Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation

Abstract

Background Cardiac allograft vasculopathy (CAV) is a major prognosis limiting factor in heart transplantation (HTx). Disease development and progression are influenced by multiple determinants, but the role of remnant cholesterol (RC) in CAV has not yet been investigated. Therefore, the present study aimed to assess the prevalence of CAV in a very long-term follow-up after orthotopic HTx and to examine the role of RC in residual inflammation despite secondary prevention. Methods Herein, is a retrospective analysis of patient data collected at the last follow-up visit in an outpatient setting. Additionally, RC levels were calculated based upon cholesterol profile. Results The study population consisted of 184 patients with a mean follow-up of 15.0 ± 6.8 years. More than 40% of the overall cohort had CAV at last follow-up. The mean RC was 27.1 ± 14.7 mg/dL. Patients with CAV had significantly elevated RC despite intensified statin treatment (p = 0.018). A positive correlation was observed between RC and interleukin-6 as a marker of residual inflammation. Elevated RC and prolonged follow-up emerged as significant factors related to CAV in a multivariate analysis (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.5–5.5, p = 0.001 and OR 3.3, 95% CI 1.4–7.7, p = 0.006, respectively), whereas mycophenolate mofetil was inversely associated with CAV (OR 0.4, 95% CI 0.2–0.9, p = 0.034). Conclusions Remnant cholesterol has proinflammatory properties and is associated with CAV development in HTx. Thus, RC should be concerned as an additional tool for risk assessment.

Diltiazem as a cyclosporine A-sparing agent in heart transplantation: Benefits beyond dose reduction

“…CAV is common in long-term follow-up after OHT and may have prognostic implications. [ 13 , 14 ] In contrast to previous reports on the potential of DZ to reduce its progression in short-term follow-up, we found no association between DZ prescription and CAV prevalence. [ 5 ] However, CAV was diagnosed significantly earlier following transplantation in patients not receiving DZ.…”

Remnant cholesterol, preinflammatory state and chronic kidney disease: association and mediation analyses

“…We found that the preinflammatory state played a mediating role in the relationship between RC and CKD, which is consistent with previous findings of the related inflammatory potential of RC in atherosclerosis [ 25 , 44 , 45 ]. The mediation suggested that RC may cause structural and functional abnormalities of the kidney through renal tissue or systematic inflammation, inducing glomerulosclerosis, renal interstitial damage, and subsequent kidney function decline [ 8 ].…”

Association between remnant cholesterol and heart failure: A prospective cohort study

“…In addition, Wadström and his colleagues studied 106,937 individuals from the Copenhagen General Population Study and 13,974 individuals from the Copenhagen City Heart Study and found that elevated RC was associated with an approximately 5-fold increased risk of peripheral artery disease, 3-fold increased risk of ischemic heart disease and 2-fold increased risk of ischemic stroke ( 9 ). Other investigations also demonstrated the relationship between elevated RC and a higher risk of aortic valve stenosis, cardiac allograft vasculopathy, non-alcoholic fatty liver disease, diabetic nephropathy and chronic kidney disease ( 10 , 19 – 22 ). To the best of our knowledge, we are the first to report the association between elevated RC and the higher risk of HF in the general population.…”