Atherosclerotic Cardiovascular Disease in CKD

Patients with chronic kidney disease (CKD) have a disproportionate burden of cardiovascular disease, and the majority die from cardiovascular causes before ever reaching kidney failure. Atherosclerotic cardiovascular disease (ASCVD), which includes coronary artery disease, cerebrovascular disease, and peripheral arterial disease, develops in CKD through the convergence of traditional risk factors and a distinct group of CKD-related, non-traditional mechanisms, including mineral and bone disorder with vascular calcification, chronic inflammation and oxidative stress, uremic toxicity, and an atherogenic dyslipidemia. Cardiovascular and kidney disease interact in a bidirectional manner in which each accelerates the other. Reflecting this unique pathophysiology, the burden of ASCVD rises steeply as kidney function declines, reaching a several-fold higher risk of myocardial infarction, stroke, and peripheral arterial disease at the lowest eGFR and highest albuminuria. Nonetheless, ASCVD in CKD remains under-recognized and undertreated, owing partly to atypical clinical presentations, conventional risk-prediction tools that underestimate risk, and to the exclusion of patients with advanced CKD from most landmark cardiovascular trials. In this review, which focuses primarily on coronary artery disease in non-dialysis-dependent CKD, we examine the epidemiology and key pathogenic mechanisms of ASCVD in this setting; and appraise diagnostic and risk-prediction approaches together with their limitations, including contemporary CKD-adapted risk equations, cardiac biomarkers, and non-invasive imaging. We also summarize the current evidence for management, spanning lipid-lowering, antiplatelet, and blood-pressure therapies, newer cardiometabolic agents (including SGLT2 inhibitors, GLP-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists), coronary revascularization, and lifestyle modification. Throughout, we highlight where high-quality, CKD-specific evidence is lacking, and we outline priority research gaps and emerging therapies directed at CKD-relevant pathways, such as inflammation. Recognizing and aggressively modifying cardiovascular risk in CKD, across both traditional and CKD-specific pathways, represents a substantial, and currently underrealized, opportunity to reduce morbidity and mortality in this high-risk population.