Hypercholesterolemia after conversion to sirolimus as primary immunosuppression and cardiac allograft vasculopathy in heart transplant recipients

Rabea Asleh, Alexandros Briasoulis, Naveen Luke Pereira, Brooks Sayre Edwards, Robert Frantz, Richard C. Daly, Amir Lerman, Sudhir S. Kushwaha

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND: Sirolimus (SRL) attenuates cardiac allograft vasculopathy (CAV) progression after heart transplantation (HT) but often results in hyperlipidemia. In this study we investigated the differential effects of SRL-based and calcineurin inhibitor (CNI)-based immunosuppression on CAV progression and clinical outcomes in HT recipients. METHODS: CAV progression was assessed by coronary intravascular ultrasound (IVUS) as changes in volumetric measurements after correction to time between the first and last follow-up IVUS exams. CAV progression rate and CAV-associated events were compared between patients with mean follow-up low-density lipoprotein (LDL) <100 mg/dl (lower level or LL) and ≥100 mg/dl (higher level or HL) in the SRL and CNI groups. RESULTS: We identified 227 patients on SRL (LL: 118; HL: 109) and 96 on CNI (LL: 56; HL: 40), with a median follow-up of 6.7 years. Clinical characteristics did not differ between the LL and HL groups and all patients were on statins. In the SRL arm, there were no significant differences in CAV progression rate and there were no differences in all-cause mortality and CAV-associated events between the LL and HL groups. In the CNI arm, the Δ change in plaque volume normalized to segment length and time of follow-up (PV/SL/year) (0.55 ± 0.53 vs 1.53 ± 2.32, p = 0.003) and Δ change in plaque index per year (defined as PV/vessel volume ratio) (3.1 ± 3.7% vs 6.3 ± 10.4%; p = 0.034) were significantly lower in the LL than the HL group. After adjusting for patient characteristics, HL was associated with higher rates of advanced CAV requiring coronary angioplasty (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.05 to 9.40, p = 0.040) and higher rates of all CAV-associated events (HR 2.2, 95% CI 1.10 to 4.54, p = 0.026) in these CNI-treated subjects. CONCLUSION: Unlike CNI-based immunosuppression, the effects of SRL on attenuating CAV progression are independent of LDL cholesterol levels post-HT.

Original languageEnglish (US)
JournalJournal of Heart and Lung Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Sirolimus
Hypercholesterolemia
Immunosuppression
Allografts
Heart Transplantation
Arm
Transplant Recipients
Confidence Intervals
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hyperlipidemias
LDL Lipoproteins
Angioplasty
LDL Cholesterol
Calcineurin Inhibitors
Mortality

Keywords

  • cardiac allograft vasculopathy
  • heart transplantation
  • hyperlipidemia
  • immunosuppression
  • outcome

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

@article{bb7f5c2f075c4ebca966d9b746531e2d,
title = "Hypercholesterolemia after conversion to sirolimus as primary immunosuppression and cardiac allograft vasculopathy in heart transplant recipients",
abstract = "BACKGROUND: Sirolimus (SRL) attenuates cardiac allograft vasculopathy (CAV) progression after heart transplantation (HT) but often results in hyperlipidemia. In this study we investigated the differential effects of SRL-based and calcineurin inhibitor (CNI)-based immunosuppression on CAV progression and clinical outcomes in HT recipients. METHODS: CAV progression was assessed by coronary intravascular ultrasound (IVUS) as changes in volumetric measurements after correction to time between the first and last follow-up IVUS exams. CAV progression rate and CAV-associated events were compared between patients with mean follow-up low-density lipoprotein (LDL) <100 mg/dl (lower level or LL) and ≥100 mg/dl (higher level or HL) in the SRL and CNI groups. RESULTS: We identified 227 patients on SRL (LL: 118; HL: 109) and 96 on CNI (LL: 56; HL: 40), with a median follow-up of 6.7 years. Clinical characteristics did not differ between the LL and HL groups and all patients were on statins. In the SRL arm, there were no significant differences in CAV progression rate and there were no differences in all-cause mortality and CAV-associated events between the LL and HL groups. In the CNI arm, the Δ change in plaque volume normalized to segment length and time of follow-up (PV/SL/year) (0.55 ± 0.53 vs 1.53 ± 2.32, p = 0.003) and Δ change in plaque index per year (defined as PV/vessel volume ratio) (3.1 ± 3.7{\%} vs 6.3 ± 10.4{\%}; p = 0.034) were significantly lower in the LL than the HL group. After adjusting for patient characteristics, HL was associated with higher rates of advanced CAV requiring coronary angioplasty (hazard ratio [HR] 3.0, 95{\%} confidence interval [CI] 1.05 to 9.40, p = 0.040) and higher rates of all CAV-associated events (HR 2.2, 95{\%} CI 1.10 to 4.54, p = 0.026) in these CNI-treated subjects. CONCLUSION: Unlike CNI-based immunosuppression, the effects of SRL on attenuating CAV progression are independent of LDL cholesterol levels post-HT.",
keywords = "cardiac allograft vasculopathy, heart transplantation, hyperlipidemia, immunosuppression, outcome",
author = "Rabea Asleh and Alexandros Briasoulis and Pereira, {Naveen Luke} and Edwards, {Brooks Sayre} and Robert Frantz and Daly, {Richard C.} and Amir Lerman and Kushwaha, {Sudhir S.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.healun.2018.07.004",
language = "English (US)",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",

}

TY - JOUR

T1 - Hypercholesterolemia after conversion to sirolimus as primary immunosuppression and cardiac allograft vasculopathy in heart transplant recipients

AU - Asleh, Rabea

AU - Briasoulis, Alexandros

AU - Pereira, Naveen Luke

AU - Edwards, Brooks Sayre

AU - Frantz, Robert

AU - Daly, Richard C.

AU - Lerman, Amir

AU - Kushwaha, Sudhir S.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - BACKGROUND: Sirolimus (SRL) attenuates cardiac allograft vasculopathy (CAV) progression after heart transplantation (HT) but often results in hyperlipidemia. In this study we investigated the differential effects of SRL-based and calcineurin inhibitor (CNI)-based immunosuppression on CAV progression and clinical outcomes in HT recipients. METHODS: CAV progression was assessed by coronary intravascular ultrasound (IVUS) as changes in volumetric measurements after correction to time between the first and last follow-up IVUS exams. CAV progression rate and CAV-associated events were compared between patients with mean follow-up low-density lipoprotein (LDL) <100 mg/dl (lower level or LL) and ≥100 mg/dl (higher level or HL) in the SRL and CNI groups. RESULTS: We identified 227 patients on SRL (LL: 118; HL: 109) and 96 on CNI (LL: 56; HL: 40), with a median follow-up of 6.7 years. Clinical characteristics did not differ between the LL and HL groups and all patients were on statins. In the SRL arm, there were no significant differences in CAV progression rate and there were no differences in all-cause mortality and CAV-associated events between the LL and HL groups. In the CNI arm, the Δ change in plaque volume normalized to segment length and time of follow-up (PV/SL/year) (0.55 ± 0.53 vs 1.53 ± 2.32, p = 0.003) and Δ change in plaque index per year (defined as PV/vessel volume ratio) (3.1 ± 3.7% vs 6.3 ± 10.4%; p = 0.034) were significantly lower in the LL than the HL group. After adjusting for patient characteristics, HL was associated with higher rates of advanced CAV requiring coronary angioplasty (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.05 to 9.40, p = 0.040) and higher rates of all CAV-associated events (HR 2.2, 95% CI 1.10 to 4.54, p = 0.026) in these CNI-treated subjects. CONCLUSION: Unlike CNI-based immunosuppression, the effects of SRL on attenuating CAV progression are independent of LDL cholesterol levels post-HT.

AB - BACKGROUND: Sirolimus (SRL) attenuates cardiac allograft vasculopathy (CAV) progression after heart transplantation (HT) but often results in hyperlipidemia. In this study we investigated the differential effects of SRL-based and calcineurin inhibitor (CNI)-based immunosuppression on CAV progression and clinical outcomes in HT recipients. METHODS: CAV progression was assessed by coronary intravascular ultrasound (IVUS) as changes in volumetric measurements after correction to time between the first and last follow-up IVUS exams. CAV progression rate and CAV-associated events were compared between patients with mean follow-up low-density lipoprotein (LDL) <100 mg/dl (lower level or LL) and ≥100 mg/dl (higher level or HL) in the SRL and CNI groups. RESULTS: We identified 227 patients on SRL (LL: 118; HL: 109) and 96 on CNI (LL: 56; HL: 40), with a median follow-up of 6.7 years. Clinical characteristics did not differ between the LL and HL groups and all patients were on statins. In the SRL arm, there were no significant differences in CAV progression rate and there were no differences in all-cause mortality and CAV-associated events between the LL and HL groups. In the CNI arm, the Δ change in plaque volume normalized to segment length and time of follow-up (PV/SL/year) (0.55 ± 0.53 vs 1.53 ± 2.32, p = 0.003) and Δ change in plaque index per year (defined as PV/vessel volume ratio) (3.1 ± 3.7% vs 6.3 ± 10.4%; p = 0.034) were significantly lower in the LL than the HL group. After adjusting for patient characteristics, HL was associated with higher rates of advanced CAV requiring coronary angioplasty (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.05 to 9.40, p = 0.040) and higher rates of all CAV-associated events (HR 2.2, 95% CI 1.10 to 4.54, p = 0.026) in these CNI-treated subjects. CONCLUSION: Unlike CNI-based immunosuppression, the effects of SRL on attenuating CAV progression are independent of LDL cholesterol levels post-HT.

KW - cardiac allograft vasculopathy

KW - heart transplantation

KW - hyperlipidemia

KW - immunosuppression

KW - outcome

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U2 - 10.1016/j.healun.2018.07.004

DO - 10.1016/j.healun.2018.07.004

M3 - Article

C2 - 30174165

AN - SCOPUS:85054070697

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

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