Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study

Authors: HORACE, REUBEN - Brown University; ROBERTS, MARY - Brown University; SHIREMAN, THERESA - Brown University; MERHI, BASMA - Rhode Island Hospital; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BOSTOM, ANDREW - Rhode Island Hospital; LIU, SIMIN - Brown University; EATON, CHARLES - Brown University

Submitted to: Nephrology Dialysis Transplantation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2021
Publication Date: 3/24/2021
Citation: Horace, R.W., Roberts, M., Shireman, T., Merhi, B., Jacques, P.F., Bostom, A.G., Liu, S., Eaton, C.B. 2021. Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study. Nephrology Dialysis Transplantation. 37(2):382-389. https://doi.org/10.1093/ndt/gfab068.
DOI: https://doi.org/10.1093/ndt/gfab068

Interpretive Summary: Remnant cholesterol refers to all the cholesterol that is not LDL or HDL cholesterol. It is associated with inflammation of the arteries and accelerated atherosclerosis. Our study is the first to demonstrate the relationship between higher remnant cholesterol levels and the risk of CVD events and all-cause mortality in renal transplant recipients. Our results showed that in stable kidney transplant recipients, higher remnant cholesterol level is associated with a 32% increased risk of CVD events and a 34% increase in all-cause mortality Our findings are important as many kidney transplant recipients receive less aggressive CVD risk factor management than would be expected given their CVD risk.

Technical Abstract: Background The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial. Methods Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at randomization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes. Results During a median follow-up of 4.0 years we documented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk {hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04-1.67]} and all-cause mortality risk [HR 1.34 (95% CI 1.01-1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87-1.64)]. Conclusions Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.