Chronic Rejection and Atherosclerosis in Post-Transplant Cardiovascular Mortality: Two Sides of the Same Coin

Abstract

Cardiovascular disease (CVD) as defined by the American Heart Association includes ischaemic heart disease, stroke, heart failure and thromboembolism [1]. Solid organ transplantation is associated with an increased risk of CVD morbidity and mortality [2], a relationship which was first observed in the context of kidney transplantation by Foley in 1998 [3]. This manifests clinically as an increased rate of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, non-fatal myocardial infarction, non-fatal stroke, unstable angina and heart failure [4,5].Increased awareness of this relationship has led to changes in clinical practice, with focus placed on minimising traditional CVD risk factors with lifestyle changes and optimisation of medical therapy. This has resulted in a moderate decline in CVD deaths over time in the post-transplant population [6], with a large-scale study using the United States Renal Data System registry reporting a reduction in CVD mortality rate after kidney transplantation from 1.21% to 0.59% between 1996 and 2014 [7].Despite this, CVD remains a leading cause of mortality in solid organ transplant recipients [8][9][10][11]. This apparent inability to adequately lower post-transplant CVD represents a significant barrier to improving long-term transplant outcomes and may be, at least in part, due to an incomplete understanding of the underlying pathophysiology.