Cardiovascular Morbidity and Mortality Is Increased Post-liver Transplantation Even in Recipients With No Pre-existing Risk Factors

Laura De Luca; Maria Kalafateli; Simone Bianchi; Norah Alasaker; Elena Buzzetti; Manuel Rodriguez-Perálvarez; Douglas Thorburn; James O'Beirne; David Patch; Gioacchino Leandro; Rachel Westbrook; Emmanuel A. Tsochatzis

Disclosures

Liver International. 2019;39(8):1557-1565. 

In This Article

Abstract and Introduction

Abstract

Background/aims: Post-liver transplant (LT) metabolic syndrome (PTMS) and cardiovascular (CVS) mortality are becoming increasingly prevalent following sustained improvements in post-LT survival. We investigated the prevalence and predictors of PTMS and CVS complications in a cohort of consecutive LT recipients.

Methods: We reviewed prospectively collected data of patients (n = 928) who underwent LT (1995–2013) and survived at least 1-year post-LT or died before that due to a major CVS complication.

Results: Median follow-up was 85 months (IQR = 106). The prevalence of PTMS was 22.4% and it developed de novo in 183 recipients (19.7%). A total of 187 (20.2%) patients developed at least one CVS event post-LT within a median of 49 months (IQR = 85). Overall mortality rate was 22.6% (n = 210). Causes of death were CVS events (n = 45, 21.4%), malignancies (21%), liver-related deaths (20%) and infections (6.7%). Independent predictors of major CVS events were: documented CVS disease pre-LT (Hazard Ratio (HR) = 3.330; 95% CI = 1.620-6.840), DM (HR = 1.120; 95% CI 1.030-1.220), hypertension (HR = 1.140; 95% CI 1.030-1.270), dyslipidaemia (HR = 1.140; 95% CI 1.050-1.240) and creatinine levels at 1 year (HR = 1.010; 95% CI = 1.005-1.013). Among LT recipients without pre-LT CVS disease or MS components (n = 432), 85 recipients developed ≥1 CVS events (19.7%) with independent predictors being DM (HR = 1.150; 95% CI = 1.010-1.320), creatinine levels at 1 year (HR = 1.020; 95% CI = 1.010-1.030) and hypertension (HR = 1.190; 95% CI = 1.040-1.360).

Conclusions: Post-LT patients are at increased risk of CVS morbidity even in the absence of pre-existing metabolic risk factors. Renal sparing immunosuppressive protocols might reduce CVS events post-LT.

Introduction

Liver transplantation (LT) has altered the prognosis of patients with advanced liver disease, significantly improving the length and quality of life. Such patients usually died within months without LT,[1] whereas LT recipients now have a 84% 1-year and 73% 5-year survival rates.[2–4] Survival following LT has been steadily improving over the last two decades, likely due to a greater surgical expertise, which reduced technical complications, a better selection of patients and improvements in the efficacy and tolerability of immunosuppressive therapy, reducing graft loss from both acute and chronic rejection.[5] Indeed, graft loss due to rejection is becoming a relatively rare cause of morbidity and mortality post-LT.[6]

Although the main cause of death after the first-year post-LT is liver related in up to 28% of patients, non-hepatic causes of death are increasing with malignancies (22%), cardiovascular disease (CVD) (11%), infection (9%) and renal failure (6%) being important causes.[7] The main causes of late mortality (>10 years) are hepatic in 40% and non-hepatic in 60% of patients, particularly de novo tumours and CVD.[8]

Metabolic syndrome (MS) is a common risk thread for each of these making the prevalence, prevention and management of post-transplant MS (PTMS) and individual metabolic derangements of increasing interest and importance. MS currently affects 20%-30% of the adult western world population.[9] It is an established risk factor for cardiovascular disease and its increasing prevalence correlates with an increasing incidence of CVD.

Liver transplant recipients have a high prevalence of risk factors for CVD, exceeding that of the general population,[10] and thus have a higher predicted risk of developing coronary heart disease.[11–13] CVD hospitalizations post-LT has increased by 115% over the last decade.[14] Recent studies from the US highlighted the high early cardiovascular morbidity and mortality following LT and have identified preoperative factors and liver disease aetiology as significant predictors.[15,16] However, there is a relevant paucity of data on the incidence and predictors of cardiovascular events following the perioperative period. Limitations of existing studies include inadequate sample size, relevantly short follow-up, incomplete data on pre- and post-LT metabolic comorbidities and lack of consensus regarding outcome definition.[17]

The aim of our study was to investigate metabolic and cardiovascular complications in a well-defined cohort of consecutive LT recipients with longitudinal follow-up, identifying the predictors of PTMS and CV events after LT.

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