Treatment with PCSK9 Inhibitor Evolocumab Improves Vascular Oxidative Stress and Arterial Stiffness in Hypercholesterolemic Patients with High Cardiovascular Risk
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Study Population
2.3. Treatment
2.4. Assessments
2.4.1. Clinical Assessments
2.4.2. Biochemical Analyses
2.4.3. Blood Pressure Measurements
2.4.4. Non-Invasive Vascular Tests
2.5. H2O2Bioassay Procedure
2.5.1. PBMCs Collection
2.5.2. Quantification of Intracellular H2O2 in PBMCs
2.6. Cell Viability Assay
2.7. Data Analysis
3. Results and Discussion
3.1. Evolocumab Treatment Decreases Intracellular H2O2Production in PBMCs
3.2. Plasma Lipids and Arterial Stiffness Improvement after Treatment with Evolocumab
3.3. H2O2 Decrease Correlates with Arterial Stiffness Improvement
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Statin and Ezetimibe (N = 8) | Ezetimibe (N = 10) |
---|---|---|
Age (years)—mean ± SD | 63.2 ± 7.3 | 69.4 ± 4.9 |
Active smokers—% | 37.5 | 10 |
Heterozygous FH—% | 62.5 | 30 |
Primary cardiovascular prevention—% | 25 | 40 |
Secondary cardiovascular prevention—% | 75 | 60 |
Cardiovascular disease—% | 75 | 40 |
Cerebrovascular disease—% | 0 | 10 |
Peripheral obliterative arterial disease—% | 12.5 | 20 |
Type 2 diabetes—% | 0 | 20 |
Hypertension—% | 50 | 70 |
History of statin intolerance—% | 50 | 80 |
Low-dose * statin treatment—% | 50 | 0 |
High-dose § statin treatment—% | 50 | 0 |
n-3 PUFA treatment—% | 25 | 0 |
Urate-lowering treatment—% | 12.5 | 10 |
Parameters | Statin and Ezetimibe (N = 8) | Ezetimibe (N = 10) | ||
---|---|---|---|---|
Baseline (Mean ± SD) | Follow-Up (Mean ± SD) | Baseline (Mean ± SD) | Follow-Up (Mean ± SD) | |
Fasting plasma glucose—mg/dL | 94.13 ± 5.08 | 93.4 ± 8 | 93.6 ± 10.04 | 99.6 ± 14.48 |
Creatinine—mg/dL | 0.81 ± 0.13 | 0.78 ± 0.15 | 0.95 ± 0.16 | 1 ± 0.18 |
eGFR—mL/min/1.73 m2 | 89.16 ± 17.11 | 90.63 ± 18.52 | 73.78 ± 15.34 | 68.11 ± 16.09 |
Serum uric acid—mg/dL | 5.05 ± 0.93 | 4.61 ± 0.85 * | 5.86 ± 0.91 | 6 ± 0.98 |
Total cholesterol—mg/dL | 212.88 ± 35.92 | 111.75 ± 12.15 * | 247.4 ± 85.19 | 138.3 ± 60.73 * |
Triglyceride—mg/dL | 137.75 ± 93.23 | 106.5 ± 64.36 * | 138.7 ± 66.67 | 153 ± 150.69 |
HDL-cholesterol—mg/dL | 58 ± 13.22 | 58 ± 11.87 | 56.2 ± 12.47 | 55.2 ± 13.58 |
Non-HDL-cholesterol—mg/dL | 154.88 ± 32.99 | 53.75 ± 8.88 * | 191.2 ± 78.63 | 83.1 ± 52.84 * |
LDL-cholesterol—mg/dL | 132.54 ± 35.94 | 33.4 ± 12.92 * | 163.46 ± 78.16 | 52.5 ± 55.33 * |
VLDL-cholesterol—mg/dL | 28.03 ± 20.09 | 21.31 ± 13.9 * | 28.16 ± 14.07 | 32.07 ± 31.59 |
Apolipoprotein-B—mg/dL | 147.2 ± 47.8 | 53 ± 20.48 * | 148 ± 41.12 | 53.63 ± 33.62 * |
Lipoprotein(a)—mg/dL | 95.72 ± 92.62 | 67.06 ± 58.42 | 42.05 ± 54.45 | 30.79 ± 42.15 * |
Total bilirubin—mg/dL | 0.5 ± 0.07 | 0.54 ± 0.12 | 0.64 ± 0.18 | 0.58 ± 0.21 |
Direct bilirubin—mg/dL | 0.13 ± 0.04 | 0.16 ± 0.09 | 0.11 ± 0.03 | 0.13 ± 0.05 * |
Indirect bilirubin—mg/dL | 0.37 ± 0.05 | 0.37 ± 0.06 | 0.54 ± 0.15 | 0.46 ± 0.17 |
Aspartate aminotransferase—U/L | 25.71 ± 7.7 | 26.71 ± 8.73 | 33.2 ± 24.79 | 31.9 ± 26.59 |
Alanine aminotransferase—U/L | 24.13 ± 10.26 | 23.5 ± 9.93 | 27.4 ± 14.97 | 24.6 ± 16.15 |
Gamma-glutamyl transferase—U/L | 36 ± 51.8 | 45.13 ± 82.16 | 32.5 ± 23.63 | 29.8 ± 13.74 |
Creatine phosphokinase—U/L | 125.25 ± 78.04 | 150.38 ± 95.58 | 393.8 ± 392.8 | 361.2 ± 398.3 |
Thyroid-stimulating hormone—μU/mL | 1.92 ± 1.09 | 2.06 ± 1.2 | 2.44 ± 0.77 | 2.03 ± 0.38 |
Parameters | Statin and Ezetimibe (N = 8) | Ezetimibe (N = 10) | ||
---|---|---|---|---|
Baseline (Mean ± SD) | Follow-Up (Mean ± SD) | Baseline (Mean ± SD) | Follow-Up (Mean ± SD) | |
Heart rate—bpm | 67.13 ± 13 | 68.75 ± 8.19 | 62.8 ± 7.18 | 64.1 ± 10.04 |
Systolic blood pressure—mmHg | 135.13 ± 14.29 | 148.13 ± 17.76 * | 142.3 ± 20.87 | 153 ± 14.31 |
Diastolic blood pressure—mmHg | 70.5 ± 10.3 | 71.1 ± 10.5 | 70.1 ± 11.1 | 75.4 ± 8.1 |
Pulse wave velocity—m/s | 11.39 ± 1.26 | 4.91 ± 2.7 ** | 11.5 ± 1.9 | 6.77 ± 2.71 * |
Ankle–brachial index (right) | 1.06 ± 0.06 | 1.1 ± 0.15 | 0.91 ± 0.23 | 1.08 ± 0.07 |
Ankle–brachial index (left) | 1.02 ± 0.18 | 1.06 ± 0.21 | 0.98 ± 0.19 | 1.1 ± 0.2 |
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Silla, A.; Fogacci, F.; Punzo, A.; Hrelia, S.; Simoni, P.; Caliceti, C.; Cicero, A.F.G. Treatment with PCSK9 Inhibitor Evolocumab Improves Vascular Oxidative Stress and Arterial Stiffness in Hypercholesterolemic Patients with High Cardiovascular Risk. Antioxidants 2023, 12, 578. https://doi.org/10.3390/antiox12030578
Silla A, Fogacci F, Punzo A, Hrelia S, Simoni P, Caliceti C, Cicero AFG. Treatment with PCSK9 Inhibitor Evolocumab Improves Vascular Oxidative Stress and Arterial Stiffness in Hypercholesterolemic Patients with High Cardiovascular Risk. Antioxidants. 2023; 12(3):578. https://doi.org/10.3390/antiox12030578
Chicago/Turabian StyleSilla, Alessia, Federica Fogacci, Angela Punzo, Silvana Hrelia, Patrizia Simoni, Cristiana Caliceti, and Arrigo F. G. Cicero. 2023. "Treatment with PCSK9 Inhibitor Evolocumab Improves Vascular Oxidative Stress and Arterial Stiffness in Hypercholesterolemic Patients with High Cardiovascular Risk" Antioxidants 12, no. 3: 578. https://doi.org/10.3390/antiox12030578
APA StyleSilla, A., Fogacci, F., Punzo, A., Hrelia, S., Simoni, P., Caliceti, C., & Cicero, A. F. G. (2023). Treatment with PCSK9 Inhibitor Evolocumab Improves Vascular Oxidative Stress and Arterial Stiffness in Hypercholesterolemic Patients with High Cardiovascular Risk. Antioxidants, 12(3), 578. https://doi.org/10.3390/antiox12030578