Accelerated and intensified calcific atherosclerosis and microvascular dysfunction in patients with chronic kidney disease

Abstract

Cardiovascular disease, and in particular coronary artery disease (CAD), remains an important contributor of morbidity and mortality among patients with chronic kidney disease (CKD). Classic symptomatology of CAD and effectiveness of established therapeutic measures is less frequent in patients with CKD. This suggests unique characteristics of CAD among patients with CKD. Two important features of CAD in CKD include increased calcific density of atherosclerotic plaques and of the vessels themselves (coronary artery calcification-CAC), as well as a decrease in microcirculatory function-or coronary microcirculatory dysfunction. A multitude of pathophysiologic pathways have been identified that contribute to CAC in CKD; less is known about the pathophysiology of microcirculatory dysfunction. It is not well established if these two processes are directly related to each other, but the combination results in a greater severity of effect on overall myocardial function and may in part explain the greater preponderance of silent myocardial infarction. Further investigation is needed to better understand these unique aspects of CAD in CKD as well as the role they play in overall CVD in this group, and ultimately therapeutics that may lessen the burden of disease.

Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review

“…Calcifications affecting conduit arteries lead to vessel stiffening, increased peripheral resistance and the risk of hypertension, cardiac hypertrophy, heart failure and cardiovascular mortality. Calcifications involving microcirculation aggravate tissue perfusion through microvascular dysfunction and they induce silent ischemic episodes [6], leading to a higher risk of cardiovascular events [7,8]. VC-related adverse outcome influences become more prominent among those with CKD [9].…”

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association

“…When present, CKM syndrome appears to accelerate the pathophysiology of atherosclerosis by augmenting inflammation, dyslipidemia, hypertension, and insulin resistance, each central contributors to the development of atherogenesis. 2 With the changing landscape of atherosclerosis that has shifted to developing countries, women, and younger individuals, current knowledge gaps include an incomplete understanding of (1) sex differences in CVD in CKM syndrome, (2) genetic underpinnings of disease that may account for some regional differences and clinical applications of genetic testing, (3) mechanisms of endothelial dysfunction in CKM syndrome (accelerated in the presence of CKD 42 ) as an early harbinger of CVD, and (4) environmental and community-level risk factors in the development of CVD. 43 In contrast to atherosclerosis, mechanisms by which CKM syndrome leads to HF and arrhythmias (and, in particular, atrial fibrillation [AFib]) are less well described.…”

Coronary Artery Disease in Chronic Kidney Disease: Need for a Heart–Kidney Team-Based Approach

“…klotho, osteoprotegerin and fetuin A). [ 20 , 21 ] CKD is characterised by extensive vascular calcification involving not just the tunica intima, but also extending into the tunica media. [ 22 ] In addition, vitamin K metabolism is deranged in CKD, leading to further reductions in inhibitors of vascular calcification (e.g.…”