both in health (13,14) and disease (15,16).MS is widely prevalent in CKD (17) and is itself a risk factor for CKD (18). Although a recent study has suggested that MS and its risk factors contribute to arterial stiffness and endothelial dysfunction in dialysis patients (19), there are no data relating to predialysis CKD. This is clearly important because targeting MS risk factors in early CKD may retard CKD progression, delaying the onset of dialysis and its associated morbidity, as well as reducing the overall risk of CVD.In this current study, we investigated the relationships of MS and its individual components to arterial stiffness and endothelial dysfunction in CKD patients across a wide range of renal function from early CKD to predialysis. Importantly, we planned to recruit patients without diabetes or cardiovascular comorbidity. We hypothesized that the presence of MS, or its components, would be associated with increased arterial stiffness and endothelial dysfunction and that these relationships would be independent of renal function and other well-established risk factors for CVD.