Roles of HDL function and sphingosine-1-phosphate in vasospastic angina

Abstract

Background

High-density lipoprotein cholesterol (HDL-C) levels are often reduced in patients with vasospastic angina (VSA), but the relevance of HDL functionality to VSA pathogenesis remains unclear. Cholesterol uptake capacity (CUC), a novel cell-free assay reflecting HDL-mediated cholesterol efflux, offers a practical measure of HDL functionality. In parallel, sphingosine-1-phosphate (S1P), an HDL-associated bioactive sphingolipid with vasoprotective properties, may also contribute to VSA. This study aimed to evaluate CUC and vasodilatory HDL components, including S1P, in patients with VSA.

Methods and Results

Seventy-seven patients, comprising 53 patients who underwent an acetylcholine (Ach) provocation test (32 VSA at diagnosis and 21 non-VSA) and an additional 24 VSA outpatients were included. Patients with VSA had higher triglyceride levels compared with non-VSA patients, but HDL-C levels were not different. Further analysis revealed that CUC was lower in VSA patients at diagnosis compared with non-VSA patients. Serum levels of sphingosine-1-phosphate (S1P), a sphingolipid associated with HDL, were elevated in the VSA group (1.74 ± 0.76 vs. 1.31 ± 0.49 µM; p < 0.01). In the VSA outpatient and Non-VSA groups, S1P levels in crude analysis were significantly associated with VSA (OR = 3.14, 95 % CI: 1.25–7.88, p = 0.01). This association remained significant across all adjusted models (Models 1–4).

Conclusions

The present study found that CUC was a novel indicator of vasospasm-related HDL dysfunctionality and that S1P is a promising biomarker for treated patients with VSA. The cholesterol efflux pathway and sphingolipid metabolism could contribute to the etiology of vasospasm.

Study registration: This clinical study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000020942).