Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre‐LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new‐onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow‐up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre‐LT evaluation. The presence or severity of pre‐LT CAD did not impact post‐LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new‐onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new‐onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12‐0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre‐LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre‐LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.
Although cardiovascular disease (CVD) is the leading cause of long-term mortality in liver transplant recipients (LTRs), the role of recently identified biomarkers of CVD risk in liver transplantation is unknown. We aimed to evaluate an extensive CVD risk profile in LTRs. Markers of CVD risk in 65 LTRs with no known history of diabetes mellitus (DM), dyslipidemia, or ischemic heart disease were compared to age-, sex-, and body mass index (BMI)-matched controls with no chronic medical disease. LTRs on corticosteroids or those with graft cirrhosis (GC) were excluded. The effect of calcineurin inhibitors on the CVD risk profile was separately analyzed in LTRs receiving either tacrolimus (Tac) or cyclosporine A (CsA). To evaluate the impact of GC, a comparison was made between LTRs with and without GC. Non-DM LTRs were matched to controls with respect to age, sex, and BMI. LTRs had similar serum high-density lipoprotein-cholesterol (HDL-C), low-density lipoproteincholesterol (LDL-C), and total cholesterol in comparison with BMI-matched controls. Proatherogenic small-dense (sd) LDL-C (33.6 6 14 versus 25.9 6 9.9 mg/dL; P < 0.001) and %sdLDL-C (30% 6 10% versus 26.4% 6 9%; P 5 0.02) were significantly higher in LTRs. In comparison with controls, LTRs had higher apolipoprotein B (apoB; 98 6 37 versus 88 6 24 mg/dL; P < 0.01), very low density lipoprotein-particle concentration (VLDL-P; 7.7 6 6.7 nmol/L versus 3.2 6 9.1 nmol/L; P < 0.001), and VLDL size (51.1 6 6.6 versus 46.5 6 6.9 nm; P < 0.001). In LTRs, VLDL size and VLDL-P were directly related to serum CsA levels (r 5 0.53, P 5 0.09, and r 5 0.63, P < 0.01, respectively) but not to Tac levels. In comparison with controls, LTRs had significantly lower total serum high-density lipoprotein-particle concentration. In comparison with those with preserved graft function, LTRs with GC had lower levels of serum atherogenic markers characterized by low sdLDL-C, apoB, triglycerides, LDL-C, and total cholesterol. In conclusion, LTRs have a proatherogenic lipoprotein profile that is not captured with a traditional lipid panel, and this suggests that a detailed serum atherogenic profile is needed to truly assess CVD risk in LTRs. Liver Transpl 21:623-630, 2015. V C 2015 AASLD. Received November 20, 2014 accepted January 28, 2015. Improvements in the medical and surgical care of liver transplant recipients (LTRs) have increased long-term survival rates and have shifted the causes of mortality from surgical and infectious complications to cardiovascular disease (CVD). 1,2 In comparison with an ageand sex-matched general population, LTRs have a much higher rate of cardiovascular events, which ranges from 9% at 5 years to 25% at 10 years after transplant. [3][4][5] The increased CVD mortality is likely multifactorial and results from a combination of
Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid‐lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty‐five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow‐up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small‐dense low‐density lipoprotein cholesterol (sdLDL‐C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P < 0.001), sdLDL‐C to low‐density lipoprotein cholesterol ratio (32.6 ± 11.6 versus 24.6 ± 10.2; P < 0.01), small‐dense low‐density lipoprotein particle concentration (sdLDL‐P; 770 ± 440 versus 486 ± 402 nmol/L; P < 0.01), very low density lipoprotein particle concentration (VLDL‐P; 7.90 ± 7.91 versus 3.86 ± 3.18 nmol/L; P < 0.01), and very low density lipoprotein size (VLDL‐size; 51.9 ± 6.4 versus 48.7 ± 6.3 nm; P = 0.06). LTRs with hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P < 0.01) but similar fasting glucose and hemoglobin A1c. Steatosis grade was directly related to sdLDL‐C, sdLDL‐P, insulin, VLDL‐P, and VLDL‐size. In multivariate analysis, the association between steatosis grade and sdLDL‐C (β = 0.03; P = 0.029), VLDL‐size (β = 0.316; P = 0.04), and low‐density lipoprotein particle size (β = –0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors. Liver Transpl 21:1395‐1402, 2015. © 2015 AASLD.
Cardiovascular disease (CVD) is an important cause of morbidity and mortality after liver transplantation (LT). Although LT is associated with dyslipidemia, particularly atherogenic lipoprotein subparticles, the impact of these subparticles on CVD‐related events is unknown. Therefore, the aim of the current study was to evaluate the impact of small dense (sdLDL‐C) low‐density lipoprotein (LDL) cholesterol (LDL‐C) on CVD events. Prospectively enrolled patients (N = 130) had detailed lipid profile consisting of traditional lipid parameters and sdLDL‐C and were followed for CVD events. The primary endpoint was a CVD composite consisting of myocardial infarction (MI), angina, need for coronary revascularization, and cardiac death. Mean age of the cohort was 58 ± 11 years, and the most common etiology of liver disease (LD) was hepatitis C virus (N = 48) and nonalcoholic steatohepatitis (N = 23). A total of 20 CVD events were noted after median follow‐up of 45 months. The baseline traditional profile was similar in patients with and without CVD events. A serum LDL‐C cutoff of 100 mg/dL was unable to identify individuals at risk of a CVD event (P = 0.86). In contrast, serum concentration of atherogenic sdLDL‐C >25 mg/dL was predictive of CVD events with a hazard ratio of 6.376 (95% confidence interval, 2.65, 15.34; P < 0.001). This relationship was independent of diabetes, hypertension, sex, ethnicity, LD, obesity, and statin use. Conclusion: sdLDL‐C independently predicted CVD events whereas LDL‐C did not. Thus, sdLDL‐C may provide a useful clinical tool in risk stratifying and managing patients after LT.
Background & Aims: Cardiovascular complications are major contributors to mortality at liver transplantation (LT). However, the impact of coronary artery disease (CAD) on these complications is not well-understood as the literature is limited by non-invasive assessment of CAD, which is suboptimal in patients with cirrhosis. Thus, the current study evaluated cardiovascular events at LT stratified according to the presence and severity of CAD quantified on coronary angiography. ated (N = 348), but analysis was restricted to patients who had coronary angiography prior to LT (N = 283). Protocol coronary angiography was performed in all patients' ages >50 years, history of CAD, abnormal cardiac stress test or risk factors for CAD.The primary outcome was a cardiovascular composite outcome including myocardial infraction (MI), cardiac arrest, stroke, cardiac death, heart failure or arrhythmia occurring within 4 weeks after LT.Results: CAD was present in 92(32.5%) patients and 32(11.3%) had obstructive CAD.During the study period, 72(25.4%) patients met the primary cardiovascular outcome, the most common being arrhythmia (N = 59 or 20.8%). Non-ST elevation MI occurred in 11(3.9%) of patients. A total of 10 deaths (3.5%) occurred, of which 6(2.1%) were attributable to cardiac death. There was no evidence of a relationship between the presence and severity of CAD and composite cardiovascular events. In multiple regression modelling, only diabetes [OR 2.62, 95%CI (1.49, 4.64), P < 0.001] was associated with the likelihood of having a cardiovascular event.Conclusion: Cardiovascular disease mortality is the most important contributor of early mortality after LT but is not related to the severity of CAD. K E Y W O R D S cardiovascular events, cirrhosis, coronary artery disease, liver transplantation 1364 | PATEL ET AL. | INTRODUC TI ONCardiovascular disease (CVD) is an important contributor to morbidity and mortality during and immediately after liver transplantation (LT). 1,2 More importantly, the presence and severity of coronary artery disease (CAD) has been linked to worse outcomes at LT. 2 The gold standard for CAD assessment is coronary angiography, but it is often deferred in many patients with decompensated cirrhosis because of perceived higher risk of complications, thereby introducing a selection bias in the published literature. [3][4][5] This is compounded further by the suboptimal diagnostic performance of non-invasive cardiac testing in patients with cirrhosis because of blunted heart rate response, body habitus, oedema, deconditioning and impaired functional status. [6][7][8] Thus, it is difficult to interpret the findings of the published literature that have evaluated the impact of underlying CAD on CVD events at the time of LT that used non-invasive cardiac assessment. 9,10 Using coronary angiography, a recent study demonstrated higher prevalence of CAD in potential LT waitlist registrants compared to the general population; 11,12 however, because of relatively small sample size, the association between CAD a...
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