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

Author:

Horace Reuben William12,Roberts Mary2,Shireman Theresa I3,Merhi Basma4,Jacques Paul5,Bostom Andrew G6,Liu Simin7ORCID,Eaton Charles B2

Affiliation:

1. Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA

2. Center for Primary Care, Prevention, Brown University, Providence, RI, USA

3. Center for Gerontology and Healthcare Research, Brown University School of Public Health, Brown University, Providence, RI, USA

4. Department of Medicine, Division of Hypertension and Kidney Diseases, Rhode Island Hospital, Providence, RI, USA

5. Nutritional Epidemiology Program, USDA Human Nutrition Research Center on Aging, Medford, MA, USA

6. Department of Medicine, Division of Hypertension and Kidney Diseases, Providence, RI, USA

7. Departments of Epidemiology and Medicine and Center for Global Cardiometabolic Health, Providence, RI, USA

Abstract

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.

Funder

National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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