Wilma Gonzalez1, Pablo I. Altieri1,2*, Hector Banchs1,2, Diego Iravedra1, Rafael Calderon2, Ivan Gonzalez-Cancel2, Carmen Gurrea2, Nelson Escobales1 and Maria Crespo1
1Department of Medicine and Physiology, University of Puerto Rico, Medical Sciences Campus, Pablo I. Altieri
2Cardiovascular Center of Puerto Rico and the Caribbean, Pablo I. Altieri
Received: 02 July, 2014; Accepted: 18 September, 2014; Published: 20 September, 2014
Pablo I. Altieri, MD, Box 8387, Humacao, Puerto Rico 00792, Tel: (787) 630-7638; Fax: (787) 725-6423; Email:
Gonzalez W, Altieri PI, Banchs H, Iravedra D, Calderon R, et al. (2014) HDL as a Biomarker of Rejection in Heart Transplant. Glob J Obes Diabetes Metab Syndr 1(1): 001-006. DOI: 10.17352/2455-8583.000001
© 2014 Gonzalez W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Metabolic syndrome; Heart transplant; HDL; Rejection
BMI: Body Mass Index; dBP: Diastolic Blood Pressure; FBS: Fasting Blood Sugar; HDL: High Density Lipoprotein; HT: Heart Transplant; LDL: Low Density Lipoprotein; MetS: Metabolic Syndrome; sBP: Systolic Blood Pressure; HDL-C= High Density Lipopoprotein Cholesterol; BP: Blood Pressure; T2D: Type 2 Diabetes; apoCIII: Apolipoprotein C-III; Lp-PLA2: Lipoprotein associated phospholipase A2; p38-MAPK: Inhibitor of Mitogen Activated Protein Kinase; SAA: Serum Amyloid A; SA-A1: Serum Amyloid A-1; MCP-1= Monocyte Chemoattractant Protein-1; Ox-PL= Oxidized Phospholipids; PON1= Paraxonase 1; SD= Standard Deviation
Background: One hundred once patients underwent heart transplants due to multiple causes. These patients included 36 females and 65 males whose mean age was 51 years.
Objective: To study metabolic and lipid changes after heart transplantation with emphasis on HDL in rejected and non rejected hearts.
Methods: The metabolic changes pre and post transplant were analyzed.
1. Body mass index (BMI): 25 ± 4 - 28 ± 5 kg/ m2 (P<0.05)
2. Systolic blood pressure (sBP): 107 ± 17 - 131 ± 20mmHg (P<0.05)
3. Diastolic blood pressure (dBP): 70 ± 13 - 81 ± 10 mmHg(P<0.05)
4. Fasting blood sugar (FBS): 107 ± 37- 117 ± 55 mg%(0.164) (non significant)
5. Cholesterol: 170 ± 55 - 189 ± 32 mg/dl(P<0.05)
6. High density lipoprotein (HDL): 38 ± 16 - 52 ± 17 mg/dl (P<0.05)
7. Low density lipoprotein (LDL): 99 ± 20- 83 ± 15 mg/dl (0.34).
8. Triglycerides: 163 ± 10 -188 ± 12 mg/dl (0.144).
Conclusions: The heart transplant patients developed metabolic syndrome (MetS). The elevated HDL levels observed after transplantation are indicative of role of immunologic reaction to chronic rejection processes. The patients who died of rejection (19) exhibited greater elevations in HDL that those who did not (47 ± 22 – 71 ± 40 mg/dl, P<0.05). Seven autopsies were performed and revealed severe atherosclerotic changes in the aorta and coronary arteries that were likely related to dysfunctional HDL. The transplanted hearts were 21 years old. The high levels and persistent elevation of HDL observed in the rejected group can be used as a biomarker of rejection and this will help to change the anti-rejection protocol to try to avoid the rejection of the implanted heart. LDL was found to be a factor in the progressive atherosclerotic process because the level was reduced post transplant.
Introduction and Background
The incidence of metabolic syndrome (MetS) is growing each year; approximately one third of the population suffers from MetS . MetSis an important issue to study because it emerges as a novel risk in cardiovascular disease events due to endothelial dysfunctions, diabetes mellitus, hypertension and dyslipidemia .
MetS is a risk factor related with cardiovascular diseases, insulin resistance, post-transplantation complications, and late morbidity and mortality [3,4]. MetS is described as by a clustering of cardiovascular risk factors that are correlated with pathophysiological defects that are indicative of metabolic burden associated with disturbances in adipose tissue, including diabetes, obesity, dyslipidemia and hypertension [3,5]. MetS is defined according to ethnicity/race, specific waist circumference and the presence of two of the following: 
a. triglycerides: >150 mg/dl
b. high density lipoprotein- cholesterol (HDL-C): < 40 mg/dl for males
c. HDL-C: <50 mg/dl for females
d. blood pressure: >130/85 mmHg
e. fasting blood sugar:>100 mg/dl
The prevalence of MetS has been strongly associated with obesity due to its fundamental control of the distribution of free fatty acids disorders including dyslipidemia and insulin resistance preceding type 2 diabetes . Visceral adipose tissue is highly susceptible to catecholamine-induced lipolysis compared to subcutaneous tissue . This visceral fat produced in patients with MetS is related to insulin sensibility, which moderates angiogenic proteins, metabolic regulators and inflammatory mediators that produced hypertension, inflammation, endothelial dysfunction and the production of atheromas [2,5]. Heart transplant patients tend to develop MetS while also presenting with dysfunctional levels of high density lipoprotein-cholesterol . This manuscript describes the changes in our population (Table 1) that lead to MetS and the consequences of MetS. Moreover, the importance of functional and dysfunctional HDL will be discussed, because changes in both are extremely important for the survival of transplanted patients (Table 2). Also, the importance of a marked and persistent elevation of HDL can be used as a biomarker of an impending rejection process (Figure 1). The HDL-C of 70 mg/dl was not chosen as a cut-off, it was the mean value of the evaluation of HDL-C in the rejected patients who died. This will lead to an aggressive change in the rejection protocol to avoid this disaster. This last observation is the main point, we want to stress in this paper- HDL levels as a biomarker in heart transplant pathophysiology.
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