Abstract
Accelerated and premature cardiovascular calcification is a hallmark of chronic kidney disease (CKD) patients. Valvular calcification (VC) is a critical indicator of cardiovascular disease and all-cause mortality in this population, lacking validated biomarkers for early diagnosis. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor recently associated with vascular calcification, pulse pressure, mineral metabolism markers and kidney function. Here, we examined the association between GRP serum levels and mitral and aortic valves calcification in a cohort of 80 diabetic patients with CKD stages 2–4. Mitral and aortic valves calcification were detected in 36.2% and 34.4% of the patients and associated with lower GRP levels, even after adjustments for age and gender. In this pilot study, univariate, multivariate and Poisson regression analysis, show that low levels of GRP and magnesium (Mg), and high levels of phosphate (P) are associated with mitral and aortic valves calcification. Receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) values of GRP for mitral (0.762) and aortic (0.802) valves calcification were higher than those of Mg and P. These results suggest that low levels of GRP and Mg, and high levels of P, are independent and cumulative risk factors for VC in this population; the GRP diagnostic value might be potentially useful in cardiovascular risk assessment.
Highlights
Chronic kidney disease (CKD), diabetes mellitus, and atherosclerosis are the clinical conditions that most contribute towards the development of cardiovascular calcification [1,2], which is a strong predictor of cardiovascular risk, while cardiovascular disease (CVD) is the most common cause of death in chronic kidney disease (CKD) patients [3]
No differences were found between groups regarding age, gender (f-m), hemoglobin, albumin, albumin to creatinine ratio in urine (ACR), duration of disease, HgA1c, Ca, calcium x phosphate (CaxP), 1.25(OH)2 Vitamin D and blood pressure (BP) (Table 1)
Receiver operating characteristic (ROC) curves werre used to evaluuaattee tthhee ddiiaaggnnoossttiicc vvaalluueeooff GGRRPP, Mg and P for aortic and mitral valves calciffiication, and the results showed that the area under the curve (AUC) of Gla-rich protein (GRP) for both aortic and mitral valves calcifification were 00.802 ±± 00..005511, 9955%% CI (0.701–0.90033)), p
Summary
Chronic kidney disease (CKD), diabetes mellitus, and atherosclerosis are the clinical conditions that most contribute towards the development of cardiovascular calcification [1,2], which is a strong predictor of cardiovascular risk, while cardiovascular disease (CVD) is the most common cause of death in CKD patients [3]. Echocardiography remains the gold standard for diagnosis and evaluation of valvular disease, but with poor predictive value for the progression rate from the early to late stage of disease, and providing limited insights into disease pathophysiology In this field, the discovery of early biomarkers related to specific pathophysiological mechanisms involved in disease pathogenesis would allow insights into causal factors, and improve time of intervention and risk stratification. We have shown that in a cohort of 80 adult diabetic patients with mild to moderate CKD, serum GRP levels progressively decrease from stage 2 to stage 4 CKD, correlating with markers of mineral metabolism, and strongly associated with vascular calcification and pulse pressure [24]. In the present study we explored, for the first time, the relationship between levels of circulating GRP and aortic and mitral valve calcification in the same cohort of diabetic patients with mild to moderate CKD (stage 2–4)
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