Abstract
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.
Highlights
METHODSAll patients were divided into three groups based on the fact of receiving lipid-lowering therapy at the time of enrollment (see Fig.)
In the course of randomized trial involving the use of different rosuvastatin doses (10 and 40 mg) in patients with metablic syndrome, both low and high statin doses significantly decreased the levels of ceramides and sphingolipids
Sphingomyelin levels decrease against the background of statin therapy; when applying starting doses of statins, these correlate with reduced levels of LDL-C
Summary
All patients were divided into three groups based on the fact of receiving lipid-lowering therapy at the time of enrollment (see Fig.). For sphingosine and sphingosine deuterated standard (d7, Avanti; USA), fragmentation of protonated parent molecules was performed at the energy of 12.5 eV down to ions with m/z 259.3 and 252.3 Da respectively, the dwell time was 35 ms. The content of sphingosine d18:0 was defined using external calibration (the standard was DL-erythro-dihidrosphingosine, Sigma; USA) based on the peak areas for MRM transitions m/z 302+·→ m/z 266.3 Da. CRS, described as a predictor for coronary artery disease mortality, was assessed using the previously reported scale involving the use of certain ceramide molecular species [8]. The differences were considered significant when р < 0.05 in all types of analysis
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