Invited commentary on low high‐density lipoprotein is a risk for vascular disease

Cardiovascular disease (CVD) remains the leading cause of death after kidney transplantation, with a mortality rate of close to 5 per 1000 patient-year, accounting for 30–50% of deaths with functioning graft [1,2]. Although transplantation significantly improves the risk of CV death in patients with end-stage renal disease (ESRD) [3], this risk still remains high; it is 50-fold higher than that prevailing in general population in younger patients. This is to some extent attributable to pre-existing CVD, inherited from pretransplant period, including left ventricular hypertrophy (LVH), coronary artery disease (CAD), arteriosclerosis and vascular calcification. Moreover, traditional risk factors for CVD, including renal dysfunction, hypertension, dyslipidemia, diabetes, and obesity either persist or develop de novo after transplantation. However, these risk factors do not completely explain the large discrepancy in the rate of CV events in this patient population. Therefore, a number of nontraditional risk factors have been incriminated. Examples of the suggested risk factors include anemia, hyperhomocysteinemia, lupus anticoagulant antibodies, proteinuria, oxidative stress, systemic inflammation, advanced glycosylation end-products (AGEs), and osteoprotegerin [4–7]. Dyslipidemia is a common metabolic complication after transplantation, present in more than 50–60% of the patients [8,9]. Immunosuppressive agents, diabetes, and obesity generally are associated with worsening of lipid abnormalities. The typical profile is that of elevated lowdensity lipoprotein cholesterol (LDL-C) and triglyceride levels and reduced high-density lipoprotein cholesterol (HDL-C). Evidence suggests that treatment of high LDLC is associated with improved CV outcomes. In the Assessment of Lescol in Renal Transplantation (ALERT) trial 2102 transplant recipients with total cholesterol 154– 347 mg/dl (4.0 to 9.0 mm) were randomized to receive fluvastatin 40 to 80 mg daily or placebo [10]. After 5 years of follow-up, fluvastatin therapy was associated with a significant (35%) reduction in the incidence of myocardial infarction (MI) and cardiac death [11]. Although the 13% reduction in the primary outcome of major adverse cardiac events (MACE; MI, death, or coronary intervention) was not statistically significant in the study period, with a 2-year extension, there was 21% reduction in the risk of MACE [12]. However, these encouraging results do not obviate the need for exploring the role of other lipid components as potential risk factors that could be therapeutic targets. High-density lipoprotein cholesterol is a strong candidate target, as it has been recognized as an antiatherogenic lipoprotein. The protective effects of HDL are multi-faceted and include reverse cholesterol transport, antithrombotic, antioxidative, and anti-inflammatory effects, promotion of nitric oxide synthesis and release, and protecting and regulating endothelial cell phenotype [13–18]. Reverse cholesterol transport from macrophages in the atherosclerotic plaque and modulation of their pro-inflammatory phenotype may be among important antiatherogenic properties of HDL [13–15]. Current data Correspondence Abdolreza Haririan MD, MPH, 22 South Greene Street, N3W143, Baltimore, MD, USA. Tel.: 1-410-328-5720; fax: 1-410-328-5685; e-mail: ahariria@medicine.umaryland.edu