Cardiovascular disease after transplantation: an emerging role of the immune system

Abstract

Cardiovascular disease (CVD) after transplantation remains a major concern. Little is known about what drives the increased cardiovascular risk in transplant recipients apart from traditional risk factors. The immune system is involved in the pathogenesis of hypertension, atherosclerosis, and coronary artery disease in the general population. Recently, inhibition of interleukin 1 - β by canakinumab versus placebo decreased the incidence of cardiovascular events. Emerging evidence points to a role of adaptive cellular immunity in the development of CVD. Especially, expansion of pro-inflammatory and antiapoptotic cytotoxic CD4 CD28 T cells is closely associated with incident CVD in various study populations including transplant recipients. The association of cytomegalovirus exposure with increased cardiovascular mortality might be explained by its capacity to upregulate these cytotoxic cells. Also, humoral immunity seems to be relevant for cardiovascular outcome in transplant recipients. Panel-reactive antibodies at baseline and donor-specific antibodies are independently associated with poor cardiovascular outcome after kidney transplantation. Cardiovascular effects of immunosuppressive drugs and statins do not only imply indirect positive or negative effects on traditional cardiovascular risk factors but also intrinsic immunological effects. How immunosuppressive drugs modify atherosclerosis largely remains elusive.

A pilot randomised controlled trial of a structured, home-based exercise programme on cardiovascular structure and function in kidney transplant recipients: the ECSERT study design and methods

“…7 Immunosuppressive agents are well known to drive traditional 3 and non-traditional cardiometabolic risk factors. 8 9 Non-traditional cardiometabolic risk factors, including endothelial dysfunction, systemic inflammation, acute rejection, anaemia and deranged bone mineral metabolism, [10][11][12] are of at least equal importance in the pathogenesis of CVD in KTRs. 7 This is further illustrated by the fact that traditional CVD risk stratification tools dramatically underestimate cardiovascular risk in patients with chronic kidney disease (CKD).…”

HLA Class II Antibodies at the Time of Kidney Transplantation and Cardiovascular Outcome: A Retrospective Cohort Study

“…[1][2][3] Emerging evidence suggests that the same might hold true in transplant recipients. [4][5][6] Atherosclerosis is the leading cause of CVD and inflammatory components participate at each stage of atherogenesis. 2,[7][8][9] Genes involved in inflammation are associated with progression of CAD in rheumatoid arthritis, inflammatory polyarthritis, systemic lupus erythematosus (SLE), type 1 diabetes and in heart transplant recipients.…”

Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients

“…1 Reductions in CV disease burden have also been noted for organ transplant recipients, 2 although the incidence remains 3-5 times higher in kidney transplant recipients than in age-matched representatives of the general population. 6 Transplant recipients today are older and carry higher burdens of chronic disease than in previous eras, 7 which is another reason that CV disease remains the most common cause of death and graft loss in RTRs. 5 In addition, a role for the adaptive cellular immune response in the development of CV in renal transplant recipients (RTRs) appears plausible in light of recent research.…”

“…5 In addition, a role for the adaptive cellular immune response in the development of CV in renal transplant recipients (RTRs) appears plausible in light of recent research. 6 Transplant recipients today are older and carry higher burdens of chronic disease than in previous eras, 7 which is another reason that CV disease remains the most common cause of death and graft loss in RTRs. 8 Identification of novel risk factors, which may allow for improved risk stratification and better tailoring of treatment for allograft recipients, is a key priority in the transplant community.…”