Evaluation of Vascular Endothelial Function in Young and Middle-Aged Women with Respect to a History of Pregnancy, Pregnancy-Related Complications, Classical Cardiovascular Risk Factors, and Epigenetics
Abstract
:1. Introduction
2. Results
2.1. Impact of A History of Pregnancy and Pregnancy-Related Complications on vascular Endothelial Function in Young and Middle-Aged Women
2.2. Impact of Classical Cardiovascular Risk Factors on Vascular Endothelial Function in Young and Middle-Aged Women
2.3. Association between Higher Expression Rates of miR-1–3p, miR-23a-3p, and miR-499a-5p in Whole Peripheral Blood and the Occurrence of Vascular Endothelial Dysfunction in Young and Middle-Aged Women
3. Discussion
4. Materials and Methods
4.1. Participants
4.2. Assessment of Vascular Endothelial Function
4.3. Blood Pressure Measurements
4.4. BMI and Waist Circumference Measurements
4.5. Biological Sampling
4.6. Gene Expression of Cardiovascular/Cerebrovascular diseAse Associated microRNAs in Whole Peripheral Blood
4.7. Statistical Analysis
5. Conclusions
6. Patent
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
RHI | Reactive Hyperemia Index |
BMI | Body Mass Index |
FPR | False Positive Rate |
GH | Gestational Hypertension |
PE | Preeclampsia |
FGR | Fetal Growth Restriction |
w/o | without |
w | with |
HELLP | Hemolysis, Elevated Liver Enzymes, Low Platelet Count |
WC | Waist Circumference |
SBP | Systolic Blood Pressure |
DBP | Diastolic Blood Pressure |
HDL | High-density Lipoprotein |
LDL | Low-density Lipoprotein |
Lp(a) | Lipoprotein A |
CRP | C-reactive Protein) |
FDA | Food and Drug Administration |
SE | Standard Error |
ANOVA | Analysis of Variance |
ANCOVA | Analysis of Covariance |
NTP | Normotensive Term Pregnancies |
CI | Confidence Interval |
OR | Odds Ratio |
LDH | Lactate Dehydrogenase |
AST | Aspartate Aminotransferase |
ALT | Alanine Aminotransferase |
AUC | Area under the Receive Operating Characteristic Curve |
EFW | Estimated Fetal Weight |
CS | Caesarean Section |
PAT | Peripheral Arterial Tonometry |
EDTA | Ethylenediaminetetraacetic Acid |
LR + | Positive Likelihood Ratio |
LR- | Negative Likelihood Ratio |
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Endothelial Function (RHI) Mean (SE) | p Value | ||
---|---|---|---|
On blood pressure treatment [no (n = 253) vs. yes (n = 11)] | Unadjusted data | 2.046 (0.041) vs. 1.916 (0.195) | p = 0.516 |
Adjusted data | 2.046 (0.041) vs. 1.921 (0.195) | p = 0.531 | |
Trombophilic gene mutations [no (n = 246) vs. yes (n = 18)] | Unadjusted data | 2.042 (0.041) vs. 2.027 (0.153) | p = 0.924 |
Adjusted data | 2.041 (0.041) vs. 2.036 (0.153) | p = 0.974 | |
Current smoking of cigarettes [non-smokers + ex-smokers (n = 228) vs. smokers (n = 36)] | Unadjusted data | 2.028 (0.043) vs. 2.119 (0.108) | p = 0.435 |
Adjusted data | 2.029 (0.043) vs. 2.113 (0.108) | p = 0.476 | |
BMI [normal (n = 156) vs. abnormal (n = 108)] (<25 vs. ≥25) | Unadjusted data | 2.101 (0.052) vs. 1.953 (0.062) | p = 0.068 |
Adjusted data | 2.099 (0.052) vs. 1.957 (0.062) | p = 0.082 | |
BMI [normal (n = 156) vs. overweight (n = 68) vs. obese (n = 40)] (<25 vs. ≥ 25–29.9 vs. ≥30) | Unadjusted data | 2.101 (0.051) vs. 1.866 (0.078) vs. 2.102 (0.101) | Normal BMI vs. overweight p = 0.036 ↓ RHI in overweight women Normal BMI vs. obese p = 1.0 |
Adjusted data | 2.099 (0.051) vs. 1.865 (0.078) vs. 2.117 (0.102) | Normal BMI vs. overweight p = 0.039 ↓ RHI in overweight women Normal BMI vs. obese p = 1.0 | |
Waist circumference [normal (n = 146) vs. abnormal (n = 118)] (<80 cm vs. ≥ 80 cm) | Unadjusted data | 2.138 (0.053) vs. 1.920 (0.059) | p = 0.006 ↓ RHI in women with waist circumference ≥ 80 cm |
Adjusted data | 2.135 (0.053) vs. 1.924 (0.059) | p = 0.008 ↓ RHI in women with waist circumference ≥ 80 cm | |
SBP [normal (n = 241) vs. abnormal (n = 23)] (<140 mmHg vs. ≥ 140 mmHg) | Unadjusted data | 2.033 (0.042) vs. 2.123 (0.135) | p = 0.526 |
Adjusted data | 2.032 (0.042) vs. 2.134 (0.135) | p = 0.471 | |
SBP [normal (n = 138) vs. prehypertension (n = 103) vs. hypertension (n = 23)] (<120 mmHg vs. ≥120–139 mmHg vs. ≥ 140 mmHg) | Unadjusted data | 2.030 (0.055) vs. 2.037 (0.064) vs. 2.123 (0.135) | Normal SBP vs. prehypertension p = 1.0 Normal SBP vs. hypertension p = 1.0 |
Adjusted data | 2.029 (0.055) vs. 2.035 (0.064) vs. 2.134 (0.136) | Normal SBP vs. prehypertension p = 1.0 Normal SBP vs. hypertension p = 1.0 | |
DBP [normal (n = 229) vs. abnormal (n = 35)] (< 90 mmHg vs. ≥ 90 mmHg) | Unadjusted data | 2.035 (0.043) vs. 2.077 (0.110) | p = 0.721 |
Adjusted data | 2.034 (0.043) vs. 2.083 (0.110) | p = 0.678 | |
DBP [normal (n = 172) vs. prehypertension (n = 57) vs. hypertension (n = 35)] (< 80 mmHg vs. ≥80–89 mmHg vs. ≥ 90 mmHg) | Unadjusted data | 2.019 (0.050) vs. 2.084 (0.086) vs. 2.077 (0.110) | Normal DBP vs. prehypertension p = 1.0 Normal DBP vs. hypertension p = 1.0 |
Adjusted data | 2.020 (0.050) vs. 2.076 (0.086) vs. 2.083 (0.110) | Normal DBP vs. prehypertension p = 1.0 Normal DBP vs. hypertension p = 1.0 | |
Serum total cholesterol [normal (n = 125) vs. abnormal (n = 139)] (≤ 5 mmol/L vs. > 5 mmol/L) | Unadjusted data | 2.004 (0.058) vs. 2.074 (0.055) | p = 0.386 |
Adjusted data | 1.999 (0.058) vs. 2.078 (0.055) | p = 0.329 | |
Serum HDL cholesterol [normal (n = 230) vs. abnormal (n = 34)] (≥ 1.2 mmol/L vs. <1.2 mmol/L) | Unadjusted data | 2.046 (0.043) vs. 2.002 (0.111) | p = 0.710 |
Adjusted data | 2.046 (0.043) vs. 2.006 (0.111) | p = 0.741 | |
Serum LDL cholesterol [normal (n = 100) vs. abnormal (n = 164)] (≤ 3 mmol/L vs. > 3 mmol/L) | Unadjusted data | 1.983 (0.065) vs. 2.074 (0.051) | p = 0.267 |
Adjusted data | 1.976 (0.065) vs. 2.079 (0.051) | p = 0.217 | |
Serum triglycerides [normal (n = 248) vs. abnormal (n = 16)] (≤ 1.7 mmol/L vs. > 1.7 mmol/L) | Unadjusted data | 2.039 (0.041) vs. 2.075 (0.162) | p = 0.827 |
Adjusted data | 2.038 (0.041) vs. 2.083 (0.162) | p = 0.786 | |
Serum Lp(a) [normal (n = 212) vs. abnormal (n = 52)] (≤ 72.0 nmol/L vs. > 72.0 nmol/L) | Unadjusted data | 2.032 (0.045) vs. 2.076 (0.090) | p = 0.665 |
Adjusted data | 2.031 (0.045) vs. 2.082 (0.090) | p = 0.609 | |
Serum CRP [normal (n = 223) vs. abnormal (n = 41)] (≤ 5 mg/L vs. > 5 mg/L) | Unadjusted data | 2.032 (0.043) vs. 2.089 (0.101) | p = 0.608 |
Adjusted data | 2.032 (0.043) vs. 2.088 (0.101) | p = 0.613 | |
Plasma homocysteine [normal (n = 229) vs. abnormal (n = 35)] (≤ 13.6 μmol/L vs. > 13.6 μmol/L) | Unadjusted data | 2.054 (0.043) vs. 1.954 (0.109) | p = 0.397 |
Adjusted data | 2.054 (0.043) vs. 1.954 (0.109) | p = 0.394 | |
Serum uric acid [normal (n = 233) vs. abnormal (n = 31)] (≤339 μmol/L vs. > 339 μmol/L) | Unadjusted data | 2.064 (0.042) vs. 1.870 (0.116) | p = 0.117 |
Adjusted data | 2.063 (0.042) vs. 1.877 (0.116) | p = 0.134 | |
Current hormonal contraceptive use [non-users + ex-users (n = 194) vs. users (n = 70)] | Unadjusted data | 2.038 (0.047) vs. 2.049 (0.077) | p = 0.901 |
Adjusted data | 2.041 (0.047) vs. 2.041 (0.078) | p = 0.991 | |
Total number of pregnancies per patient [1 (n = 61) vs. 2 (n = 115) vs. 3+ (n = 88)] | Unadjusted data | 2.050 (0.083) vs. 2.117 (0.061) vs. 1.935 (0.069) | 1 pregnancy vs. 2 pregnancies p = 1.0 1 pregnancy vs. 3+ pregnancies p = 0.857 |
Adjusted data | 2.044 (0.083) 2.114 (0.061) vs. 1.943 (0.071) | 1 pregnancy vs. 2 pregnancies p = 1.0 1 pregnancy vs. 3+ pregnancies p = 1.0 | |
Total parity per patient [1 (n = 77) vs. 2 (n = 150) vs. 3+ (n = 37)] | Unadjusted data | 2.038 (0.074) vs. 2.071 (0.053) vs. 1.927 (0.107) | 1 child vs. 2 children p = 1.0 1 child vs. 3+ children p = 1.0 |
Adjusted data | 2.038 (0.074) vs. 2.066 (0.053) vs. 1.943 (0.109) | 1 child vs. 2 children p = 1.0 1 child vs. 3+ children p = 1.0 | |
Infertility treatment [no (n = 226) vs. yes (n = 38)] | Unadjusted data | 2.021 (0.043) vs. 2.161 (0.105) | p = 0.216 |
Adjusted data | 2.017 (0.043) vs. 2.183 (0.106) | p = 0.149 |
Prevalence of Vascular Endothelial Dysfunction | Group 1 (%) | Group 2 (%) | p Value | OR (95% CI) |
---|---|---|---|---|
On blood pressure treatment [no (n = 253) vs. yes (n = 11)] | 83 (32.81%) | 3 (27.27%) | 0.702 | 0.768 (0.199–2.971) |
Trombophilic gene mutations [no (n = 246) vs. yes (n = 18)] | 80 (32.52%) | 6 (33.33%) | 0.943 | 1.038 (0.376–2.865) |
Current smoking of cigarettes [non-smokers + ex-smokers (n = 228) vs. smokers (n = 36)] | 78 (34.21%) | 8 (22.22%) | 0.158 | 0.550 (0.239–1.263) |
BMI [normal (n = 156) vs. abnormal (n = 108)] (<25 vs. ≥25) | 48 (30.77%) | 38 (35.19%) | 0.452 | 1.221 (0.725–2.057) |
BMI | ||||
[normal (n = 156) vs. overweight (n = 68)] (<25 vs. ≥25–29.9) | 48 (30.77%) | 29 (42.65%) | 0.087 | 1.673 (0.929–3.014) |
[normal (n = 156) vs. obese (n = 40)] (<25 vs. ≥30) | 48 (30.77%) | 9 (22.50%) | 0.307 | 0.653 (0.289–1.478) |
Waist circumference [normal (n = 146) vs. abnormal (n = 118)] (<80 cm vs. ≥ 80 cm) | 41 (28.08%) | 45 (38.14%) | 0.084 | 1.579 (0.941–2.650) |
SBP [normal (n = 241) vs. abnormal (n = 23)] (<140 mmHg vs. ≥140 mmHg) | 82 (34.02%) | 4 (17.39%) | 0.114 | 0.408 (0.134–1.240) |
SBP | ||||
[normal (n = 138) vs. prehypertension (n = 103)] (<120 mmHg vs. ≥120–139 mmHg) | 49 (35.51%) | 33 (32.04%) | 0.574 | 0.856 (0.498–1.471) |
[normal (n = 138) vs. hypertension (n = 23)] (<120 mmHg vs. ≥140 mmHg) | 49 (35.51%) | 4 (17.39%) | 0.096 | 0.382 (0.123–1.188) |
DBP [normal (n = 229) vs. abnormal (n = 35)] (<90 mmHg vs. ≥90 mmHg) | 79 (34.50%) | 7 (20.0%) | 0.094 | 0.475 (0.199–1.135) |
DBP | ||||
[normal (n = 172) vs. prehypertension (n = 57)] (<80 mmHg vs. ≥80–89 mmHg) | 62 (36.05%) | 17 (29.82%) | 0.393 | 0.754 (0.395–1.440) |
[normal (n = 172) vs. hypertension (n = 35)] (<80 mmHg vs. ≥90 mmHg) | 62 (36.05%) | 7 (20.00%) | 0.072 | 0.444 (0.183–1.075) |
Serum total cholesterol [normal (n = 125) vs. abnormal (n = 139)] (≤5 mmol/L vs. >5 mmol/L) | 39 (31.30%) | 47 (33.81%) | 0.651 | 1.127 (0.672–1.888) |
Serum HDL cholesterol [normal (n = 230) vs. abnormal (n = 34)] (≥1.2 mmol/L vs. <1.2 mmol/L) | 75 (32.61%) | 11 (32.35) | 0.976 | 0.988 (0.458–2.134) |
Serum LDL cholesterol [normal (n = 100) vs. abnormal (n = 164)] (≤3 mmol/L vs. >3 mmol/L) | 32 (32.0%) | 54 (32.91%) | 0.808 | 1.068 (0.628–1.817) |
Serum triglycerides [normal (n = 248) vs. abnormal (n = 16)] (≤1.7 mmol/L vs. >1.7 mmol/L) | 81 (32.66%) | 5 (31.25%) | 0.907 | 0.937 (0.315–2.787) |
Serum Lp(a) [normal (n = 212) vs. abnormal (n = 52)] (≤72.0 nmol/L vs. >72.0 nmol/L) | 71 (33.49%) | 15 (28.85%) | 0.522 | 0.805 (0.414–1.564) |
Serum CRP [normal (n = 223) vs. abnormal (n = 41)] (≤5 mg/L vs. >5 mg/L) | 75 (33.63%) | 11 (26.83%) | 0.974 | 0.991 (0.586–1.678) |
Plasma homocysteine [normal (n = 229) vs. abnormal (n = 35)] (≤13.6 μmol/L vs. >13.6 μmol/L) | 72 (31.44%) | 14 (40.0%) | 0.316 | 1.454 (0.700–3.021) |
Serum uric acid [normal (n = 233) vs. abnormal (n = 31)] (≤339 μmol/L vs. >339 μmol/L) | 72 (30.90%) | 14 (45.16%) | 0.115 | 1.842 (0.861–3.938) |
Current hormonal contraceptive use [non-users + ex-users (n = 194) vs. users (n = 70)] | 64 (32.99%) | 22 (31.43%) | 0.811 | 0.931 (0.518–1.674) |
Total number of pregnancies per patient | ||||
[1 (n = 61) vs. 2 (n = 115)] | 17 (27.87%) | 32 (27.83%) | 0.995 | 0.998 (0.499–1.995) |
[1 (n = 61) vs. 3+ (n = 88)] | 17 (27.87%) | 37 (42.05%) | 0.078 | 1.878 (0.931–3.788) |
Total parity per patient | ||||
[1 (n = 77) vs. 2 (n = 150)] | 24 (31.17%) | 49 (32.67%) | 0.819 | 1.071 (0.593–1.934) |
[1 (n = 77) vs. 3+ (n = 37)] | 24 (31.17%) | 13 (35.14%) | 0.672 | 1.196 (0.522–2.742) |
Infertility treatment [no (n = 226) vs. yes (n = 38)] | 75 (33.19%) | 11 (28.95%) | 0.606 | 0.820 (0.386–1.743) |
RHI (Non-Normal Distribution) | Data Distribution | Pearson Correlation Coefficient, p Value | Spearman’s Coefficient of Rank Correlation (rho), p Value |
---|---|---|---|
age | Non-normal distribution | - | ρ = −0.046, p = 0.457 |
BMI | Non-normal distribution | - | ρ = −0.063, p = 0.307 |
Waist circumference | Non-normal distribution | - | ρ = −0.081, p = 0.188 |
SBP | Non-normal distribution | - | ρ = 0.079, p = 0.199 |
DBP | Non-normal distribution | - | ρ = 0.044, p = 0.478 |
Heart rate at rest | Non-normal distribution | - | ρ = 0.051, p = 0.407 |
Serum total cholesterol | Non-normal distribution | - | ρ = 0.015, p = 0.810 |
Serum HDL cholesterol | Non-normal distribution | - | ρ = −0.030, p = 0.631 |
Serum LDL cholesterol | Non-normal distribution | - | ρ = −0.002, p = 0.973 |
Serum triglycerides | Non-normal distribution | - | ρ = −0.008, p = 0.903 |
Serum Lp(a) | Non-normal distribution | - | ρ = −0.002, p = 0.981 |
Serum CRP | Non-normal distribution | - | ρ = 0.057, p = 0.357 |
Plasma homocysteine | Non-normal distribution | - | ρ = −0.020, p = 0.753 |
Serum uric acid | Normal distribution | r = −0.111, p = 0.072 | ρ = −0.111, p = 0.072 |
Time elapsed since the delivery | Non-normal distribution | - | ρ = 0.014, p = 0.816 |
Total number of pregnancies per patient | Non-normal distribution | - | ρ = −0.114, p = 0.064 |
Total parity per patient | Non-normal distribution | - | ρ = −0.037, p = 0.548 |
NTP (n = 74) | GH (n = 48) | PE (n = 114) | FGR (n = 28) | Diagnostic Groups (Normal vs. Diseased) | p Value (ANOVA, ANCOVA) | ||
RHI | Unadjusted data | 2.066 (0.075) | 1.907 (0.093) | 2.094 (0.060) | 1.989 (0.122) | NTP vs. GH | p = 1.0 |
NTP vs. PE | p = 1.0 | ||||||
NTP vs. FGR | p = 1.0 | ||||||
Adjusted data | 2.068 (0.075) A | 1.910 (0.093) A | 2.091 (0.060) A | 1.987 (0.122) A | NTP vs. GH | p = 1.0 | |
NTP vs. PE | p = 1.0 | ||||||
NTP vs. FGR | p = 1.0 | ||||||
NTP (n = 74) | PE w/o SF (n = 28) | PE w SF (n = 86) | DiagnosticGroups (Normal vs. Diseased) | p Value (ANOVA, ANCOVA) | |||
RHI | Unadjusted data | 2.066 (0.075) | 2.200 (0.121) | 2.059 (0.069) | NTP vs. PE w/o SF | p = 1.0 | |
NTP vs. PE w SF | p = 1.0 | ||||||
Adjusted data | 2.066 (0.075) A | 2.201 (0.122) A | 2.059 (0.069) A | NTP vs. PE w/o SF | p = 1.0 | ||
NTP vs. PE w SF | p = 1.0 | ||||||
NTP (n = 74) | Early PE (n = 40) | Late PE (n = 74) | DiagnosticGroups (Normal vs. Diseased) | p Value (ANOVA, ANCOVA) | |||
RHI | Unadjusted data | 2.066 (0.075) | 2.074 (0.102) | 2.104 (0.075) | NTP vs. early PE | p = 1.0 | |
NTP vs. late PE | p = 1.0 | ||||||
Adjusted data | 2.066 (0.075) A | 2.074 (0.102) A | 2.105 (0.075) A | NTP vs. early PE | p = 1.0 | ||
NTP vs. late PE | p = 1.0 | ||||||
NTP (n = 74) | PE w/o HELLP (n = 98) | PE w HELLP (n = 16) | DiagnosticGroups (Normal vs. Diseased) | p Value (ANOVA, ANCOVA) | |||
RHI | Unadjusted data | 2.066 (0.075) | 2.067 (0.065) | 2.256 (0.160) | NTP vs. PE w/o HELLP | p = 1.0 | |
NTP vs. PE w HELLP | p = 0.848 | ||||||
Adjusted data | 2.066 (0.075) A | 2.067 (0.065) A | 2.256 (0.161) A | NTP vs. PE w/o HELLP | p = 1.0 | ||
NTP vs. PE w HELLP | p = 0.852 | ||||||
NTP (n = 74) | PE w/o FGR (n = 98) | PE w FGR (n = 16) | DiagnosticGroups (Normal vs. Diseased) | p Value (ANOVA, ANCOVA) | |||
RHI | Unadjusted data | 2.066 (0.075) | 2.104 (0.065) | 2.029 (0.161) | NTP vs. PE w/o FGR | p = 1.0 | |
NTP vs. PE w FGR | p = 1.0 | ||||||
Adjusted data | 2.066 (0.075) A | 2.104 (0.065) A | 2.028 (0.162) A | NTP vs. PE w/o FGR | p = 1.0 | ||
NTP vs. PE w FGR | p = 1.0 | ||||||
NTP (n = 74) | Early FGR (n = 9) | Late FGR (n = 19) | DiagnosticGroups (Normal vs. Diseased) | p Value (ANOVA, ANCOVA) | |||
RHI | Unadjusted data | 2.066 (0.085) | 2.038 (0.243) | 1.965 (0.168) | NTP vs. early FGR | p = 1.0 | |
NTP vs. late FGR | p = 1.0 | ||||||
Adjusted data | 2.065 (0.085) A | 2.037 (0.245) A | 1.969 (0.169) A | NTP vs. early FGR | p = 1.0 | ||
NTP vs. late FGR | p = 1.0 |
Prevalence of Vascular Endothelial Dysfunction | Case, n (%) | NTP, n (%) | p Value | OR (95% CI) |
---|---|---|---|---|
Pregnancy-related complications irrespective of the severity of the disease | ||||
PE | 29 (25.44%) | 24 (32.43%) | 0.299 | 0.711 (0.373–1.353) |
GH | 18 (37.50%) | 24 (32.43%) | 0.565 | 1.250 (0.584–2.674) |
FGR | 15 (53.57%) | 24 (32.43%) | 0.053 | 2.404 (0.989–5.842) |
Women with a history of FGR with respect to the disease severity | ||||
Early FGR | 6 (66.67%) | 24 (32.43%) | 0.057 | 4.167 (0.959–18.102) |
Late FGR | 9 (47.37%) | 24 (32.43%) | 0.229 | 1.875 (0.674–5.219) |
Women with a history of PE with respect to the disease severity | ||||
PE w/o SF | 6 (21.43%) | 24 (32.43%) | 0.280 | 0.568 (0.204–1.585) |
PE w SF | 23 (26.74%) | 24 (32.43%) | 0.432 | 0.761 (0.385–1.504) |
Early PE | 13 (32.50%) | 24 (32.43%) | 0.994 | 1.003 (0.441–2.281) |
Late PE | 16 (21.62%) | 24 (32.43%) | 0.141 | 0.575 (0.275–1.201) |
PE w/o HELLP | 27 (27.55%) | 24 (32.43%) | 0.488 | 0.792 (0.410–1.530) |
PE w HELLP | 2 (12.50%) | 24 (32.43%) | 0.128 | 0.298 (0.063–1.416) |
PE w/o FGR | 24 (24.49%) | 24 (32.43%) | 0.251 | 0.676 (0.346–1.320) |
PE w FGR | 5 (31.25%) | 24 (32.43%) | 0.927 | 0.947 (0.296–3.032) |
microRNA | Normal Endothelial Function RHI > 1.67 (n = 178) Median (25th Percentile–75th Percentile) | Endothelial Dysfunction RHI ≤ 1.67 (n = 86) Median (25th Percentile–75th Percentile) | p Value |
---|---|---|---|
miR-1-3p | 4.170 (1.970–12.300) × 10−2 | 6.840 (3.780–13.000) × 10−2 | p = 0.008 |
miR-16-5p | 0.868 (0.625–1.249) | 0.933 (0.708–1.147) | p = 0.548 |
miR-17-5p | 1.044 (0.674–1.664) | 1.174 (0.820–1.669) | p = 0.421 |
miR-20a-5p | 1.085 (0.550–1.633) | 0.995 (0.549–1.521) | p = 0.672 |
miR-20b-5p | 1.051 (0.595–1.535) | 1.111 (0.564–1.592) | p = 0.677 |
miR-21-5p | 0.180 (0.101–0.293) | 0.200 (0.133–0.295) | p = 0.215 |
miR-23a-3p | 0.109 (0.051–0.200) | 0.123 (0.073–0.239) | p = 0.030 |
miR-24-3p | 0.204 (0.139–0.293) | 0.213 (0.148–0.298) | p = 0.726 |
miR-26a-5p | 0.346 (0.188–0.542) | 0.406 (0.248–0.536) | p = 0.163 |
miR-29a-3p | 0.187 (0.112–0.335) | 0.211 (0.119–0.388) | p = 0.460 |
miR-92a-3p | 1.759 (1.208–2.560) | 1.704 (1.144–2.589) | p = 0.759 |
miR-100-5p | 0.975 (0.554–1.880) × 10−3 | 1.000 (0.514–1.720) × 10−3 | p = 0.950 |
miR-103a-3p | 0.759 (0.397–1.294) | 0.944 (0.493–1.365) | p = 0.095 |
miR-125b-5p | 0.257 (0.121–0.447) × 10−2 | 0.254 (0.140–0.449) × 10−2 | p = 0.808 |
miR-126-3p | 0.178 (0.097–0.279) | 0.191 (0.115–0.279) | p = 0.442 |
miR-130b-3p | 0.345 (0.177–0.677) | 0.379 (0.251–0.698) | p = 0.301 |
miR-133a-3p | 7.440 (2.840–15.500) × 10−2 | 7.890 (3.870–18.600) × 10−2 | p = 0.221 |
miR-143-3p | 1.320 (0.614–2.920) × 10−2 | 1.430 (0.792–2.990) × 10−2 | p = 0.485 |
miR-145-5p | 7.450 (4.710–11.100) × 10−2 | 7.860 (4.630–12.000) × 10−2 | p = 0.758 |
miR-146a-5p | 0.844 (0.482–1.267) | 0.845 (0.490–1.240) | p = 0.997 |
miR-155-5p | 0.962 (0.680–1.448) | 1.129 (0.731–1.599) | p = 0.353 |
miR-181a-5p | 0.153 (0.086–0.245) | 0.161 (0.093–0.254) | p = 0.708 |
miR-195-5p | 3.240 (1.150–8.860) × 10−2 | 3.770 (1.360–9.730) × 10−2 | p = 0.600 |
miR-199a-5p | 2.420 (1.320–5.180) × 10−2 | 2.880 (1.510–5.890) × 10−2 | p = 0.223 |
miR-210-3p | 8.840 (5.680–14.300) × 10−2 | 9.150 (5.640–14.800) × 10−2 | p = 0.953 |
miR-221-3p | 0.353 (0.190–0.601) | 0.340 (0.212–0.550) | p = 0.675 |
miR-342-3p | 2.194 (1.409–3.206) | 2.296 (1.752–3.532) | p = 0.341 |
miR-499a-5p | 9.400 (3.160–17.000) × 10−2 | 14.600 (3.710–34.700) × 10−2 | p = 0.010 |
miR-574-3p | 0.108 (0.067–0.175) | 0.110 (0.081–0.175) | p = 0.375 |
microRNA | Data Distribution RHI (Non-Normal Distribution) | Spearman’s Coefficient of Rank Correlation (rho), p Value |
---|---|---|
miR-1-3p | Non-normal distribution | ρ = −0.156, p = 0.012 weak negative correlation (↓ RHI ≈ ↑ miR-1-3p) |
miR-16-5p | Non-normal distribution | ρ = −0.157, p = 0.361 |
miR-17-5p | Non-normal distribution | ρ = −0.083, p = 0.179 |
miR-20a-5p | Non-normal distribution | ρ = −0.034, p = 0.581 |
miR-20b-5p | Non-normal distribution | ρ = −0.060, p = 0.331 |
miR-21-5p | Non-normal distribution | ρ = −0.102, p = 0.102 |
miR-23a-3p | Non-normal distribution | ρ = −0.154, p = 0.013 weak negative correlation (↓ RHI ≈ ↑ miR-23a-3p) |
miR-24-3p | Non-normal distribution | ρ = −0.055, p = 0.381 |
miR-26a-5p | Non-normal distribution | ρ = −0.101, p = 0.103 |
miR-29a-3p | Non-normal distribution | ρ = −0.060, p = 0.332 |
miR-92a-3p | Non-normal distribution | ρ = 0.025, p = 0.692 |
miR-100-5p | Non-normal distribution | ρ = −0.002, p = 0.981 |
miR-103a-3p | Non-normal distribution | ρ = −0.086, p = 0.165 |
miR-125b-5p | Non-normal distribution | ρ = −0.001, p = 0.987 |
miR-126-3p | Non-normal distribution | ρ = −0.047, p = 0.453 |
miR-130b-3p | Non-normal distribution | ρ = −0.066, p = 0.291 |
miR-133a-3p | Non-normal distribution | ρ = −0.054, p = 0.385 |
miR-143-3p | Non-normal distribution | ρ = −0.104, p = 0.092 |
miR-145-5p | Non-normal distribution | ρ = −0.052, p = 0.402 |
miR-146a-5p | Non-normal distribution | ρ = −0.022, p = 0.727 |
miR-155-5p | Non-normal distribution | ρ = −0.006, p = 0.918 |
miR-181a-5p | Non-normal distribution | ρ = −0.051, p = 0.411 |
miR-195-5p | Non-normal distribution | ρ = −0.073, p = 0.239 |
miR-199a-5p | Non-normal distribution | ρ = −0.114, p = 0.065 |
miR-210-3p | Non-normal distribution | ρ = −0.042, p = 0.505 |
miR-221-3p | Non-normal distribution | ρ = −0.041, p = 0.512 |
miR-342-3p | Non-normal distribution | ρ = −0.035, p = 0.572 |
miR-499a-5p | Non-normal distribution | ρ = −0.193, p = 0.002 weak negative correlation (↓ RHI ≈ ↑ miR-499a-5p) |
miR-574-3p | Non-normal distribution | ρ = −0.102, p = 0.100 |
Normal Pregnancies (n = 74) | PE (n = 114) | FGR (n = 28) | GH (n = 48) | p-Value 1 | p-Value 2 | p-Value 3 | |
---|---|---|---|---|---|---|---|
At follow-up | |||||||
Age (years) Age (range) | 38.49 ± 0.40 31–50 | 38.05 ± 0.41 28–52 | 38.11 ± 0.65 32–45 | 38.67 ± 0.68 31–58 | 1.000 | 1.000 | 1.000 |
Time elapsed since delivery (years) | 5.74 ± 0.21 | 5.52 ± 0.21 | 5.25 ± 0.35 | 4.96 ± 0.31 | 1.000 | 1.000 | 0.259 |
Family medical history Angina or heart attack in a first degree relative before the age of 60 years | 1 (1.35%) | 2 (1.75%) | 0 (0%) | 1 (2.08%) | - | - | - |
Dispensarisation at Dpt. of Cardiology (valve problems and heart defects) | 0 (0%) | 1 (0.88%) Sinus tachycardia | 1 (3.45%) Leaky heart valve | 2 (4.17%) Mitral valve prolapse | - | - | - |
On blood pressure treatment | 1 (1.35%) | 7 (6.14%) | 0 (0%) | 3 (6.25%) | - | - | - |
Lipid-lowering medication | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | - | - | - |
DM type I | 0 (0%) | 1 (0.88%) | 0 (0%) | 1 (2.08%) | - | - | - |
DM type II | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | - | - | - |
Rheumatoid arthritis | 0 (0%) | 0 (0%) | 1 (3.45%) | 2 (4.17%) | - | - | - |
Chronic venous insufficiency | 0 (0%) | 0 (0%) | 0 (0%) | 1 (2.08%) | - | - | - |
Thrombosis | 1 (1.35%) | 2 (1.75%) | 1 (3.45%) | 0 (0%) | - | - | - |
Trombophilic gene mutations | 0 (0%) | 10 (8.77%) | 4 (14.29%) | 4 (8.33%) | - | - | - |
Presence of risk factors for chronic kidney disease | 0 (%) | 1 (0.88%) Haematuria | 0 (0%) | 2 (4.17%) Abnormal kidney structure (n = 1) Glomerulonephritis in childhood (n = 1) | - | - | - |
Chronic kidney disease | 0 (%) | 1 (0.88%) Nephrotic syndrome | 0 (0%) | 0 (0%) | - | - | - |
Smoking of cigarettes | |||||||
Non-Smoker | 46 (62.16%) | 70 (61.40%) | 22 (78.57%) | 31 (64.58%) | - | - | - |
Ex-smoker | 17 (22.97%) | 28 (24.56%) | 2 (7.14%) | 12 (25.0%) | - | - | - |
Smoker | 11 (14.86%) | 16 (14.04%) | 4 (14.29%) | 5 (10.42%) | - | - | - |
BMI | |||||||
Normal (<25) | 56 (75.68%) | 62 (54.39%) | 19 (67.86%) | 19 (39.58%) | - | - | - |
Overweight (≥25-<30) | 15 (20.27%) | 32 (28.07%) | 3 (10.71%) | 18 (37.50%) | - | - | - |
Obese (≥30) | 3 (4.05%) | 20 (17.54%) | 6 (21.43%) | 11 (22.92%) | - | - | - |
Waist circumference | |||||||
Normal (< 80cm) | 54 (72.97%) | 59 (51.75%) | 18 (64.29%) | 15 (31.25%) | - | - | - |
Central Obesity (≥80 cm) | 20 (27.03%) | 55 (48.25%) | 10 (35.71%) | 33 (68.75%) | - | - | - |
SBP | |||||||
Normal (<120 mmHg) | 56 (75.68%) | 48 (42.11%) | 17 (60.71%) | 17 (35.42%) | - | - | - |
Prehypertension (≥120–<140 mmHg) | 18 (24.32%) | 53 (46.49%) | 11 (39.29%) | 21 (43.75%) | - | - | - |
Hypertension (≥140 mmHg) | 0 (0%) | 13 (11.40%) | 0 (0%) | 10 (20.83%) | - | - | - |
DBP | |||||||
Normal (<80 mmHg) | 66 (89.19%) | 65 (57.01%) | 18 (64.29%) | 23 (47.92%) | - | - | - |
Prehypertension (≥80–<90 mmHg) | 6 (8.11%) | 30 (26.32%) | 7 (25.0%) | 14 (29.16%) | - | - | - |
Hypertension (≥90 mmHg) | 2 (2.70%) | 19 (16.67%) | 3 (10.71%) | 11 (22.92%) | - | - | - |
Heart rate at rest | |||||||
Bradycardia (< 60 bpm) | 7 (9.46%) | 6 (5.26%) | 3 (10.71%) | 4 (8.33%) | - | - | - |
Normal (60–100 bpm) | 66 (89.19%) | 108 (94.74%) | 25 (89.29%) | 42 (87.50%) | - | - | - |
Tachycardia (>100 bpm) | 1 (1.35%) | 0 (0%) | 0 (0%) | 2 (4.17%) | - | - | - |
Serum total cholesterol | |||||||
Normal (2.9–5.0 mmol/L) | 35 (47.30%) | 53 (46.49%) | 15 (53.57%) | 22 (45.83%) | - | - | - |
High (>5.0 mmol/L) | 39 (52.70%) | 61 (53.51%) | 13 (46.43%) | 26 (54.17%) | - | - | - |
Serum HDL cholesterol | |||||||
Normal (1.2–2.7 mmol/L) | 69 (93.24%) | 100 (87.72%) | 24 (85.71%) | 37 (77.08%) | - | - | - |
Low (<1.2 mmol/L) | 5 (6.76%) | 14 (12.28%) | 4 (14.29%) | 11 (22.92%) | - | - | - |
Serum LDL cholesterol | |||||||
Normal (1.2–3.0 mmol/L) | 35 (47.30%) | 38 (33.33%) | 12 (42.86%) | 15 (31.25%) | - | - | - |
High (>3.0 mmol/L) | 39 (52.70%) | 76 (66.67%) | 16 (57.14%) | 33 (68.75%) | - | - | - |
Serum triglycerides | |||||||
Normal (0.45–1.7 mmol/L) | 73 (98.65%) | 105 (92.11%) | 25 (89.29%) | 45 (93.75%) | - | - | - |
High (>1.7 mmol/L) | 1 (1.35%) | 9 (7.89%) | 3 (10.71%) | 3 (6.25%) | - | - | - |
Serum Lp(a) | |||||||
Normal (0–72.0 nmol/L) | 63 (85.14%) | 85 (74.56%) | 22 (78.57%) | 42 (87.50%) | - | - | - |
High (>72.0 nmol/L) | 11 (14.86%) | 29 (25.44%) | 6 (21.43%) | 6 (12.50%) | - | - | - |
Serum CRP | |||||||
Normal (0–5.0 mg/L) | 69 (93.24%) | 93 (81.58%) | 20 (71.43%) | 41 (85.42%) | - | - | - |
High (>5.0 mg/L) | 5 (6.76%) | 21 (18.42%) | 8 (28.57%) | 7 (14.58%) | - | - | - |
Plasma homocysteine | |||||||
Normal (4.4–13.6 µmol/L) | 64 (86.49%) | 98 (85.96%) | 23 (82.14%) | 44 (91.67%) | - | - | - |
High (>13.6 µmol/L) | 10 (13.51%) | 16 (14.04%) | 5 (17.86%) | 4 (8.33%) | - | - | - |
Serum uric acid | |||||||
Normal (143–339 µmol/L) | 71 (95.95%) | 99 (86.84%) | 22 (78.57%) | 41 (85.42%) | - | - | - |
High (>339 µmol/L) | 3 (4.05%) | 15 (13.16%) | 6 (21.43%) | 7 (14.58%) | - | - | - |
Hormonal contraceptive use | |||||||
No | 26 (35.14%) | 29 (25.44%) | 7 (25.0%) | 15 (31.25%) | - | - | - |
In the past | 25 (33.78%) | 54 (47.37%) | 12 (42.86%) | 26 (54.17%) | - | - | - |
Yes | 23 (31.08%) | 31 (27.19%) | 9 (32.14%) | 7 (14.58%) | - | - | - |
Total number of pregnancies per patient | |||||||
1 | 7 (9.46%) | 37 (32.46%) | 8 (28.57%) | 9 (18.75%) | - | - | - |
2 | 35 (47.30%) | 46 (40.35%) | 13 (46.43%) | 21 (43.75%) | - | - | - |
3+ | 32 (43.24%) | 31 (27.19%) | 7 (25.0%) | 18 (37.50%) | - | - | - |
Total parity per patient | |||||||
1 | 11 (14.86%) | 39 (34.21%) | 11 (39.29%) | 16 (33.33%) | - | - | - |
2 | 50 (67.57%) | 59 (51.75%) | 15 (53.57%) | 26 (54.17%) | - | - | - |
3+ | 13 (17.57%) | 16 (14.04%) | 2 (7.14%) | 6 (12.50%) | - | - | - |
Infertility treatment | |||||||
Yes | 3 (4.05%) | 23 (20.18%) | 6 (21.43%) | 6 (12.50%) | - | - | - |
No | 71 (95.95%) | 91 (79.82%) | 22 (78.57%) | 42 (87.50%) | - | - | - |
During gestation | |||||||
Maternal age at delivery (years) | 32.78 ± 0.38 | 32.26 ± 0.41 | 32.86 ± 0.58 | 33.65 ± 0.61 | 1.000 | 1.000 | 1.000 |
GA at delivery (weeks) | 39.85 ± 0.10 | 35.91 ± 0.33 | 35.23 ± 0.67 | 38.64 ± 0.21 | <0.001 | <0.001 | 0.106 |
Fetal birth weight (g) | 3390.14 ± 41.55 | 2403.45 ± 80.99 | 1831.43 ± 125.48 | 3226.46 ± 69.50 | <0.001 | <0.001 | 1.000 |
Mode of delivery | |||||||
Vaginal | 69 (93.24%) | 19 (16.67%) | 6 (21.43%) | 21 (43.75%) | <0.001 | <0.001 | <0.001 |
CS | 5 (6.76%) | 95 (83.33%) | 23 (78.57%) | 27 (56.25%) | |||
Fetal sex | |||||||
Boy | 37 (50.00%) | 49 (42.98%) | 15 (53.57%) | 23 (47.92%) | 0.345 | 0.747 | 0.822 |
Girl | 37 (50.00%) | 65 (57.02%) | 13 (46.43%) | 25 (52.08%) | |||
Blood pressure (mmHg) | |||||||
Systolic | 120.70 ± 1.13 | 157.32 ± 1.49 | 127.21 ± 3.06 | 148.73 ± 2.17 | <0.001 | 0.232 | <0.001 |
Diastolic | 75.85 ± 0.76 | 98.71 ± 1.01 | 78.07 ± 2.18 | 94.96 ± 1.45 | <0.001 | 1.000 | <0.001 |
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Hromadnikova, I.; Kotlabova, K.; Dvorakova, L.; Krofta, L. Evaluation of Vascular Endothelial Function in Young and Middle-Aged Women with Respect to a History of Pregnancy, Pregnancy-Related Complications, Classical Cardiovascular Risk Factors, and Epigenetics. Int. J. Mol. Sci. 2020, 21, 430. https://doi.org/10.3390/ijms21020430
Hromadnikova I, Kotlabova K, Dvorakova L, Krofta L. Evaluation of Vascular Endothelial Function in Young and Middle-Aged Women with Respect to a History of Pregnancy, Pregnancy-Related Complications, Classical Cardiovascular Risk Factors, and Epigenetics. International Journal of Molecular Sciences. 2020; 21(2):430. https://doi.org/10.3390/ijms21020430
Chicago/Turabian StyleHromadnikova, Ilona, Katerina Kotlabova, Lenka Dvorakova, and Ladislav Krofta. 2020. "Evaluation of Vascular Endothelial Function in Young and Middle-Aged Women with Respect to a History of Pregnancy, Pregnancy-Related Complications, Classical Cardiovascular Risk Factors, and Epigenetics" International Journal of Molecular Sciences 21, no. 2: 430. https://doi.org/10.3390/ijms21020430