Chronic kidney disease, systemic microvascular dysfunction and heart failure

The high prevalence of cardiovascular disease and heart failure in people with chronic kidney disease (CKD) has conventionally been attributed to hypertension and epicardial coronary artery disease (CAD). Coronary artery occlusion may cause myocardial infarction and/or dysfunction, a reduced left ventricular ejection fraction (LVEF), and heart failure (HFrEF). Prolonged hypertension will lead to left ventricular hypertrophy and fibrosis, which may cause heart failure with a preserved LVEF (HFpEF), often in the absence of CAD. Systemic microvascular dysfunction may link hypertension, CKD, cardiometabolic disease, and heart failure; CKD may amplify this process, particularly in advanced disease, without necessarily being the initiating lesion. Prevention of end-stage kidney disease and heart failure is an important therapeutic goal for patients with hypertension and mild CKD, but event rates are low, requiring large, long-term trials to provide definitive evidence. Accordingly, CKD and HFpEF should be considered overlapping manifestations of systemic microvascular dysfunction, driven variably by CKD, cardiometabolic disease, or bidirectional cardiorenal interactions. Imaging markers of microvascular dysfunction and end-organ dysfunction should evolve from descriptive tools to mechanistic endpoints and potential therapeutic targets.