Table 1.
Plasma levels of lipids, lipoprotein lipids, lipoprotein mass, apolipoproteins and biomarkers in hypertriglyceridemic male subjects at baseline (D0), the effect of treatment with Pitavastatin calcium (4 mg/day; D180) for 180 days, and comparison with a healthy, normolipidemic control group
| Parameter | HTG Subjects (n = 12) |
Control Subjects | ||
|---|---|---|---|---|
| Baseline D0 | D180 | % Change (D180 vs. D0) | ||
| Total cholesterol (mg/dl) | 232.2 ± 17.6 | 161.7 ± 5.7∗∗∗ | −30% | 171.4 ± 8.0§§a |
| Triglycerides (mg/dl) | 215.9 ± 16.0 | 127.7 ± 8.1∗∗∗ | −41% | 75.3 ± 11.1§§§,###a |
| LDL-cholesterol (mg/dl) | 153.0 ± 6.2 | 96.1 ± 5.8∗∗∗ | −37% | 100.4 ± 6.4§§§a |
| ApoB (mg/dl) | 102.0 ± 4.2 | 72.8 ± 5.1∗∗∗ | −29% | 80.3 ± 12.6a |
| Lp(a)a (mg/dl) | 8.8 (0.5–24.9) | 8.5 (0.9–32.2) | −3% | <10.0a |
| Non-HDL-C (mg/dl) | 185.9 ± 15.8 | 113.5 ± 4.5∗∗∗ | −39% | 115.0 ± 8.5§§ |
| RLP-C (mg/dl) | 39.1 ± 12.9 | 17.5 ± 4.1 | −55% | 14.6 ± 3.8§,∗ |
| HDL-cholesterol (mg/dl) | 46.3 ± 2.8 | 48.2 ± 3.6 | +4% | 56.4 ± 3.0§a |
| Total HDL mass (mg/dl) | 201.0 ± 3.1 | 200.6 ± 3.9 | 0 | 261.2 ± 4.8§§§,###a |
| HDL2 mass (mg/dl) | 103.7 ± 4.8 | 96.0 ± 8.9 | −7% | 145.1 ± 5.6§,#a |
| HDL3 mass (mg/dl) | 97.3 ± 4.3 | 104.6 ± 5.8 | +8% | 116.1 ± 3.2§,#a |
| HDL2b mass (mg/dl) | 39.6 ± 3.7 | 35.2 ± 4.1 | −11% | 71.4 ± 6.9§§§,###a |
| HDL2a mass (mg/dl) | 64.1 ± 3.3 | 60.8 ± 5.5 | −5% | 73.7 ± 5.1§,#a |
| HDL3a mass (mg/dl) | 60.5 ± 2.7 | 64.9 ± 3.8 | +7% | 67.8 ± 5.6a |
| HDL3b mass (mg/dl) | 26.0 ± 1.3 | 28.5 ± 1.5 | +10% | 31.2 ± 3.2a |
| HDL3c mass (mg/dl) | 10.7 ± 0.8 | 11.1 ± 0.8 | +4% | 17.1 ± 1.9§§,##a |
| Pre-β1-HDL (mg/dl) | 6.9 ± 1.0 | 6.0 ± 0.9 | −13% | 2.3 ± 0.2§§§,###b |
| LpAI (mg/dl) | 28.1 ± 2.1 | 27.8 ± 3.3 | −1% | 47.0 ± 0.8§§§,###e |
| LpAI:AII (mg/dl) | 72.2 ± 3.4 | 78.7 ± 3.4∗ | +9% | 99 ± 0.9§§§,###e |
| ApoAI (mg/dl) | 100.3 ± 4.8 | 106.6 ± 5.7 | +6% | 147.1 ± 4.2§§§,###a |
| ApoAII (mg/dl) | 24 ± 1.0 | 26.1 ± 1.6 | +9% | 35.2 ± 0.1§§§,###c |
| ApoAI/ApoAII ratio | 4.2 ± 0.2 | 4.1 ± 0.2 | −2% | 4.2 ± 0.1 |
| ApoE (mg/dl) | 4.3 ± 0.2 | 3.3 ± 0.1∗∗∗ | −24% | 4.1 ± 0.7b |
| ApoCII (mg/dl) | 16.7 ± 2.7 | 6.5 ± 1.6∗∗ | −61% | 4.6 ± 0.4§§§d |
| ApoCIII (mg/dl) | 10.3 ± 1.2 | 7.8 ± 0.8 | −25% | 9.9 ± 0.5#d |
| Sphingosine-1-phosphate (nmol/L) | 187.2 ± 32.6 | 155.6 ± 37.8 | −17% | ND |
| ApoM (mg/dl) | 0.25 ± 0.01 | 0.22 ± 0.01 | −10% | ND |
| SAA (mg/L) | 26.5 ± 3 | 19.3 ± 2∗ | −27% | ND |
| oxLDL (μg/dl) | 84.0 ± 4.8 | 56.4 ± 3.6∗ | −34% | ND |
| Lp-PLA2 mass (ng/ml) | 223 ± 17 | 205.2 ± 15∗∗∗ | −8% | ND |
| Lp-PLA2 activity (UI/L) | 234 ± 11 | 192 ±12∗∗∗ | −18% | ND |
| Paraoxonase (mU/μl) | 28.1 ± 0.01 | 34.4 ± 0.01∗∗ | +24% | ND |
| hsCRP (mg/L) | 1.6 ± 0.2 | 1.6 ±0.2 | 0 | ND |
| CETP mass (μg/ml) | 2.4 ± 0.1 | 2.0 ± 0.1∗∗ | −18% | ND |
| CETP activity (pmol/ml/min) | 50.3 ± 3.0 | 42.3 ±2.0∗∗ | −16% | ND |
| LCAT activity (%) | 67.1 ± 0.5 | 68.4 ± 0.6∗∗ | +2% | ND |
CETP, CETP, cholesteryl ester transfer protein; ND, not determined.
Values in HTG subjects are expressed as means ± SEM (n = 12 unless stated otherwise). ND, not determined. Due to an asymmetric distribution, Lp(a) levels are expressed as median (minimum-maximum). ∗∗∗P < 0.001, ∗∗0.001 < P < 0.01, and ∗0.01 < P < 0.05 for values at D0 versus D180; §§§P < 0.001, §§0.001 < P<0.01, and §0.01 < P < 0.05 for values at D0 versus Control subjects; ###P < 0.001, ##0.001 < P < 0.01, and #0.01 < P < 0.05 for values at D180 versus Control group. Details of assay methods are provided in the text. Non-HDLC (as TC-HDLC) and ApoAI/ApoAII ratio were calculated with GraphPadPrism 8.4.2 using baseline-corrected function with HDL-C and ApoAII as baseline values (34). Remnant lipoprotein-cholesterol (RLP-C) was calculated as previous (34). Statistical analyses for D0 versus D180 data were performed as paired t-tests (for parameters with Gaussian distribution) or Wilcoxon’s test (for parameters without Gaussian distribution).
Data for the effect of pitavastatin treatment on several baseline parameters in plasma (total cholesterol, triglycerides, LDL-C, apoB, Lp(a), non-HDL-C, RLP-C, HDL-C, chemical masses of total HDL and HDL subclasses, pre-β1-HDL, LpAI and LpAI:AII, apoAI and apoAII, apoE, apoCII, apoCIII, CETP mass and activity and LCAT activity were extracted from reference (34). Data for the effect of statin treatment on baseline levels of oxLDL, paraoxonase activity, LpPLA2 mass and activity, and SAA levels were reported earlier (35), as were data for apoM and S1P levels (26).
Data in control subjects (n = 25 for pre-β1-HDL; n = 10 for ApoE, respectively) (36).
Data in control subjects (n = 1635) (37).
Data in control subjects (n = 25) (38).
Data in control subjects (n = 233) (39).