Atherosclerotic Plaque Fissuration and Clinical Outcomes in Pre-Diabetics vs. Normoglycemics Patients Affected by Asymptomatic Significant Carotid Artery Stenosis at 2 Years of Follow-Up: Role of microRNAs Modulation: The ATIMIR Study
Abstract
:1. Background
2. Research Design and Methods
2.1. Study Inclusion and Exclusion Criteria
2.2. Laboratory Analysis
2.3. MicroRNAs Isolation and Reverse-Transcription Real Time PCR (qRT-PCR)
2.4. Carotid Ultrasound
2.5. Intervention: Endarterectomy and Carotid Revascularization
2.6. Clinical Visits, Data Collection and Analysis
2.7. Major Adverse Cardiac Events Definition
2.8. Study Endpoints
2.9. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patients Characteristics | NG n (125) | PDNMU n (73) | PDMU n (36) | p |
---|---|---|---|---|
Age, years | 66.7 ± 6.5 | 68.8 ± 7.2 | 69.7 ± 9.2 | 0.104; 0.130; 0.891 |
Males, n (%) | 87 (69.6) | 52 (71.2) | 25 (69.4) | 0.752; 0.562; 0.412 |
Patients characteristics | ||||
Hypertension, n (%) | 86 (64.8) | 61 (83.6) | 31 (86.1) | 0.05 *; 0.011 **; 0.256 |
Hypercholesterolemia, n (%) | 84 (67.2) | 58 (79.5) | 29 (80.5) | 0.001 *; 0.004 **; 0.150 |
Cigarette smoking, n (%) | 17 (13.6) | 10 (13.6) | 5 (13.9) | 0.859; 0.870; 0.451 |
Ischemic heart disease, n (%) | 45 (36) | 35 (47.9) | 18 (50) | 0.05 *; 0.04 **; 0.120 |
BMI (kg/m2) | 26.8 ± 1.9 | 28.4 ± 1.8 | 28.0 ± 1.7 | 0.001 *; 0.001 **; 0.145 |
Systolic blood pressure (mmHg) | 124.7 ± 10.1 | 129.4 ± 12.8 | 129.5 ± 9.1 | 0.018 *; 0.007 **;0.530 |
Diastolic blood pressure (mmHg) | 72.1 ± 6.7 | 77.7 ± 7.1 | 76.1 ± 7.9 | 0.035 *; 0.05 **;0.189 |
Heart rate | 84 ± 8 | 83 ± 6 | 84 ± 6 | 0.175; 0.321; 0.128 |
HbA1C (%) | 5.3 ± 0.4 | 6.2 ± 0.8 | 5.8 ± 0.4 | 0.010 *; 0.022 **; 0.050 *** |
Blood glucose (mmol/L) | 86.8 ± 15.3 | 127.8 ± 18.1 | 105.6 ± 15.5 | 0.001*; 0.05 **; 0.032 *** |
HOMA-IR | 4.1 ± 0.25 | 5.1 ± 0.69 | 5.0 ± 0.72 | 0.045*; 0.05 **; 0.05 *** |
Total cholesterol, mg/dL | 178 ± 32 | 206 ± 44 | 187 ± 25 | 0.001 *; 0.018 **; 0.001 *** |
HDL cholesterol, mg/dL | 46.8 ± 10.6 | 40.2 ± 15.8 | 42.9 ± 12.6 | 0.005 *; 0.012 **; 0.05 *** |
LDL cholesterol, mg/dL | 103.9 ± 35.1 | 128.1 ± 48.4 | 114.3 ± 27.5 | 0.035 *; 0.048 **; 0.050 *** |
Triglycerides, mg/dL | 131.3 ± 23.2 | 167.9 ± 44.9 | 134.5 ± 40.7 | 0.004 *; 0.133; 0.05 *** |
Creatinine, mg/dL | 1.0 ± 0.1 | 1.1 ± 0.2 | 1.0 ± 0.1 | 0.082; 0.141; 0.520 |
Plaque characteristics | ||||
Stenosis severity, % | 75.8 ± 4.1 | 76.8 ± 4.8 | 75.9 ± 4.4 | 0.207; 0.315; 0.135 |
Plaque morphology: | ||||
-Fibrous, n (%) | 37 (29.6) | 16 (21.9) | 9 (25) | 0.168; 0.171; 0.180 |
-Fibro atheromatous, n (%) | 43 (34.4) | 21 (28.8) | 11 (30.6) | 0.208; 0.121; 0.560 |
-Atheromatous, n (%) | 45 (36) | 36 (49.3) | 16 (44.4) | 0.05 *; 0.05 **; 0.120 |
Active therapy (%) | ||||
Aspirin, n (%) | 107 (85.6) | 65 (89) | 33 (91.6) | 0.120; 0.132; 0.891 |
Warfarin, n (%) | 3 (2.4) | 2 (2.7) | 1 (2.8) | 0.252; 0.230; 0.158 |
β-Blockers, n (%) | 66 (52.8) | 39 (53.4) | 19 (52.7) | 0.270; 0.260; 0.713 |
Calcium-channel blockers, n (%) | 3 (2.4) | 4 (5.5) | 2 (5.5) | 0.05 *; 0.03 **; 0.301 |
Statins, n (%) | 112 (89.6) | 67 (91.8) | 32 (91.6) | 0.001 *; 0.002 **; 0.253 |
ACE inhibitors, n (%) | 41 (32.8) | 36 (49.3) | 17 (47.2) | 0.001 *; 0.001 **; 0.320 |
Diuretic agents, n (%) | 6 (4.8) | 8 (10.9) | 4 (11.1) | 0.05 *; 0.03 **; 0.301 |
ARBs, n (%) | 21 (16.8) | 21 (28.8) | 10 (27.7) | 0.001 *; 0.001 **; 0.289 |
NG n (125) | PDNMU n (73) | PDMU n (36) | p Value | |
---|---|---|---|---|
Baseline miRs’ expression | ||||
miR-24, A.U. | 182.15 ± 57.86 | 1120,04 ± 206.64 | 458,97 ± 167.74 | <0.05 *,**,*** |
miR-27, A.U. | 0.91 ± 0.04 | 2.06 ± 0.21 | 1.54 ± 0.30 | <0.05 *,**,*** |
miR-100, A.U. | 0.77 ± 0.04 | 1.76 ± 0.22 | 0.80 ± 0.12 | <0.05 *,*** |
miR-126, A.U. | 45.64 ± 23.49 | 108.65 ± 42.71 | 134.22 ± 70.58 | >0.05 |
miR-133, A.U. | 10.82 ± 1.44 | 14.96 ± 2.22 | 9.14 ± 2.16 | >0.05 |
miRs’ expression at 2 years of follow up | ||||
miR-24, A.U. | 11.21 ± 6.36 | 98.25 ± 21.08 | 51.24 ± 17.88 | <0.05 *,**,*** |
miR-27, A.U. | 0.13 ± 0.02 | 0.95 ± 0.10 | 0.58 ± 0.09 | <0.05 *,**,*** |
miR-100, A.U. | 0.028 ± 0.0004 | 0.089 ± 0.006 | 0.059 ± 0.001 | <0.05 *,**,*** |
miR-126, A.U. | 2.79 ± 1.98 | 29.55 ± 5.89 | 10.43 ± 5.84 | <0.05 *,**,*** |
miR-133, A.U. | 0.30 ± 0.06 | 1.74 ± 0.28 | 0.94 ± 0.28 | <0.05 *,**,*** |
Inflammatory markers at baseline | ||||
CRP (mmol/L) | 0.82 ± 0.31 | 1.13± 0.49 | 1.10 ± 0.46 | <0.05 *,** |
IL6 (pg/mL) | 3.49 ± 0.38 | 4.41 ± 0.52 | 4.36 ± 0.43 | <0.05 *,** |
TNFα (pg/mL) | 5.56 ± 0.92 | 6.96 ± 0.56 | 6.92 ± 0.54 | <0.05 *,** |
Inflammatory markers at 2 years of follow up | ||||
CRP (mmol/L) | 0.41 ± 0.10 | 0.92 ± 0.22 | 0.73± 0.28 | <0.05 *,**,*** |
IL6 (pg/mL) | 3.10 ± 0.31 | 4.19 ± 0.22 | 3.52 ± 0.31 | <0.05 *, **,*** |
TNFα (pg/mL) | 4.72 ± 0.71 | 6.52 ± 0.49 | 5.54 ± 0.38 | <0.05 *,**,*** |
Number of MACE, n (%) | 8 (6.4) | 27 (36.9%) | 6 (16.6) | <0.05 *,**,*** |
Risk Factors | HR | CI 95% | p Value | HR | CI 95% | p Value |
---|---|---|---|---|---|---|
Age | 0.939 | 0.876–1.006 | 0.075 | 0.970 | 0.930–1.013 | 0.169 |
BMI | 0.970 | 0.926–1.261 | 0.327 | 1.070 | 0.809–1.414 | 0.637 |
Hypertension | 1.188 | 0.643–2.196 | 0.582 | 0.620 | 0.176–2.187 | 0.457 |
Dyslipidemia | 1.707 | 0.921–3.163 | 0.089 | 1.425 | 0.560–3.629 | 0.457 |
Metformin therapy | 0.185 | 0.085–0.401 | 0.001 | 0.386 | 0.053–2.823 | 0.348 |
Glucose blood values | 1.014 | 1.009–1.020 | 0.001 | 1.020 | 1.001–1.038 | 0.029 * |
Cholesterol blood values | 1.012 | 1.004–1.019 | 0.002 | 1.013 | 0.999–1.027 | 0.074 |
ACEi | 1.325 | 0.650–2.702 | 0.439 | 0.583 | 0.159–2.137 | 0.416 |
Statins | 0.883 | 0.450–1.730 | 0.716 | 0.501 | 0.166–1.503 | 0.217 |
Pre-diabetes | 3.003 | 1.531–5.869 | 0.001 | 1.021 | 0.688–1.201 | 0.195 |
Atheromatous carotid plaque | 6.388 | 2.949–13.838 | 0.001 | 5.373 | 1.251–11.079 | 0.024 * |
IL 6 | 6.246 | 3.195–12.210 | 0.001 | 1.283 | 0.020–4.003 | 0.350 |
miR-24 | 5.001 | 1.781–6.122 | 0.001 | 3.842 | 1.768–19.222 | 0.011 * |
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Sardu, C.; Modugno, P.; Castellano, G.; Scisciola, L.; Barbieri, M.; Petrella, L.; Fanelli, M.; Macchia, G.; Caradonna, E.; Massetti, M.; et al. Atherosclerotic Plaque Fissuration and Clinical Outcomes in Pre-Diabetics vs. Normoglycemics Patients Affected by Asymptomatic Significant Carotid Artery Stenosis at 2 Years of Follow-Up: Role of microRNAs Modulation: The ATIMIR Study. Biomedicines 2021, 9, 401. https://doi.org/10.3390/biomedicines9040401
Sardu C, Modugno P, Castellano G, Scisciola L, Barbieri M, Petrella L, Fanelli M, Macchia G, Caradonna E, Massetti M, et al. Atherosclerotic Plaque Fissuration and Clinical Outcomes in Pre-Diabetics vs. Normoglycemics Patients Affected by Asymptomatic Significant Carotid Artery Stenosis at 2 Years of Follow-Up: Role of microRNAs Modulation: The ATIMIR Study. Biomedicines. 2021; 9(4):401. https://doi.org/10.3390/biomedicines9040401
Chicago/Turabian StyleSardu, Celestino, Pietro Modugno, Gaetano Castellano, Lucia Scisciola, Michelangela Barbieri, Lella Petrella, Mara Fanelli, Gabriella Macchia, Eugenio Caradonna, Massimo Massetti, and et al. 2021. "Atherosclerotic Plaque Fissuration and Clinical Outcomes in Pre-Diabetics vs. Normoglycemics Patients Affected by Asymptomatic Significant Carotid Artery Stenosis at 2 Years of Follow-Up: Role of microRNAs Modulation: The ATIMIR Study" Biomedicines 9, no. 4: 401. https://doi.org/10.3390/biomedicines9040401