title: Sirolimus and cardiovascular disease risk in liver transplantation.
abstract: BACKGROUND
  Two adverse effects of sirolimus are hypertriglyceridemia and hypercholesterolemia. These elevated levels often lead clinicians to discontinue the sirolimus from concerns of an increased cardiovascular disease (CVD) risk; however, evidence suggests that sirolimus might be cardioprotective. There are no published reports of sirolimus CVD in liver transplantation.
  
  
  METHODS
  We reviewed all 1812 liver recipients who underwent transplantation from 1998 to 2010, identifying a cohort using sirolimus as part of the initial immunosuppression (SRL Cohort) and a control group of the remaining patients from this period where SRL was never given (Non-SRL Control). A prospectively maintained database identified all episodes of myocardial infarction (MI), congestive heart failure (CHF), abdominal aortic aneurysm (AAA), and cerebrovascular accident and tracked triglyceride, high-density and low-density lipoproteins, and total cholesterol levels. A Framingham Risk Model calculated the predicted 10-year risk of CVD for both groups.
  
  
  RESULTS
  The SRL Cohort (n=406) is older, more predominantly male, with more pretransplantation hypertension and diabetes and posttransplantation hypertension compared to Non-SRL Controls (n=1005). The SRL Cohort has significantly higher triglyceride, low-density lipoprotein, and cholesterol levels at 6 months and 1 year. There is no difference in MI incidence in the SRL Cohort (1.0% vs. 1.2%) and no difference in AAA, cerebrovascular accident, and CHF. The Framingham Risk Model predicts that the SRL Cohort should have almost double the 10-year risk of CVD compared to the Non-SRL Control (11% vs. 6%).
  
  
  CONCLUSIONS
  Sirolimus causes hypertriglyceridemia and hypercholesterolemia, but it does not increase the incidence of MI or other CVDs. Considering the SRL Cohort has more cardiac risk factors and nearly double 10-year predicted CVD risk, the fact that the CVD incidence is similar suggests that sirolimus is in fact cardioprotective.
authors.affiliation: Department of Surgery, Baylor University Medical Center, Dallas, TX 75246, USA. greg.mckenna@baylorhealth.edu
authors.forename: Greg J
authors.initials: GJ
authors.lastname: McKenna
authors.forename: James F
authors.initials: JF
authors.lastname: Trotter
authors.forename: Erik
authors.initials: E
authors.lastname: Klintmalm
authors.forename: Richard
authors.initials: R
authors.lastname: Ruiz
authors.forename: Nicholas
authors.initials: N
authors.lastname: Onaca
authors.forename: Giuliano
authors.initials: G
authors.lastname: Testa
authors.forename: Giovanna
authors.initials: G
authors.lastname: Saracino
authors.forename: Marlon F
authors.initials: MF
authors.lastname: Levy
authors.forename: Robert M
authors.initials: RM
authors.lastname: Goldstein
authors.forename: Goran B
authors.initials: GB
authors.lastname: Klintmalm
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014280:Triglycerides / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D014280:Triglycerides; D002784:Cholesterol; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus