Severe coronary artery calcifications in chronic kidney disease patients, coupled with inflammation and bone mineral disease derangement, promote major adverse cardiovascular events (MACE) through vascular remodeling.

Abstract

Cardiovascular (CV) diseases persist as the foremost cause of morbidity/mortality among chronic kidney disease (CKD) patients. This paper examines the values of coronary artery calcifications (CAC) and biomarkers of CV on major adverse CV events (MACE)/CV death in a sample of 425 non-dialysis CKD patients. At inclusion, patients underwent chest multidetector computed tomography for CAC scoring and biomarkers of CV risk including CRP, mineral metabolism markers, FGF-23, α-Klotho, osteoprotegerin, TRAP5b, sclerostin, Matrix-Gla-Protein (both dephosphorylated-uncarboxylated and total-uncarboxylated) and GDF-15 were measured. Patients were followed for a median of 3.61 years [25th-75th percentiles=1.92-6.70]. Our results reported that CAC was a major independent factor of MACE/CV mortality showing a hazard ratio of 1.71 95% confidence interval=[1.00-2.93] after adjustment for age, gender, diabetes and history of CV events for patients with CAC>300. Interestingly, CAC effect was further enhanced in the presence of low levels of 25(OH) vitamin D3 or α-Klotho and high levels of iPTH, hsCRP, FGF-23, osteoprotegerin, sclerostin, dp-ucMGP or GDF-15. CAC constitutes a significant CV risk, further exacerbated by inflammation, hyperparathyroidism and regulation of bone molecules implicated in calcification progression. This finding aligns with the original concept of multiple hits. Consequently, addressing the detrimental environment that fosters plaque vulnerability, reducing chronic low-grade inflammation, and normalizing mineral metabolism markers (such as vitamin D and PTH) and bone-regulating molecules may emerge as a viable therapeutic strategy.