Markers of increased atherosclerotic risk in patients with chronic kidney disease: a preliminary study

Abstract

Background: The prevalence of chronic kidney disease is rising continuously. Cardiovascular disease is among leading causes of death and premature mortality of patients with chronic kidney disease. Even the earliest stages of chronic kidney disease are associated with higher risk of subsequent coronary heart disease. The aim of this study was to determine markers of increased risk of atherosclerosis in CKD.

Methods: The study group consisted of a total of 80 patients (20 patients with stage I/II CKD, 20 with stage III CKD, 20 stage IV CKD and 20 stage V/dialysis) and 24 healthy volunteers. Levels of proteins (osteoprotegerin, osteopontin, osteocalcin, matrix γ-carboxyglutamic acid protein, fetuin A, MMP-2, MMP-9, TIMP-1, TIMP-2) and biochemical parameters were measured to analyse their influence on atherosclerosis risk in CKD patients. Cardiac echocardiography was performed to assess structural integrity and function, presence of left ventricular hypertrophy and systolic and diastolic function dysfunction.

Results: This study shows that the prevalence of ventricular hypertrophy (95.3 %) and diastolic dysfunction (93.2 %) in CKD patients is high. Also E/E' ratio was significantly higher (13.6 ± 4.4, p = 0.001), tricuspid insufficiency (27.3 in CKD I/II vs. 71.4 in CKD V, p = 0.016), contractile dysfunction (33.3 in CKD I/II vs. 78.9 in CKD V, p = 0.040), mitral valve calcification (0 in CKD I/II vs. 28.6 in CKD V, p = 0.044) and aortic valve calcification (0 in CKD I/II vs. 61.9 in CKD V, p = 0.0008) were significantly more frequent in patients with CKD stage V/dialysis than in other groups. Only MMP-2, MMP-2/TIMP-2 ratio and TIMP-1 differed significantly between groups.

Conclusions: This study shows high prevalence of ventricular hypertrophy and diastolic dysfunction in CKD patients. Contractile dysfunction, mitral and aortic valve calcification in HD patients were significantly more frequent than in patients with other CKD stages. Significantly increased levels of MMP-2, MMP-2/TIMP-2 ratio and lower TIMP-1 suggests that these factors may be involved in the pathogenesis of atherosclerosis in CKD patients.