Lipid levels in sickle‐cell disease associated with haemolytic severity, vascular dysfunction and pulmonary hypertension

Abstract

Pulmonary hypertension (PH) in sickle cell disease (SCD) is an emerging and important clinical problem. In a single-institution adult cohort of 365 patients, we investigated lipid and lipoprotein levels and their relationship to markers of intravascular hemolysis, vascular dysfunction and PH. In agreement with prior studies, we confirm significantly decreased plasma levels of total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in SCD vs. ethnically-matched healthy controls. Several cholesterol parameters correlate significantly with markers of anemia, but not endothelial activation or PH. More importantly, serum triglyceride levels are significantly elevated in SCD compared to controls. Elevated triglyceride levels correlate significantly with markers of hemolysis (lactate dehydrogenase and arginase; both p<0.0005), endothelial activation (soluble E-selectin, p<0.0001; soluble P-selectin, p=0.02; soluble vascular cell adhesion molecule-1, p=0.01), inflammation (leukocyte count, p=0.0004; erythrocyte sedimentation rate, p=0.02) and PH (amino-terminal brain natriuretic peptide, p=0.002; prevalence of elevated tricuspid regurgitant velocity (TRV), p<0.001). In a multivariate analysis, triglyceride levels correlate independently with elevated TRV (p=0.002). Finally, forearm blood flow studies in adult patients with SCD demonstrate a significant association between increased triglyceride/HDL-C ratio and endothelial dysfunction (p<0.05). These results characterize elevated plasma triglyceride levels as a potential risk factor for PH in SCD.

Hypocholesterolemia is associated negatively with hemolysate lipid peroxidation in sickle cell anemia patients

“…Hypocholesterolemia is the most frequently reported lipid abnormality besides decreased lipoprotein and increased triglyceride levels in the sickle plasma [16]. However, the pathophysiology of these abnormalities is obscure.…”

Defective lipid metabolism in sickle cell anaemia subjects in vaso-occlusive crisis

“…Despite intense research for over 4 decades, mechanism of lipid homeostasis alteration in SCA subjects is not yet fully understood 11. The observed lower levels of TC, HDL and LDL in the combined SCA subjects (SSCA and VOC) are not novel findings.…”

“…However, it is worthy of note that this lipid phenotype is generally recognized as a risk factor for cardiovascular diseases. Zorca et al 11. reported that elevated plasma TG is a potential risk factor for pulmonary hypertension (PH) in SCA subjects.…”

Intravascular hemolysis and the pathophysiology of sickle cell disease

“…This is also correct. Published data evidence the involvement of oxidative stress (79,100,105,108,113,115,116,121,123,132,134,135), inflammation (9, 22, 27, 32, 101, 105-108, 115, 124-127, 134), dyslipidemia (135)(136)(137)(138), microparticles (89,122,123,139), and vasoactive peptides (110,111,(140)(141)(142)(143). These additional pathways (depicted in Figure 2) are potentially additive or synergistic to intravascular hemolysis-like mechanisms.…”