Changes in plasma sphingolipid levels against the background of lipid-lowering therapy in patients with premature atherosclerosis

About authors

1 Central State Medical Academy of the Department of Presidential Affairs of the Russian Federation, Moscow, Russia

2 City Clinical Hospital № 51, Moscow, Russia

3 Institute of Biochemical Physics named after N. M. Emanuel, Moscow, Russia

4 Lomonosov Moscow State University, Moscow, Russia

Correspondence should be addressed: Larisa O. Minushkina
Marshala Timoshenko, 19, str. 1А, Moscow, 121359; ur.liam@anikhsunim

About paper

Funding: RFBR grant 19-04-00870А, Sphingolipidome Analysis of Cardiovascular Disease Markers.

Author contribution: Rogozhina AA — sampling, data acquisition; Alessenko AV — project management; Kurochkin IN — data analysis; Minushkina LO — data analysis, manuscript writing; Gutner UA, Shupik MA, Maloshitskaya OA — sample preparation, laboratory tests, data analysis; Lebedev AT, Zateyshchikov DA — study planning, data analysis, manuscript editing.

Compliance with ethical standards: the study was approved by the Ethics Committee of City Clinical Hospital № 51, Moscow (protocol № 02/19 dated February 7, 2019). Informed consent was submitted by all patients.

Received: 2021-05-24 Accepted: 2021-06-13 Published online: 2021-06-23

Lipid-lowering drugs affect standard lipoproteins. However, we have no knowledge of changes in other plasma lipids upon treatment. The study was aimed to assess the dynamic changes in cholesterol, high- and low-density lipoproteins (HDL and LDL), triglycerides, and sphingolipids against the background of lipidlowering therapy in patients with premature coronary artery disease, atherosclerosis and hypercholesterolemia. A total of 18 patients were enrolled (the average age was 53 ± 6.7 years): in group 1, six patients received starting statin doses; group 2 included six patients, who failed to achieve LDL target levels against the background of treatment with starting statin doses, and received escalated statin doses; seven patients in group 3 failed to achieve LDL target levels against the background of treatment with maximum tolerated doses of statins and ezetimibe, and received alirocumab. Sphingolipid levels were assessed by mass spectrometry. In group 1, the decreased levels of ceramide Cer 14:1 (p = 0.046) and sphingomyelins SM 22:1, SM 22:0, SM 24:0 (p = 0.028) were observed. There were no significant changes in the levels of total cholesterol, LDL-C, HDL-C, and triglycerides. In group 2, the significantly decreased levels of total cholesterol (p = 0.028), LDL (p = 0.043), sphingomyelins SM 18:1, SM 24:1 and SM 26:1, and ceramide Cer 16:1 (p = 0.028) were observed. The level of Cer 22:1 significantly increased (p = 0.028). In group 3, total cholesterol decreased by 36.2%, and LDL-C (p = 0.018) decreased by 60.1% compared to baseline (ΔLDL-C = –2.67 ± 3.12); the elevated levels of ceramide Cer 22:1 (p = 0.028) were observed. It has been shown, that decreased sphingomyelin levels are associated with statin therapy and correlate with decreased levels of LDL-C. No significant dynamic changes in ceramides and ceramide risk against the background of statin therapy were observed, however, PCSK9 inhibitor added to therapy reduced the Cer 16:0/24:0 ratio.

Keywords: atherosclerosis, sphingomyelins, sphingosine, ceramides, lipid-lowering therapy