Circulating miR-208b and miR-34a Are Associated with Left Ventricular Remodeling after Acute Myocardial Infarction
Abstract
:1. Introduction
2. Results
2.1. Baseline Clinical Characteristics of the Study Population
2.2. Circulating miRNA Levels Reflect LV Remodeling after AMI
2.3. Circulating miRNAs as Potential Predictors of LV Remodeling after AMI
2.4. Prognostic Value of Circulating miRNAs after AMI
2.5. Reclassification Analyses for the Circulating miRNAs in Predicting LV Remodeling after AMI
3. Discussion
4. Experimental Section
4.1. Participants
4.2. Plasma Collection and Storage
4.3. RNA Preparation
4.4. MiRNA Determination
4.5. Statistical Analysis
4.6. Ethics Statement
5. Conclusions
Acknowledgments
Conflicts of Interest
- Author ContributionsConceived and designed the experiments: Fucheng He. Performed the experiments: Pin Lv, Mingxia Zhou, Jing He. Analyzed the data: Pin Lv, Weiwei Meng, Xuehan Ma. Contributed reagents/materials/analysis tools: Shuling Dong, Xianchun Meng, Xi Wang. Wrote the paper: Pin Lv, Xue Zhao.
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Characteristics | Total patients (n = 359) | Remodeling (n = 116) | Non-remodeling (n = 243) | p1 | Experienced endpoint (n = 83) | No endpoint (n = 276) | p2 |
---|---|---|---|---|---|---|---|
Age (years) | 58 ± 14 | 59 ± 12 | 57 ± 15 | 0.587 | 57 ± 11 | 58 ± 14 | 0.805 |
Male/female (n/n) | 301/58 | 97/19 | 204/39 | 0.937 | 75/8 | 226/50 | 0.066 |
Current smoking, n (%) | 190 (53%) | 64 (55%) | 124 (51%) | 0.462 | 44 (53%) | 146 (53%) | 0.986 |
Diabetes mellitus, n (%) | 57 (16%) | 22 (19%) | 35 (14%) | 0.269 | 15 (18%) | 42 (15%) | 0.533 |
Hypertension, n (%) | 172 (48%) | 60 (52%) | 109 (45%) | 0.223 | 33 (40%) | 139 (50%) | 0.090 |
Hyperlipidaemia, n (%) | 126 (35%) | 44 (38%) | 78 (32%) | 0.275 | 32 (38%) | 94 (34%) | 0.452 |
SBP (mmHg) | 123 ± 21 | 127 ± 25 | 120 ± 16 | 0.155 | 122 ± 28 | 124 ± 18 | 0.824 |
DBP (mmHg) | 76 ± 12 | 77 ± 9 | 74 ± 12 | 0.949 | 74 ± 15 | 77 ± 12 | 0.360 |
TC (mmol/L) | 3.99 ± 1.07 | 3.80 ± 0.94 | 4.16 ± 1.15 | 0.112 | 3.73 ± 1.15 | 4.07 ± 1.04 | 0.199 |
TG (mmol/L) | 1.55 ± 0.91 | 1.61 ± 0.98 | 1.50 ± 0.85 | 0.564 | 1.58 ± 1.01 | 1.54 ± 0.89 | 0.859 |
HDL (mmol/L) | 1.03 ± 0.30 | 1.00 ± 0.26 | 1.07 ± 0.32 | 0.289 | 0.95 ± 0.24 | 1.07 ± 0.31 | 0.125 |
LDL (mmol/L) | 2.41 ± 0.82 | 2.23 ± 0.57 | 2.43 ± 0.97 | 0.093 | 2.15 ± 0.70 | 2.49 ± 0.84 | 0.089 |
AMI onset to sample (h; median(range)) | 6 (2–10) | 6 (2–10) | 6 (2–10) | 0.473 | 6 (3–10) | 6 (2–10) | 0.293 |
discharge to follow up (days; median(range)) | 176 (121–226) | 170 (121–214) | 182 (133–226) | 0.248 | 179 (134–214) | 172 (121–226) | 0.322 |
Serum biomarkers during admission (median(IQR)) | |||||||
Peak CK (U/L) | 1536 (239,6839) | 1474 (191,5805) | 1609 (286,7017) | 0.119 | 1616 (253,6378) | 1390 (193,7082) | 0.094 |
Cardiac troponin T (ng/mL) | 12.33 (0.088,53.32) | 15.65 (0.35,58.44) | 10.65 (0.004,47.21) | 0.015 | 13.13 (0.54,63.46) | 12.07 (0.005,49.57) | 0.075 |
Nt-pro-BNP (pg/mL) | 350 (145,807) | 507 (212,1057) | 279 (81,733) | 0.003 | 567 (253,1189) | 233 (116,773) | 0.001 |
Medications, n (%) | |||||||
Beta-blockers | 305 (85%) | 100 (86%) | 205 (84%) | 0.674 | 67 (81%) | 238 (86%) | 0.218 |
Calcium antagonists | 118 (33%) | 44 (38%) | 74 (30%) | 0.158 | 33 (40%) | 85 (31%) | 0.128 |
ACEI/ARB | 219 (61%) | 66 (57%) | 153 (63%) | 0.270 | 44 (53%) | 175 (63%) | 0.089 |
Statins | 352 (98%) | 114 (98%) | 238 (98%) | 0.831 a | 83 (100%) | 269 (97%) | 0.143 a |
Anti-platelet therapy | 359 (100%) | 116 (100%) | 243 (100%) | 1.000 | 83 (100%) | 276 (100%) | 1.000 |
Diuretic | 126 (35%) | 47 (41%) | 79 (33%) | 0.137 | 35 (42%) | 91 (33%) | 0.124 |
Treatment, n (%) | |||||||
CAG | 291 (81%) | 93 (80%) | 198 (81%) | 0.767 | 68 (82%) | 223 (81%) | 0.818 |
Thrombolysis | 183 (51%) | 60 (52%) | 123 (51%) | 0.844 | 41 (49%) | 142 (51%) | 0.743 |
PCI | 244 (68%) | 74 (64%) | 170 (70%) | 0.242 | 55 (66%) | 189 (68%) | 0.705 |
Pre-discharge echo (median(IQR)) | |||||||
LVEDV (mL) | 108 (97,119) | 108 (89,119) | 108 (103,119) | 0.595 | 106 (89,121) | 109 (98,119) | 0.334 |
LVESV (mL) | 47 (37,54) | 48 (37,56) | 47 (38,53) | 0.489 | 45 (37,54) | 47 (38,54) | 0.772 |
LVEF (%) | 60 (56,64) | 60 (56,64) | 60 (56,63) | 0.412 | 60 (56,66) | 60 (56,63) | 0.394 |
Follow-up echo (median(IQR)) | |||||||
LVEDV (mL) | 120 (102,131) | 124 (110,132) | 112 (100,122) | 0.034 | 121 (104,132) | 120 (102,130) | 0.850 |
LVESV (mL) | 49 (41,55) | 48 (38,55) | 49 (45,55) | 0.427 | 51 (44,57) | 48 (39,55) | 0.366 |
LVEF (%) | 55 (49,61) | 51 (47,58) | 59 (55,63) | 0.027 | 54 (48,62) | 56 (52,60) | 0.575 |
Change between discharge and follow-up (median(IQR)) | |||||||
ΔLVEDV (mL) | 10 (2,18) | 18 (14,24) | 3 (−4,5) | 0.000 | 17 (13,26) | 5 (−3,15) | 0.000 |
ΔLVESV (mL) | 2 (−1,4) | 4 (1,6) | 1 (−2,4) | 0.005 | 4 (2,7) | 2 (−1,4) | 0.022 |
ΔLVEF (%) | −6 (−8,2) | −9 (−13,2) | 1 (−4,4) | 0.000 | −6 (−11,2) | −1 (−3,3) | 0.003 |
MiRNAs | ΔCt/ΔΔCt | Remodeling (n = 116) | Non-remodeling (n = 243) | p1 | Experienced endpoint (n = 83) | No endpoint (n = 276) | p2 |
---|---|---|---|---|---|---|---|
miR-208b | ΔCt | 2.86 ± 1.30 | 4.04 ± 1.61 | 0.000 | 2.47 ± 1.48 | 3.50 ± 1.39 | 0.004 |
ΔΔCt | −1.94 ± 1.27 | 0 | −1.35 ± 1.48 | 0 | |||
miR-34a | ΔCt | 3.06 ± 1.12 | 4.06 ± 1.59 | 0.001 | 2.93 ± 1.63 | 3.77 ± 1.54 | 0.035 |
ΔΔCt | −1.32 ± 1.12 | 0 | −0.94 ± 1.63 | 0 |
Model a without miR-208b | Model a with miR-208b | Reclassification | ||||||
---|---|---|---|---|---|---|---|---|
Predicted risk | <10% | 10%–30% | >30% | Total | Increased risk, n (%) | Decreased risk, n (%) | NRI b | p |
Patients with remodeling (n = 116) | ||||||||
<10% | 27 | 9 | 5 | 41 | ||||
10%–30% | 4 | 35 | 4 | 43 | ||||
>30% | 0 | 3 | 29 | 32 | ||||
Total | 31 | 47 | 38 | 116 | 18 (15.5) | 7 (6.0) | ||
Patients without remodeling (n = 243) | ||||||||
<10% | 98 | 3 | 2 | 103 | ||||
10%–30% | 5 | 99 | 3 | 107 | ||||
>30% | 0 | 3 | 30 | 33 | ||||
Total | 103 | 105 | 35 | 243 | 8 (3.3) | 8 (3.3) | ||
NRI b | 0.095 | 0.039 |
Model a without miR-34a | Model a with miR-34a | Reclassification | ||||||
---|---|---|---|---|---|---|---|---|
Predicted risk | <10% | 10%–30% | >30% | Total | Increased risk, n (%) | Decreased risk, n (%) | NRI b | p |
Patients with remodeling (n = 116) | ||||||||
<10% | 26 | 7 | 3 | 36 | ||||
10%–30% | 5 | 35 | 7 | 47 | ||||
>30% | 0 | 4 | 29 | 33 | ||||
Total | 31 | 46 | 39 | 116 | 17 (14.7) | 9 (7.8) | ||
Patients without remodeling (n = 243) | ||||||||
<10% | 93 | 4 | 3 | 100 | ||||
10%–30% | 4 | 97 | 5 | 106 | ||||
>30% | 0 | 7 | 30 | 37 | ||||
Total | 97 | 108 | 38 | 243 | 12 (4.9) | 11 (4.5) | ||
NRI b | 0.065 | 0.177 |
Model a without miR-208b and miR-34a | Model a with miR-208b and miR-34a | Reclassification | ||||||
---|---|---|---|---|---|---|---|---|
Predicted risk | <10% | 10%–30% | >30% | Total | Increased risk, n (%) | Decreased risk, n (%) | NRI b | p |
Patients with remodeling (n = 116) | ||||||||
<10% | 25 | 11 | 3 | 39 | ||||
10%–30% | 4 | 35 | 8 | 47 | ||||
>30% | 0 | 4 | 26 | 30 | ||||
Total | 29 | 50 | 37 | 116 | 22 (19.0) | 8 (6.9) | ||
Patients without remodeling (n = 243) | ||||||||
<10% | 89 | 6 | 3 | 98 | ||||
10%–30% | 8 | 95 | 6 | 109 | ||||
>30% | 0 | 6 | 30 | 36 | ||||
Total | 97 | 107 | 39 | 243 | 15 (6.2) | 14 (5.8) | ||
NRI b | 0.117 | 0.025 |
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Lv, P.; Zhou, M.; He, J.; Meng, W.; Ma, X.; Dong, S.; Meng, X.; Zhao, X.; Wang, X.; He, F. Circulating miR-208b and miR-34a Are Associated with Left Ventricular Remodeling after Acute Myocardial Infarction. Int. J. Mol. Sci. 2014, 15, 5774-5788. https://doi.org/10.3390/ijms15045774
Lv P, Zhou M, He J, Meng W, Ma X, Dong S, Meng X, Zhao X, Wang X, He F. Circulating miR-208b and miR-34a Are Associated with Left Ventricular Remodeling after Acute Myocardial Infarction. International Journal of Molecular Sciences. 2014; 15(4):5774-5788. https://doi.org/10.3390/ijms15045774
Chicago/Turabian StyleLv, Pin, Mingxia Zhou, Jing He, Weiwei Meng, Xuehan Ma, Shuling Dong, Xianchun Meng, Xue Zhao, Xi Wang, and Fucheng He. 2014. "Circulating miR-208b and miR-34a Are Associated with Left Ventricular Remodeling after Acute Myocardial Infarction" International Journal of Molecular Sciences 15, no. 4: 5774-5788. https://doi.org/10.3390/ijms15045774