Dynamic changes of the composition of plasma HDL particles in patients with cardiac disease: Spotlight on sphingosine-1-phosphate/serum amyloid A ratio.

Several epidemiological studies reported an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and atherosclerotic cardiovascular disease (ASCVD). However, therapeutic interventions targeted at raising HDL-cholesterol failed to improve cardiovascular outcomes, suggesting that HDL components distinct from cholesterol may account for the anti-atherothrombotic effects attributed to this lipoprotein. Sphingosine-1-phosphate (S1P) and the acute phase protein serum amyloid A (SAA) have been identified as integral constituents of HDL particles. Evidence suggests that S1P and SAA levels within HDL particles may be affected by inflammation and oxidative stress, which are coexisting processes underlying ASCVD. Because SAA, an inflammation-related marker, and S1P, an anti-atherothrombotic marker, have relatively clear opposite characteristics among the HDL-associated proteins, the approach of assessing the two markers simultaneously may provide new insights in clinical practice (S1P/SAA Index). This review focuses on evidence in support of the concept that the S1P/SAA Index may affect the HDL atheroprotective properties and may, therefore represent a potential target for therapeutic interventions.

Determination of Sphingosine-1-Phosphate in Human Plasma Using Liquid Chromatography Coupled with Q-Tof Mass Spectrometry.

Evidence suggests that high-density lipoprotein (HDL) components distinct from cholesterol, such as sphingosine-1-phosphate (S1P), may account for the anti-atherothrombotic effects attributed to this lipoprotein. The current method for the determination of plasma levels of S1P as well as levels associated with HDL particles is still cumbersome an assay method to be worldwide practical. Recently, a simplified protocol based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the sensitive and specific quantification of plasma levels of S1P with good accuracy has been reported. This work utilized a triple quadrupole (QqQ)-based LC-MS/MS system. Here we adapt that method for the determination of plasma levels of S1P using a quadrupole time of flight (Q-Tof) based LC-MS system. Calibration curves were linear in the range of 0.05 to 2 µM. The lower limit of quantification (LOQ) was 0.05 µM. The concentration of S1P in human plasma was determined to be 1 ± 0.09 µM (n = 6). The average accuracy over the stated range of the method was found to be 100 ± 5.9% with precision at the LOQ better than 10% when predicting the calibration standards. The concentration of plasma S1P in the prepared samples was stable for 24 h at room temperature. We have demonstrated the quantification of plasma S1P using Q-Tof based LC-MS with very good sensitivity, accuracy, and precision that can used for future studies in this field.

A snapshot of lipid levels in the Republic of Ireland in 2017.

BACKGROUND: Abnormalities in blood lipid levels are causally linked with cardiovascular disease and pancreatitis. Data is limited regarding lipid abnormalities in Ireland. AIMS: As part of a cholesterol awareness campaign, we performed a pilot study of current lipid levels to preliminarily assess the extent and pattern of lipid abnormalities in Ireland. METHODS: Non-fasting, full lipid profiles and glucose measurements were performed in 259 people (32 on lipid-lowering medication and 225 untreated) using a validated Cholestech LDX machine. Untreated participants included 95 men and 130 women, aged 51 ± 16 years. RESULTS: The mean ± SD, total, low-density lipoprotein (LDL), high-density lipoprotein cholesterol (HDL) and median(IQR) non-HDL cholesterol and triglyceride levels in untreated individuals were 5.0 ± 1.1, 2.8 ± 1.0, 1.5 ± 0.5 and 3.4 (2.8-4.3), 1.6 (1.0-2.3) mmol/l respectively. Glucose was 5.3 (4.8-5.8) mmol/l. Glucose > 7.8 mmol/l occurred in 10 individuals (4%). Using defined criteria for non-fasting lipid levels, 60% of participants had some form of lipid abnormality with a frequency of 47% having a total cholesterol > 5, 35% with LDL > 3.0, 26% with HDL < 1.0/1.2, 33% with triglycerides > 2.0 and 32% with non-HDL cholesterol > 3.9 mmol/l. Three individuals had untreated LDL > 5 mmol/l (i.e. a ratio of 1:75 of those tested) and eight people had HDLc < 0.7 (1:28) and four had triglyceride above 7.3 mmol/l (1:56). CONCLUSIONS: This pilot study reveals significant lipid abnormalities which require further larger more detailed lipid studies to assess the true burden of lipid abnormalities in Ireland. Cascade screening and genetic testing of relatives of those with severe lipid abnormalities should be considered.