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The Risk of Cardiovascular Disease Is Not Increasing Over Time Despite Aging and Higher Comorbidity Burden of Kidney Transplant Recipients

Lam, Ngan N. MD, MSc; Kim, S. Joseph MD, PhD; Knoll, Gregory A. MD, MSc; McArthur, Eric MSc; Lentine, Krista L. MD, PhD; Naylor, Kyla L. MES; Li, Alvin H. BHSc; Shariff, Salimah Z. PhD; Ribic, Christine M. MD, MSc; Garg, Amit X. MD, PhD

doi: 10.1097/TP.0000000000001155
Original Clinical Science-General

Background: Cardiovascular death remains the leading cause of mortality in kidney transplant recipients. Cardiovascular events are associated with significant morbidity. However, current trends in cardiovascular events after kidney transplantation are poorly understood.

Methods: We conducted a retrospective study using healthcare databases in Ontario, Canada, to determine whether the incidence of cardiovascular events after kidney transplantation has changed from 1994 to 2009. Our primary endpoint was a 3-year composite outcome of posttransplant death or major cardiovascular event (myocardial infarction, coronary angioplasty, coronary artery bypass graft surgery, stroke).

Results: Recipients (n = 4954) were older and had more baseline comorbidity in recent years. A total of 445 recipients (9.0%) died or experienced a major cardiovascular event within 3 years of transplantation. There was no significant change in the incidence of the composite outcome or death-censored cardiovascular events over time (P = 0.41 and 0.92, respectively). After adjusting for age, sex, and comorbidities, the risk of death or major cardiovascular event steadily declined across the years of transplant (2006-2009 adjusted hazard ratio, 0.70; P = 0.009; referent 1994-1997). When recipients were matched on age, sex, and date of cohort entry to members of the general population and to the chronic kidney disease population, the risk was lowest in the general population and highest in the chronic kidney disease population.

Conclusion: Despite transplant centers accepting recipients who are older with more comorbidities in recent years, the 3-year cumulative incidence of death or major cardiovascular event has remained stable over time.

A Canadian retrospective registry study suggests that mortality or major cardiovascular event has remained stable over time despite the increase in age and number of comorbidities of kidney transplant recipients. Nevertheless, the reasons behind this observation are unclear.

1 Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

2 Division of Nephrology, Department of Medicine, University of Toronto, Toronto, ON, Canada.

3 Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.

4 Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, ON, Canada.

5 Institute for Clinical Evaluative Sciences (ICES), Toronto, ON, Canada.

6 Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO.

7 Division of Abdominal Transplantation, Department of Surgery, Saint Louis University School of Medicine, St. Louis, MO.

8 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

9 Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.

10 Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada.

11 Division of Nephrology, Department of Medicine, Western University, London, ON.

Received 14 October 2015. Revision received 19 December 2015.

Accepted 8 January 2016.

A.X.G. received an investigator-initiated grant from Astellas and Roche to support a CIHR-funded prospective study on living kidney donation and his institution receives unrestricted funding from Pfizer. He is also supported by a Dr. Adam Linton Chair in Kidney Analytics. There are no other conflicts of interest to declare.

This project was conducted at the Institute for Clinical Evaluative Sciences (ICES) Western Site. ICES is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. ICES Western is funded by an operating grant from the Academic Medical Organization of Southwestern Ontario. This project was conducted with members of the provincial ICES Kidney, Dialysis and Transplantation Research Program (www.ices.on.ca), which receives programmatic grant funding from the CIHR. Parts of this material are based on data and information compiled and provided by the Canadian Institutes of Health Information (CIHI). However, the analyses, conclusions, opinions and statements expressed herein are those of the author, and not necessarily those of CIHI. NNL was supported by a KRESCENT New Investigator Award. KLN was supported by a CIHR Fellowship and the Canadian National Transplant Research Program Astellas Training Award.

All authors conceived of the study. N.N.L., E.M., and A.X.G. participated in the performance of the research and collection of the data. N.N.L., E.M., and A.X.G. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. N.N.L. drafted the article. All authors revised the article.

Correspondence: Ngan N. Lam, MD, MSc, University of Alberta, 13-106 Clinical Sciences Building, 11350-83 Avenue NW, Edmonton, AB, Canada T6G 2G3, (nlam@ualberta.ca).

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